CYTOPROTECTIVE EFFECTS OF NICORANDIL ON HYPOTHERMIC INJURY TO IMMATURE CARDIAC MYOCYTES : Comparison with Nitroglycerin, Diltiazem and Prostaglandin E_1

  • ORITA HIROYUKI
    The Second Department of Surgery, Yamagata University School of Medicine
  • FUKASAWA MANABU
    The Second Department of Surgery, Yamagata University School of Medicine
  • HIROOKA SHIGEKI
    The Second Department of Surgery, Yamagata University School of Medicine
  • UCHINO HIDEAKI
    The Second Department of Surgery, Yamagata University School of Medicine
  • FUKUI KANA
    The Second Department of Surgery, Yamagata University School of Medicine
  • KOHI MINORU
    The Second Department of Surgery, Yamagata University School of Medicine
  • WASHIO MASAHIKO
    The Second Department of Surgery, Yamagata University School of Medicine

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The purpose of this study was to evaluate the functional and biochemical effects of nicorandil (NRD), nitroglycerin (NTG), diltiazem (DTZ) and prostaglandin E_1 (PGE) on cardiac myocytes incubated under hypothermic conditions. Cardiac myocytes were isolated from neonatal rat ventricles and cultured for 4 days with MCDB 107 medium. Myocytes (12.5×10^5 myocytes/flask) were then incubated at 4℃ for 24 h in media containing various concentrations of NRD, NTG, DTZ or PGE. After hypothermic incubation, creatine kinase (CK) and lactate dehydrogenase (LDH) were measured. The myocytes were cultured for an additional 24 h at 37℃ to evaluate the recovery of myocyte beating rate. In the nicorandil groups, 10^<-4> M NRD showed a significantly increased beating rate recovery compared to the control (44% vs 25% respectively, as a percentage of the baseline values; i.e., beating rate prior to hypothermic incubation) . Although treatment with 10^<-6> M diltiazem showed no beneficial effects (10^<-6> M;25%, control; 30%), beating was not observed at all with 10^<-4> M or 10^<-5> M DTZ. There were no significant changes among the NTG and PGE groups. The release of CK and LDH was significantly suppressed with 10^<-4> M NRD (10^<-4> M: 24.1 mlU/flask, 257.2; control: 125.4, 459.5, respectively). In contrast, 10^<-4> M DTZ showed significantly increased CK and LDH levels compared to its respective control (10^<-4> M: 203.3 mlU/flask, 883.4; control: 112.3, 457.4, respectively). There were no significant differences in CK and LDH levels among the NTG and PGE groups. In conclusion, nicorandil has protective effects on immature myocytes that may make it suitable for cardiac preservation in the neonatal period.

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