ATP-sensitive potassium channel activation mimics the protective effect ofischaemic preconditioning in the rat isolated working heart after prolonged hypothermic storage

1. Ischaemic preconditioning (TP) can significantly reduce the extent of in farct size, contractile dysfunction and necrosis in hearts from a number of animal species. Activation of ATP-sensitive potassium channels has been im plicated in this process. The aims of the present study were to determine t he extent to which TP preserves haemodynamic function in the rat isolated w orking heart model after prolonged hypothermic storage and to examine the i nvolvement of activation of potassium channels in this process. 2. Hearts from Wistar rats were perfused on a Langendorff apparatus. After stabilization in working mode, baseline measurements of heart rate, aortic flow, coronary flow and cardiac output were performed. Hearts were randomiz ed to one of six treatment groups: (i) untreated control; (ii) IP; (iii) 3 min perfusion with 200 mu mol/L pinacidil; (iv) pinacidil vehicle; (v) 3 mi n perfusion with 10 mu mol/L glibenclamide before IP; and (vi) 3 min perfus ion with glibenclamide then pinacidil, Hearts were stored in an extracellul ar-based preservation solution for 6 or 12 h at 2-3 degrees C, remounted on the perfusion apparatus, stabilized as before and then haemodynamic measur ements were repeated, after which time heart water contents were determined . 3. Recovery of haemodynamic function was markedly enhanced in the LP and pi nacidil-treated groups compared with untreated and vehicle controls. These beneficial effects were completely blocked by glibenclamide. These results suggest that strategies for activating potassium channels in donor hearts m ay protect organs during hypothermic storage prior to transplantation.