Orita H, Fukasawa M, Hirooka S, Fukui K, Kohi M, Washio M
Second Department of Surgery, Yamagata University School of Medicine, Japan.
Cardiovasc Drugs Ther. 1994 Feb;8(1):129-35. doi: 10.1007/BF00877101.
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.
本研究的目的是评估尼可地尔和硝酸甘油对在低温条件下培养的心肌细胞的功能和生化作用。尼可地尔是一种具有硝酸盐 - 钾通道激动剂混合活性的冠状动脉扩张剂。从新生大鼠心室分离心肌细胞，并用MCDB 197培养基培养4天。然后将心肌细胞（12.5×10⁵个心肌细胞/培养瓶）在含有不同浓度尼可地尔（NRD）或硝酸甘油（NTG）的培养基中于4℃孵育24小时。低温孵育后，测量肌酸磷酸激酶（CPK）和乳酸脱氢酶（LDH）。将心肌细胞在37℃再培养24小时，以评估心肌细胞搏动率的恢复情况。在尼可地尔组中，10⁻⁴M NRD与对照组相比显示出显著的搏动率恢复（分别为对照组的44.2%和24.6%；即低温孵育前的搏动率）。硝酸甘油处理对搏动率恢复或心肌细胞中CPK和LDH的释放均无影响。然而，与对照组相比，10⁻⁴M尼可地尔显著抑制了CPK和LDH的释放（10⁻⁴M NRD：分别为24.1、257.2；对照组：分别为125.4 mIU/培养瓶、459.5 mIU/培养瓶）。因此，尼可地尔在低温孵育后显示出心肌细胞功能活性约两倍的恢复，且生化影响较小，因此可能适用于心脏保存。
