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Simulation of late potentials and arrhythmias by use of a three-dimensional heart model: casuality of peri-infarctional slow conduction in ventricular fibrillation.

A three-dimensional heart model was constructed to simulate late potentials and ventricular fibrillation (VF). The model consisted of 50,000 discrete elements having a 1.5-mm spatial resolution. Each element represented excitable ventricular tissue, including a conduction system, and was characterized with classical features of the action potential, refractory period, and conduction velocity (theta). An infarcted area on the lateral wall was identified as dead (inexcitable) cells or scar tissue, and peri-infarctional (PI) cells with slow conduction. Body surface potentials were calculated by using the boundary element method. When theta of PI cells was reduced below 0.3 m/s, late potentials became evident after the J point of simulated electrocardiograms (ECGs), and VF was induced by applying four consecutive premature stimuli. However, when Purkinje fibers were removed, VF could not be initiated. Late potentials were induced when slow conduction was present. The presence of PI slow conduction and Purkinje fibers, which were normally contained in the model, was essential for the induction of VF.

Computer Simulation↗

Effect of calcium channel antagonists on cocaine-induced malignant arrhythmias: protection against ventricular fibrillation.

It is increasingly apparent that cocaine can provoke lethal cardiac events, including ventricular fibrillation (VF). Cocaine-induced accumulation of intracellular calcium could contribute significantly to the development of these lethal arrhythmias. In order to test this hypothesis, a 2-min coronary occlusion was initiated during the last minute of exercise in instrumented mongrel dogs. Twenty-eight animals were selected in which this test failed to induce ventricular arrhythmias. The test was repeated after cocaine HCl (1.0 mg/kg). Cocaine significantly (P < .01) increased heart rate, left ventricular pressure and d(left ventricular pressure)/dt maximum, and elicited VF in 21 animals. The cocaine exercise+ischemia test was repeated in the animals that developed VF after the pretreatment with the following calcium channel antagonists: diltiazem (n = 8, 1.0 mg/kg), flunarizine (n = 7, 2.5 mg/kg), magnesium sulfate (n = 7, 100 mg/kg), nifedipine (n = 7 100 micrograms/kg), Ro 40-5967 (n = 7, 1.0 mg/kg) and verapamil (n = 6, 250 micrograms/kg). Diltiazem, flunarizine, nifedipine, Ro 40-5967 and verapamil completely suppressed cocaine-induced VF, whereas magnesium prevented VF in five of seven animals. Many of the calcium channel antagonists attenuated the heart rate and systolic pressure increases provoked by cocaine, as well as the heart rate increase induced by the ischemia. Heart rate was therefore matched to the cocaine values by ventricular pacing (verapamil+pace, n = 5), whereas the pressure increases were prevented by nitroprusside (n = 4). Even with heart rate held constant, verapamil prevented VF, whereas nitroprusside failed to protect any animal. Thus, myocardial calcium entry may play a critical role in cocaine-induced VF, whereas calcium antagonists can prevent these malignant arrhythmias independently of their vascular action.

Animals↗

Effect of standard-dose versus high-dose epinephrine on myocardial high-energy phosphates during ventricular fibrillation and closed-chest CPR.

