Biomedical subjects

O H Tovar

Publications and source records attributed to O H Tovar.

8 recordsLinked to original sources

PubMed2000

Electrophysiological deterioration during long-duration ventricular fibrillation.

BACKGROUND: Probability of survival from sudden cardiac arrest caused by ventricular fibrillation (VF) decreases rapidly with fibrillation duration. We hypothesized that cellular ischemia/fibrillation-induced electrophysiological deterioration underlies decreased survival. METHODS AND RESULTS: We determined fibrillation monophasic action potential (MAP) morphology including action potential frequency content, duration, cycle length, developing diastolic intervals, and amplitude as a function of ischemic fibrillation duration in 10 isolated rabbit hearts. We also correlated ECG frequency (used clinically) and MAP amplitude and frequency. Fibrillation cycle length and diastole duration increased, whereas APD(100) shortened significantly with time (P:<0.001). Between 1 and 3 minutes, diastole appeared primarily as the result of APD(100) shortening, with only small changes in cycle length. Between 2 and 5 minutes, diastole increased primarily as the result of increased cycle length. Diastole developed progressively from 5% of VF cycles at 5 seconds to approximately 100% of VF cycles by 120 seconds (P:<0.001). Diastole increased from 1% of cycle length at 5 seconds to 62% at 5 minutes. Its duration increased from 4.7 ms at 5 seconds to 90 ms at 5 minutes (P:<0.001). Both MAP and ECG 1/frequency closely correlated with fibrillation cycle length. CONCLUSIONS: These results show a rapid and progressive electrophysiological deterioration during fibrillation, leading to electrical diastole between fibrillation action potentials. This rapid deterioration may explain the decreased probability of successful resuscitation after prolonged fibrillation. Therefore, a greater understanding of cellular deterioration during fibrillation may lead to improved resuscitation methods, including development of specific defibrillator waveforms for out-of-hospital cardiac arrest.

Action Potentials↗

PubMed2000

Electrophysiology of ventricular fibrillation and defibrillation.

The survival rate from ventricular fibrillation is very high for short-duration fibrillation (<30 secs) but decreases to approximately 3% to 30% in out-of-hospital conditions. During short-duration fibrillation, action potentials occur rapidly with no intervening period of electrical diastole; a shock defibrillates by interacting with the fibrillation action potential to produce a uniformly long postshock extension of refractoriness. In contrast, during long-duration fibrillation, ischemia-induced degradation of cellular electrophysiology occurs, which causes intervening periods of electrical diastole between fibrillation action potentials and, thus, slowing of fibrillation frequency. A successful defibrillation shock must now not only prolong refractoriness when delivered during the action potential but must also excite cells during the periods of depolarized diastole. Biphasic waveforms enhance both effects by causing premature membrane repolarization with the first pulse, thereby allowing sodium channel recovery from inactivation so that the second pulse produces better-formed responses both during the cellular action potential and during the depolarized diastole. Therefore, biphasic waveforms remain superior to monophasic waveforms for treatment of long-duration fibrillation. Improved understanding of the ischemia-induced changes in cellular electrophysiology will suggest further improvements in both defibrillator waveforms and resuscitation techniques.

Animals↗

PubMed2000

Electrophysiologic deterioration after one-minute fibrillation increases relative biphasic defibrillation efficacy.

INTRODUCTION: The probability of survival decreases to 70% after 2 minutes of ventricular fibrillation. Biphasic shocks are more effective than monophasic shocks in terminating short-duration (<30 sec) ventricular fibrillation. We tested the hypotheses that developing ischemia changes the electrophysiologic characteristics of fibrillation and that the relative efficacy of biphasic shocks increases as electrophysiologic characteristics deteriorate. METHODS AND RESULTS: Monophasic (12 msec) and biphasic (6/6 msec) shocks (1 to 4 A) were tested in random order in isolated rabbit hearts after 1-minute ischemic fibrillation. Monophasic action potentials showed only a sporadic occurrence of electrical diastole after 5 seconds of fibrillation (24% of action potentials in the right ventricle and 18% in the left ventricle). After 60 seconds of fibrillation, diastole (17.83+/-1.14 msec in the right ventricle and 21.52+/-1.16 msec in the left ventricle) appeared after almost every action potential (P < 0.0001 compared with 5 sec), despite a lack of change in fibrillation cycle length and dominant frequency. Monophasic I50 was 2.89 A, and biphasic I50 was 1.4 A (77% reduction in energy). Normalized curve width decreased 28%. Retrospective analysis showed that shocks delivered early in the fibrillation action potential had a greater probability of succeeding (89%) than shocks delivered late (30%; P < 0.001). CONCLUSION: After 1-minute ischemic fibrillation, diastolic intervals occur during fibrillation. Therefore, defibrillation shocks have an approximately 29% probability of interacting with the fibrillation action potential during diastole. At this time, biphasic shocks produced a more deterministic defibrillation threshold and became even more efficacious (I50 B/M = 0.48) than at short fibrillation durations (I50 B/M = 0.7).

