CARDIOPROTECTIVE EFFECTS OF PINACIDIL PRETREATMENT AND LAZAROID (U74500A) PRESERVATION IN ISOLATED RAT HEARTS AFTER 12-HOUR HYPOTHERMIC STORAGE

Background Two important processes in the preservation of the function of donor hear-ts are the maintenance of ATP-sensitive potassium chann el activity during myocardial ischemia and the scavenging of reactive oxygen species formed during reperfusion. The aim of this study was to compare the effect of three protocols on the preservation of hemodyna mic function in isolated rat hearts after hypothermic storage. These p rotocols were: (1) pretreatment of the heart with a potassium channel opener (200 mu M pinacidil); (2) storage of the heart in an aspartate- enriched extracellular cardioplegic solution containing the lazaroid a ntioxidant, U74500A (30 mu M); and (3) a combination of protocols 1 an d 2. Methods, Hearts from Wistar rats were perfused on a Langendorff a pparatus. After stabilization in working mode, baseline measurements o f heart rate, coronary and aortic flow, and cardiac output were perfor med. Hearts (n=6 in each group) were then randomized to protocols 1-3, untreated controls, or vehicle-treated controls. Hearts were stored i n extracellular-based preservation solution for 12 hr at 2-3 degrees C , remounted on the perfusion apparatus, and stabilized as before; hemo dynamic measurements were then repeated. Results. Recovery of hemodyna mic function was enhanced by pinacidil pretreatment or incorporation o f lazaroid in the storage solution, but the combination of these two t reatments produced the best results. Conclusions. Combined pharmacolog ical activation of ATP-sensitive potassium channels before cardioplegi a and the addition of U74500A to the preservation solution is associat ed with significantly enhanced hemodynamic function in the isolated ra t heart after 12 hr of hypothermic storage. These data suggest a novel use for these agents in the transplantation context.