Incidence Of Spontaneous Ventricular Fibrillation Research Articles

Prevalence of the Brugada-Type Electrocardiogram and Incidence of Brugada Syndrome in Patients With Sick Sinus Syndrome

In the present study, clarification of the prevalence of the Brugada-type electrocardiogram (ECG) and the incidence of spontaneous ventricular fibrillation (VF) that occurred with the Brugada-type ECG in patients with sick sinus syndrome (SSS) was determined. A total of 487 consecutive patients (men 45%, mean age 69.9+/-12.3 years), who were defined as having an indication for cardiac pacemaker (PM) for SSS, were investigated. The ECG before an initial PM implantation and occurrence of VF or sudden cardiac death (SCD) was examined retrospectively. Brugada-type ECG was found in 14 patients (2.87%) including 4 (0.82%) with type 1 and 10 (2.05%) with type 2. During the follow-up period of 7.2+/-5.4 years, 2 out of the 4 patients with type 1 ECG had experienced a VF episode after the device implantation. In 10 patients with type 2 ECG, none had VF or SCD. The incidence of spontaneous VF (Brugada syndrome) in SSS patients was calculated as 14.1 per 100 person-years with type 1 ECG. The prevalence of typical Brugada-type (type 1) ECG in SSS patients seems to be higher compared with the general population. In addition, SSS patients with the typical Brugada-type ECG might be a high risk for spontaneous VF.

Chronic oral pretreatment with the angiotensin converting enzyme inhibitor, trandolapril decreases ventricular fibrillation in acute ischaemia and reperfusion.

The effect of chronic angiotensin converting enzyme (ACE) inhibition on the incidence of fatal ventricular fibrillation during regional myocardial ischaemia and reperfusion is not known. A reduction in cardiac angiotensin II and/or a vagomimetic response may result in antiarrhythmic activity. Pigs pre-treated with the ACE inhibitor trandolapril 0.3 mg.kg-1 or placebo orally for 10 days were subjected to thoracotomy. The left anterior descending coronary artery was ligated (CAL) for 20 min and reperfused for 45 min. Trandolapril decreased cardiac ACE activity and prevented the fall in the ventricular fibrillation threshold (VFT) during ischaemia: after 5 min of ischaemia the VFT in the trandolapril group was 25.5 +/- 4.6 mA (mean +/- SEM) vs 13.1 +/- 2.2 mA in the placebo group (P < 0.05). Trandolapril also decreased the incidence of spontaneous ventricular fibrillation during reperfusion to 1/6 vs 6/7 in the placebo group (P < 0.05). Heart rate in the trandolapril group fell. During ischaemia, trandolapril increased blood flow in the non-ischaemic zone, but decreased blood flow in the central ischaemic zone of the left ventricle. Similarly it decreased tissue levels of phosphocreatine in this zone. During reperfusion trandolapril increased blood flow both in non-ischaemic and central ischaemic zones. Chronic oral pre-treatment with trandolapril resulted in marked antifibrillatory effects which were associated with inhibition of cardiac ACE activity and a decreased heart rate.

Antiarrhythmic and Metabolic Effects of Indoramin During Acute Regional Ischemia and Reperfusion in Isolated Rat Heart

The antiarrhythmic effect of alpha 1-adrenoceptor antagonists during myocardial ischemia and reperfusion remains controversial. The potential antiarrhythmic properties of indoramin, an alpha 1-antagonist, were assessed in the isolated perfused rat heart during regional ischemia and during sustained reperfusion. Coronary artery ligation (CAL) decreased the ventricular fibrillation threshold (VFT) of control hearts from 9.1 +/- 1.3 (pre-CAL, mean +/- SEM) to 2.1 +/- 0.5 mA 15 min post-CAL (p less than 0.0001). Perfusion with indoramin 10(-8) M (alpha 1-receptor antagonistic concentration) started 5 min prior to CAL did not prevent the fall in VFT after CAL. Indoramin 10(-6) M prevented the fall in VFT after CAL relative to the control group. Indoramin 10(-5) M markedly increased the VFT before CAL from 9.9 +/- 1.0 to 28.6 +/- 2.9 mA (p less than 0.0001) and prevented the fall in VFT after CAL. During reperfusion, indoramin 10(-5) M decreased the incidence of spontaneous ventricular fibrillation (VF) to 1 of 6 vs. 6 of 6 in the control group (p less than 0.02). Indoramin 10(-5) M preserved adenosine triphosphate in the reperfused myocardium: 2.82 +/- 0.06 vs. 2.16 +/- 0.21 mumol/g in the control group (p less than 0.05). Specific alpha 1-antagonist properties of indoramin did not appear to be involved in the antiarrhythmic effects.

