Inhibition of Mitochondrial Permeability Transition Pore: A Possible Mechanism for Cardioprotection Conferred by Pretreatment with Tanshinone IIA.

The objective of this study was to determine whether the mitochondrial permeability transition pore plays a role in cardioprotection induced by tanshinone IIA. Isolated rat hearts were subjected to 30 min regional ischemia by ligation of the left anterior descending artery followed by 120 min reperfusion. Ischemic preconditioning (IPC) was achieved by two 5-min periods of global ischemia separated by 5 min of reperfusion. Pretreatment with tanshinone reduced the infarct size which was associated with improved recovery of left ventricular contractility as with IPC. Perfusion with 100 muM 5-hydroxydecanoate (5-HD) attenuated the cardioprotection induced by tanshinone. In mitochondria isolated from untreated hearts, tanshinone inhibited pore opening dose-dependently, and this effect was abolished by blocking the mitochondrial ATP sensitive potassium channel with 5-HD. We conclude that pretreatment with tanshinone IIA provides similar cardioprotection to IPC, this effect may be via inhibiting the pore opening during reperfusion, and the mitochondrial ATP sensitive potassium channel may play a role in mediating the pore inhibition induced by tanshinone IIA.