Menadione mimics the infarct-limiting effect of preconditioning in isolated rat hearts

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 281; no. 2; p. H590
• Main Authors: Yue, Y, Krenz, M, Cohen, M V, Downey, J M, Critz, S D
• Format: Journal Article
• Language: English
• Published: United States 01-08-2001
• Subjects: Animals; Free Radicals - metabolism; Ischemic Preconditioning, Myocardial; Male; Mitochondria, Heart - metabolism; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Rats; Rats, Wistar; Vitamin K - pharmacology; Vitamin K - therapeutic use
• ISSN: 0363-6135
• DOI: 10.1152/ajpheart.2001.281.2.h590

The role of mitochondrial free radicals in the cardioprotective effect of ischemic preconditioning was examined in isolated buffer-perfused rat hearts. Infarct size in control rat hearts subjected to 30 min of regional ischemia and 120 min of reperfusion was 32.6 +/- 3.4% of the risk zone. Ischemic preconditioning (3 cycles of 5-min global ischemia/5-min reperfusion) before the same regional ischemia and reperfusion protocol significantly reduced infarct size to 2.6 +/- 0.8% of the risk zone. Perfusion with menadione (3.0 microM), a generator of mitochondrial free radicals, in lieu of preconditioning ischemia significantly reduced infarction to 10.9 +/- 2.7%. N-2-mercaptopropionylglycine (1.0 mM), a free radical scavenger, blocked the protection of menadione, significantly increasing infarction to 23.5 +/- 1.1%. Myxothiazol (0.6 microM), a site III mitochondrial inhibitor, blocked the protection of menadione and significantly increased infarction to 25.2 +/- 3.8%. The infarct-limiting effect of menadione was attenuated to 19.7 +/- 1.5% of the risk zone by 10 microM SB203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor. Furthermore, menadione significantly increased p38 MAPK phosphorylation to a level 5.6-fold over basal. These results indicate that free radicals that originate within mitochondria can activate p38 MAPK and protect hearts against infarction.