The effect of hypothermia on the occurrence of the calcium paradox

Reperfusion of isolated rat hearts with Ca2+-containing medium, after a short Ca2+-free perfusion period, results in irreversible cell damage (calcium paradox). In this investigation the effect of hypothermia during (a) the Ca2+-free perfusion period and (b) the phase of reperfusion with Ca2+-containing medium was studied. Failure of the heart to recover mechanical activity, and creatine kinase release were used to define cell damage. Ca2+-free perfusion was performed at 37 degrees, 30 degrees, 25 degrees and 20 degrees C. Hypothermia during the Ca2+-free period was unable to prevent the calcium paradox. At 37 degrees C a Ca2+-free perfusion was perfusion period of 4 min was sufficient to lead to failure of the hearts to recover mechanical activity and to induce massive enzyme release upon reintroduction of Ca2+. At 20 degrees C the Ca2-free perfusion had to be continued for 25 min to induce failure to recover mechanical activity, and for 80 min to induce massive enzyme release upon reperfusion with Ca2+-containing medium. Hypothermia (10 degrees - 15 degrees C) during the reperfusion phase resulted in a moderate release of creatine kinase. Massive enzyme release occurred as soon as the temperature of the perfusate was raised above 25 degrees C.