Postconditioning attenuates cardiocyte ultrastructure injury and apoptosis by blocking mitochondrial permeability transition in rats

OBJECTIVE: The effect of inhibiting mitochondrial permeability transition (MPT) on cardioprotection induced by ischaemic postconditioning remains debatable. The aim of the present study was to investigate whether ischaemic postconditioning attenuates cardiomyocyte ultrastructure injury and apoptosis by blocking MPT. METHODS AND RESULTS: Sprague-Dawley rats were randomly allocated to eight groups (n = 12) including sham without ischaemia (I), control given 30 min 1 and 5 min or 120 min reperfusion (R), postconditioning (Post) treated the same as control and 3 cycles of 10 s R and 10 s I before R, preconditioning (Pre) treated the same as control and 3 cycles of 5 min 1 and 5 min R before 30 min 1, and other groups treated the same as control or Post and given cyclosporin A (CsA) or atractyloside (Atr). Infarct size was evaluated by TTC, ultrastructure by electron microscope, MPT by spectrophotometry, and apoptosis by TUNEL. Compared with the control treatment, the Post, CsA and Pre treatments had smaller infarct size, less reduction in optical density at 540 nm (OD540) for MPT (20.2% +/- 2.3% versus 12.1% +/- 1.8%, 11.2% +/- 3.3% and 12.1% +/- 5.6%, P < 0.01, respectively), lower mitochondrial score (2.09 +/- 0.27 versus 1.27 +/- 0.27, 0.97 +/- 0.26 and 1.28 +/- 0.32, P < 0.01, respectively) and percentage of apoptosis (34.9% +/- 2.6% versus 17.5% +/- 1.7%, 17.6% +/- 2.1% and 17.2% +/- 2.1%, P < 0.01, respectively). Post-induced cardioprotection was abrogated by Atr and failed to be enhanced by CsA. CONCLUSIONS: Blockage of MPT may be involved in attenuation of ultrastructure injury and apoptosis by ischaemic postconditioning.