WO2013049903A1 - Multidirectional cardiac defibrillation device with optimised switching; method and use thereof - Google Patents

Abstract

The present invention relates to a multidirectional cardiac defibrillation device capable of applying successive monophase or biphase shocks in three different directions, in that an electric current flows through three pairs of strategically separated electrodes during a period of less than 100 ms. The present invention also relates to the method of use and to the use thereof.

Description

 Patent Descriptive Report for: "DEVICE FOR MULTI-DIRECTIONAL HEART DEFIBRILATION WITH OPTIMIZED KEY; METHOD AND USE".

 Field of the Invention

 The present invention relates to the field of biomedical instrumentation. More specifically, the present invention relates to a key-optimized multidirectional cardiac defibrillation device and its method of use.

 Background of the Invention

 Cardiovascular diseases have been responsible for more than 30% of the human mortality rate in recent years (Ministry of Health, 2008; World Health Organization, 2004; American Heart Association, 2011). The cardiac rhythm abnormality known as ventricular fibrillation (VF) is a type of arrhythmia with high lethality potential, and the main cause of sudden death due to cardiac arrest. Therefore, the study of the mechanisms associated with this type of arrhythmia and the therapeutic approaches for its reversal is of fundamental importance.

The main mechanism involved in the maintenance of VF is the recess, where a wave of depolarization, when propagated, finds, for example, electrically refractory, which results in wave division and reentrant propagation in relatively stable circuits. In general, the recess is favored by the increased spatial dispersion of refractoriness. The existence of several small waves of depolarization spreading simultaneously in different directions, in different regions of the heart muscle, support fibrillation and irregular rhythm.

The mechanisms that initiate and maintain VF include arousal (ectopic activity) and propagation (recess) changes, which may be combined. For example, Pogwizd & Corr ^' , in a paper entitled "Mechanisms underlying the development of ventricular fibrillation during early yocardial ischemia" published in Circ Res, 66: 672-695 in 1990, proposed that the generation of reentrant circuits in myocardial ischemia may be associated. the occurrence of intramural conduction delay, which would allow the reexcitation of cells from adjacent regions whose excitability would have already been recovered, causing an ectopic activation. On the other hand, this same phenomenon would favor transmural indentation, which would support the VF.

For reversal of VF, electrical defibrillation is the only therapeutic procedure available today, see work by Koster and colleagues, entitled "Definition of successful defibrillation" published in Crit Care Med, 34: 423-426 in 2006. According to this work, this procedure consists of applying a high-powered electrical stimulus to the heart, either directly or through the chest. The electric current that flows through the heart is a function of shock energy and tissue impedance. Major factors that determine impedance include electrode size and proper coupling with the cardiac surface (in the case of direct defibrillation).

 Ventricular defibrillation is recognized as a probabilistic event, however, a higher intensity of shock is associated with a higher percentage of defibrillation success, according to the work of Chen and colleagues entitled "Current concepts of ventricular defibrillation" published in J Cardiovasc Electrophysiol. , 9: 553-562 in 1998 and Chattipakorn & Chattipakorn entitled

"Electrophysiological concept of ventricular defibrillation mechanism" published in J Med Assoe Thai, 87: 1394-1401 in 2004.

Defibrillation success also depends on how quickly the normal heart rate is restored as it relates inversely to the duration of the event. fibrillation, with the probability of death after the onset of arrhythmia increasing by 10% for each minute without treatment.

 Defibrillators are electromedical equipment designed to generate and apply intense and brief shocks of electrical current through electrodes positioned directly on the cardiac musculature, or indirectly through the thorax, in order to reverse arrhythmias.

 These devices are classified according to the output waveform as single phase (damped sine wave) or biphasic (truncated or rectilinear exponential wave). Its operation is based on the storage of electric energy in a capacitor, with charge voltages that vary according to the capacitance value, and the maintenance of this charge condition until the time determined for discharge.

Schwarz recommends in his paper entitled "Biphasic shocks compared with monophasic damped sine wave shocks for direct ventricular defibrillation during open heart surgery" published in Anesthesiology, 98: 1063-1069 in 2003 that the energy to begin single-phase transthoracic defibrillation should be 200 J and do not exceed 360 J, whereas with the biphasic waveform, lower energy values (<200 J) with equivalent or greater effectiveness are used. For discharges applied directly to the At the heart, the equipment is designed to limit the power to 50 J to prevent further damage to the myocardium.

 Defibrillator calibration is commonly performed according to the energy dissipated over a 50 resist resistive load, corresponding to cardiac and / or thoracic impedance.

The most effective strategy for ending VF is the application of an intense electric shock, according to the work of Dosdall et al. Entitled "Mechanisms of defibrillation" published in Annu Rev Biomed Engin, 12: 233-258 in 2010. However, the The application of high intensity electric fields (E) can cause undesirable effects, such as depression of contractile function and cell damage, probably due to electroporation of the cardiac myocyte membrane and subsequent Ca ²⁺ cell overload, as described in Tung's work entitled "Detrimental effects of electric fields on cardiac muscle" published in Proc IEEE, 84: 366-378 in 1996; Krauthamer & Jones, entitled "Calcium dynamics in cultured heart cells exposed to defibrillator-type electric shocks" published in Life Sci, 60: 1977-1985 in 1997; Soares in a paper entitled "Contractile Commitment of Isolated Cardiac Tissue after High Intensity Electric Field Stimulation." 74 P. Master's Degree in Biomedical Engineering by the Faculty of Electrical and Computation of Unicamp, Campinas, SP in 2003 and in the paper by Oliveira and collaborators entitled "Cytosolic Ca ²⁺ accumulation in ventricular myocytes after stimulation with high-intensity electric fields (HEF)" published in Biophys J, 88 (suppl. 1) , abstr 1514 in 2005.

Importantly, Ca ²⁺ overload can generate spontaneous activity in myocytes, generating ectopic foci. In addition, induction of persistent depolarization and / or cell damage in certain regions may favor the formation of conduction blocks that may lead to a new arrhythmogenic recess circuit for arrhythmia perpetuation, which may contribute to the failure of defibrillation.

US Patent 7,096,063, filed March 19, 2004 in the name of MEDTRONIC, INC. and entitled "Method and apparatus for delivering multi-directional defibrillation waveforms" describes a method and device that stores energy for discharge through a plurality of electrodes. In this document, there is a temporal overlap with simultaneous shocks, which may involve a greater risk of deleterious effects given the spatial sum of the resulting electric vectors in discrete regions of the heart, so that certain sets of cells would be exposed to high intensity fields. , favoring the emergence of conduction block and arrhythmia maintenance. In addition, in that document there is the possibility of sequential shocks with no established time lag for electrical stimulation, which may lead to shocks coinciding with the vulnerable myocardial period, ie during the relative refractory period and soon after repolarization, may give rise to new depolarization fronts, causing the arrhythmia to restart.

Therefore, perfecting the stimulation procedure, making it more efficient and safer, is essential for the effective treatment of cardiac arrhythmias. Multidirectional stimulation of isolated cells, seeking to maximize the excitatory effect of the electric field, has been studied as an approach to minimize stimulatory field intensity; Among the works, we can highlight Lima, entitled: "Effect of Electric Field Direction on the Isolated Ventricular Myocyte Stimulation Threshold" published as Master's Dissertation of the School of Electrical and Computer Engineering by Unicamp, Campinas, SP in 1999; Bassani et al. Entitled "Combining stimulus direction and waveform for optimization of threshold stimulation of isolated ventricular myocytes" published in Physiol Meas, 27: 851- 863, 2006; and Fonseca and collaborators entitled "Multidirectional cardiac cell stimulation: instrumentation and experimentation" presented at the XXI Brazilian Congress of Biomedical Engineering in Salvador, BA in October 2008.

This approach has also been tested for application in the heart in situ, with sequential stimuli applied across multiple electrode pairs in different orientations and configurations, as highlighted in the work of Chang and colleagues entitled "Double and triple sequential shocks reduce ventricular defibrillation threshold in dogs with and without myocardial infarction "published in the J Am Coll Cardiol, 8: 1393 - 1405 in 1986; Jones et al., Entitled "Internai cardiac defibrillation in man: pronounced improvement with sequential pulse delivery in two different lead orientations" published in Circulation, 73: 484 - 491 in 1986; Jones et al., Titled ⁿ Internai cardiac defibrillation: single and sequential pulses and a variety of lead orientations "published in Pacing Clin Electrophysiol, 1: 583 - 591 in 1988; Exner et al., Titled" Combination biphasic waveform plus sequential pulse defibrillation improves defibrillation nonthoracotomy efficacy of a lead system "published in ^J" Am Coll Cardiol, 23: 317-322 1994; Kerber et al. Entitled "Overlapping sequential pulses: a new waveform for transthoracic defibrillation" published in Circulation, 89: 2369-2379 in 1994; Thakur et al., Entitled "Irect Comparison of Monophasic, Biphasic, and Sequential Pulse Defibrillation over a Single Current Pathway" published in Can J Cardiol, 12: 407-411 in 1996; Pagan-Carlo et al., Entitled "Encircling overlapping multipulse shock waveforms for transthoracic defibrillation" published in J. Am Coll Cardiol, 32: 2065-2071 in 1998; Zheng et al. Entitled "Reduction of the internal atrial defibrillation threshold with balanced orthogonal sequential shocks" published in J Cardiovasc Electrophysiol, 13: 904-909 in 2002. However, in these cases, the interval between shocks in different directions has not been taken in consideration.

