Cardioprotection by ischemic preconditioning preserves mitochondrial function and functional coupling between adenine nucleotide translocase and creatine kinase

This study investigates the effect of ischemic preconditioning on mitochond rial function, including functional coupling between the adenine nucleotide translocase and mitochondrial creatine kinase. which is among the first re actions to be altered in ischemia. Three groups of Langendorff-perfused rat hearts were studied: a control group. a group subjected to 30 min ischemia followed by 15 min reperfusion. and a group subjected to ischemic precondi tioning prior to 30 min ischemia and 15 min reperfusion. Ischemic precondit ioning significantly delayed the onset and amplitude of contracture during ischemia, decreased enzymatic release. and improved the recovery of heart c ontractile Function after reperfusion. Mitochondrial function M as assessed in permeabilized skinned fibers. The protective effect of preconditioning was associated with preservation of mitochondrial Function. as evidenced bq maintenance of the high k(12) For ADP in regulation of mitochondrial respi ration and V-max of respiration, the near absence of respiratory stimulatio n by exogenous cytochrome c, and preservation of functional coupling betwee n mitochondrial creatine kinase and adenine nucleotide translocase. These d ata suggest that ischemic preconditioning preserves the structure-function of the intermembrane space. perhaps by opening the mitochondrial ATP-sensit ive K+ channel. The consequence is preservation of energy transfer processe s from mitochondria to ATP-utilizing sites in the cytosol. Both of these fa ctors may contribute to cardioprotection and better functional recovery of preconditioned hearts. (C) 2001 Academic Press.