IN-VITRO EVALUATION OF NICORANDIL, DILTIAZEM, AND PROSTAGLANDIN E(1) ON HYPOTHERMIC INJURY TO IMMATURE MYOCYTES

The purpose of the present study was to evaluate the functional and bi ochemical effects of nicorandil (NRD), diltiazem (DTZ), or prostagland in E(1) (PGE) on cardiac myocytes incubated under hypothermic conditio ns. Cardiac myocytes were isolated from neonatal rat ventricles and cu ltured for 4 days with MCDB 107 medium. Myocytes (12.5 X 10(5) myocyte s/flask) were then incubated at 4 degrees C for 24 hr in media contain ing various concentrations of NRD, DTZ, or PGE. After hypothermic incu bation, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) w ere measured. The myocytes were then cultured for an additional 24 hr at 37 degrees C to evaluate the recovery of myocyte beating rate. In t he nicorandil groups, 10(-4) M NRD showed significantly increased beat ing rate recovery compared to control (44.2% vs 24.6%, respectively, a s a percentage of control, i.e., beating rate prior to hypothermic inc ubation). Treatment with 10(-6) M diltiazem showed no beneficial effec ts (10(-6) M: 25.2%; control: 29.8%); however, beating was not observe d at 10(-4) or 10(-5) M. There were no significant changes among the P GE groups. The release of CPK and LDH was significantly suppressed wit h 10(-4) M NRD (10(-4) M: 24.1, 257.2 MIU/flask; control: 125.4, 459.5 mIU/flask, respectively). However, 10(-4) IM DTZ showed significantly increased CPK and LDH levels compared to the control (10(-4) M: 203.3 , 883.4 mIU/flask; control: 112.3, 457.4 mIU/flask, respectively). The re were no significant differences for CPK and LDH levels among the PG E groups. In conclusion, nicorandil has protective characteristics for immature myocytes that may be suitable for cardiac preservation in th e neonatal period. (C) 1995 Academic Press, Inc.