 Fonseca et al., In their 2008 paper, demonstrated that the application of multidirectional shocks, keyed short enough to not exceed the duration of ventricular (rat) BP, produced excitatory recruitment comparable to or even greater than that of shocks in several directions with range> 2 s.

As can be seen no prior art document describes or much less suggests using the optimized keyed multidirectional defibrillation, ie with the defibrillatory discharge applied in different directions and keyed so that the sequence lasts less than the refractory period of myocardial tissue.

 Summary of the Invention

 To solve the aforementioned problems, the present invention will provide significant advantages over existing cardiac defibrillation devices, enabling an increase in their performance and having a more favorable cost / benefit ratio.

 The present invention relates to a multidirectional cardiac defibrillation device capable of delivering mono- or biphasic sequential shocks in three different directions by passing electric current through three strategically separated electrode pairs within a period of less than 100 ms.

The power supply of the device of the present invention was powered by a DC voltage source consisting of a sealed lead acid rechargeable battery. The circuit consisted of a voltage regulator that provided +5 V to the control circuit and the interface of the equipment with the user, and a switching power supply responsible for raising the voltage to the required load levels of three. capacitors in which they stored the defibrillatory discharge. Each capacitor discharged energy in each direction.

 Brief Description of the Drawings

 The structure and operation of the present invention, together with its additional advantages, may be better understood by reference to the accompanying drawings and the following description:

 Figure 1 shows a block diagram of the multidirectional defibrillation device of the present invention;

 Figure 2 shows a schematic circuit of the power supply and switching source of the multidirectional defibrillation device of the present invention;

 Figure 3 shows a schematic control circuit of the multidirectional defibrillator of the multidirectional defibrillation device of the present invention;

Figure 4 shows a switching circuit, for example ^the multidirectional orientation 0 defibrillation device of the present invention;

 Figure 5 shows a clock graph for

20 ms for the activation of the switching desfibrilatoria discharge in ^the directions 0, 60 and 120 °;

Figure 6 shows the complete circuit of the multidirectional defibrillation device of the present invention; Figure 7 shows the electrodes, in the form of concave discs, formed by a spherical cap, part of a sphere cut by a plane;

 Figures 8A, 8B, 8C, 8D, 8E and 8F show the electrode support piece developed by prototyping with polycarbonate / abs plastic material for the present invention;

 Figure 9 shows the 30-ms monodirectional (left) and multidirectional (right) defibrillatory discharge waveforms for energy levels 1 to 7J (indicated on each panel;

 Figure 10 shows the 20-ms monodirectional (left) and multidirectional (right) defibrillatory discharge waveforms for energy levels 1 to 7J (indicated on each panel).

 Figures 11A and 11B show graphs of defibrillation probability curves as a function of applied energy (J) obtained from single- and multi-directional pig heart (open chest) defibrillation using 30 (A) and 20 ms defibrillatory pulses duration (B). The dots indicate the means and their standard error values;

Figure 12 shows a graph of the defibrillation probability curves as a function of energy applied (J), obtained from mono and multidirectional defibrillation in 6 animals in which the paired design could be used. The dots indicate the means and their standard error values;

 Figure 13 shows the energy levels required for different probabilities of success in cardiac defibrillation determined in the same animals with mono and multidirectional shocks. Data are presented as mean ± standard error. * P <0.05 vs. monodirectional shock; and

 Figure 14 shows a block diagram of the power circuit of the optimized keyed multidirectional cardiac defibrillation device of the present invention;

 Annex 1 (A, B and C) shows the multidirectional defibrillation device of the present invention developed for application of defibrillatory pulses in three directions; and

 Annex 2 shows the defibrillation gauntlets, each with an arc in which are located 3 concave disc-shaped metal electrodes, charge (green) and trigger (red) buttons, and coiled cable with connector.

Detailed Description of the Invention

Although the present invention may be susceptible to different embodiments, it is shown in the drawings and in the Following detailed discussion, a preferred embodiment with the understanding that the present embodiment is to be considered an exemplification of the principles of the invention and is not intended to limit the present invention to that illustrated and described herein.

 The effectiveness of the electric field in stimulating a cell is greatest when it is oriented parallel to the major axis of the cell. In the heart, the cells are arranged in different orientations, so a stimulus in a given direction should excite only one set of cells. For more widespread arousal, it is necessary to increase the intensity of the electrical stimulus.

 With stimulation in more than one direction (multidirectional), it is possible to excite a larger number of cells with a lower stimulus intensity. In the case of cardiac defibrillation, which usually employs strong shocks that can damage the myocardium, reducing the intensity of shock by multidirectional stimulation implies greater safety in the defibrillation process.

A recognized cause of failure in electrical defibrillation is the excitement of cells in the so-called vulnerable period, which favors the resettlement of ventricular fibrillation by defibrillation shock itself. With the application of multidirectional shocks in a shorter period to the duration of the myocardial refractory period, when the cell is not electrically excitable, the restart of fibrillation is minimized, which increases and defibrillation efficiency. This means greater cell recruitment without re-excitation.

 The results obtained by a defibrillation modality of the present invention showed that the optimized switching multidirectional defibrillation allowed a significant reduction of the applied energy level, which is expected to reduce the incidence and severity of the deleterious effects caused by the high intensity electric fields. used for cardiac defibrillation, thus contributing to greater defibrillation success (decreasing the likelihood of arrhythmia recurrence) and a lower degree of myocardial injury.

The technique developed for cardiac defibrillation using a multidirectional defibrillator of the present invention is based on the delayed delivery of shocks in 3 different directions to electrically recruit more myocardial cells, but the stimulation process, which lasts less than of the refractory period, is brief enough that the cells are excited by only 1 of the shocks. In addition, the device developed by the present invention allows defibrillation multi-directional optimized switching is applied using a single portable defibrillator (vs. multiple defibrillators coupled by a synchronizer device) and a single pair of gauges / paddles (as opposed to multiple pairs of heart-attached electrodes), which facilitates use of this method in the clinical condition.

 Therefore, the succession of multi-directional shocks with optimized lag allows rapid excitation of cells with different orientations to ensure that the myocardium is not stimulated during the period of vulnerability and that if the cardiac cell is excited by a given stimulus, it will not respond. others during the same stimulatory cycle, thus minimizing the onset of conduction block and reexcitation. The non temporal overlap of the stimuli avoids the sum of electric vectors, avoiding the generation of very high fields over a given myocardial region.

 Optimized multi-directional defibrillation of the present invention is a process whereby shocks in more than one direction are keyed with millisecond lag so that the sequence lasts less than the myocardial refractory period.

The multidirectional defibrillation device developed by the present invention is capable of applying single or two-phase sequential shocks in three different directions by passing electric current through three strategically separated electrode pairs within a period of less than 100 ms.

 The equipment was powered by a DC voltage source consisting of a sealed lead-acid rechargeable battery. The circuit consisted of a voltage regulator that provided +5 V to the control circuit and the interface of the equipment with the user, and a switched source responsible for raising the voltage to the required charging levels of three capacitors in which the discharge was stored. defibrillation. Each capacitor discharged the energy in one direction.

A microcontroller is responsible for generating sequential firing pulses (rectangular voltage pulses, 5 V) for the activation of semiconductor switches that allowed the defibrillatory shock to be discharged in all three directions. The pulses were generated in such a way as to trigger with a slight lag the switching on each pair of electrodes. With each trigger command, only one pulse sequence is generated. The switching circuit consists of three electronic switches (triacs) which, when triggered by the gate clocks, discharge the voltage stored in the capacitors, thus allowing the passage of electric current through the heart in each direction of stimulation. Current conduction is limited to clock duration only.

 Pulse transformers were used to ensure triacs trip when a 1 kHz pulse train from the control circuit is maintained in one of its inputs, and also to electrically isolate the control circuit from the power circuit to be triggered.

