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Differences in ischemia-reperfusion-induced endothelial changes in hearts perfused at constant flow and constant pressure

Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

Submitted 24 January 2008 ; accepted in final form 17 September 2008

Isolated hearts subjected to ischemia-reperfusion (I/R) exhibit depressed cardiac performance and alterations in subcellular function. Since hearts perfused at constant flow (CF) and constant pressure (CP) show differences in their contractile response to I/R, this study was undertaken to examine mechanisms responsible for these I/R-induced alterations in CF-perfused and CP-perfused hearts. Rat hearts, perfused at CF (10 ml/min) or CP (80 mmHg), were subjected to I/R (30 min global ischemia followed by 60 min reperfusion), and changes in cardiac function as well as sarcolemmal (SL) Na⁺-K⁺-ATPase activity, sarcoplasmic reticulum (SR) Ca²⁺ uptake, and endothelial function were monitored. The I/R-induced depressions in cardiac function, SL Na⁺-K⁺-ATPase, and SR Ca²⁺-uptake activities were greater in hearts perfused at CF than in hearts perfused at CP. In hearts perfused at CF, I/R-induced increase in calpain activity and decrease in nitric oxide (NO) synthase (endothelial NO synthase) protein content in the heart as well as decrease in NO concentration of the perfusate were greater than in hearts perfused at CP. These changes in contractile activity and biochemical parameters due to I/R in hearts perfused at CF were attenuated by treatment with L-arginine, a substrate for NO synthase, while those in hearts perfused at CP were augmented by treatment with N^G-nitro-L-arginine methyl ester, an inhibitor of NO synthase. The results indicate that the I/R-induced differences in contractile responses and alterations in subcellular organelles between hearts perfused at CF and CP may partly be attributed to greater endothelial dysfunction in CF-perfused hearts than that in CP-perfused hearts.

endothelial function; nitric oxide; calpain activity; cardiac performance; subcellular activities