Production Of Ventricular Fibrillation Research Articles

Treatment and prevention of ventricular fibrillation: Are there better agents?

Ventricular fibrillation occurs in diverse clinical settings and differing pathogenic mechanisms make it unlikely that a single drug treatment will be universally effective. Drugs may be used as an adjunct to electrical defibrillation in circulatory collapse, to prevent recurrence after successful resuscitation or as a prophylactic treatment in high-risk patients. Various drugs are available for intravenous administration in the acute management of ventricular fibrillation and the choice among them will depend on several factors: proven efficacy, comparative efficacy and their safety including haemodynamic effects. Although several drugs have been shown to suppress ventricular ectopic beats and ventricular tachycardia, ventricular fibrillation and sudden death can occur despite abolition of these less serious ventricular arrhythmias [ 11. Animal studies have suggested the concept of separate ‘antiarrhythmic’ and ‘antilibrillatory’ action of drugs. Drugs with antifibrillatory properties increase the energy threshold for production of ventricular fibrillation while many conventional antiarrhythmic drugs have no effect [2,3]. However, an effect on fibrillation threshold does not necessarily indicate a reduction in energy requirements for successful electrical defibrillation. The major criticism of such models is that the substrate for generation of ventricular fibrillation is usually different in clinical ventricular fibrillation. Lignocaine and bretylium are the current standard drugs for management of acute ventricular fibrillation. This review examines the claims of other antiarrhythmic drugs to supplant or supplement these agents (Table I). Figure 1 shows a representation of the normal cardiac action potential. Initial depolarisation (phase 0) is achieved by rapid influx of sodium ions which is slowed by agents which belong to class 1 of the Vaughan Williams and Singh classification. These compounds are subdivided by their effect on the duration of the action potential: Class la drugs lengthen it, Class lb shorten it, while Class lc have no effect. Class II drugs are the beta blockers which have no direct effect on the action potential but antagonise myocardial stimulation by catecholamines. The Class III agents delay phase 3 repolarisation and prolong the duration of the action potential. Class IV drugs are calcium channel blockers which reduce the influx of calcium into cells, in particular reducing the spontaneous depolarisation of phase 4 in the atrio-

Role of α- and β-Adrenergic Activation in Ventricular Fibrillation Death of Corticoid-Pretreated Rats

Death in ventricular fibrillation was induced consistently in desoxycorticosterone acetate-pretreated rats by the β-adrenergic agonist isoproterenol but not by norepinephrine or epinephrine, both of which possess α- as well as β-adrenergic activity. Aminophylline, which enhances β-adrenergic activity, and phenoxybenzamine, an α-receptor blocking agent, were used to study the roles of α- and β-adrenergic stimulation in the production of ventricular fibrillation. With the addition of aminophylline, both norepinephrine and epinephrine produced death in ventricular fibrillation, and the existing cardiotoxicity of isoproterenol was potentiated. Similarly, in the presence of phenoxybenzamine, doses of norepinephrine and epinephrine that had been well tolerated became lethal. Interventions that favor β-adrenergic preponderance, either by enhancing β-effects or by blocking protective α-adrenergic activation, apparently increase the arrhythmogenic propensity of norepinephrine and epinephrine in steroid-pretreated rats. The similarity of some forms of stress to the experimental protocol of chronic steroid treatment followed by acute catecholamine exposure is discussed.

THE EFFECT OF ACONITINE, ADRENALIN AND PROCAINE, AND CHANGES IN THE IONIC CONCENTRATION IN THE PRODUCTION OF VENTRICULAR FIBRILLATION IN A HIBERNATOR (HEDGEHOG) AND A NON-HIBERNATOR (GUINEA-PIG) AT DIFFERENT TEMPERATURES.

THE EFFECT OF ACONITINE, ADRENALIN AND PROCAINE, AND CHANGES IN THE IONIC CONCENTRATION IN THE PRODUCTION OF VENTRICULAR FIBRILLATION IN A HIBERNATOR (HEDGEHOG) AND A NON-HIBERNATOR (GUINEA-PIG) AT DIFFERENT TEMPERATURES.

Excitability of the normally beating heart.

The electrical and mechanical responses to single square wave stimuli applied to spontaneously beating hearts in situ were examined. Shocks were delivered through a time delay circuit triggered by the voltage of the R wave of the ECG. The silver-silver chloride electrodes were 3 mm apart and their position on the ventricular surface kept constant throughout an experiment Stimuli were separated by 20–30 heart beats. The plotted excitability curve (strength-interval) was found to be smooth without any indication of transient variations in threshold. Single stimuli of various durations (up to 100 msec.) and amplitudes (up to 25 ma) were ineffective for the production of ventricular fibrillation. Apparently excitability recovery for a small and localized myocardial area is synchronous and smooth.

Electrolyte studies in experimentalanimals during hypothermia

Summary Data on physiologic alteration in dogs undergoinggeneral body cooling and rewarming are presented. Heart rate, mean arterial pressures, platelets and white cell counts all showed significant decreases at low temperature levels (22° to 25°C.). Serum potassium concentrations were foundto be greatly increased just prior to ventricular fibrillation in the cold state. Prolonged acidosis or alkalosis did not alter this elevation. Electrocardiographic patterns were fairlyconstant with deep cooling and could be used to predict impending difficulty. It is suggested that a relative tissue hypoxia associated with low coronary flow is a factor in the production of ventricular fibrillation during profound hypothermia.

Role of hyperkalemia in production of ventricular fibrillation following hypercapnia.

Summary and Conclusions1. Dogs regularly show an increase in plasma potassium concentration during breathing of 30% and 40% CO2 mixtures. Immediately following return to air breathing, there is a further sharp rise in this concentration. This secondary rise reaches a peak after 5 minutes of air breathing. 2. Concentration of plasma potassium following 4 hrs of high CO2 breathing is not as high as that which is necessary to produce fibrillation or arrest when KCl solution is administered as an intravenous drip to normal or acidotic dogs. 3. Rapid return to air breathing following 30 minutes of high CO2 breathing does not produce cardiac arrhythmias, ventricular fibrillation, or cardiac arrest in dogs. However, when this rapid elevation in blood pH and/or fall in pCO2 takes place in the presence of sub-lethal but elevated plasma potassium concentrations, cardiac arrest or ventricular fibrillation may occur. Although this does not provide an explanation of the mechanism involved, it appears that the combinat...

Production of ventricular fibrillation and defibrillation in dogs by means of accurately measured shocks across exposed heart.

Production of ventricular fibrillation and defibrillation in dogs by means of accurately measured shocks across exposed heart.

Production of ventricular fibrillation by alternating currents: Wégria, René, and Wiggers, Carl J.: Am. J. Physiol. 131: 119, 1940

Production of ventricular fibrillation by alternating currents: Wégria, René, and Wiggers, Carl J.: Am. J. Physiol. 131: 119, 1940