Spontaneous and electrically induced ventricular arrhythmias during acute ischemia superimposed on 2 week old canine myocardial infarction

The arrhythinogenic effect of acute reversible myocardial ischemia before and 2 weeks after experimental myocardial infarction was investigated in 37 dogs that underwent reversible 10 min occlusion of the first major marginal branch of the left circumflex coronary artery. Subsequently, 24 of the dogs underwent experimental myocardial infarction with permanent left anterior descending coronary ligation, and 13 dogs served as sham-operated controls. Two weeks later, an open chest programmed electrical stimulation was performed in the 13 sham-operated and 24 postinfarction dogs to determine its accuracy in predicting the ventricular arrhythmias that develop during a subsequent episode of acute reversible ischemia. After programmed electrical stimulation, the left circumflex marginal branch was reversibly occluded for 10 min at the same site.The incidence of spontaneous ventricular fibrillation during reversible left circumflex marginal coronary occlusion did not differ from the first to the second study in sham-operated dogs, whereas in the postinfarction dogs, it increased from 13% before infarction to 54% after infarction (p = 0.005). The outcome of programmed electrical stimulation predicted spontaneous ventricular arrhythmias during coronary occlusion in only 21% of the postinfarction dogs. The accuracy of programmed electrical stimulation was 42% and its predictive value was 47% in detecting the dogs with spontaneous ventricular fibrillation.Regional myocardial blood flow measurements by microsphere technique identified the severity of reversible ischemia in the infarct border and periinfarction zones as a correlate of spontaneous ventricular fibrillation during coronary occlusion. In contrast, total infarct size correlated with electrically induced but not with spontaneous ventricular arrhythmias.

The activity of molsidomine in experimental models of ischemic cardiac disease

The cardioprotective and antithrombotic activity of molsidomine, a novel therapeutic agent for the treatment of coronary heart disease, was investigated in a series of animal models of myocardial ischemia. Molsidomine given to dogs with marked ST segment elevation (epicardial electrogram), induced by a reduction of left descending coronary artery (LAD) flow to 20% to 30% of the original value, resulted within 40 minutes in complete normalization of ECG changes. In another animal model molsidomine given either before or after occlusion of the LAD significantly reduced infarct size. All these molsidomine effects were accompanied by a marked lowering of preload, resulting in a reduction of extravascular coronary artery resistance and in increased blood flow toward the ischemic zones. In a model of myocardial ischemia and reperfusion in the anesthetized dog, molsidomine had a marked protective effect against the incidence of spontaneous ventricular fibrillation. This effect could also be attributed to the anti-ischemic activity of molsidomine, which would reduce the disparity between the refractory periods in normal and ischemic areas and thus increase ventricular stability. The antithrombotic activity of molsidomine was investigated in dogs in which the left circumflex coronary artery was electrically stimulated, a procedure that leads to thrombotic occlusion. Molsidomine in a dose-dependent manner prevented coronary thrombotic occlusion and reduced thrombus wet weight and the size of the resulting infarction. These effects of molsidomine were not related to its hemodynamic activity, since nitroglycerin and isosorbide dinitrate had similar hemodynamic effects but did not prevent coronary thrombosis. The antithrombotic activity of molsidomine is probably related to its ability to lower coronary venous blood thromboxane levels.

Effect of molsidomine on spontaneous ventricular fibrillation following myocardial ischemia and reperfusion in the dog.

The effect of the novel antianginal agent molsidomine on the incidence of spontaneous ventricular fibrillation during myocardial ischemia and reperfusion was investigated in the anesthetized dog. Molsidomine was administered as an intravenous bolus at the dose of 0.05 mg/kg. Twenty minutes later, the left anterior descending coronary artery was occluded for 90 min. During the occlusion period, molsidomine was given as a continuous intravenous infusion at the dose of 0.5 micrograms/kg per ml per min. After release of the occlusion, the animals that survived were monitored for another 30 min. Control animals received saline. In the control animals, coronary occlusion was accompanied by an increase in heart rate, heart contractility, left ventricular end-diastolic pressure, and blood pressure as well as by ventricular arrhythmias. Molsidomine either abolished or reduced both hemodynamic and electrical changes. During the reperfusion period, 10 out of 12 control animals died, and the deaths were from ventricular fibrillation; one out of eight molsidomine-treated animals also died of ventricular fibrillation. It is postulated that the protective effect of molsidomine rests on its hemodynamic effects resulting in a shift in blood flow toward the ischemic zones and, consequently, in an increase in ventricular electrical stability.