 For direct defibrillation (i.e. contact of the electrodes with the heart surface under open chest condition), a handle / shovel model has been developed which each presents three (3) concave disc-shaped electrodes, 304 surgical stainless steel, polished and brushed, 1 mm thick. Each electrode was fixed to a support shaft attached to an arc, which contains internal channels for the wires to pass through. The support base of the electrodes was developed by prototyping technique, consisting of polycarbonate / abs, and has three holes of 5 mm diameter for electrode installation.

The lateral electrodes were positioned at 60 ² with respect to the central hole to establish the directions of application of the shocks. In the upper part of the central hole, a circular base for an aluminum cylinder, covered with electrostatic paint, for the purpose of coupling the part with the electrodes to the handle to protect the wiring connected to the electrodes, as well as to lengthen the part and thus facilitate the handling of the electrodes inside the cavity. thoracic The grip handles were designed to minimize the possibility of operator contact with the electrodes and conductive parts, and contained a button to trigger the charging of capacitors and another to trigger the discharge tripping. To connect the contact between all electrodes and switches to the defibrillator, two coiled electrical cables through 5-way connectors were used.

 Preferred Modality of the Present Invention

Multidirectional defibrillator

The multidirectional defibrillator of the present invention was developed based on the switching circuit that allows electrical stimulation of isolated ventricular myocytes in 3 directions and 60 ° separation angle, as in the work of Fonseca et al. Entitled: "Multidirectional cardiac cell stimulation" : instrumentation and experimentation "presented at the 21st Brazilian Congress of Biomedical Engineering. Salvador, BA in October 2008 and incorporated herein in its entirety by reference, as well as in the prototype of a conventional defibrillator that provides cushioned single-phase internal sinusoidal defibrillation discharge, presented in Viana's paper entitled: "'Defibrillator Prototype Assembly and Experimental Analysis in Anesthetized Dogs" - Electrical Engineering Degree - Pontifical Catholic University of Minas Gerais, Poços de Caldas, MG. 2007, also incorporated herein in its entirety by reference.

The developed device of the present invention provides capacitive discharge monopolar waveform (RC - resistor / capacitor) voltage pulses and is capable of delivering shocks: a) in a single direction (monodirectional, ie as used in conventional defibrillators), by passing electric current between only one pair of electrodes (one electrode in each paddle); or b) sequential shocks in three different directions (multidirectional) by passing current through three strategically separated electrode pairs at an angle of 60 °. Multidirectional discharge switching is designed to be fast enough (60-90 ms total) to allow direct electrical stimulation of the heart in all three directions within the duration of cardiac PA in large mammals (200 ms in swine at room temperature). 37 ° C, as shown in the work of Roscher et al. Entitled “Effects of dopamine on porcine myocardial action potentials and contractions at 37 ° C and 32 ° C” published in Acta Anaesthesiol Scand, 45: 421-426 in 2001). Thus, most cardiac cells respond to only one of the stimuli applied.

 The intensity of the defibrillator pulses was dependent on the energy level selected on a continuous scale from 0.48 to 7.31 J. The energy delivered during a defibrillator shock was calculated according to the equation published in the works of Bardy et al. Entitled "Prospective comparison of sequential pulse and single pulse defibrillation with use of two different clinically available systems "published in J Am Col Cardiol, 14: 165-171 in 1989; and Dosdall & Sweeney's work entitled "Extended charge banking model of dual path shocks for implantable cardioverter defibrillators" published in Biomed Engin Online, 7: 22-35 in 2008, both of which are incorporated herein by reference in their entirety.

 1 ,

 Energy = - C V (equation 1)

 2

where Energy is given in J, C is the capacitance (in Ρ) of the energy storage capacitors, and V is the voltage capacitor load (V) required for each power level.

 Table 1 represents the charge voltage required for power levels from 1 to 7 J using capacitors with fixed capacitance of 100 μΡ. This capacitance was chosen with the purpose of reducing the charge voltage required for each energy level and, consequently, reducing the applied electric field (E, in V / cm) and the peak current during defibrillation, thus minimizing possible damage to the myocardium. However, the equipment may use different capacitors to generate different levels of electrical voltage.

 Table 1 shows the capacitor charge voltage calculated (equation 1) for energy levels to be selected for direct defibrillation discharge, and the respective electric current X, calculated by Ohm's law (V = R. I), where R = 50 Ω, to simulate heart impedance according to the Brazilian Association of Technical Standards.

 Energy (J) Charge Voltage (V) Current

 1.0 141.4 2.8

 2.0 200.0 4.0

3.0 244.9 4.9 4.0 282.8 5.6

 5.0 316, 6.3

 6.0 346.4 6.9

 7.0 374.1 7.4

 The multi-directional defibrillator, as shown in the block diagram of Figure 1, consists of a power supply that supplies a regulated voltage to the control and interface circuits of the equipment, as well as providing the capacitor charging voltage according to the level. selected power (Table 1).

 The isolation circuit is designed to ensure electrical isolation between the low voltage circuit (control circuit) of the high power circuit (switching circuit), and also to ensure that the switching actuation in each direction to trigger the defibrillation discharge. The electronic circuits corresponding to each of the diagram blocks will be described as follows: Power Supply

The power supply of the device of the present invention was powered by a DC voltage source consisting of a sealed, valve-regulated rechargeable lead acid battery of 6.0 V and 4.5 Ah (mod. UP-645 Unipower, Unicoba Ind. Electronic Components, São Paulo, SP). For recharging, an electronic sealed battery charger was used 6.0 V _DC and 0.4 Ah (mod. FCB 64AL, Hayonik Ind. Com. Electronic Prod., Londrina, PR).

This circuit was comprised of a voltage regulator (mod. LM2940CT-5.0, National Semiconductor Co., Santa Clara, CA, USA), which provided +5 V to the control circuit and the user interface, and a switching power supply responsible for raising the voltage to the required load levels of the capacitors responsible for storing the defibrillation discharge (0 to 382 V). The switching power supply incorporates an adjustable switching regulator (mod. LM2577-ADJ, National Semiconductor Co., Santa Clara, CA, USA) that switches the high frequency current to maintain a stabilized DC output voltage. The switched regulator was connected to a transformer (mod. TR 70415, Ralp Industrial, Alvorada, RS), designed on the Thornton NP-23 / 17-4900-IP6 core for 1:10 loop ratio, with Ni = 4 turns , Li = 78.4 μΗ, N ₂ = 40 turns, L ₂ = 7.84 mH, and 52 kHz frequency), and its output was connected to a fast rectifier diode UF4007 (1.0 A, 1000 V, Fairchild Semiconductor, San Jose, CA, USA), as shown in Figure 2.

Thus, at the transformer output, the voltage was high corresponding to the energy level to be applied, and was adjusted by a multi-turn potentiometer. 100 kQ (5% accuracy, linear). Under this output voltage was a voltage divider consisting of a 1 resist (1/8 W, 5%) resistor and a 20 kQ 3296 trimpot (10% adjustable vertical potentiometer, Kingtronics Int. Co., Hong Kong , China). Thus, there was a voltage of 0-5 V serving as a sample to the control circuit, and proportional to 141-382 V.

 The switching on of the switching power source was initiated manually by a green push button switch (mod. R16-503AD) on one of the defibrillation knobs.

Control circuit

To control the defibrillation discharge switching, the selection of the single or multidirectional triggering mode, and the presentation via LCD display of the data regarding the selected voltage and the respective power level, the PIC 16F818-I / P microcontroller was used. (Microchip Technol. Inc., Chandler, AZ, USA), an integrated circuit that pulls together all the circuits needed to make a complete programmable digital system. Structurally the device has 18 pins (16 input / output pins, V _S if + V _DD ), and consists of a processor, 128 bytes of data (RAM) and program memory (EEPROM), internal 4-oscillator MHz, and has 5 channels of integrated analog / digital (A / D) converters.

The programming of the functions to be performed by the microcontroller was developed in assembly language, and the program was written and loaded by the MPLAB ^® IDE (Microchip Technol) recording software. Inc., Chandler, AZ, USA) for the microcontroller to execute all instruction cycles.

 The YEAR port A / D converter (pin 17) was used to record the signal of the load voltage samples (0-5 V, analog magnitude) in order to generate the digital representation of these voltage levels and provide an LCD display (16 columns x 2 character lines, with blue backlight; mod. LCD-016 002B, Vishay Intertechnol., Shelton, CT, USA) the VOLTAGE (in V) and ENERGY (in J) variables. The energy was calculated internally to the microcontroller through programming, according to equation 1, in which it stored at each moment in its memory registers samples of the capacitor charge voltage.

The microcontroller was configured to communicate with the display via the RA1, RA2, and RB0-RB3 ports (pins 18, 1, and 6 through 9, respectively), while the display received the microcontroller data on pins 4, 6, 11- 14 The display pins 1 and 3 accounted for the contrast, which was adjusted by a 10 kQ trimpot (10%, Kingtronics Int. Co., Hong Kong, China); pin 2 received +5 V power, pins 5, 7-10 were grounded (GND), and pins 15 and 16 were used for backlighting of the display.

