IN-VITRO PROTECTIVE EFFECTS OF NICORANDIL ON HYPOTHERMIC INJURY TO IMMATURE CARDIAC MYOCYTES - COMPARISON WITH NITROGLYCERIN

The purpose of the present study was to evaluate the functional and bi ochemical effects of nicorandil and nitroglycerin on cardiac myocytes incubated under hypothermic conditions. Nicorandil is a coronary vasod ilator with mixed nitrate-potassium channel agonist activity. Cardiac myocytes were isolated from neonatal rat ventricles and cultured for 4 days with MCDB 197 medium. Myocytes (12.5 x 10(5) myocytes/flask) wer e then incubated at 4 degrees C for 24 hours in media containing vario us concentrations of nicorandil (NRD) or nitroglycerin (NTG). After hy pothermic incubation, CPK and LDH were measured. The myocytes were cul tured for an additional 24 hours at 37 degrees C to evaluate the recov ery of the myocyte beating rate. In the nicorandil group, 10(-4) M NRD showed a significant beating rate recovery compared to control (44.2% vs. 24.6%, respectively, as a percent of control; i.e., beating rate prior to hypothermic incubation). Nitroglycerin treatment had no effec t on either beating rate recovery or release of CPK and LDH from myocy tes. However, the release of CPK and LDH was significantly suppressed by 10(-4) M nicorandil compared to the control(10(-4) M NRD: 24.1, 257 .2; control: 125.4 mIU/flask, 459.5 mIU/flask, respectively). Thus nic orandil showed an approximate twofold recovery of myocyte functional a ctivity after hypothermic incubation with only minor biochemical effec ts, and therefore may be suitable for cardiac preservation.