STUDY OBJECTIVE: To evaluate the effects of standard-dose versus high-dose epinephrine on myocardial high-energy phosphate metabolism during resuscitation from cardiac arrest. DESIGN: Prospective, nonrandomized, controlled study using a swine model of cardiac arrest and resuscitation. INTERVENTIONS: After anesthesia, intravascular pressure instrumentation, and ten minutes of ventricular fibrillation arrest, closed-chest CPR was begun. After three minutes of CPR, animals were allocated to receive either 0.02 mg/kg i.v. standard-dose epinephrine (eight) or 0.2 mg/kg i.v. high-dose epinephrine (nine). The animals underwent thoracotomy and rapid-freezing transmural myocardial core biopsy for high-energy phosphate analysis 3.5 minutes after epinephrine administration. High-energy phosphate values were blindly determined using high-pressure liquid chromatography. RESULTS: Intravascular pressure (mm Hg) and high-energy phosphate (nmol/mg protein) results for standard-dose epinephrine versus high-dose epinephrine are, respectively, coronary perfusion pressure, 15.3 +/- 7.8 versus 23.7 +/- 5.5 (P = .0009); phosphocreatine, 0.4 +/- 0.8 versus 6.2 +/- 4.4 (P = .0003); adenosine triphosphate, 9.8 +/- 4.8 versus 12.7 +/- 5.7 (P = .30); adenosine diphosphate, 5.4 +/- 2.1 versus 6.1 +/- 1.3 (P = .41); and adenylate charge, 0.68 +/- 0.12 versus 0.72 +/- 0.12 (P = .87). CONCLUSION: High-dose epinephrine does not deplete myocardial high-energy phosphate when given in this model of prolonged ventricular fibrillation. High-dose epinephrine increases coronary perfusion pressure compared with standard-dose epinephrine. High-dose epinephrine administration repletes phosphocreatine during closed-chest CPR, thereby increasing myocardial energy stores.

Adenosine↗

[Effect of peridural blockade of the heart on the ventricular fibrillation threshold in dogs].

Experiments were conducted on dogs with determination of the ventricular fibrillation threshold in animals with intact heart and with myocardial infraction in case of trimecaine injection into the peridural space at the T1--T2 level. The fibrillation threshold was elevated both on account of resorptive trimecaine action and due to the block of the sympathetic heart innervation.

Acetanilides↗

[Clinical aspects of ventricular fibrillation in the development of myocardial infarction].

We report 13 patients who suffered ventricular fibrillation (VF) during the in-hospital course of an acute myocardial infarction (AMI). We compare the clinical features of this patients with other two groups; patients without VF and patients with intraventricular conduction defects. In 38% of the cases VF appeared after 5th day of the AMI. The group of patients with VF was characterized by an increased incidence of heart failure, supra-ventricular and ventricular premature beats, and also intra-ventricular conduction defects. In 2 patients VF appeared during the course of treatment with therapeutic doses of lidocaine. Sixty two percent of the patients with VF were discharged alive. We recommend that patients with AMI who display the above mentioned risk factor, should remain in the coronary care unit for a more prolonged period of time. By proceeding in this way, we had the opportunity to observe and immediately treat 5 further patients with AMI and VF. All of them recovered.

Aged↗

Short-acting beta-adrenergic antagonist esmolol given at reperfusion improves survival after prolonged ventricular fibrillation.

BACKGROUND: High catecholamine concentrations are cytotoxic to cardiac myocytes. We hypothesized that myocardial interstitial catecholamine levels are greatly elevated immediately after long-duration ventricular fibrillation (VF), defibrillation, and reperfusion and that the short-acting beta-antagonist esmolol administered at reperfusion would protect against this catecholamine surge and improve survival. METHODS AND RESULTS: In part 1 of this study, catecholamines from myocardial interstitial fluid (ISF) and aortic and coronary sinus plasma were quantified by use of 3H-labeled radioenzymatic assay in 8 open-chest, anesthetized pigs. Eight minutes of electrically induced VF was followed by internal defibrillation and reperfusion. By 4 minutes of VF, ISF norepinephrine increased significantly, from 1.3+/-0.3 to 7.4+/-2.4 ng/mL. Epinephrine increased significantly, from 0.4+/-0.2 to 1.5+/-0.7 ng/mL. ISF norepinephrine and epinephrine peaked at 219.2+/-92.1 and 63.7+/-25.1 ng/mL after defibrillation and reperfusion and decreased significantly to 12.2+/-3.5 and 6.7+/-3.1 ng/mL 23 minutes after defibrillation. Transcardiac catecholamine changes were similar. In part 2, 8 minutes of VF was followed by external defibrillation in anesthetized, closed-chest pigs. Animals received 1.0 mg/kg esmolol (n=8) or saline (n=8) intravenously at the start of cardiopulmonary resuscitation (CPR). Advanced cardiac life support, including CPR and epinephrine, was delivered to both groups. Esmolol before reperfusion improved return of spontaneous circulation and 4-hour survival (7/8 versus 3/8 survivors, chi2 P<0.05). CONCLUSIONS: Transcardiac and ISF norepinephrine and epinephrine levels are briefly massively elevated after 8 minutes of VF, defibrillation, and reperfusion. A short-acting beta-antagonist administered immediately after defibrillation improves return of spontaneous circulation and 4-hour survival after this prolonged VF.

