The isolated Langendorff-perfused rat heart, subjected to coronary artery occlusion and reperfusion consistently developed ventricular arrhythmias. The incidence of hearts with ventricular premature extrasystoles, ventricular tachycardia, and fibrillatioon ventricular fibrillation could be abolished in the presence of an extracellular potassium concentration of 12 mmol-litre--1, whereas with 4.5 mmol-litre--1 all hearts developed all the ventricular arrhythmias including fibrillation. This predictable occurrence of ventricular arrhythmias was used to assess the antiarrhythmic effect of lignocaine with particular reference to its effect on the spontaneously occurring reperfusion ventricular fibrillation. Lignocaine decreased the incidence of all ventricular arrhythmias both during ischaemia and on reperfusion in a concentration-related fashion.

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A B S T R A C T The relation between myocardial tissue cyclic AMP (cAMP) and the vulnerability to ventricular fibrillation was assessed in the isolated perfused rat heart by measurement of ventricular fibrillation threshold (VFT) and vulnerable period duration (VP). Exogenous dibutyryl cyclic AMP (DBcAMP) reduced VFT and increased VP by a concentration-related action whereas exogenous cAMP did not. Theophylline (1.0 mmol/liter) increased the tissue content of cAMP by 58% (P < 0.001) and caused a leftward shift in the concentration-response curve to DBcAMP. An effect of cAMP on VFT and VP could be shown in the presence of phosphodiesterase inhibition by theophylline. 3-1-Adrenergic receptor blockade with atenolol did not alter the concentration-response curve for VFT when DBcAMP was administered. Epinephrine (100 nmol/liter to 1 ,umol/liter) also increased vulnerability to VF; this effect was accompanied by a concentration-related increase in tissue cAMP, but inconsistent changes in tissue ATP, phosphocreatine and potassium. The concentration-response curve of VFT to epinephrine was shifted leftward by theophylline and rightward by atenolol.The increases in vulnerability to fibrillation in the isolated perfused rat heart, in response to DBcAMP, theophylline or epinephrine, could be related more closely to changes of tissue cAMP than to effects on tissue high energy phosphates or potassium. The effect of epinephrine and theophylline on vulnerability to ventricular fibrillation is mediated via alterations in the intracellular level of cAMP in the isolated perfused rat heart.