Substrate dependence of reoxygenation arrhythmias in the isolated rat heart

Isolated rat hearts perfused with various substrates were subjected to oxygen restriction followed by sudden reoxygenation. The incidence of ventricular arrhythmias occurring after reoxygenation appeared to be dependent on the substrate present during oxygen restriction; it was low with glucose (11 mM) and significantly higher with oleic acid (FFA to albumin molar ratio 4), with beta-hydroxy butyrate (11 mM), with acetate (11 mM) or without added substrate. When verapamil (1 muM) was also present in the medium, these arrhythmias were largely prevented. When glucose or verapamil were present during the reoxygenation period only, the incidence of reoxygenation arrhythmias was high. Tissue levels of long-chain acyl-CoA increased during oxygen restriction under all substrate conditions tested. At the moment when reoxygenation was started they were most elevated in hearts perfused with oleic acid. Verapamil did not influence levels of long-chain acyl-CoA. The amount of creatine-kinase (CK) released from the heart after reoxygenation did not correlate with the observed arrhythmias and was greatest in hearts perfused with oleic acid. Verapamil protected against CK release in the absence of added substrate, but not when oleic acid was present. It is concluded that ventricular arrhythmias after reoxygenation are not necessarily caused by FFA or long-chain acyl-CoA.