M. N. Laclau, S. Boudina, J. B. Thambo, L. Tariosse, G. Gouverneur, S. Bonoron-Adèle, V. A. Saks, K. D. Garlid and P. Dos Santos. Cardioprotection by Ischemic Preconditioning Preserves Mitochondrial Function and Functional Coupling Between
Adenine Nucleotide Translocase and
Creatine Kinase. Journal of Molecular and Cellular Cardiology (2001) 33, 947-956. This study investigates the effect of ischemic preconditioning on mitochondrial function, including functional coupling between the
adenine nucleotide translocase and
mitochondrial creatine kinase, which is among the first reactions 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 preconditioning prior to 30 min
ischemia and 15 min reperfusion. Ischemic preconditioning significantly delayed the onset and amplitude of
contracture during
ischemia, decreased enzymatic release, and improved the recovery of heart contractile function after reperfusion. Mitochondrial function was assessed in permeabilized skinned fibers. The protective effect of preconditioning was associated with preservation of mitochondrial function, as evidenced by maintenance of the high K(1/2)for
ADP in regulation of mitochondrial respiration and V(max)of respiration, the near absence of respiratory stimulation by exogenous
cytochrome c, and preservation of functional coupling between
mitochondrial creatine kinase and
adenine nucleotide translocase. These data suggest that ischemic preconditioning preserves the structure-function of the intermembrane space, perhaps by opening the mitochondrial
ATP-sensitive K(+)channel. The consequence is preservation of energy transfer processes from mitochondria to
ATP-utilizing sites in the cytosol. Both of these factors may contribute to cardioprotection and better functional recovery of preconditioned hearts.