Ventricular Fibrillation Threshold In Dogs Research Articles

Effect of amiodarone on dispersion of ventricular repolarization in a canine congestive heart failure model

The effects of amiodarone on ventricular electrophysiological parameters, especially the dispersion of ventricular repolarization, were investigated in a canine model of congestive heart failure (CHF). Dogs were randomized to either a control, amiodarone, CHF, or CHF+amiodarone group. Dogs in the CHF and CHF+amiodarone groups underwent 4-5weeks of rapid ventricular pacing; dogs in the control and amiodarone groups underwent sham operation only. Amiodarone (20 mg/kg per day) was administered orally, beginning on postoperative Day 1, in the treatment groups; ventricular electrophysiological variables were evaluated 4-5weeks after rapid pacing or sham operation. In CHF dogs, the transmural dispersion ventricular repolarization time (TDVRT) increased significantly. Amiodarone significantly decreased the TDVRT in CHF dogs. The ventricular fibrillation threshold (VFT) decreased in the CHF group. Amiodarone increased the VFT in CHF dogs. The TDVRT increased in CHF dogs, but amiodarone decreased TDVRT and increased VFT in these dogs. These results suggest a beneficial effect of amiodarone on malignant arrhythmias and may provide the basis for its use in CHF patients.

Proarrhythmic Effects of Intravenous Vasopressors

To review the electrophysiologic properties and the in vitro, ex vivo, animal, and human data regarding proarrhythmic effects of intravenous vasopressors. A comprehensive (MEDLINE) search (1960-1994) was conducted for dopamine, epinephrine, norepinephrine, phenylephrine, and methoxamine. In vitro and ex vivo studies and investigations performed in animals or humans reporting electrophysiologic and/or proarrhythmic effects of the above intravenous vasopressors were selected. A comprehensive search of all human studies involving these agents was conducted to reveal any proarrhythmic effects that may have been reported. In addition, case reports of proarrhythmic effects associated with these agents were reviewed. Data regarding electrophysiologic and proarrhythmic effects of these agents were extracted from in vitro, ex vivo, animal, and human studies. Because few studies with the specific purpose of investigating proarrhythmic effects of vasopressors have been performed in humans, all studies involving these drugs for evaluation of hemodynamic effects, clinical efficacy, or other endpoints in humans were reviewed. In addition, data were extracted from case reports of proarrhythmic effects associated with these agents. Dopamine increases automaticity in Purkinje fibers and has a biphasic effect on action-potential duration. Dopamine has caused both atrial and ventricular tachyarrhythmias in animals. Human data have revealed dose-related sinus tachycardia, with few reports of clinically significant ventricular arrhythmias. Epinephrine shortens sinus cycle length, increases atrial and ventricular automaticity, promotes atrioventricular nodal conduction, and decreases ventricular effective refractory period (ERP). It is well known to induce ventricular fibrillation and decrease the ventricular fibrillation threshold (VFT) in ex vivo models as well as intact animals. In humans, epinephrine may cause dose-related sinus tachycardia, supraventricular arrhythmias, or, more commonly, ventricular arrhythmias. Norepinephrine increases automaticity of the sinoatrial node, atria, and ventricles; promotes atrioventricular nodal conduction; and decreases ventricular ERP. In vitro/ex vivo and animal data have shown that norepinephrine significantly decreases VFT. Although electrophysiologic studies suggest that norepinephrine may be proarrhythmic, few supporting data exist in humans. Phenylephrine demonstrates differential electrophysiologic effects in atrial and ventricular tissue. Most data suggest that phenylephrine causes prolongation of the ventricular ERP. Rather than being proarrhythmic, phenylephrine may be protective against arrhythmias. The drug elevates VFT in dogs. In humans, phenylephrine effectively terminates supraventricular tachycardias and may be protective against ventricular arrhythmias. Like phenylephrine, methoxamine elevates the repetitive extrasystolic, atrial, and ventricular fibrillatory thresholds. Methoxamine also may have antiarrhythmic effects because of alpha-receptor stimulation and reflex vagal activity. Despite the relatively low risk of arrhythmogenicity associated with intravenous vasopressors, patients should be monitored for potential proarrhythmic effects and appropriate action taken as necessary. Critically ill patients often have concurrent conditions, electrolyte disturbances, and underlying arrhythmias that predispose them to a higher risk of vasopressor proarrhythmic effects. Controlled data supporting the proarrhythmic potential of intravenous vasopressors in humans are lacking. Sinus tachycardia, asymptomatic ventricular ectopic activity, and other ventricular or supraventricular arrhythmias have been reported in association with dopamine and epinephrine. Phenylephrine and methoxamine have been associated with sinus bradycardia, but otherwise may be antiarrhythmic. Intravenous vasopressors appear relatively safe w