Programming has been configured so that port RB5 (pin 11) is responsible for selecting the single-way triggering mode (when a lever-type switch remained in the "open" position) or multi-directional triggering (when the switch was closed for GND) as shown. in Figure 3. Pins 5 (V _ss ) and 14 (V _DD ) were connected to GND and +5 V power respectively. At output RB4 (pin 10), a 1 kHz pulse train was generated, which was used to ensure the triggering of the switching.

Monodirectional Shooting Control

 One-way firing was performed when the lever-type switch (pin 11) located on the front panel of the equipment was positioned in the one-way position. In this way, the microcontroller was programmed to generate the clock only at output RA4 (pin 3). This output corresponded to the central electrodes of the gauntlets.

Multidirectional Shooting Control By selecting the multi-directional defibrillation mode, at the time of shock release, the microcontroller generated the trigger pulses following the three programmed outputs (pins 2, 3 and 16), corresponding to one pulse for each direction (0 ^o , 60 ° and 120 °). The pulses were generated so as to trigger the switching delayed by 20 or 30 ms for each pair of electrodes, so that the last stimulus was applied 60 ms after the first trigger, and 20 or 30 ms after the second trigger, totaling an application time of 60 or 90 ms.

 Switching, isolation and energy storage circuits

 The switching was performed by three electronic switches that, when activated, discharged the voltage stored in the capacitors, thus allowing the passage of electric current through the heart in a given direction of stimulation.

The switching source provided the charging voltage to the capacitors according to the energy level selected for application. The power supply was connected in parallel to the positive terminal of three 100 iF capacitors (mod. UPT2G101MHD, Nichicon Corp., Kyoto, Japan) via a 6A10 rectifier diode (6.0 A, 1000 V, Rectron Semiconductor Inc., Chino, CA, USA), directly polarized to each of them. To the negative terminals of the capacitors, another 6A10 diode was connected, directly polarized with the switched source GND, as shown in Figure 4.

Between the diode cathode and the positive terminal of each capacitor, a Triode for Alternating Current (TRIAC TIC226M, 8.0 A, 600 V, Power Innov., Inc., Lindon, UT, USA) was connected, which is a component. semiconductor that conducts two-way electrical current and acts as a voltage-actuated electronic switch. This component has the Anodol (pin 1), Anode2 (pin 2) terminals and a trip terminal (gate, pin 3), and remains in a non-conducting state until it receives a gate trip voltage pulse from the control. Thus, once the capacitors are charged, the discharge occurs with current passing through the TRIACs only when the clock is received at the gate, and the voltage stored in the capacitors is discharged only during the clock period, as shown in Figure 5. The connection of the control circuit to the gate of the TRIACs was performed by pulse transformers (with 1: 1 ratio, mod. TP-1: 1 / 4T, Thornton Eletrônica, Vinhedo, SP), components powered by voltage pulses in TRIACs should be tripped to prevent short circuiting of the switches. semiconductors and ensure that the control circuit is electrically isolated from the power circuit to be driven. Thus, at one of its inputs, the pulse transformer received the clocks via a BC548C transistor (Motorola Semiconductors, Hong Kong, China), in series with a 100 Ω (1/8 W, 5%) resistor. ) to limit current, and on the other input received, by means of a 470 Ω (1/8 W, 5%) resistor, in series with a BC548C transistor, 1 kHz constant frequency pulse train as a guarantee of the switching trip. Finally, one of the outputs of the pulse transformers was connected to the TRIACs gate and the other to Anode1. Multidirectional defibrillator assembly

 The electrical circuit design for the multidirectional defibrillation device of the present invention was developed with ISIS software (Figure 6), part of the Proteus Professional Suite Design 7.7 application (Labcenter Electronics, Ontario, Canada), which also contains ARES software for development. circuit board (PCI) layout template. After the project was carried out, a file was generated for PCI (Alfapress PCI, Campinas, SP) and subsequent welding of the components.

As shown in Annex IA, the PCI and battery were allocated in a bench cabinet type box (mod. BO 62609, of dimensions 307 x 257 x 65 mm, Phoenix Mecano With. Tec. Ltda., São Paulo, SP), and the components were connected to the front and rear panel. The panels were constructed in APD / CEB / UNICAMP, made of PVC plastic, with adhesives attached to the front (indicating switch functions, power level selection and outputs for defibrillation electrodes, annex 1B) and rear (charge inlet). battery and fuse, attachment 1C). On the top of the box, a sticker with warnings and instructions on how to operate the equipment was attached. The stickers were made using Coreldraw® Graphics Suite X5 (Corel Corporation, Ottawa, Canada).

Defibrillation Gauntlets and Electrodes

The electrodes were used as a means of contact between the defibrillator and the heart surface to apply the defibrillator discharge. Due to the need for the use of 3 pairs of electrodes (vs. only 1 in conventional defibrillation) and the establishment of contact of the 6 electrodes with the cardiac surface, there was concern about the size of the electrodes. Although reducing the surface area of the electrodes was necessary for proper contact, it could not be greatly reduced as an excessive increase in electrical current density could cause burns to the cardiac tissue during defibrillation. The minimum recommended area for defibrillation electrodes for internal use in pediatrics (900 mm ² ; ASSOCIATION FOR THE ADVANCEMENT OF MEDICAL INSTRUMENTATION. Cardiac defibrillator devices. ANSI / AAMI DF2-1996. Arlington (VA)) was adopted for each electrode. AAMI in 1996. American National Standard., BRAZILIAN ASSOCIATION OF TECHNICAL STANDARDS Electromedical Equipment - Part 2-4: Particular Requirements for the Safety of Cardiac Defibrillators ABNT NBR IEC 60601-2-4: 2005. Rio de Janeiro, 2005, incorporated herein in its entirety by reference).

Six concave discs were manufactured in polished and brushed 304 surgical stainless steel with a thickness of 1 mm (Nova Inox, Campinas, SP). The height of the concavity, which aims to improve contact with the heart surface, was 2 mm, the same as the electrodes sold for pediatric internal defibrillation (mod. 7252-4, Instramed, Porto Alegre, RS) used by Viana (2007). ), incorporated herein in its entirety by reference. The disk diameter was calculated by taking into account the area of a spherical cap, according to the work of Harris & Stocker entitled "Spherical cap. In New: Handbook of Mathematics and Computational Science. New York: Springer-Verlag, 1998, and incorporated herein in its entirety by reference as shown in Figure 7.

The diameter was calculated by adopting a minimum spherical cap area of 900 mm ² and a concavity height of 2 mm, reaching a value of 34 mm, which is in accordance with ABNT NBR IEC 60601-2 -4 ( 2005) and AAMI / ANSI DF 2 (1996), incorporated herein in its entirety by reference.

 Each electrode was fitted with a stainless steel support shaft, 5 mm in diameter and 10 mm in length. Once the fixation was completed, an electrostatic powder painting with white paint (JPS Pinturas Especiais, Campinas, SP) was made on the back of the electrodes and on the shaft for electrical isolation of these parts, preventing some of the energy from being dissipated. contact with tissues other than the myocardium.

The support base of the electrodes was developed by prototyping technique, which consists of manufacturing physical objects directly from three-dimensional virtual objects generated by software, by a melt deposition modeling process, by extrusion of heated plastic filaments, in successive layers until the formation of the object completely. The various layers receive both the material for the construction of the object and a material used as a support for suspended surfaces, which is removed by post-processing with ultrasound.

The final piece was made of polycarbonate / abs, and had three 5 mm diameter holes for electrode installation (Figure 8A). Regarding the central hole, other holes were positioned at 60 ° to form the shock application direction ^(the 0, 60 ° and 120 °) as shown in Figure 8B. The lateral rods were hollow ducts for passage of the welded wiring to the electrodes (Figure 8C). In the upper part of the central hole, a circular base was built to fit an aluminum cylinder (9 mm in diameter and 140 mm in length), covered with electrostatic painting, with the purpose of coupling the part with the electrodes to the handle. handle to protect the wiring attached to the electrodes as well as to lengthen the part and thus facilitate the handling of the electrodes within the chest cavity (Figure 8D).

All holes remained hollow to the rear of the part, and their opening was enlarged to allow welding of the wires (Figure 8E). The void space of this welding area was subsequently filled with Siqmol silicone rubber (hardness: 6022, gray, Siqplás Ind. Com., Sao Paulo, SP) to prevent waste from entering, and finally closed with caps made of the same. part material (Figure 8F).

