Calpain inhibitor (BSF 409425) diminishes ischemia/reperfusion-induced damage of rabbit heart mitochondria

Calpains are involved in ischemia/reperfusion-induced changes of myocard. To obtain information on the action of calpain on mitochondria, the effect of a new developed calpain inhibitor (CI) BSF 409425 on the ischemia/reperfusion-induced damage of rabbit heart mitochondria was investigated. Rabbit hearts were subjected to 45 min of global ischemia followed by 60 min of reperfusion in the presence or absence of 10 nM CI. Mitochondrial properties were characterized by skinned fiber technique with pyruvate + malate as substrates. In the presence of CI, the decrease of state 3 respiration and the increase of state 4 respiration after ischemia and reperfusion were clearly smaller than without CI resulting in significantly smaller changes of respiratory control index, too. Ischemia/reperfusion-caused leaks in mitochondrial inner and outer membranes were diminished by CI. It is concluded that mitochondria are a target of calpain which reinforces the damage of oxidative phosphorylation and mitochondrial membranes during ischemia/reperfusion. (C) 2002 Elsevier Science Inc. All rights reserved.