ENDOGENOUS ADENOSINE SUPPRESSES NOREPINEPHRINE-INDUCED VENTRICULAR ARRHYTHMIAS IN RAT-HEART

Adenosine is an antiarrhythmic substance particularly effective in cat echolamine-dependent tachycardias. Although endogenous adenosine subst antially accumulates in catecholamine-stimulated hearts, little is kno wn about the antiarrhythmic potency of endogenous adenosine in this co ndition. Therefore, we sought to demonstrate a potential antifibrillat ory effect of endogenous adenosine either by blockade of adenosine rec eptors with 8-phenyltheophylline (8-PT) or by suppression of endogenou s adenosine release with nitrobenzyl-6-thioinosine (NBTI). The study w as performed in spontaneously beating Langendorff-perfused rat hearts. Adenosine release into the effluent was determined by HPLC methods. C atecholamine stimulation was induced by perfusing the hearts with nore pinephrine (1 mu mol/l) for 30 min, which caused ventricular tachycard ia (VT) in 31 % and ventricular fibrillation (VF) in 25 % of control h earts (n = 35). When 8-PT (10 mu mol/l) was added to the perfusion buf fer prior to norepinephrine, the incidence of VT and VF increased to 7 9 and 68 %, respectively. The addition of X-PT did not affect the cate cholamine-dependent formation of adenosine. Perfusion of the hearts wi th NBTI (10 mu mol/l) prior to norepinephrine reduced adenosine releas e and increased the occurrence of both VT (65 %) and VF (40 %). In sum mary, the results indicate that adenosine is an endogenous antiarrhyth mic substance, which accumulates in catecholamine-stimulated myocardiu m to a level, which effectively suppresses the occurrence of ventricul ar arrhythmias.