钾通道开放剂心脏超极化停搏保护效果的研究

目的 对比观察大量三磷酸腺苷（ＡＴＰ）敏感性钾通道开放剂吡那地尔对常温／低温体外循环（ＣＰＢ）心脏超极化停跳缺血心肌的保护作用。方法 １８只犬随机分３组,每组６只,低温超极化组（ＬＨ）：阻断升主动脉后,心脏灌注４℃含吡那地尔停跳液,ＣＰＢ血温为２６～２８℃,开放前复温至３７℃,全心缺血６０ｍｉｎ,恢复灌注３０ｍｉｎ;常温超极化组（ＷＨ）：ＣＰＢ血温３５～３７℃,心脏灌注３７地７０含吡那地尔（５０μｍｏｌ／Ｌ）停跳液,余同ＬＨ组;对照组（Ｃ）;无吡那地尔的标准Ｓｔ、Ｔｈｏｍａｓ停跳液,余３７℃含昆那地尔（５０ｕｍｏｌ／Ｌ）停跳液,余同ＬＨ组;对照组（Ｃ）：无吡那地尔的标准Ｓｔ．Ｔｈｏｍａｓ停跳液,余同ＬＨ组,对比观察吡那地尔心脏超极化停跳不同时相各项指标的变化。结果 （１）停复跳情况：ＬＨ组、Ｃ组灌注后心脏停跳较

Hyperpolarized cardiac arrest with ATP-sensitive potassium channel opener on myocardial protection during CPB

OBJECTIVE: To investigate the myocardial protective effects of pinacidil-induced hyperpolarized arrest and compare them with those induced with depolarized hyperkalemic arrest. METHODS: 18 dogs were equally divided into three groups. In the hypothermic hyperpolarization group (LH group), after aortic cross-clamping, a single dose of 4 degrees C pinacidil containing St. Thomas cardioplegic was infused through the aortic root. Temperature during CPB was kept between 26 - 28 degrees C and warmed to 37 degrees C before aortic declamping. Global ischemia lasted 60 min and then reperfusion started for 30 min. In the normothermic hyperpolarized group (WH group), the same procedure was set as in the LH group, except maintaining temperature of 35 - 37 degrees C for CPB and pinacidil solution. In the control group (group C), no pinacidil in St. Thomas solution was the only difference to the other 2 groups. Cardiac arrest and its recovery, the ultrastructure of the myocardium and hemodynamic during ischemia and after reperfusion were observed in the 3 groups. RESULTS: (1) The percentages of normal mitochondria and glycogen were not changed significantly during ischemia and after reperfusion in the LH group, but declined markedly in the group C at ischemic 30, 60 min, and reperfusion for 20 min (P < 0.01). In the WH group, they were lower than those of the group LH, but higher than those of the group C before ischemia. (2) The recoveries of CO, SV, CI, LVSW, RVSW, MAP in the LH group were significantly better than those in the other two groups after reperfusion for 15 minutes and 30 minutes (P < 0.05 or 0.01). However, they were much better in the WH group than in the group C (P < 0.05 or 0.01). (3) The time from cardioplegic infusion to cardiac arrest was shorter in the group C and the group LH than in the group WH. CONCLUSIONS: Myocardial protection for global ischemia during CPB could be well achieved with hyperpolarized cardiac arrest induced by ATP-sensitive potassium channel opener, pinacidil, especially in the hypothermic state. The protection is weaker in normothermia but is still stronger than that with traditional depolarized arrest.