Relation of cardiac surface QRST distributions to ventricular fibrillation threshold in dogs.

The relation between ventricular fibrillation threshold (VFT) and cardiac surface QRST area distributions was studied in eight pentobarbital-anesthetized dogs. Unipolar epicardial electrograms were recorded from 64 sites evenly distributed on the right and left ventricles. Localized areas of short repolarization properties were produced by directing five intensities of light onto the surface of the anterior right ventricle through apertures of three sizes. VFT, measured at the center of the lesion, decreased during warming and had a high negative correlation to the change (warming-control) in QRST area (delta QRST1) in the electrogram recorded from the center of the lesion. This correlation was independent of lesion size. For the six experiments, the correlation coefficients for 400-, 800-, and 1,600-mm2 lesions averaged -0.95, -0.94, and -0.96, respectively. The correlation between VFT and delta QRST1 without regard to lesion size averaged -0.88. VFT also had a negative correlation to root mean square (RMS)delta QRST because of warming. RMS delta QRST was calculated from the change in QRST areas (warming-control) in all 64 electrograms. The correlation between VFT and RMS delta QRST was dependent on lesion size. For all experiments, the correlation between VFT and RMS delta QRST averaged -0.97, -0.93, and -0.93 for 400-, 800-, and 1,600-mm2 lesions, respectively. The correlation between VFT and RMS delta QRST without regard to lesion size, however, was considerably lower, -0.59. The results of this study provide the first direct evidence that VFT is correlated with cardiac surface QRST area distributions.

Mechanism of the effect of bretylium on the ventricular fibrillation threshold in dogs

Experiments were performed to determine the importance of sympathetic blockade vs a direct myocardial effect as a mechanism for the antifibrillatory action of bretylium. The ventricular fibrillation (VF) threshold was determined in open-chest, anesthetized dogs by scanning the vulnerable period with either a single electrical stimulus (10 ms) or a train of electrical stimuli (14 pulses, 4 ms, 100 Hz). Using the train-of-pulses technique, the VF threshold increased from 6.8 ± 0.6 mA to 29.7 ± 6.4 mA 15 minutes after a 10-mg/kg intravenous bolus of bretylium (p < 0.001, n = 8). There was no further significant change in the train-of-pulses VF threshold at 2 or 4 hours. Beta-adrenergic blockade with timolol (0.2 mg/kg) increased the train-of-pulses VF threshold from 6.7 ± 1.6 mA to 24.5 ± 5.2 mA (p >; 0.01 n = 8) and prevented any further significant change in response to bretylium. When single electrical pulses were used to scan the vulnerable period, bretylium at doses of 10 mg/kg (n = 8) and 100 mg/kg (n = 6) did not alter the VF threshold over a 4-hour observation period. The administration of timolol, alone or in combination with bretylium, did not significantly alter the single-pulse VF threshold. The failure of bretylium to alter the single-pulse VF threshold was not dependent on the site of stimulation. Stimulation of the right sympathetic cardiac nerves showed that 15 minutes of bretylium treatment was sufficient to completely inhibit adrenergic neuronal transmission to the myocardium. The data indicate that bretylium has little direct antifibrillatory action on the normal canine myocardium. The ability of bretylium to elevate the VF threshold determined with a train of stimuli appears to be primarily a result of adrenergic neuronal blockade.