Adrenergic beta-Antagonists↗

Ventricular fibrillation in Wolff-Parkinson-White syndrome, type A.

A young individual who developed ventricular fibrillation following atrial fibrillation in the WPW syndrome is presented. The precise cardiac rhythm diagnosis is extremely important for proper management. When the QRS morphology is bizarre and the ventricular rate is very fast (200 to 300 b.p.m.) in atrial fibrillation, the WPW syndrome should be considered as the underlying disorder. Digitalis should be avoided in this circumstance because anomalous conduction may be accelerated by the drug, leading to deterioration of the clinical picture and even death. When an antiarrhythmic drug is to be used, intravenous lidocaine is the drug of choice. For the prophylactic measure, oral quinidine or procainamide is equally effective for atrial fibrillation with anomalous conduction in the WPW syndrome.

Adult↗

Detecting ventricular fibrillation using efficient techniques for computing a normalized autocorrelation.

With the introduction of the multifunction implantable pacemaker/cardioverter/defibrillator, it is increasingly important to detect and identify arrhythmias automatically. Detection of ventricular fibrillation by analysis of the autocorrelation function is widely used on surface lead ECG analysis, but due to the computational demand is not practical for use in an implantable defibrillator. In this paper, results using three computationally efficient algorithms for estimating the normalized autocorrelation are compared with the true normalized autocorrelation for discriminating polymorphic ventricular tachycardia/ventricular fibrillation (PMVT/VF) from monomorphic ventricular tachycardia (MVT) using signals available to an implantable defibrillator.

Algorithms↗

Prostacyclin prevents ventricular fibrillation in a canine model of sudden cardiac death.

The antifibrillatory, antithrombotic and hemodynamic properties of intraventricular prostacyclin (PGI2) application were studied in conscious canine model of sudden cardiac death. In anesthetized dogs, a wire electrode was implanted into the left circumflex coronary artery (LCX) and acute myocardial ischemia was produced by 90 min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. An intracardiac pressure transducer measured ventricular pressure, heart rate, filling pressure and dP/dt. The ECG was obtained from subcutaneous chest needles. Six days later while in ambulatory state, a 180 microA DC current was applied for 4 h to the LCX intimal lining in Tris-HCl (n = 10) and PGI2-treated dogs (50 and 100 ng/kg/min, 11 and 12 dogs, respectively). Myocardial injury and coronary thrombosis induced by electrical stimulation produced ventricular fibrillation in all vehicle-treated dogs at 145 +/- 33 min (mean +/- S.D.). In PGI2-treated hearts only 2 animals fibrillated at 150 +/- 29 min and 180 +/- 52 min following 50 and 100 ng/kg/min of the prostanoid, respectively. Thus, 18/23 PGI2-treated dogs survived 4 h electrical stimulation of the artery. Within the LAD perfusion zone infarction was observed of equal volumes in vehicle and PGI2-treated animals. No ischemia occurred distal to the LCX coronary thrombosis. Ventricular pressure fell in all groups. Heart rate increased in the controls and those animals treated with 50 ng/kg/min PGI2 while 100 ng/kg/min PGI2 increased heart rate by 22 +/- 5% (p less than 0.05). Filling pressure increased in controls but fell in the PGI2-treated hearts. The results indicate that PGI2 can prevent ventricular fibrillation resulting from acute ischemia at a site distant to previous myocardial ischemia with superimposed intimal injury and coronary thrombosis. The PGI2 properties are due to prevention of coronary thrombosis and the occlusion of the artery. Antifibrillatory effects of the prostanoids are suggested.

