Inosine increases anoxic tolerance and postischaemic restitution of the heart: experimental studies on possible mechanism(s) of action

Abstract

Various experimental models were utilized to determine the in vivo cardiac actions underlying the presumptive therapeutic benefit of the naturally occurring adenine nucleoside, inosine. 1. In pentobarbital-anaesthetized dogs coronary vasodilator responses to arterial hypoxia were augmented and postanoxic depression of cardiac contractile force was prevented by i.v. infusion of inosine (5 mg X kg-1 X min-1). 2. Thermographic observations demonstrated in the in situ dog heart a significant inosine-induced epicardial warming (coronary flow increase) which was resistant to P1-purinergic blockade (aminophylline). 3. Following total cardiopulmonary bypass and cardioplegic cardiac arrest of 90 min duration in the dog, inosine administration (5 mg X kg-1 X min-1) evoked a lasting increase in myocardial contractile force and cardiac output. 4. In Langendorff perfused guinea pig hearts subjected to normothermic ischaemia of 1 hour duration and treated with inosine (0.05 mg X min-1), the release of cytoplasmatic enzymes (CK-MB, alpha-HBDH) and myoglobin was significantly less than in untreated ischaemic controls. In the two latter series of experiments (3 and 4) the inosine action was contrasted by the deleterious effect of catecholamines (noradrenaline and isoproterenol) administered in moderate or small doses, respectively. It was concluded that inosine has cardioprotective actions partly related to and partly independent of its influence on coronary blood supply, suggesting that administration of the nucleoside may be useful in various surgical attempts directed to myocardial salvage.