 The grip handles are designed to minimize the possibility of operator contact with the electrodes and conductive parts as recommended by ABNT NBR IEC 60601-2-4 (2005), incorporated herein in its entirety by reference. Two handles were constructed from 32 mm diameter and 140 mm long nylon dowels, which were later connected to the aluminum rod and polycarbonate / abs piece, with the three electrodes each. At the top of each handle, push-buttons were fitted, one for charging the capacitors (green) and the other for discharging (red). To connect the contact between all the electrodes and the switches to the defibrillator, two 5300 mm long and 5 mm diameter coiled electric cables were used, with 5 twisted contact paths, 3 ways for connection to the electrodes and 2 for the keys (Seat Telecom Ind. Com. Fios e Cabos Ltda., Salto, SP).

Finally, an Ml6 male 5-wire cable connector (ITC Connectors, Embú Guaçu, SP) was added to each end of the electrical cables to connect the lead leads to the respective M16 female 5-wire connectors located on the defibrillator panel. multidirectional. Annex 2 shows the final set of electrode handles.

 The multidirectional defibrillator tests were performed at APD / CEB / UNICAMP, and consisted of the waveform analysis of the monodirectional and multidirectional discharges, in terms of voltage versus time, according to the selected level of energy to be applied. Accordingly, the assay of the device of the present invention was performed by specifying the energy delivered to a resistive load of 50 Ω, which simulates the patient's impedance, as recommended by IEC 60601-2-4 (2005), incorporated herein by all by reference. Resistive load variations were made in order to observe the possible changes in the final waveform of the defibrillatory discharge.

 The pulse waveforms released by the microcontroller and the defibrillator discharge performed by switching were acquired on a digital oscilloscope (mod. DSO3062A, Agilent Technologies Inc., Santa Clara, CA, USA) connected to a computer using the software. DSO3000 Series Scope Connect Software (Version 04.02.10, Agilent Technologies Inc., Santa Clara, CA, 2005).

In vivo testing methodology Ten young (8 weeks old) Large-White female pigs, average weight 20 ± 3 kg, with conventional sanitary standard, from a specialized breeder (Geraldo Vermeulen, Holambra, SP) were used. The animals were housed in individual pens at the NMCE / FCM / UNICAMP Surgical Technique Discipline, receiving filtered chlorinated water and industrial feed ad libitum, where they did not undergo experimental manipulation until the experiments were performed. No fasting period was observed prior to the experiments.

The experimental and animal maintenance protocol was approved by the Ethics Committee on Animal Use, Institute of Biology, UNICAMP (CEUA / IB / UNICAMP; Protocol No ² 2251-1.).

Prior to the start of the experiments, all animals received pre-anesthetic ketamine medication (10 mg / kg. Im). The animal was then taken to the operating room and placed in Claude-Bernard's gutter. Venous access was performed in the auricle for administration of fentanyl hydrochloride and sodium thiopental (12.5 μg / kg and 25 mg / kg, respectively, iv). After orotracheal intubation, the animal was maintained on controlled ventilation (tidal volume of 10 ml / kg and approximately 50% inspired oxygen fraction). Were connected electrodes electrocardiogram for monitoring cardiac electrical activity (physiographer, mod. Biomonitor 7, Bese-Bio System Engineering and Equipment SA, Belo Horizonte, MG). After local asepsis with iodized alcohol, thoracotomy was performed by electrocautery (mod. SS 500, WEM, Ribeirão Preto, SP), ribs spacing with Finochietto retractor and pericardium opening. The heart was periodically moistened with saline during the experiments. The depth of anesthesia was constantly monitored, and additional doses of anesthetic were administered as needed.

Experimental Protocol

 Two preliminary experiments were performed to familiarize the experimenter with the new paddle system, as well as to test the equipment design and the handles / electrodes, and to determine the power range of shocks required to reverse fibrillation. Based on the results of these tests, the necessary adaptations were made to the size of the electrodes and the support piece.

In the experimental group (N = 10), it was used in the same animal, the two modalities of shock (mono and multidirectional), trying to minimize differences between animals that could interfere in the results. Shocks from Two modalities were applied alternately during the course of the experiment, so that both modalities were tested in parallel during different phases of the experiment, in which time variation of the energy level required for defibrillation could be observed.

Ventricular fibrillation was induced by brief direct contact of the terminals of a commercial 9.0 V _DC battery with the ventricular surface to apply a microampere direct current as described by Viana (2007), incorporated herein in its entirety by reference.

 The battery contact location was maintained the same for successive mono and multi-directional shock testing. Immediately prior to induction of ventricular fibrillation, the specially developed pad arches were positioned, preferably orienting the electrode pairs in the baso-apical direction to allow direct contact of the electrodes with the cardiac surface.

After confirmation of the establishment of VF, defibrillatory shocks were applied. The shocks were applied in alternating episodes, in mono and multidirectional modalities. From one episode to a given mode, 2 energy levels were obtained: one insufficient and the other sufficient to produce ventricular defibrillation. If the first applied level was successful, the energy of the next shocks (same mode) was reduced until it was unable to reverse the arrhythmia. If unsuccessful with the first level, energy was increased in subsequent shocks until defibrillation was produced. Then began a new episode for the other modality, and so on.

 In case of failure of the defibrillator under test to reverse ventricular fibrillation, a conventional transthoracic defibrillator (mod. Cardiomax, Instramed, Porto Alegre, RS) was used, with the application of biphasic 360 J shocks. retractor, the ribs were approximated, and the shocks were externally applied to the thoracic cavity. In addition, the internal defibrillator prototype developed by Viana (2007), incorporated herein in its entirety by reference, was also used for this purpose, directly applying to the heart 5-7 J single-phase shocks through pediatric paddles (mod 7252-4, Instramed, Porto Alegre, RS) for reversal of fibrillation. In the period required for defibrillator recharging, internal cardiac massage was performed to prevent complete disruption of circulation.

0 restoration of sinus rhythm after shock (ie, successful defibrillation procedure) was observed visually and by electrocardiographic A 5-15 minute interval was observed between successive attempts to induce fibrillation-defibrillation.

 Testing on each animal continued until refraction-induced shock reversal fibrillation was observed with either the transthoracic defibrillator or the Viana (2007) prototype, incorporated herein in its entirety by reference. Anesthesia was then deepened and euthanized by lethal injection of 19.1% KC1, with observation of the animal's death during observation for 20 minutes.

Mono and multidirectional discharge

As already mentioned, the selection of the monodirectional modality implies defibrillatory discharge only in the central electrode pair of the gauges, while when the multidirectional modality is selected, lagged shocks are delivered through the three electrode pairs. The discharge desfibrilatória in each direction ^(the 0, 60 ° and 120 °) was activated whenever the charge switching TRIACs remained in the driving state. Therefore, the duration of the shocks was determined by the duration of the TRIAC gate clock train, which was initially set to 30 ms. So in In the monodirectional mode, a single shock lasting 30 ms was delivered, which was also the duration of the shock delivered in each of the 3 directions in the multidirectional mode, with a total duration of defibrillatory discharge of 90 ms. Subsequently, shorter shocks (20 ms) were applied, with a total duration of the 60 ms discharge period.

 The peak voltage reached during discharge for each power level was the same amplitude for both modes, and was proportional to the initial voltage required for the capacitor load as shown in Table 1.

 The single phase RC discharge waveform of the developed equipment is characterized by voltage drop as an exponential function of time. Figure 9 and 10 show the mono and multi-directional defibrillatory waveforms in tension according to the selected energy level (1-7 J) for the 30 and 20 ms durations, respectively. The tests were performed under a resistive load of 50 sim, simulating the impedance of the heart. Multidirectional Electric Defibrillation In Vivo

The result of the survival analysis is a set of points that describes the probability of defibrillation as a function of the energy applied. At these points, it was possible to successfully adjust a sigmoid function (R ² > 0.97 in all cases), which allows the determination of the energy level required for a given probability of defibrillation success. Table 2 and Figure 11A show the results obtained from experiments performed on 4 animals using 30 ms switching pulses for mono and multidirectional shock modalities. There was no significant difference in the curve Hill coefficient in the different modalities.

 Although the curve for multidirectional shocks was shown to be shifted to the left (Figure 11A), the difference between the energy values required for a 50% defibrillation probability (E50) did not reach statistical significance given the overlap of their confidence intervals for 95% (P> 0.05), which, however, was minimal (Table 3).

On the other hand, for 20 ms long pulses (6 animals; Table 4 and Figure 11B), a clear parallel deviation (characterized by closer Hill coefficient values in both curves) to the left of the stimulation curve was observed. multidirectional. For this shock duration, E50 values were markedly lower (P <0.01) for the multidirectional modality. We can see that this difference was primarily due to the increased efficiency of the multidirectional mode, and no to the drop in efficiency of one-way shocks.

 Table 2 shows the parameters of the defibrillation probability curve for mono and multidirectional shock modalities with 30 ms pulse duration. E50: Shock energy required for a 50% probability of defibrillation success. Values are presented as mean ± standard error, followed by the confidence interval of the mean to 95% (in parentheses).