Animals↗

PubMed1998

Probability of induction and stabilization of ventricular fibrillation with epinephrine.

Clinical studies suggest that epinephrine facilitates ventricular fibrillation (VF) although mechanisms remain unclear. We tested the hypothesis that epinephrine increases the probability of inducing VF and stabilizes VF in association with shortening of fibrillation action potential duration. VF was induced in isolated, New Zealand White rabbit hearts (n=16) under control conditions and in the presence of 0.9 micro M/l epinephrine. Monophasic action potentials were recorded during sinus rhythm, pacing, and fibrillation. Epinephrine reduced fibrillation p80 by 80%, from 23+/-4 to 4.6+/-1 V (P<0.05); and reduced fibrillation p90 by 82%, from 29.3+/-5.4 to 5.4+/-1.9 V (P<0.05). Epinephrine also reduced the probability of spontaneous termination of VF during the first 5 s of VF from 29 to 8% (P<0.05). Epinephrine significantly decreased mean fibrillation cycle length from 104.5+/-2 to 75.7+/-2.3 ms (P<0.001). Mean action potential duration (60% repolarization) decreased from 76+/-3 to 40+/-3 ms (P<0.0003). Frequency analysis showed a mean dominant frequency during VF of 10.0+/-0.2 Hz under control conditions and 13. 3+/-0.3 Hz with epinephrine (P<0.0001). These results suggest that epinephrine increases the probability of VF induction and decreases the probability of spontaneous defibrillation. Stabilization of fibrillation is associated with shortening of action potential duration and fibrillation cycle length, which may allow a greater number of fibrillation waves in the ventricle.

Action Potentials↗

PubMed1997

Epinephrine facilitates cardiac fibrillation by shortening action potential refractoriness.

Epinephrine released during ventricular tachycardia (VT) or early fibrillation (VF) appears to be instrumental in stabilizing fibrillation. However, mechanisms remain unclear. Effects of epinephrine on refractory period at normal sinus rates depend on basic cycle length, but effects at short cycle lengths, typical of VT/VF, are unknown. Therefore, the goal of this study was to determine whether epinephrine shortens action potential duration and refractoriness at these short cycle lengths. To simulate early VT/VF, myocardial cell aggregates (n = 35) were paced using field stimulation (5 ms rectangular waveform) at cycle lengths of 200, 180, 160 and 140 ms, which occur during in situ fibrillation: normal sinus rhythm was simulated by pacing at 600 and 400 ms intervals. Action potentials and excitation threshold were recorded with intracellular microelectrodes under control conditions, with 0.9 microM/l epinephrine, and with 0.9 microM/l epinephrine and 0.5 microM/l propranolol. At short cycle lengths, epinephrine significantly shortened action potential duration and refractoriness compared to control. At a cycle length of 160 ms, action potential duration was reduced by 14 ms at 60% repolarization (P < 0.0002) and stimulation threshold by 18% (P < 0.02). Epinephrine also allowed pacing at a cycle length of 140 ms, not achievable under control conditions. Because epinephrine decreases action potential duration at short cycle length in situ, re-entry wavefronts are less likely to encounter refractory tissue: fibrillation is more likely to occur and to remain stabilised. Reduction in action potential duration and excitation threshold were reversed by propranolol, suggesting that epinephrine effects are produced by beta-stimulation.

Action Potentials↗

PubMed1997

Relationship between "extension of refractoriness" and probability of successful defibrillation.