Carbon monoxide and ventricular fibrillation threshold in dogs with acute myocardial injury

In a blind, randomized study, the effect of breathing 100 p.p.m. of CO versus compressed, purified air for 2 hours on ventricular fibrillation threshold (VFT) was investigated in 21 dogs with acute myocardial injury. The mean arterial carboxyhemoglobin was 1.16 per cent in the air control period, 1.07 per cent after air, 1.08 per cent in the CO control period, and 6.34 per cent after CO. In comparison to air, CO increased the mean arterial carboxyhemoglobin (P < 0.001). One dog developed spontaneous ventricular fibrillation 100 minutes after CO. Mean VFTs in the other 20 dogs were 12.8 ± 6.8 milliamperes in the CO control period, 8.1 ± 3.8 milliamperes after CO, 11.2 ± 6.0 milliamperes in the air control period, and 15.0 ± 5.1 milliamperes after air. In comparison to air, CO decreased the VFT (P < 0.001). These data show that breathing 100 p.p.m. of CO for 2 hours reduces the VFT in dogs with acute myocardial injury.

Effect of stimulation of somatic nerves on the ventricular fibrillation threshold in dogs

Summary The data indicate that activation of somatic afferent fibers can produce a change in cardiac sympathetic activity which may influence development of arrhythmias under certain conditions. In this study, the VFT was lowered significantly by stimulation of somatic afferent fibers belonging to Groups II to IV. The decrease in VFT was probably due to increased sympathetic activity to the heart, since β-adrenergic blockade prevented the change in VFT during nerve stimulation. Recently, Theroux and associates 28 have shown that premedication of conscious dogs with morphine prevents the occurrence of ventricular fibrillation in the first few minutes following abrupt coronary artery occlusion. It was thought that morphine prevented the excitement reaction (which was characterized by marked agitation and struggling) in response to the ischemic pain associated with the coronary occlusion. According to the present study, morphine may have interrupted the somatosympathetic reflux associated with the pain and excitement and prevented the reflex increase in sympathetic activity to the heart. These observations deserve further, study, especially with regard to the effect of morphine on somatosympathetic reflexes. An alternate explanation is that morphine may have produced an increase in vagal efferent activity, which has been shown to antagonize the influence of the sympathetic nervous system on the heart 3 .

Influence of excitability on the ventricular fibrillation threshold in dogs

The influence of the excitability threshold on the ventricular fibrillation threshold was studied in dogs during myocardial ischemia and potassium and aprindine infusion. Interventions that influenced excitability threshold were associated with similar changes in ventricular fibrillation threshold although the percent change in both values differed. Although it is possible that the interventions studied caused parallel but independent changes in excitability threshold and ventricular fibrillation threshold, it is likely that the excitability threshold influences the ventricular fibrillation threshold. An increase in excitability threshold could result in an increase in ventricular fibrillation threshold in spite of an increase in the actual tendency of the heart to fibrillate spontaneously. Such discordance between the “electrical stability of the heart” and the ventricular fibrillation threshold was found during myocardial ischemia.

Effect of verapamil on experimental arrhythmias

Verapamil 0.25–1.0 mg/kg i.v. did not significantly elevate the ventricular fibrillation threshold in dogs. It did not antagonize the deslanoside arrhythmias, but inhibited transiently the arrhythmias induced by either electrical stimulation of the posterior hypothalamus or bilateral carotid occlusion incats. Effect of verapamil on the aconitine-induced rapid firing of the isolated atria and ventricles of the young rabbit and chick embryos was also studied with the microelectrode technique. In doses of 5, 10 and 20 μg/ml, it suppressed the rapid firing of the cardiac preparations, the exception of the ventricles of the rabbit. Antiarrythmic action of verapamil in such high concentration seems to be due to non-specific inhibition of Na + channels of the myocardial cells.

Effect of tetrodotoxin on experimental arrhythmias

Effects of tetrodotoxin (TTX) on the ventricular fibrillation threshold (VFT) in dogs and on various types of arrhythmias in cats were studied. TTX, 2–4 μg/kg i.v., raises VFT in dogs. TTX, 2–4 μg/kg i.v., suppressed Deslanoside- or aconitine-induced arrhythmias, and those induced by bilateral carotid occlusion or by electrical stimulation of the posterior hypothalamus in cats, but the effects are transient. TTX may exert its anti-arrhythmic effect in situ by acting on myocardium and nerve axons.

Effect of Alcohol on the Ventricular Fibrillation Threshold in Dogs

Effect of Alcohol on the Ventricular Fibrillation Threshold in Dogs