The effect of hypothermia on mitochondrial function on ischaemic and reperfused myocardium

26 THE EFFECT OF HYPOTHERMIA ON MITOCHONDRIAL FUNCTION ON ISCHAEMIC AN'D REPER FUSED MYOCARDIUM. R.FERRARI,F.DI LISA,R.RADDINO,MP.LANTI,WG.NAYLER. -Cattedra di Cardiologia Parma University ,Italy; Cardiothoracic Institute London University,U.K. . The ability of hypothennia to preserve cardiac metabolism during ischae mia was evaluated in isolated and perfused rabbit hearts.Ischaemia was in= duced abolishing coronary flow and the wall temperature was maintained either at 37",34"and 28".The hearts were consequently reperfused at 37"for30! After each experimental condition tissue ATP and CP were assayed and the mitichondria harvest.Their oxidative phosphorilating and ATP generating capacity was established as well as their Ca"content.The hearts that were made ischaemic and maintained at 37" were severely depleted in ATP and CP contents,their mitochondria accumulated Ca*and their oxidative pho sphorilatig activity was impaired.During reperfusion mitochondrial Ca"was further increased and mitochondrial function further reduced.The diastolic pressure increased and there was no recovery of sistolic pressure. The hearts made ischaemic and maintained at 28" were protected.There was a less marked rise in mitochondrial Ca"concentration after ischaemia and reperfusion;the mitochondria recovered the capacity of utilizing 02 and of generating ATP. That was coincident with an almost complete recove ry of mechanical performance. Hypotermia at 34' during ischemia provoked only a partial protection. These results indicate that hypothermia,lower than 34',may protect the mitochondial function of ischaemic and reperfused myocardium.

MITOCHONDRIAL STRUCTURE AND FATTY ACID METABOLISM IN ISCHEMIA. D. Feuvray and J. Plouet. Laboratoire de Physiologie Comparee, UniversitE de Paris-Sud, 91405 Orsay, France. Mitochondrial ultrastructure and levels of acyl derivatives of CoA and carnitine were studied in mitochondria isolated from aerobic and ischemic rat hearts. Isolated hearts were perfused for 60 minutes under control or ischemic (whole-heart ischemia) conditions in the presence or absence of a high level of fatty acid (1.5 mM palmitate). Mitochondria isolated from both control and ischemic hearts receiving no palmitate did not show any obvious difference in structure. However, major differences were observed between mitochondria obtained from control and ischemic hearts receiving palmitate. Many amorphous densities were present in the isolated mitochondria of ischemic hearts. These amorphous densities looked very similar to those seen in the intact tissue under comparable situations (Feuvray, D., Am.J.Physiol., 240, 1981). Mitochondrial levels of long-chain acyl CoA were practically the same for control and ischemic hearts receiving the same substrate. On the other hand, levels of long-chain acyl carnitine in mitochondria of ischemic hearts were twice those found in control hearts. Moreover, a higher level of long-chain acyl carnitine was associated with the mitochondria isolated from ischemic hearts receiving palmitate. This high level of acyl carnitine correlated with the appearance of amorphous densities in the mitochondria. (Supported by grants from DGRST and INSERM).