Animals↗

[Ventricular fibrillation: the current methods for analysing the degree of irregularity of the process].

Ventricular fibrillation has traditionally been described as "chaotic" and in recent years there has been discussions that fibrillation may be an instance of deterministic chaos in the context of nonlinear dynamical systems theory. The current paper summarizes modern methods of mathematical analysis of the degree of electrical irregularities of the heart during VF. The traditional methods of Fourier analysis of electrocardiographic data as well as concepts of chaos theory--fractal dimension, entropy, reconstruction of attractors and some new methods such as spatial coherence have been considered. The results are discussed in context of mathematical models and hypothesis of mechanisms of VF.

Animals↗

Near-infrared measurement of cerebral oxygenation. Correlation with electroencephalographic ischemia during ventricular fibrillation.

BACKGROUND: The application of phase-modulated near-infrared techniques for measurement of the oxygen saturation of cerebral tissue requires both validation by conventional measures of cerebral oxygenation and determination of normal and abnormal values. This study was undertaken to validate phase-modulated near-infrared measurements of cerebral oxygen saturation by comparing them with electroencephalographic evidence of cerebral ischemia during implantation of cardioverting defibrillators. This comparison also yields an estimate of the ischemic threshold as measured with near-infrared techniques. METHODS: Electroencephalograms and near-infrared measurements were performed during 85 episodes of ventricular fibrillation in ten patients. Light at 754, 785, and 816 nm was modulated at 200 MHz, transmitted through the skull, and the path lengths of the reflected light were determined by measuring the phase shifts. The electroencephalogram was inspected for changes during the hypotension associated with the arrhythmia and the oxygen saturation was calculated from the near-infrared path lengths. Changes in oxygen saturation were then compared with electroencephalographic evidence of cerebral ischemia. RESULTS: The mean saturation before fibrillation was 56.5% +/- 1.2 (SEM). In 40 (47%) of the events, electroencephalographic evidence of ischemia was observed. Such changes were related to the minimum saturation observed during ventricular fibrillation (44% +/- 2.5 vs. 56% +/- 1.9 in the absence of electroencephalographic changes; P < 0.001). The ischemic threshold was estimated to be 47% saturation. The sensitivity of this technique was estimated to be 0.6, the specificity 0.84, and the predictive accuracy 0.73. CONCLUSIONS: Near-infrared measurements reflect changes in cerebral oxygenation as indicated by electroencephalographic evidence of cerebral ischemia.

Aged↗

Outcome of ventricular fibrillation developing during percutaneous coronary interventions in 19,497 patients without cardiogenic shock.

Ventricular fibrillation (VF) developing out of hospital or even in hospital has a reported prognosis for survival that is <50%. We examined the prognosis for VF in 19,497 patients undergoing percutaneous coronary intervention and identified 164 who had VF (0.84%). The time to defibrillation was <1 minute and was successful in all without sequelae. Thus, VF developing in the catheterization laboratory is unique in terms of prognosis.

Aged↗

Chaos and the transition to ventricular fibrillation: a new approach to antiarrhythmic drug evaluation.