Extra-adrenergic mechanisms responsible for the effects of glucose-insulin-potassium solution on vulnerability to ventricular fibrillation

In 53 chloralose-anesthetized dogs, the actions of glucose (10 mg/kg per min), insulin (0.025 U/kg per min) and potassium (0.025 mEq/kg per min) on the ventricular fibrillation and repetitive extrasystole thresholds were examined. Measurements were initially made in the control state and then repeated at 30, 60 and 120 minutes of infusion of glucose-insulin-potassium solution at a constant rate of 1.23 ml/min. The dogs received on the average 36 g of glucose, 44 U of insulin and 44 mEq of potassium over a 2 hour period. In the nonischemic myocardium, the infusion raised the threshold for ventricular fibrillation and repetitive extrasystole to a peak of 94 and 61 percent, respectively, without significantly changing serum potassium or circulating catecholamine concentration. In the ischemic myocardium, the incidence of spontaneous ventricular fibrillation during 10 minutes of coronary occlusion was reduced from 83 percent in the control state to 17 percent with glucose-insulin-potassium infusion. However, the infusion did not alter the incidence of ventricular fibrillation associated with reperfusion. Because cardio-cardiac sympathetic reflexes are elicited in response to coronary occlusion, the effect of glucose-insulin-potassium infusion on ventricular vulnerability during left stellate ganglion stimulation and norepinephrine infusion was investigated. The infusion completely prevented the reduction in the vulnerable period threshold during stellate stimulation and norepinephrine infusion. Furthermore, the peak protection afforded by the infusion was greater than that achieved with beta adrenergic blockade and was still present in catecholamine-depleted hearts. It is concluded that infusion of glucose-insulin-potassium solution protects against ventricular fibrillation in the normal and ischemic canine heart but not during reperfusion. This protection may be due in part to antagonism of adrenergic activity; however, the primary influence of the solution is mediated by extra-adrenergic mechanism.

The effects of lidocaine on the ventricular fibrillation threshold and primary ventricular fibrillation following acute experimental coronary occlusion.

Experiments were performed on 39 anaesthetized open-chest dogs (BW 16-33 kg) to examine the effect of lidocaine on the frequency of primary ventricular fibrillation (VF) and the time course of the ventricular fibrillation threshold (VFT) (train of stimuli-method) following acute coronary artery occlusion, and also to study the effects of lidocaine on the VFT of non-ischaemic heart at different therapeutic and high non-therapeutic doses. At effective plasma levels of lidocaine usually reached in clinical therapy (130-480 micrograms/l) there was no measurable increase in VFT compared to control values. The drop in VFT following acute ligation of the left anterior descending coronary artery (LAD) was neither eliminated nor even merely diminished. After occlusion of the left circumflex coronary artery (CIR), the incidence of spontaneous VF was not reduced in comparison to a control group. With regard to the doses administered and the plasma levels of lidocaine achieved, only the application of clinically extremely high or toxic doses resulted in increases in VFT in the non-ischaemic heart.

Protective effect of verapamil on vulnerability to ventricular fibrillation during myocardial ischaemia and reperfusion.

The effects of verapamil on vulnerability to ventricular fibrillation were studied in 55 chloralose-anaesthetised dogs. Ventricular fibrillation threshold was measured before and during a 10 min period of left anterior descending coronary artery occlusion and following abrupt release of occlusion. The action of intravenous verapamil (0.01 mg.kg-1.min-1, following a 0.1 mg.kg-1 bolus) on vulnerability to fibrillation was examined before and during coronary artery occlusion and reperfusion. While the infusion of verapamil did not alter the ventricular fibrillation threshold in the nonischaemic myocardium, the vulnerable period threshold was raised and the incidence of spontaneous ventricular fibrillation was reduced both after coronary artery occlusion and release. Since cardiocardiac sympathetic reflexes are elicited in response to coronary artery occlusion, the effect of verapamil on vulnerability during left stellate ganglion stimulation and during noradrenaline infusion was investigated. Verapamil completely prevented the reduction in vulnerable period threshold during sympathetic nerve stimulation or noradrenaline infusion. This study suggests that the antifibrillatory action of verapamil during coronary artery occlusion may be, in part, related to antagonism of enhanced adrenergic input to the heart, while the mechanism of protection during reperfusion is as yet uncertain.

