Calcium-free reperfusion prevents mitochondrial calcium accumulation but exacerbates injury

Excessive accumulation of intracellular calcium has been proposed as a mediator of cell injury during ischemia and reperfusion. To test whether restriction of extracellular calcium might ameliorate hepatic injury following hypothermic ischemic preservation, isolated perfused rat livers were reperfused with a medium with normal extracellular calcium (mM-Ca) or no added calcium (microM-Ca) following 26 hr preservation at 4 degrees C. During reperfusion mitochondria from mM-Ca livers accumulated calcium and respiratory activity declined. Although mitochondrial calcium accumulation was prevented by microM-Ca reperfusion, damage to respiratory activity was exacerbated. Edema formation and loss of gluconeogenesis were similarly exacerbated in microM-Ca. This accelerated damage was not reversed by subsequent restoration of calcium. These results demonstrate that rather than ameliorating cell injury, calcium deprivation during reperfusion exacerbates damage to mitochondrial and cellular functions. Thus, cellular or mitochondrial calcium accumulation does not appear to be a sine qua non for hepatocyte injury during reperfusion following hypothermic ischemia.