Table 2: Defibrillation probability curve parameters for mono and multidirectional shock modalities

 Multidirectional Monodirectional Mode

E50 (J) 4.701 ± 0.147 4.179 ± 0.084

 (4,363-5,040) (3,992-4,365)

Coefficient of 0.486 ± 0.064 0.356 ± 0.027

Hill (0.338-0.63) (0.296-0.416)

Table 3 shows the parameters of the defibrillation probability curve for mono and multidirectional shock modalities with pulse duration of 20 ms. E50: Shock energy required for a 50% probability of defibrillation success. Values are presented as mean ± standard error, accompanied by the confidence interval from the average to 95% (in parentheses) and 99% (in brackets).

 Multidirectional Monodirectional Mode

E50 (J) 4.011 ± 0.062 2.893 ± 0.035

 (3,880-4,141) (2,820-2,965)

 [3,833-4,188] [2,795-2,991]

 Coefficient 0.401 ± 0.021 0.424 ± 0.012

 Hill (0.358-0.444) (0.395-0.452)

 [0.342-0.459] [0.386-0.462]

For a more detailed comparison, data obtained from 6 animals were used, in which it was possible to obtain a sufficient number of points with each modality (minimum of 5 pairs of energy values) to obtain a satisfactory fit curve (R ² > 0.97 in all cases). In this case, from individual curves for both modalities, it was possible to determine means and respective standard errors of energy values required for different defibrillation probabilities, using the paired design to compare the efficiency of the 2 defibrillation modalities (ie in the same animal). This is of great importance because, although care has been taken to standardize the experimental conditions as much as susceptibility to defibrillation in the pig population studied (P <0.001 between curves of different animals; Mantel-Haenszel logrank test).

 Table 4 and Figure 12 show the results obtained only in these animals. The curves of Figure 12 were determined from the pool of all experimentally surveyed points (i.e. general curve, not individual). A marked left shift of the curve for multidirectional defibrillation can be observed (P <0.01; Table 4). The observed deviation was parallel, judging by the similar values of the Hill coefficient. This similarity was also observed when comparing the means of the individual values (single direction: 0.901 ± 0.119; multidirectional: 0.944 ± 0.109; P = 0.833, Student's t-test for paired samples), although these values were higher than those estimated for the curve. general.

Table 4 shows the parameters of the defibrillation probability curve for mono and multidirectional shock modalities applied to the same pig population (N = 6). E50: Shock energy required for a 50% probability of defibrillation success. Values are presented as mean ± standard error, followed by the 95% confidence interval of the mean. (in parentheses) and 99% (in brackets).

 Table 4: Defibrillation probability curve parameters for mono and multidirectional shock modalities, applied to the same pig population

 Multidirectional Monodirectional Mode

E50 (J) 3.996 ± 0.042 2.965 ± 0.035

 (3,908-4,083) (2,892-3,037)

 [3,877-4,114] [2,867-3,063]

Coefficient of 0.455 ± 0.019 0.447 ± 0.0-015

Hill (0.4160.495) (0.417-0.477)

 [0.440-0.509] [0.406-0.487]

The left parallel deviation of the curve obtained with the application of multidirectional shocks would imply a greater efficiency of this new defibrillation modality, compared to the monodirectional one, for a wide probability range of defibrillation success. To test this prediction, the average energy values required for the probability of 50, 75 and 90% of success were compared. The averages, calculated from the individual values obtained from the curves adjusted to the experimental points of each animal, are presented in Table 5 and Figure 13.

As can be observed in all cases, even for a high probability of success (90%), pulse energy levels required for ventricular fibrillation reversal were significantly lower with multidirectional pacing than with monodirectional pacing (P <0.05;Student's t-test for paired samples).

 Table 5 shows the mono and multidirectional defibrillatory shock energy (mean ± standard error) required for the 50%, 75% and 90% probability of defibrillation success.

 Table 5: Mono and Multidirectional Defibrillation Shock Energy

 Probability 0, 50 0, 75 0.90 defibrillation

 Energy (J), odality 3, 95 ± 0, 47 4, 52 ± 0, 45 5, 09 ± 0, 43 monodirectional

 Energy (J), mode 3.16 + 0.53 * 3.68 ± 0.58 * 4.25 ± 0.63 * very directional

 The success of defibrillation is characterized by the end of VF after the application of high intensity electric shocks, with the resumption of temporal and spatial coordination of the spread of ventricular electrical activity.

Successful electrical defibrillation of the heart requires the application of high intensity fields may reach 100 V / cm, which, however, may cause effects favoring the resettlement of VF (such as conduction block) and deleterious effects on myocardial cells, such as contractile dysfunction and persistent electroporation, which results in depolarization, overload of calcium, and cell death. On the other hand, there is a positive relationship between defibrillation success and shock intensity (see Figures 11 and 12). Therefore, the development of approaches that allow effective defibrillation with lower stimulus intensity is an important challenge in the areas of Cardiology and Biomedical Engineering.

 The production of both excitatory and deleterious effects of electric fields on the heart is known to depend on the orientation of the field relative to the cell axis or the myocardial fiber bundle: lower intensities are required when the field is applied parallel to the axis. greater than when the application is transversal to it. This has been attributed to the difference in the field's effectiveness in affecting the redistribution of charges on the cell membrane faces, which generates Vm variation that leads to ion channel opening or electropore formation.

Thus, the application of E at a given intensity may or may not result in excitation (ie, bringing Vm to threshold), depending on their relative orientation; The same would be true for electroporation induction. However, in the heart, the muscle fibers are arranged in several directions, particularly in the ventricle, in whose walls the muscle bundles are organized in spiral and circular patterns. A shock delivered between a pair of electrodes with a given orientation will have a different impact on different myocardial cells and may be harmless to some and even lethal to others, depending on their intensity. Therefore, pacing in more than one direction would, in theory, be an approach that could increase the effectiveness of electrical defibrillation.

 The switch designed for the device of the present invention fulfilled the objective of applying multidirectional defibrillatory discharge over a period of 60-90 ms, shorter than the ventricular PA duration in pig ventricular myocytes, in which the up to 90% repolarization duration is about 210 ms at 37 ° C.

In the present invention, the TRIAC was used as the electronic component responsible for the switching of the multidirectional defibrillatory discharge, which differed from the previous project for multidirectional stimulation of isolated in vitro myocytes, in which the switching was performed by means of relays. TRIAC was chosen to avoid the prolongation of total discharge duration due to delay caused during relay switching. The results of bench and in vivo tests showed that, in fact, there was no unwanted change in the duration of the discharge.

The results of the paired design experiments indicate that the application of shocks in more than one direction represented an increase in the defibrillation process efficiency, since the probability of defibrillation success was higher for a given stimulus intensity. With this pacing mode, the energy level required by shock was about 20% lower than with conventional (monodirectional) defibrillation for virtually the entire defibrillation probability range. Based on the demonstration by Fonseca et al. (2008), that multidirectional stimulation is more effective by promoting excitatory recruitment of larger numbers of cells with a given stimulus intensity, it seems plausible to suppose that, in the case of the present study, this mechanism would be involved. in multidirectional defibrillation. In other words, at insufficient energy levels for monodirectional defibrillation, multidirectional stimulation would recruit myocytes whose spatial orientation would be unfavorable for recruitment by shock delivered in only one direction, leading to defibrillatory success.

 In summary, in the present invention a device has been developed which has been tested for the direct application of mono and multidirectional defibrillator shocks. In vivo testing revealed that multidirectional stimulation allowed for a 20% reduction in the required intensity of shocks over a wide range of defibrillatory success probabilities.

 Preferred Modality of the Present Invention

Figure 14 shows a device power circuit (1) consisting of a DC voltage source from a sealed lead acid rechargeable battery (5). This circuit (1) consisted of a voltage regulator (6), which provided +5 V to the control circuit (2), and a switched source (7) responsible for raising the voltage to the required capacitor charging levels ( 20-22) responsible for storing the defibrillation discharge. The switching source (7) incorporates an adjustable switching regulator which switches the high frequency current to maintain a stabilized DC output voltage. The switched regulator was connected to a transformer and its output was connected to a fast rectifier diode. Thus, the voltage was high (9) corresponding to the energy level to be applied, and was adjusted by a multi-turn potentiometer (8). A resistive voltage divider (10) provided a maximum voltage of 5 V to the control circuit (2), thus providing a sample of the capacitor charging voltage (20-22) and proportional to the source output voltage (9). . The actuation of the switching source (7) to initiate the load was done manually by a key present in one of the defibrillation handles.