The "extension of refractoriness" hypothesis, which suggests that the shock halts fibrillation by extending the refractory period, has not been directly tested. Defibrillation (5 isolated rabbit hearts; 111 episodes) was attempted by 8-ms pulses (65% tilt) delivered through epicardial patches. Monophasic action potentials were recorded in a low current density region (6.3 V/cm at 90% success). Fifty shocks failed to convert; 61 shocks successfully defibrillated. Postshock response duration (from shock to repolarization) was significantly longer for successful type A (with no postshock activations) defibrillation (102.3 +/- 7.5 ms) than for unsuccessful defibrillation (47.6 +/- 4.3 ms; P < 0.0001) for shocks occurring during the last 40% of the fibrillation action potential. Probability of success and postshock response duration both increased with current intensity. However, at each intensity, response durations for successful defibrillation were significantly longer than those for unsuccessful defibrillation. A minimum prolongation of 75 ms was associated with type A defibrillation. These results suggest that shock-induced response duration correlates with successful defibrillation and that a response of 75 ms is required to completely block fibrillation wavefronts.

Action Potentials↗

PubMed1995

Threshold reduction with biphasic defibrillator waveforms. Role of charge balance.

Mechanism underlying improved defibrillation efficacy of biphasic waveforms at low shock intensities remain poorly understood. Recent studies suggest that biphasic waveforms produce a longer mean postshock response throughout the ventricle. This prolongs the cellular refractory period, blocks fibrillation wave fronts, and causes fibrillation to cease. Previous studies showed that hyperpolarizing monophasic waveforms, delivered during the refractory period, can shorten action potential duration (APD90), which would be deleterious for defibrillation. This study tested the hypothesis that a balanced-charge biphasic waveform produces a longer mean total mean APD than a comparable monophasic waveform by preventing this shortening in hyperpolarized regions as well as by prolonging APD in depolarized regions. To test this hypothesis, the authors examined transmembrane potential changes produced by hyperpolarizing and depolarizing monophasic and balanced-charge symmetrical biphasic waveforms using a computer model of the ventricular action potential. Shock intensities within the low-intensity "window," where biphasic waveforms defibrillate with higher efficacy than monophasic waveforms (1.5-3 times diastolic threshold), were used. Results show that biphasic S2 produced a significantly longer response both under hyperpolarizing and depolarizing conditions. The hyperpolarizing/depolarizing biphasic S2 produced a prolonged response with a well-defined plateau. Following the depolarizing/hyperpolarizing S2, APD90 did not shorten as with the hyperpolarizing monophasic S2. Rather, repolarization continued near the original S1 times course, but with slight prolongation of S1 APD90. These results suggest that biphasic waveforms enhance the prolonged refractory periods required for defibrillation throughout the heart, including regions exposed to both anodal and cathodal stimulation.

Action Potentials↗

PubMed1995

Biphasic defibrillation waveforms reduce shock-induced response duration dispersion between low and high shock intensities.

Mechanisms underlying defibrillation threshold reduction with biphasic waveforms remain unclear. The interaction of local shock-induced voltage gradients, which change with distance from the shocking electrode, and the state of membrane repolarization results in different cellular responses that may influence the success of defibrillation. We used intracellular microelectrodes and S1S2 pacing protocols in myocardial cell aggregates to determine the effects of shock intensity and waveform on refractory period responses during simulated fibrillation (3 s of S1 pacing at 180-ms cycle length). We simulated defibrillation by electric field stimulation S2 using 8-ms monophasic (MS2) and 4/4 biphasic (BS2) waveforms (65% total tilt) delivered at intensities of 1.5, 3, and 5 times S1 diastolic threshold, or approximately 2 to 7 V/cm. Responses following MS2 varied with S2 intensity and coupling interval (P < .001). When averaged over the last 10 ms of the refractory period, MS2 produced a negligible response (8.8 +/- 1.4 ms) at 1.5 times diastolic threshold and a prolonged response (53.0 +/- 3.1 ms) at 5 times diastolic threshold (P < .01). In contrast, BS2 response duration did not change significantly (P - NS) between 1.5 times diastolic threshold (35.1 +/- 12.6 ms) and 5 times diastolic threshold (46.2 +/- 2.7 ms). Our results suggest that biphasic waveforms not only prolong response duration at low shock intensity but reduce dispersion of refractoriness produced by differing local potential gradients generated by defibrillation shocks compared with monophasic waveforms. Preventing dispersion of refractoriness and prolonging shock-induced responses may improve biphasic waveform efficacy at low shock intensity.

Action Potentials↗