氯胺酮对离体大鼠心肌细胞的毒性作用

Cardiotoxicity of ketamine in isolated myocardial cells of neonatal rat

目的:探讨氯胺酮对心肌细胞的毒性作用。方法:将经原代培养成活4天后的大鼠心肌细胞分为四组,A组为对照组,B、C、D三组分别加入氯胺酮1×10^(-5)、1×10^(-4)及1×10^(-3)mol/L。实验开始后2、4、8及24小时评定心肌细胞搏动功能、细胞酶及培养液中电解质改变,并观察形态学变化。结果:B组各时点搏动频率均明显加快(P<0.05和P<0.01),C及D组搏动频率减慢(P<0.05和P<0.01),D组在8小时和24小时细胞呈部分搏动或无搏动。随剂量递增及作用时间延长,细胞形态学变化逐渐明显,LDH、AST、CK释放量逐渐增加。结论:氯胺酮浓度为1×10^(-5)mol/L时有正性变时性和变力性作用;浓度≥1×10^(-4)mol/L时,则有明显的抑制作用。

Objective: To investigate ketamine cardiotoxicity profile. Method:Four day-old spontaneously contracting neonatal primary myocardial cell cultures obtained from 2-to 3-day-old Wistar rats were divided into 4 groups, group A as control and group B,C and D treated with ketamine(1×10^(-5), 1×10^(-4)and 1×10^(-3)mol/L)for 2 to 24 h. The contractility, morphology,cytoplasmic enzyme (LDH, AST and CK) release content of myocardial cell and the concentration of electrolytes (k^+, Na^+, Ca^(2+) and Cl^-) in the medium were measured 2,4,8 and 24 h following ketamine administration. Result:In group B the beating rates of neonatal myocardial cell cultures increased (P<0.05 and P<0.01), while group C and D spontaneously contracting was slow(P<0.05 and P<0.01). The cells showed partly beating or no beating at 8 and 24 h in group D. 1he adverse effects on morphology and enzemy release of the cell cultures of ketamine were in a concentration and time-dependent manner. Conclusion:The lowest concentrations of ketamine (1×10^(-5)mol/L) has positive chronotropic and inotropic action,while high concentrations of ketamine(≥1×10^(-4)mol/L)have significant direct myocardial depressant action.