Effect of exogenous adenosine deaminase on arrhythmias and the release of adenine nucleotide catabolites in isolated rat hearts with coronary occlusion and reperfusion.
In isolated perfused rat hearts with occlusion of the left coronary artery the release of adenosine and its degradation products inosine, hypoxanthine, xanthine and uric acid was investigated with and without exogenous addition of adenosine deaminase. In the control experiments large amounts of the adenine nucleotide catabolites appeared in the perfusate during coronary reperfusion. The greater part was represented by adenosine and inosine. During the coronary occlusion itself only a minor increase in the release of adenine nucleotide catabolites was observed, compared with the basal release before the coronary occlusion. Depending on the duration of the coronary occlusion more or less severe tachyarrhythmias occurred during the reperfusion of the previously ischaemic myocardium. Reperfusion-induced ventricular fibrillation was associated with a significant increase in the release of adenine nucleotide catabolites, compared with non-fibrillating hearts. In the presence of exogenously-added adenosine deaminase the release of adenine nucleotide catabolites from reperfused hearts was further increased. Adenosine itself, however, almost completely disappeared from the perfusate. In adenosine-deaminase treated hearts the incidence of reperfusion-induced fibrillation increased, thereby contributing to the enhanced release of adenine nucleotide catabolites. However, the release was also increased by the enzyme when only the fibrillating hearts were considered, suggesting that rapid elimination of adenosine from the interstitial space also directly increases the release of adenine nucleotide catabolites from the heart.
Bernauer
W
W
Department of Pharmacology, University of Freiburg, Federal Republic of Germany.
D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D007288:Inosine / Q000378:metabolism; D008297:Male; D015425:Myocardial Reperfusion; D051381:Rats; D011919:Rats, Inbred Strains
D007288:Inosine; D000243:Adenosine Deaminase; D000241:Adenosine