Mechanisms of ischemic preconditioning effects on Ca2+paradox-induced changes in heart

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Abstract
The effects of ischemic preconditioning (IP) on changes in cardiac performance and sarcoplasmic reticulum (SR) function due to Ca2+ paradox were investigated. Isolated perfused hearts were subjected to IP (three cycles of 3-min ischemia and 3-min reperfusion) followed by Ca2+-free perfusion and reperfusion (Ca2+paradox). Perfusion of hearts with Ca2+-free medium for 5 min followed by reperfusion with Ca2+-containing medium for 30 min resulted in a dramatic decrease in the left ventricular (LV) developed pressure and a marked increase in LV end-diastolic pressure. Alterations in cardiac contractile activity due to Ca2+paradox were associated with depressed SR Ca2+-uptake, Ca2+-pump ATPase, and Ca2+-release activities as well as decreased SR protein contents for Ca2+-pump and Ca2+ channels. All these changes due to Ca2+paradox were significantly prevented in hearts subjected to IP. The protective effects of IP on Ca2+ paradox changes in cardiac contractile activity as well as SR Ca2+-pump and Ca2+-release activities were lost when the hearts were treated with 8-(p-sulfophenyl)-theophylline, an adenosine receptor antagonist; KN-93, a specific Ca2+/calmodulin-dependent protein kinase II (CaMK II) inhibitor; or chelerythrine chloride, a protein kinase C (PKC) inhibitor. These results indicate that IP rendered cardioprotection by preventing a depression in SR function in Ca2+ paradox hearts. Furthermore, these beneficial effects of IP may partly be mediated by adenosine receptors, PKC, and CaMK II.

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