EFFECTS OF CAFFEINE ON ISCHEMIA-REPERFUSION INJURY IN ISOLATED RAT HEARTS

Cardiac sarcoplasmic reticulum (SR) plays an important role in regulat ion of the intracellular Ca2+ concentration. It is well known that int racellular Ca2+ overload is one cause of reperfusion injury. Thus, it is predicted that reperfusion injury of myocardium can be prevented by eliminating the Ca2+ overload. This study examined the effects of caf feine, a SR blocker, on reperfusion injury in isolated perfused rat he arts. Working hearts were reperfused for 25 min after 30 or 50 min of ischemia. Caffeine (10(-4)M) was administered during the period of isc hemia or the initial 5 min of reperfusion. The left ventricular pressu re and the electrocardiogram were recorded. Rate-pressure products wer e calculated as an index of cardiac function. Adenine nucleotides were measured by high-performance liquid chromatography to assess energy c harge. The administration of caffeine for a short period during the in itial reperfusion significantly improved cardiac function in the heart s. Caffeine pretreatment during 50 min of ischemia, though, resulted i n deterioration of both energy charge and cardiac function. Caffeine d id not affect the incidence of either ventricular fibrillation or reve rsion to sinus rhythm. The energy charges were lower in the preparatio ns with sustained ventricular fibrillation.