Sudden cardiac death resulting from ventricular fibrillation can be separated into 2 components: initiation of tachycardia and degeneration of tachycardia to fibrillation. Clinical drug studies such as CAST and SWORD demonstrated that focusing exclusively on the first component is inadequate as a therapeutic modality. The hope for developing effective pharmacological therapy rests on a comprehensive understanding of the second component, the transition from tachycardia to fibrillation. We summarize evidence that the transition from tachycardia to fibrillation is a transition to spatiotemporal chaos, with similarities to the quasiperiodic transition to chaos seen in fluid turbulence. In this scenario, chaos results from the interaction of multiple causally independent oscillatory motions. Simulations in 2-dimensional cardiac tissue suggest that the destabilizing oscillatory motions during spiral-wave reentry arise from restitution properties of action potential duration and conduction velocity. The process of spiral-wave breakup in simulated cardiac tissue predicts remarkably well the sequence by which tachycardia degenerates to fibrillation in real cardiac tissue. Modifying action potential duration and conduction velocity restitution characteristics can prevent spiral-wave breakup in simulated cardiac tissue, suggesting that drugs with similar effects in real cardiac tissue may have antifibrillatory efficacy (the Restitution Hypothesis). If valid for the real heart, the Restitution Hypothesis will support a new paradigm for antiarrhythmic drug classification, incorporating an antifibrillatory profile based on effects on cardiac restitution and the traditional antitachycardia profile (classes 1 through 4).

Anti-Arrhythmia Agents↗

Influence of tedisamil on the initiation and maintenance of ventricular fibrillation: chemical defibrillation by Ito blockade?

We examined the effects of tedisamil on ventricular fibrillation (VF) elicited by regional ischemia and by reperfusion in isolated rat hearts (n = 12/group). During 30 min of ischemia, 0.1, 0.55, and 3 microM tedisamil had no influence on the incidence of VF (an index of VF initiation). However, sustained VF (SVF, defined as that lasting greater than 120 s, an index of VF maintenance) was reduced in a concentration-dependent manner from 73 to 54, 17 (p less than 0.05), and 0% (p less than 0.05), respectively. Tedisamil caused sinus bradycardia but this was not the basis for tedisamil's antiarrhythmic activity since SVF was also inhibited in separate groups of hearts that were paced throughout the study. Tedisamil had no effect on reperfusion-induced VF initiation. However, VF maintenance was, again, inhibited, with SVF incidence reduced from 75% to 40, 20, and 0% (p less than 0.05), respectively, by increasing concentrations of tedisamil. A similar effect was, again, observed in paced hearts. The average cycle length of the electrogram during VF correlated with preceding width of the ventricular complex; both of these variables were concentration-dependently increased by tedisamil and mean values of each correlated inversely with the incidence of SVF. The ratio of SVF cycle length to ventricular tachycardia cycle length was 1:3, and this ratio was conserved in the presence and absence of drug. The data are consistent with a drug-induced increase in the probability of spontaneous termination of multiple wave-front re-entry.

Action Potentials↗

Levels of short (1-15 ms) electrical shocks from a 50 Hz supply inducing ventricular fibrillation in hyperbaric helium and oxygen.

An investigation was undertaken to determine the ventricular fibrillation (VF) threshold of anaesthetised dogs subjected to external application of electric shocks between a foreleg and a hindleg. The shocks were 2-15 ms sections of 50 Hz sine waveform starting at peak current and were applied at a known time in the heart cycle. The object of the experiment was to determine if there was an increase in cardiac susceptibility to electrically induced VF at 31 atmospheres absolute (atm abs) in a helium and oxygen environment. The duration and position of that part of the cardiac cycle most vulnerable to induction of VF by electrocution was found (seven animals) using 4 ms shocks and then the minimum fibrillating current for shocks of 2-15 ms (min FC2-15) delivered at the most vulnerable point of the cycle (five animals). Body resistance was calculated from the data so gathered. Fibrillation thresholds were not changed by compression and there were no significant changes in the vulnerable period of the cardiac cycle. Min FC2 was significantly higher than for other durations under both control (3.21 A, SD 1.08) and test conditions (3.26 A, SD 0.39), p = 0.001. There was no difference in body resistance at 31 atm abs (395.5, SD 12.9) from control values at 1 atm abs (396.7, SD 10.9). From these data it was concluded that the heart is no more susceptible to the induction of VF at 31 atm abs in a helium oxygen environment and additional safety factors are unnecessary from this point of view.