Effect of nitroglycerin on vulnerability to ventricular fibrillation during myocardial ischemia and reperfusion

The effect of nitroglycerin on vulnerability to ventricular fibrillation was examined in 44 chloralose-anesthetized dogs. In 19 animals ventricular fibrillation threshold was measured before and during a 10 minute period of occlusion of the left anterior descending coronary artery followed by abrupt release of occlusion. Fibrillation threshold was determined using the single stimulus and train of stimuli methods. The influence of nitroglycerin on vulnerability was assessed with and without prevention of the drug's hypotensive effect by intravenous injection of phenylephrine. In the nonischemic myocardium, infusion of nitroglycerin alone or in combination with phenylephrine did not alter the ventricular fibrillation threshold. However, during both coronary occlusion and reperfusion, administration of nitroglycerin alone afforded partial protection against vulnerability to ventricular fibrillation. Nearly complete protection was imparted by combined administration of nitroglycerin and phenylephrine. The incidence of spontaneous ventricular fibrillation during reperfusion was significantly reduced by combined administration of nitroglycerin and phenylephrine. It is concluded that infusion of nitroglycerin decreases susceptibility to ventricular fibrillation during both acute myocardial ischemia and reperfusion and that this beneficial action is substantially enhanced when the drug's hypotensive effect is prevented.

Neural basis for the genesis and control of arrhythmias associated with myocardial infarction.

Alterations of autonomic tone appear to have important effects on the electrical stability of the heart. Since altered electrical stability, ventricular fibrillation, is the cause of death in the majority of patients who die from ischemic heart disease, the effects of the autonomic nervous system on ventricular electrical stability have been examined. Increased vagal tone increases the electrical stability of the heart and reduces the incidence of spontaneous ventricular fibrillation after coronary occlusion. These salutary effects of increased cholinergic tone appear to be mediated by cholinergic innervation of the ventricular conducting system. Conversely, increased adrenergic tone decreases the electrical stability of the heart and increases the propensity of the heart to develop ventricular arrhythmias during coronary occlusion. The interaction of the adrenergic and cholinergic system during myocardial ischemia may be one of the important determinants of survival in patients with coronary artery disease and acute myocardial infarction.

Enhancement of electrical stability of acutely ischemic myocardium by edrophonium.

Recently we demonstrated that vagal stimulation increases ventricular fibrillation threshold (VFT) and decreases the incidence of spontaneous ventricular fibrillation during acute coronary occlusion. Assuming this protective effect of the vagus to be mediated through acetylcholine release, we hypothesized that inhibition of acetylcholinesterase, a potential clinical intervention, would also enhance electrical stability of acutely ischemic myocardium. A balloon cuff was placed around the left anterior descending coronary artery (LAD) and left ventricular and atrial electrodes were implanted in 10 dogs. Five to seven days later VFT was determined (VFT was defined as the minimum current required to produce ventricular fibrillation). During nonischemic conditions VFT was 42 ± 8 ma; when edrophonium was infused (1-2 mg/kg/min), VFT increased to 77 ± 11 ma ( P &lt; 0.005). During ischemia induced by LAD occlusion VFT fell to 19 ± 4 ma. Edrophonium increased VFT during ischemia to 52 ± 13 ma ( P &lt; 0.005), a level not significantly different from preischemic values. These results suggest that enhanced electrical stability of ventricular myocardium produced by vagal stimulation is mediated by acetylcholine release, and that inhibitors of acetylcholinesterase may provide a new means of therapy for arrhythmias occurring during acute myocardial ischemia.

Nitroglycerin-induced reduction in the incidence of spontaneous ventricular fibrillation during coronary occlusion in dogs

Previous investigations have demonstrated that nitroglycerin reduces ischemic injury and enhances ventricular electrical stability during coronary occlusion in dogs. These beneficial effects were potentiated by preventing drug-induced hypotension with alpha adrenergic agonists. To determine whether nltroglycerin can prevent spontaneous post-occlusion ventricular fibrillation, 27 open chest dogs were assigned in random fashion to two groups—control (saline infusion) and nitroglycerin-treated (0.45 mg intravenous bolus infusion followed by 0.3 mg/ min continuous infusion). After 10 minutes of infusion the left anterior descending and septal coronary arteries were occluded at their origins. Hypotensive effects of nitroglycerin were prevented by intermittent intravenous doses of methoxamine; mean arterial pressure and heart rate in control and treated animals were thus indistinguishable. Infusions continued until ventricular fibrillation occurred or 30 minutes elapsed. Twelve of 13 control dogs died with ventricular fibrillation; only 7 of 14 nitroglycerin-treated dogs died ( P < 0.05). Thus, nitroglycerin may be capable of exerting important and unique beneficial effects in patients with acute myocardial infarction since, with its hypotensive effects obviated by alpha adrenergic agonists, it markedly diminishes ischemic injury, enhances ventricular electrical stability, and significantly reduces the incidence of spontaneous ventricular fibrillation in an experimental model of acute myocardial infarction.