Adenosine triphosphate-dependent potassium channel modulation and cardioplegia-induced protection of human atrial muscle in an in vitro model of myocardial stunning

Objectives: Although adenosine triphosphate-dependent potassium channel ope ners have been shown to enhance cardioplegic protection in animal myocardiu m, there is a lack of data on human cardiac tissues. We aimed at determinin g, on human atrial muscle, whether adenosine triphosphate-dependent potassi um channels are involved in protection caused by high-potassium cardioplegi a and whether adenosine triphosphate-dependent potassium channel activation might improve cardioplegic protection in an in vitro model of myocardial s tunning. Methods: Human atrial trabeculae were obtained from adult patients undergoi ng cardiac operations. Tn an organ bath at 37 degrees C, the preparations w ere subjected to 60 minutes of hypoxia at a high stimulation rate either in Tyrode solution (control. n = 17) or in St Thomas' Hospital solution witho ut additives (n = 6) or associated with 100 nmol/L bimakalim (n = 7) or 1 m u mol/L glibenclamide (n = 7, followed by 60 minutes of reoxygenation and 1 5 minutes of positive inotropic stimulation with 1 mu mol/L dobutamine. Results: Atrial developed tension was reduced by hygoxia to 27% +/- 5% of b aseline and incompletely recovered after reoxygenation to 38% +/- 7%, where as dobutamine restored contractility to 74% +/- 7% of basal values. St Thom as' Hospital solution with or without bimakalim improved developed tension after reoxygenation and dobutamine (P < .0001 vs control), whereas glibencl amide inhibited these protective effects of cardioplegic arrest (P =.001 vs St Thomas' Hospital solution). After reoxygenation, the protective effect of bimakalim disappeared at a high pacing rate (400- and 300-ms cycle Lengt h) bur recovered during dobutamine superfusion. Conclusions: Adenosine triphosphate-dependent potassium channels are likely involved in the cardioprotective effects of cardioplegia in human atrial t rabeculae and adenosine triphosphate-dependent potassium channel activation with bimakalim used as an additive to car cardioplegia enhanced protection .