A PIC 16F818 microcontroller (11) was used for the control of the defibrillatory discharge switching, the selection of the monodirectional or multidirectional tripping mode, and the presentation of data regarding the selected voltage and the respective energy level. By means of an analog-to-digital converter present in the microcontroller (11), the signal of the load voltage samples (10) (0-5 V, analog quantity) was recorded in order to generate the digital representation of the voltage level. selected, convert it to energy levels and make them available on display (12). A pulse train (13) at a frequency of 1 kHz was generated and used to ensure, by means of pulse transformers (17-19), the switching trigger (23-25). For triggering the defibrillatory discharge in only one direction, the microcontroller (11) has been programmed to generate a pulse firing only for the central electrodes of the gauntlets (15). With the selection of the multidirectional defibrillation mode, at the moment of the shock discharge triggering, manually performed by a key present in the second defibrillation handle, three triggers were generated in sequence (14-16), corresponding to one pulse for each one. stimulation direction ^(the 0, 60 ° and 120 °). The pulses were generated in order to trigger the 20 ms delayed switching for each pair of electrodes, so that the last stimulus was applied 40 ms after the first trigger, and 20 ms after the second trigger, totaling an application time. 60 ms.

The switching was performed by three electronic keys (23-25) which, when activated, discharged the voltage stored in the capacitors (20-22), thus allowing the passage of electrical current through the heart in each direction of stimulation. . As mentioned, the switched source 7 provided the charging voltage to capacitors 20-22 according to the selected power level 8 for application. The source (7) was connected in parallel to the positive terminal of three (20-22) capacitors with 100 μΡ capacitance through a rectifier diode, directly polarized to each one (26- 28). To the negative terminals of the capacitors, another diode was connected (29-31), directly polarized with the switched source GND (7). Between the diode cathode (26-28) and the positive terminal of each capacitor (20-22), a model TIC226 23-25 TRIAC was connected, a semiconductor component that conducts two-way electrical current and acts as an electronic switch. by tension. These components (23-25) have the Anodol, Anode2 terminals and a gate terminal, and remain in a non-conducting state until they receive a gate trip voltage pulse (32-34) from the control circuit. (14-16). Thus, once the capacitors 20-22 are charged, the discharge occurs with current passing through the TRIACs 23-25 only when the clock is received at gate 32-34, and the voltage stored in the capacitors (20-22) is discharged only during the clock period.

The isolation circuit (3) consisted of pulse transformers (17-19) (1: 1 ratio of turns) and were used to trigger the TRIACs (23- 25) and also to ensure that the control circuit (2) were electrically isolated from the power circuit (4) to be triggered. Thus, at one of its inputs, the pulse transformers (17-19) received the clocks via a BC548C transistor, in series with a 100 Ω resistor to limit current (14-16), and on the other input (13) received, by means of a 470 Ω resistor in series with a BC548C transistor, pulse train with a constant frequency of 1 kHz for guarantee of the switching trip. Finally, one of the outputs of the pulse transformers (17-19) was connected to the gate of TRIACs 32-34, and the other to the Anodol (35-37).

 As can be seen above the main application of the cardiac defibrillation device of the present invention is in the process of electrical defibrillation of the heart of humans and other animals, which is the only known procedure for the treatment of high lethal arrhythmias, both in the process of direct defibrillation, as well as transthoracic, and for different waveforms of defibrillatory shocks. Stimulation technology, as proposed, can also be applied to cardioverters and cardiac pacemakers (implantable or not) and other stimulators of multicellular preparations.

Therefore, the new technique developed by the present invention for cardiac defibrillation by means of a multidirectional defibrillator is based on the delayed delivery of shocks in 3 different directions in order to electrically recruit more myocardial cells. The stimulation process, which lasts less than the refractory period, is brief enough that the cells are excited by only 1 of the shocks.

 In addition, the developed device of the present invention allows optimal keyed multidirectional defibrillation to be applied using a single portable defibrillator (vs. multiple defibrillators coupled by a synchronizer device) and a single pair of handles / paddles (as opposed to multiple pairs of electrodes attached to the heart), which facilitates the use of this method in the clinical condition.

 Thus, while only some embodiments of the present invention have been shown, it will be appreciated that various omissions, substitutions and changes in the optimized keyed multidirectional cardiac defibrillation device of the present invention and its method may be made by one of ordinary skill in the art without depart from the spirit and scope of the present invention.

It is expressly provided that all combinations of elements that perform the same function in substantially the same manner, to achieve the same results, are within the scope of the invention. Substitutions of elements from one described embodiment to another are also fully intended and contemplated. One must also understand that the drawings are not necessarily to scale, but that they are only of a conceptual nature. The intent is therefore to be limited as indicated by the scope of the appended claims.

Claims

 1. Multidirectional cardiac defibrillation device characterized by the fact that it provides shock-shifted 3-way shifting with a power supply that provides a regulated voltage to the control and interface circuits of the equipment; It also provides the charging voltage of the capacitors according to the selected power level.

 Multidirectional cardiac defibrillation device according to claim 1, characterized in that it allows optimized keyed multidirectional defibrillation to be applied using a single portable defibrillator and a single pair of handles / paddles.

 Multidirectional cardiac defibrillation device according to claim 1, characterized in that the application of successive shocks in different directions is brief enough that the cells are excited by only 1 of the shocks.

Multidirectional cardiac defibrillation device according to claim 1, characterized in that the succession of shocks Multidirectional with optimized lag allows rapid excitation of cells with different orientations, ensuring that the myocardium is not stimulated during the period of vulnerability.

 Multidirectional cardiac defibrillation device according to claim 1, characterized in that when the cardiac cell is excited by a given stimulus, it will not respond to the next during the same stimulatory cycle, thereby minimizing the onset of conduction block and reexcitation.

 Multidirectional cardiac defibrillation device according to claim 1, characterized in that it is capable of delivering sequentially single-phase or two-phase sequential shocks within a period of less than 100 ms in three different directions by passing electric current through three pairs of electrodes.

 Multidirectional cardiac defibrillation device according to claim 1, characterized in that the power to said device is supplied by a DC voltage source consisting of a rechargeable battery.

8. Cardiac defibrillation device Multidirectional power supply according to Claim 1, characterized in that the switching power supply circuit is responsible for raising the voltage to the levels required for charging three capacitors, in which they store the energy for the defibrillatory discharge.

 Multidirectional cardiac defibrillation device according to claim 8, characterized in that each capacitor discharges energy in each direction.

 Multidirectional cardiac defibrillation device according to claim 8, characterized in that a microcontroller is responsible for generating sequential firing pulses for the activation of semiconductor switches that enable the defibrillatory shock to be discharged in all three directions.

 Multidirectional cardiac defibrillation device according to claim 10, characterized in that said sequential pulses are rectangular 5 V voltage pulses.

Multidirectional cardiac defibrillation device according to claim 10, characterized in that the pulses are generated in such a way as to trigger the delayed switching at each pair of electrodes.

 Multidirectional cardiac defibrillation device according to claim 10, characterized in that only one pulse sequence is generated at each trigger command.

 Multidirectional cardiac defibrillation device according to claim 8, characterized in that the switching circuit consists of three electronic switches (TRIACs) which, when triggered by the gate clocks, discharge the stored voltage in the capacitors, thus allowing electrical current to pass through the heart in each direction of stimulation.

 Multidirectional cardiac defibrillation device according to claim 14, characterized in that pulse transformers are used to ensure triac triggering when a 1 kHz pulse train from one of its inputs is maintained. control circuit and also to electrically isolate the control circuit from the power circuit to be driven.

Multidirectional cardiac defibrillation device according to claim 1, characterized by the fact that for direct defibrillation is used a handle / shovel that each has 3 (three) electrodes in the form of concave discs.

 Multidirectional cardiac defibrillation device according to claim 16, characterized in that each electrode, consisting of a concave brushed surgical steel disc, was fixed to a support shaft attached to an arch containing internal channels for wire passage.

 Multidirectional cardiac defibrillation device according to claim 17, characterized in that with said prototyping technique it has three holes of -5 mm in diameter for electrode installation.

19. Multi cardiac defibrillation device according to claim 17, characterized by the fact that the side electrodes are positioned on the support base 60 with respect to the central electrode to establish the shock application direction.

Multidirectional cardiac defibrillation device according to claim 17, characterized in that at the top of the central hole, a circular base is fitted for the fitting of an aluminum cylinder, covered with electrostatic paint for coupling the part with the electrodes to the handle handle, protecting the wiring attached to the electrodes, as well as for lengthening the part and facilitating the handling of the parts. electrodes inside the thoracic cavity.

 Multidirectional cardiac defibrillation device according to claim 20, characterized in that the grip handles are designed to minimize the possibility of operator contact with the electrodes and conductive parts, and contain a button to trigger charging. capacitors and another to trigger the discharge trip.

