BENEFICIAL-EFFECTS OF THE ATP-SENSITIVE K+ CHANNEL OPENER CROMAKALIM ON RECOVERY OF CARDIAC-FUNCTION FROM CARDIOPLEGIC ARREST IN ISOLATED-PERFUSED RAT HEARTS

We investigated the effects of cromakalim, an ATP sensitive (K-ATP(+)) channel opener, and glibenclamide, an K-ATP(+) channel blocker on cardiac function when given before the cardioplegic arrest in isolated working rat heart model. Hearts were subjected to normothermic (37 degrees C) ischemic arrest for 35 min with St. Thomas' Hospital cardioplegic solution followed by reperfusion for 15 min and then again converted to working heart mode to assess the postischemic recovery rates of aortic flow (AoF), cardiac output (CO), stroke volume (SV), coronary flow (CF) and heart rate (HR). Pretreatment with cromakalim (0.3, 1 mu M) given in the perfusion solution improved the recovery rates of AoF, CO, SV and CF from the control Values of 48.6+/-2.9%, 53.8+/-3.5%, 56.6+/-4.9% and 74.6+/-3.2% to 86+/-3.8%, 90.4+/-2.5%, 92+/-1.7% and 102.2+/-5.2%, respectively with 1 mu M of cromakalim. When glibenclamide (1 mu M) was added, the recovery rates of AoF and CO were only partially improved compared with the control group. The recovery rates of cardiac function after the cromakalim treatment were, therefore, better than those with glibenclamide. These results indicate that the pretreatment with cromakalim in addition to ST. Thomas' Hospital cardioplegic solution more effectively preserves the cardiac function after ischemia and reperfusion than that does glibenclamide in the rat heart.