A direct protective effect of sulphinpyrazone on ischaemic and reperfused rat hearts.

Initiation of 60 min ischaemia to rat isolated hearts produced a depression in developed tension and heart rate. Subsequent reperfusion caused a greatly exacerbated creatine phosphokinase (CPK) efflux and limited functional recovery. Sulphinpyrazone (100 ng ml-1 and 1 microgram ml-1) significantly reduced CPK release, particularly after reperfusion, the lower concentration being more effective. A reduction in the mechanical depression during ischaemia and enhanced recovery after reperfusion were seen only with 100 ng ml-1 sulphinpyrazone. Heart rate and coronary perfusion pressure were unaffected by drug treatment. The reduction in reperfusion-induced CPK efflux by 100 ng ml-1 sulphinpyrazone was maximal when the drug was present throughout the perfusion period although some protection was evident when sulphinpyrazone was present either during ischaemia or reperfusion only. An enhanced recovery in contractility was seen only when the drug was present throughout all phases of perfusion. It is suggested that sulphinpyrazone exerts a direct protective effect on the heart particularly during reperfusion. The degree of protection is critically dependent on the concentration of sulphinpyrazone.