P151Cardioprotection by pharmacological agents targeting mitochondria is preserved in isolated aged rat hearts

Whether cardioprotective strategies are still effective in elderly is a matter of debate. The present study was purported to assess the persistence of the protective effects of pharmacological agents targeting mitochondria in old Sprague-Dawley rats. Methods. To this aim isolated hearts from old (20-24 mo) and adult (4-6 mo) animals subjected to a protocol of 30 min ischemia/120 min reperfusion were randomized to receive throughout the postischemic reperfusion: no intervention, magnesium orotate (MO), magnesium chloride (MgCl2) and orotic acid (OA) at 5 x 10 (-3) M. The effects on functional recovery and infarct size were compared to the ones elicited by CsA at 2 x 10(-7) M, the classic mitochondrial permeability transition pore (mPTP) desensitizer. In a second group of experiments, cardiac mitochondria were isolated at 15 min of postischemic reperfusion for the assessment of respiratory function and calcium retention capacity. Results. Acute administration of MO and MgCl2 (but not of OA) during the postischemic reperfusion was associated with a significant recovery of left ventricular developed pressure and infarct size reduction in both adult and old animals. Cardioprotection was comparable to the one elicited by CsA. In mitochondria isolated from the old animals and energized with complex I (but not complex II) substrates, all the pharmacological agents were equally effective in protecting against the loss of outer mitochondrial membrane integrity, albeit to a lesser degree compared to adult mitochondria. Also, MO, MgCl2, and CsA (but not OA) prevented the calcium triggered-opening of mPTP. Conclusion. High dose of magnesium containing-pharmacological agents and cyclosporine A were effective in protecting heart mitochondria in aged rodents during the postischemic reperfusion. This work was supported by a grant of the Ministry of National Education, CNCS–UEFISCDI, project number PN-II-ID-PCE-2012-4-0512.