KRN2391和克罗卡林对大鼠离体心脏的保护作用

Cardioprotection Effects of KRN2391 and Cromakalim on Isolated Rat Heart

目的：比较两种不同的 Ａ Ｔ Ｐ敏感性钾通道开放剂 Ｋ Ｒ Ｎ２３９１（ Ｋ Ｒ Ｎ）和克罗卡林（ Ｃ Ｒ）对大鼠离体心脏心功能的影响及缺血后的心脏保护作用。方法：将离体心脏进行完全缺血 ２５ ｍ ｉｎ，观察再灌注３０ ｍ ｉｎ 时心功能的变化。结果：１～２０ μｍ ｏｌ／ Ｌ Ｋ Ｒ Ｎ 及１～２０ μｍ ｏｌ／ Ｌ Ｃ Ｒ均能显著增加冠脉灌流量。２０ μｍ ｏｌ／ Ｌ Ｋ Ｒ Ｎ 及 １０ μｍ ｏｌ／ Ｌ Ｃ Ｒ 可明显降低心脏收缩功能，１ μｍ ｏｌ／ Ｌ Ｋ Ｒ Ｎ 和１ μｍ ｏｌ／ Ｌ Ｃ Ｒ较对照组均有改善缺血后心功能的作用，此作用可完全被格列本脲所阻断。结论：两药均有明显冠脉扩张作用，大剂量应用可降低心脏收缩功能，用不影响心功能的剂量两者均有对缺血后心脏的保护作用，此作用与 Ａ Ｔ Ｐ敏感性钾通道开放有关。

Objective:This study was designed to compare the infuluence two structurally different ATP sensitive potassium channel openers KRN2391(KRN) and cromakalim(CR) on cardiac function and postischemic cardioprotection effects for isolated rat hearts. Methods:After 30 min reperfusion following 25 min absolution ischemia, the change of cardiac function of isolated rat heart was observed. Results:1～20 μnol/L KRN and 1～20 μmol/L CR significantly increased coronary flow; 20 μmol/L KRN and 10 μmol/L CR produced the reduction in cardiac systolic function. Pretreatment with 1 μmol/L KRN and 1 μmol/L CR resulted in a significant improvement in postischemic cardiac function. These effects were completely blocked by Glibenclamide. Methods:After 30 min reperfusion following 25 min absolution ischemia, the change of cardiac function of isolated rat heart was observed. Results:1～20 μnol/L KRN and 1～20 μmol/L CR significantly increased coronary flow; 20 μmol/L KRN and 10 μmol/L CR produced the reduction in cardiac systolic function. Pretreatment with 1 μmol/L KRN and 1 μmol/L CR resulted in a significant improvement in postischemic cardiac function. These effects were completely blocked by Glibenclamide. After 30 min reperfusion following 25 min absolution ischemia, the change of cardiac function of isolated rat heart was observed. Results:1～20 μnol/L KRN and 1～20 μmol/L CR significantly increased coronary flow; 20 μmol/L KRN and 10 μmol/L CR produced the reduction in cardiac systolic function. Pretreatment with 1 μmol/L KRN and 1 μmol/L CR resulted in a significant improvement in postischemic cardiac function. These effects were completely blocked by Glibenclamide. Results:1～20 μnol/L KRN and 1～20 μmol/L CR significantly increased coronary flow; 20 μmol/L KRN and 10 μmol/L CR produced the reduction in cardiac systolic function. Pretreatment with 1 μmol/L KRN and 1 μmol/L CR resulted in a significant improvement in postischemic cardiac function. These effects were completely blocked by Glibenclamide. Conclusion:KRN and CR had a significant vasodilator activity. High dosage produced the reduction in cardiac systolic function. A certain dosage of KRN and CR had a protective effect on the postischemic myocardium. These effects might be related to the activation of ATP sensitive potassium channels.