Effect of the potassium-channel opener nicorandil as an adjunct to cardioplegia on myocardial preservation in isolated rabbit hearts.

Abstract

We studied the effect of nicorandil on the hemodynamic, biochemical, and ultrastructural changes in rabbit hearts (n = 50) rendered cardioplegic with a single injection of Bretschneider's HTK solution over 30 min or 60 min at 37 degrees C or 15 degrees C, followed by reperfusion at 37 degrees C for 60 min. Particular attention was focused on the aspects of dose-response relationship, temperature sensitivity, and ischemic tolerance. Isolated hearts were prepared for modified Langendorff circulation using modified Krebs-Henseleit bicarbonate solution bubbled with a 95% O2(-5)% CO2 gas mixture, to which nicorandil (0, 0.1, 1, and 5 mM) was added. The optimal concentration of nicorandil was 1mM, which increased the recovery of left ventricular (LV) function, affecting coronary flow and the myocardial cyclic adenosine monophosphate, but not the myocardial concentrations of adenine nucleotide compounds or total calcium. These effects were abolished by the addition of glibenclamide to the HTK, but they were not diminished by a high potassium (K+) concentration of 20mM. The addition of nicorandil 1mM to the HTK at 15 degrees C did not improve the recovery of LV function. Our result suggested that nicorandil used adjunctly prevents LV functional depression after 30min, and possibly 60min of cardioplegia at 37 degrees C, and that this effect is not disturbed by a high K+ concentration up to 20 mM. However, nicorandil has temperature sensitivity whereby it loses its efficacy at 15 degrees C.