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

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 30min or 60min at 37°C or 15°C, followed by reperfusion at 37°C for 60min. Particular attention was focused on the aspects of doseresponse 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 nicroandil was 1 mM, 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 20 mM. The addition of nicorandil 1 mM to the HTK at 15°C did not improve the recovery of LV function. Our result suggested that nicorandil used adjunctly prevents LV functional depression after 30 min, and possibly 60 min of cardioplegia at 37°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°C.