Effects of timolol on adenine nucleotide catabolism in cat hearts with acute regional ischaemia.

The effects of the beta-adrenergic blocking agent timolol on cardiac function and adenine nucleotide metabolism were investigated in cats with 45 min of acute ischaemia following coronary occlusion. Regional myocardial blood flow was measured by 15 micron radiolabelled microspheres, and adenine nucleotides and their degradation products were measured by high performance liquid chromatography in 16 tissue regions in each cat. During ischaemia, cats treated with timolol exerted a reduced cardiac performance as judged from reduced heart rate and cardiac contractility; consequently preocclusion tissue blood flow was reduced compared with a control group of cats. The ATP concentration was less severely depleted in ischaemic regions of the left ventricle in cats treated with timolol. The energy charge was reduced to a lesser extent in ischaemic regions, and in intermediate flow ranges the contents of the inosine and hypoxanthine/xanthine were reduced compared with untreated cats. These results indicate that the beta-adrenergic blocking agent timolol might protect the myocardium within a 45 min ischaemic period. The mechanism for this effect is most probably related to the reduction in overall cardiac performance.