The influence of calcium antagonists on the adenine nucleotide metabolism in the guinea-pig working heart during ischaemia and reperfusion

Abstract

With the aim of gaining more insight into the metabolism of adenine nucleotides in working normoxic guinea-pigs and in hearts subjected to 45 min of global ischaemia and subsequent reperfusion for 25 min, we evaluated the effect of nifedipine, verapamil, diltiazem, bepridil, CERM 11956, lidoflazine, mioflazine and dipyridamole on the adenine nucleotide catabolite levels in these hearts. The drugs were applied at the concentrations that reduced the aortic dP/dt of normoxic working hearts by 10% (EC10) and 30% (EC30). In globally ischaemic hearts there was a large accumulation of adenine nucleotide catabolites. Inosine proved to be the major catabolite. The drugs, with the exception of bepridil, CERM 11956 and dipyridamole (3 mumol/l), decreased the accumulation of catabolites. In hearts treated with mioflazine and dipyridamole the amount of adenosine increased. A deficit in the balance between adenine nucleotides and catabolites indicated that in globally ischaemic hearts there was a large accumulation of inosine monophosphate. Indeed, a substantial amount of inosine monophosphate was determined in untreated hearts, and hearts treated with nifedipine (EC30) and mioflazine (EC10). During the first 5 min of reperfusion a large quantity of catabolites, mainly inosine, was washed out. During 20 min of subsequent reperfusion in untreated hearts and in nifedipine and mioflazine-treated hearts the efflux of catabolites returned to normoxic values. Similar to the effect in ischaemic hearts, in early perfusate from lidoflazine, mioflazine and dipyridamole-treated hearts the adenosine/inosine ratio was increased.(ABSTRACT TRUNCATED AT 250 WORDS)