Description:
Objective: During cardioplegia, which is often used in cardiac surgery, the heart issubjected to global ischemia/reperfusion injury, which can result in a post-operativeimpairment of cardiac function. Mitochondria permeability transition pores (MPTP) playa key role in cardiomyocyte survival after ischemia/reperfusion injury. It was shown inclinical settings that blockers of MPTP like cyclosporine might have a positive influenceon cardiac function after cardioplegic arrest. Olesoxime, which is a new drug with MPTPblocking activity, has been introduced as a neuroprotective therapeutic agent. This drughas not been investigated on a possible positive effect in ischemia/reperfusion injury inhearts. Therefore, the aim of our study was to investigate possible effects of olesoximeon cardiac recovery after cardioplegic arrest.Methods: We evaluated 14 mature Chinchilla bastard rabbits of 1,500–2,000 g. Rabbithearts were isolated and perfused with constant pressure according to Langendorff. Afterinduction of cardioplegic arrest (30 ml 4◦C cold Custodiol cardioplegia without and with 5μmol/L olesoxime, n = 7 each) the hearts maintained arrested for 90-min. Thereafter, thehearts were re-perfused for 60min. At the end of each experiment left ventricular sampleswere frozen in liquid nitrogen for ATP measurements. Furthermore, heart slices wereembedded in paraffin for histological analysis. During the entire experiment hemodynamicand functional data such as left ventricular pressure (LVP), dp/dt(max) and (min), pressurerate product (PRP), coronary flow, pO2, and pCO2 were also assessed.Results: Histological analysis revealed that despite the same ischemic burden forboth groups markers of nitrosative and oxidative stress were significantly lower in theolesoxime group. Moreover, hearts of the olesoxime-group showed a significantly fasterand better hemodynamic recovery during reperfusion. In addition, tissue ATP-levels weresignificantly higher in the olesoxime treated hearts.Conclusions: Olesoxime significantly protected the cardiac muscle fromischemia/reperfusion injury.