Kamigaki M, Ichihara K, Abiko Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Jpn J Pharmacol. 1994 Jun;65(2):121-9. doi: 10.1254/jjp.65.121.
We examined whether opening of the ATP-sensitive potassium (KATP) channels in the ischemic myocardium plays an important cardioprotective role during ischemia. Dogs were anesthetized with sodium pentobarbital (30 mg/kg, i.v.). Sixty minutes after treatment of the dog with glibenclamide (0.3 or 3 mg/kg, i.v.), the LAD was ligated. At 3 or 15 min after LAD ligation, left ventricular tissue was taken from the ischemic region to measure tissue metabolite levels. After ischemia, the tissue levels of ATP and creatine phosphate decreased to 49-74% and 26-34%, respectively, and lactate level increased to 380-660%. Ischemia (either 3 or 15 min) increased the levels of G6P and F6P and decreased the FDP level, indicating the inhibition of glycolysis. Glibenclamide at either dose decreased the level of blood glucose by 20-30% and increased the blood insulin level twice. The decrease in ATP and increase in lactate due to ischemia were significantly enhanced by glibenclamide at a dose of 3 mg/kg. The increase in G6P due to 15 min of ischemia were also enhanced significantly by 0.3 and 3 mg/kg of glibenclamide. Glibenclamide worsened the metabolic alterations produced by ischemia. These results suggest that KATP channels that can be inhibited by glibenclamide may perform some functions in the ischemic myocardium.
我们研究了缺血心肌中ATP敏感性钾（KATP）通道的开放在缺血期间是否发挥重要的心脏保护作用。用戊巴比妥钠（30mg/kg，静脉注射）麻醉犬。用格列本脲（0.3或3mg/kg，静脉注射）处理犬60分钟后，结扎左前降支（LAD）。在结扎LAD后3或15分钟，从缺血区域获取左心室组织以测量组织代谢物水平。缺血后，ATP和磷酸肌酸的组织水平分别降至49 - 74%和26 - 34%，而乳酸水平升高至380 - 660%。缺血（3或15分钟）增加了6-磷酸葡萄糖（G6P）和6-磷酸果糖（F6P）的水平并降低了1,6-二磷酸果糖（FDP）水平，表明糖酵解受到抑制。两种剂量的格列本脲均使血糖水平降低20 - 30%，并使血胰岛素水平升高两倍。3mg/kg剂量的格列本脲显著增强了缺血导致的ATP降低和乳酸增加。0.3和3mg/kg的格列本脲也显著增强了15分钟缺血导致的G6P增加。格列本脲使缺血产生的代谢改变恶化。这些结果表明可被格列本脲抑制的KATP通道可能在缺血心肌中发挥某些功能。