Animals↗

Dispersion of cell-to-cell uncoupling precedes low K+-induced ventricular fibrillation.

We hypothesize that hypokalemia-related electrolyte imbalance linked with abnormal elevation of intracellular free Ca2+ concentration can cause metabolic disturbances and subcellular alterations resulting in intercellular uncoupling, which favor the occurrence of malignant arrhythmias. Langendorff-perfused guinea pig heart (n = 44) was subjected to a standard Tyrode solution (2.8 mmol/l K+) followed by a K+-deficient solution (1.4 mmol/l K+). Bipolar ECG of the left atria and ventricle was continuously monitored and the incidence of ventricular fibrillation was evaluated. Myocardial tissue sampling was performed during stabilization, hypokalemia and at the onset of fibrillation. Enzyme activities of succinic dehydrogenase, glycogen phosphorylase and 5-nucleotidase were determined using in situ catalytic histochemistry. The main gap junction protein, connexin-43, was labeled using mouse monoclonal antibody and FITC conjugated goat antimouse antibody. Ultrastructure was examined by transmission electron microscopy. The free Ca2+ concentration was measured by the indo-1 method in ventricular cell cultures exposed to a K+-free medium. The results showed that sustained ventricular fibrillation appeared within 15-30 min of low K+ perfusion. This was preceded by ectopic activity, episodes of bigeminy and tachycardia. Hypokalemia induced moderate reversible and sporadically irreversible subcellular alterations of cardiomyocytes and impairment of intercellular junctions, which were heterogeneously distributed throughout myocardium. Patchy areas with decreased enzyme activities and diminished immunoreactivity of connexin-43 were found. Furthermore, lack of external K+ was accompanied by an increase of intracellular Ca2+. The prevention of Ca2+ overload by either 1 mmol/l Ni2+ (Na+/Ca2+ inhibitor), 2.5 micromol/l verapamil, 10 micromol/l d-sotalol or 10 micromol/l tedisamil was associated with the protection against fibrillation. The results indicate that hypokalemia induces Ca2+ overload injury and disturbances in intercellular coupling. Dispersion of these changes throughout the myocardium may serve as the basis for microreentry circuits and thus favor fibrillation occurrence.

Animals↗

Differences in the activation patterns between sustained and self-terminating episodes of human ventricular fibrillation.

BACKGROUND: Experimental studies have suggested that R-R interval dynamics during ventricular fibrillation (VF) have organized features, but whether dynamic behavior of non-sustained VF differs from sustained VF is unknown. AIM: The purpose of this study was to investigate whether the dynamics of R-R intervals during non-sustained VF differs from the dynamics during sustained VF. METHODS: A group of 67 patients undergoing routine implantable cardioverter defibrillator (ICD) testing was studied. Forty-three VF events containing mean of 38 local cardiac activation intervals before the termination by ICD shock were analyzed. From intracardiac electrogram recordings, the ratio between the short and long term variability (SD1/SD2) and fractal scaling exponent (alpha) were analyzed. After the initial analyses, data sets were randomized and reanalyzed. Local activation dynamics were then also compared in seven patients with both sustained and spontaneously terminating VF episodes. RESULTS: Randomization caused a change in the VF dynamics from organized toward less organized dynamics (alpha) from 1.08 +/- 0.57 to 0.81 +/- 0.45, P < 0.05 and SD1/SD2 from 0.80 +/- 0.23 to 1.04 +/- 0.20, P < 0.01). Spontaneously terminating VF showed more organized dynamics than sustained VF terminated by shock (P < 0.05). CONCLUSIONS: Local cardiac activation dynamics during initial phase of human VF shows organized dynamics. Spontaneously terminating VF episodes have more structured dynamics than sustained VF. Thus, the dynamic behavior of local cardiac activation intervals may be related to the maintenance of ventricular tachyarrhythmias.

Aged↗