 Multidirectional cardiac defibrillation device according to claim 16, characterized in that for connecting the contact between all electrodes and switches to the defibrillator, two coiled electrical cables through 5-way connectors are used.

Multidirectional cardiac defibrillation device according to claim 1, characterized in that it provides voltage pulses with capacitive discharge monopolar waveform (RC - resistor / capacitor, or may provide discharge). single-pole, RLC - resistor / inductor / capacitor, as well as truncated or rectilinear exponential bipolar waveform) and is capable of delivering shocks:

 a) in a single direction (monodirectional); or

 b) sequential shocks in three different directions

(multidirectional).

 Multidirectional cardiac defibrillation device according to claim 23, characterized in that the multidirectional discharge switch is designed to be fast enough for a total of approximately 60-90 ms to allow direct electrical stimulation of the heart in the three directions within the duration of cardiac BP in large mammals.

 Multidirectional cardiac defibrillation device according to claim 23, characterized in that the monodirectional direction occurs by the passage of electric current between only one pair of electrodes, that is, one electrode in each paddle.

Multidirectional cardiac defibrillation device according to claim 23, characterized in that the multideritional direction occurs by passing current through three strategically separated electrode pairs at an angle of 60 °.

Multidirectional cardiac defibrillation device according to claim 1, characterized in that the intensity of the defibrillatory pulses may be dependent on the energy level selected on a button on the instrument front panel.

 Multidirectional cardiac defibrillation device according to claim 1, characterized in that the isolation circuit is designed to ensure electrical isolation between the low voltage circuit (control circuit) of the high power circuit (control circuit). keying), and also ensure the activation of the switching in each direction to trigger the defibrillatory discharge.

 Multidirectional cardiac defibrillation device according to claim 1, characterized in that an electronic sealed battery charger is used for recharging the device.

Multidirectional cardiac defibrillation device according to claim 1, characterized in that the switching source incorporates an adjustable switching regulator which switches the high-frequency current to maintain a stabilized DC output voltage.

Multidirectional cardiac defibrillation device according to claim 1, characterized in that the keyed regulator is connected to a transformer designed on the Thornton NP-23 / 17-4900-IP6 core for 1: 10, with Ni = 4 turns, Li = 78.4 μΗ, N ₂ = 40 turns, L ₂ = 7.84 mH, and 52 kHz frequency), and its output was connected to a fast rectifier diode UF4007 1.0 A, 1000 V.

 Multidirectional cardiac defibrillation device according to claim 1, characterized in that the voltage at the transformer output is high corresponding to the energy level to be applied and is adjusted by a multivolt potentiometer.

 Multidirectional cardiac defibrillation device according to claim 36, characterized in that under this output voltage there is a voltage divider for taking samples of the charging voltage from the capacitors.

Multidirectional cardiac defibrillation device according to claim 1, characterized in that for the control of the defibrillatory discharge single or multi-directional triggering mode and the LCD display of the data for the selected voltage and its power level, a microcontroller is used, an integrated circuit that gathers in one device all the circuits necessary to make a complete system. programmable digital.

Multidirectional cardiac defibrillation device according to claim 34, characterized in that the digital microcontroller system has input / output pins, V _S if + V _DD , and consists of a processor, memory bytes of (RAM) and program (EEPROM), internal oscillator, and has integrated analog / digital (A / D) converter channels.

Multidirectional cardiac defibrillation device according to claim 34, characterized in that the programming of the functions to be performed by the microcontroller was developed in assembly language, and the program was written and loaded by the MPLAB recorder software. ^® IDE for the microcontroller to perform all instruction cycles.

Multidirectional cardiac defibrillation device according to claim 35, characterized by the fact that the A / D converter is used to perform the signal recording of the load voltage samples (0-5 V, analog quantity), generating the digital representation of these voltage levels and making available on an LCD display the TENSION (in V) and ENERGY (in J) variables.

 Multidirectional cardiac defibrillation device according to claim 37, characterized in that the energy is calculated internally to the microcontroller by means of programming which at each moment stores in its memory registers samples of the load voltage of the capacitors.

 Multidirectional cardiac defibrillation device according to claim 34, characterized in that the microcontroller is configured to communicate with a display.

 Multidirectional cardiac defibrillation device according to any one of claims 34 to 39, characterized in that the contrast and backlight adjustment are possible on the display.

Multidirectional cardiac defibrillation device according to claim 34, characterized in that the programming is configured so that the microcontroller is responsible for controlling selecting the one-way or multi-directional shooting mode.

 Multidirectional cardiac defibrillation device according to claim 34, characterized in that a pulse train at the frequency of 1 kHz is generated at one of the microcontroller outputs, which is used to ensure the triggering of the switch.

 Multidirectional cardiac defibrillation device according to claim 34, characterized in that the firing in only one direction is effected when the switch, located on the front panel of the device, is positioned in the monodirectional position.

Multidirectional cardiac defibrillation device according to claim 34, characterized in that with the selection of the multidirectional defibrillation mode, at the moment of the shock discharge triggering, the microcontroller generates three lagged, sequentially triggered pulses. the three outputs programmed, corresponding to a pulse for each direction (0 ^o, 60 ° and 120 °).

Multidirectional cardiac defibrillation device according to claim 1, characterized by the fact that the switching is performed by three electronic switches that, when activated, discharged the voltage stored in the capacitors, thus allowing the passage of electric current through the heart in a given direction of stimulation.

 Multidirectional cardiac defibrillation device according to claim 1, characterized in that the switching source responsible for supplying the charging voltage is connected in parallel to the positive terminal of three capacitors by means of a power rectifier diode; directly polarized to each of them.

 Multidirectional cardiac defibrillation device according to claim 46, characterized in that to the negative terminals of the capacitors, another connected power diode, directly polarized with the switching source GND.

Multidirectional cardiac defibrillation device according to claim 46, characterized in that between the diode cathode and the positive terminal of each capacitor, a Triad for Alternating Current (TRIAC TIC226M, 8.0 A, 600) is connected. V), or other switching elements such as Field Effect Transistor (FETs), Insulated Gate Bipolar Junction may be used. Transistors (IGBTs), Silicon Controlled Rectifiers (SCRs), to alternate capacitor voltage discharge and build the defibrillation waveform.

 Multidirectional cardiac defibrillation device according to claim 48, characterized in that the TRIAC is a semiconductor component conducting two-way electrical current and having the terminals Anodol (pin 1), Anode2 (pin 2) and a trip terminal (gate, pin 3), and remains in a non-conducting state until it receives a gate trip voltage pulse from the control circuit.

 Multidirectional cardiac defibrillation device according to claim 49, characterized in that once the capacitors are charged, the discharge occurs with current passing through the TRlACs only when the clock is received at the gate, and the voltage stored in capacitors is discharged only during the clock period, interrupting the switching and current flow.

Multidirectional cardiac defibrillation device according to claim 6, characterized in that the electrodes are used as a means of contact between the defibrillator and the surface of the heart or chest for delivery of the discharge. defibrillation.

 Multidirectional cardiac defibrillation device according to claim 16, characterized in that for direct defibrillation two handles were constructed from nylon billets which were subsequently connected to a rod and the polycarbonate / abs piece. , with the three electrodes each.

 Multidirectional cardiac defibrillation device according to claim 52, characterized in that the push-button buttons responsible for charging the capacitors and the other triggering the discharge are fitted to the top of each handle.

 Multidirectional cardiac defibrillation device according to claim 53, characterized in that in addition two coiled electrical cables were used and at each end of the cables a 5-contact male cable connector was added for connection of the lead electrodes. to the respective 5-contact female connectors located on the multidirectional defibrillator panel.

Method of using the device as defined by claims 1 to 54, characterized in that the cardiac defibrillation device Multidirectional with optimized switching delivers shocks in more than one direction, keyed with millisecond lag, so that the sequence lasts less than the myocardial refractory period.

 Method of use according to claim 55, characterized in that the pulses are generated so as to trigger the 20-30 ms delayed switching for each pair of electrodes, so that the last stimulus is applied 40-40. 60 ms after the first trigger, and 20-30 ms after the second trigger, totaling an application time of 60-90 ms.

 Use of the device as defined by claims 1 to 54 characterized in that it is for the application of electrical defibrillation of the heart of humans and other animals.

 Use of the device according to claim 57, characterized in that it is for the treatment of high lethal arrhythmias in both direct and transthoracic defibrillation processes.

 59. Use of the device according to claim

57, characterized by the fact that it can be applied to defibrillators, cardioversors and cardiac pacemakers and other stimulators of multicellular preparations.

60. Use of the device according to claim 59, characterized by the fact that said cardiac pacemakers may or may not be implantable.

 Use of the device according to any one of claims 57 to 59, characterized in that it can be applied to single-phase (either positive or negative polarity), biphasic (having a positive polarity and negative polarity pulse) shocks.