Improved cardiac function after prolonged hypothermic ischemia with the Na+/H+ exchange inhibitor HOE 694

摘要: Background. Na + /H exchange represents an important mechanism for pH regulation in the cardiac cell that, however, may paradoxically mediate tissue damage reperfused myocardium. We investigated whether inhibition of exchanger can protect heart against after prolonged hypothermic storage with use selective inhibitor 3-methylsulfonyl-4-piperidinobenzoyl-guanidine methanesulfonate (HOE 694). Methods. After equilibration, isolated rabbit hearts were arrested a 3 minute infusion modified St. Thomas' cardioplegic solution and subsequently maintained ischemic arrest at 4°C 12 hours before reperfusion 37°C 60 minutes. Left ventricular function creatine kinase release measured intervals throughout reperfusion. High-energy phosphate adenine nucleotide content determined cardioplegia, end 12-hour period, HOE 694 (1 μmol/L) was administered either cardioplegia (study 1) or selectively only 2). Results. In study 1, systolic untreated recovered to less than 40% preischemic values associated greater 1,000% percent sustained elevation left end-diastolic pressure. contrast, recovery 694-treated significantly accelerated improved approximately 80%, whereas pressure increased 300% baseline. Significant protection also occurred those which while drug effective if given during cardioplegia. Creatine not affected except 2, where it lower minutes added time Tissue metabolite by treatment. Conclusions. This shows marked protective effect subjected ischemia strongly suggests that antiport inhibitors could play role myocardial preservation.