In vitro protective effects of nicorandil on hypothermic injury to immature cardiac myocytes: comparison with nitroglycerin

Abstract

The purpose of the present study was to evaluate the functional and biochemical effects of nicorandil and nitroglycerin on cardiac myocytes incubated under hypothermic conditions. Nicorandil is a coronary vasodilator 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) were then incubated at 4 degrees C for 24 hours in media containing various concentrations of nicorandil (NRD) or nitroglycerin (NTG). After hypothermic incubation, CPK and LDH were measured. The myocytes were cultured for an additional 24 hours at 37 degrees C to evaluate the recovery 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 effect on either beating rate recovery or release of CPK and LDH from myocytes. 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 nicorandil showed an approximate two-fold recovery of myocyte functional activity after hypothermic incubation with only minor biochemical effects, and therefore may be suitable for cardiac preservation.