PRONOUNCED ANTIARRHYTHMIC EFFECTS OF PRECONDITIONING IN ANESTHETIZED DOGS - IS ADENOSINE INVOLVED

Although there is good evidence that adenosine contributes to the ability of ischaemic preconditioning to reduce myocardial ischaemic damage (infarct size) there is no evidence that it contributes to the marked antiarrhythmic effects of this endogenous protective mechanism, We have examined this in anaesthetized open-chest mongrel dogs by administering the non-selective adenosine receptor blocking drug 8-sulfophenyltheophylline (8-SPT) (1mg/1kg) given by intracoronary administration 10 min before both 5 min preconditioning coronary artery occlusions and also before the prolonged 25 min LAD occlusion i.e. in a total dose of 3 mg/kg. The only haemodynamic effect of 8-SPT was a reduction in coronary (LAD) blood flow and an increase in cardiovascular resistance. It was difficult to precondition dogs in the presence of 8-SPT; the number of ventricular premature beats was significantly higher (61 +/- 6 v 8 +/- 4; P<0.01) during the initial preconditioning occlusion and the incidence of ventricular fibrillation during the preconditioning procedure was higher in the presence of the drug (5/11 v 4/20; P<0.05). Nevertheless, it was still possible to precondition these dogs in the presence of the drug. No VF occurred during the prolonged occlusion (cf. 50% in the controls) and the number of episodes of ventricular tachycardia, and the number of ventricular premature beats in dogs preconditioned in the presence of 8-SPT was similar to those in dogs preconditioned without 8-SPT and significantly (P<0.01 or P<0.05) less than in control, non-preconditioned dogs. Other indices of ischaemia (epicardial ST-segment elevation and the degree of inhomogeneity of ventricular activation) were more marked in those dogs given 8-SPT, We conclude that although adenosine does not contribute to the antiarrhythmic effects of ischaemic preconditioning in this species, there is evidence that it acts as an ''endogenous myocardial protective substance'', We suggest that ischaemic preconditioning involves a number of endogenous mediators acting at receptor level; these include bradykinin, nitric oxide and prostacyclin as well as adenosine.