吡那地尔血液超极化停搏对离体兔心脏的保护作用

The protective effect of hyperpolarizing blood cardioplegia on isolated rabbit hearts

目的 探讨ATP敏感性钾通道开放剂吡那地尔(Pinacidil)血液超极化停搏对离体兔心脏的保护作用。方法 选用兔48只,制作离体心脏模型,随机分为六组:常温高钾组(A组),常温高钾含血组(B组),低温高钾组(C组),低温高钾含血组(D组),常温血液超极化组(E组),低温血液超极化组(F组),每组8只。对比观察六组停复跳时间,停跳前后心率、心律及复跳后情况,左室收缩力及左室内压(LVP),心肌腺苷酸含量、MDA含量及光镜结果。结果 (1)在各组中E、F两组停跳时间最长,而复跳时间最短,复跳后规则有力,左室内压(LVP)及左室收缩力均恢复至缺氧前水平。(2)E、F两组ATP、TAN含量及EC值显著高于其余各组同期值,MDA含量最低,且心肌组织结构保存良好。结论ATP敏感性钾通道开放剂Pinacidil诱导的血液超极化停搏,能够降低心肌ATP的消耗,减少脂质过氧化物的形成,促进离体心脏功能的恢复,对离体心脏的保护效果明显优于传统的高钾去极化停搏。

Objective To compare the myocardial protective effect of pinacidil-induced hyperpolarized and hyperkalemic depolarized cardiac arrest on isolated rabbit heart under different temperature. Methods Forty-eight rabbits of both sexes weighing 2.0-2.5 kg were sacrificed by a knock on the head. Their hearts were excised and perfused in a Langendorff apparatus with an oxygenated Krebs-Hensleit buffer (KHB)(37℃). The study was divided into six groups: A normothermic hyperkalemic cardioplegia; B normothermic hyperkalemic blood cardioplegia; C hypothermic hyperkalemic cardioplegia; D hypothermia hyperkalemic blood cardioplegia; E normothermic hyperpolarizing blood cardioplegia; F hypothermic hyperpolarizing blood cardioplegia. Three pieces of myocardial tissue were obtained from apex of left ventricle at the end of the study for determination of myocardial adenine nucleotide and lipid peroxide content and microscopic examination. The following were recorded : (1) cardiac arrest time: the time from perfusion with cardioplegic solution to the beginning of cardiac arrest. (2) heart beat recovery time ;the time from reperfusion with KHB to the beginning of normal heart beat. (3) changes in HR, left ventricle developed pressure and myocardial contractility before and after cardiac arrest. Results The cardiac arrest time was longer and the time for the heart to restart was shorter in the two hyperpolarizing blood cardioplegia groups (group E and F) than that in the other 4 groups. No arrhythmia occurred in group E and F. Left ventricle developed pressure(LVDP) and left ventricle contractility recovered quickly after reperfusion with KHB was started and were restored to the pre-ischemia level after 20 min in group E and F. The levels of ATP, TAN and EC were higher and the MDA level was lower in group E and F than those in the other 4 groups. Myocardial structure was less injuried in group E and F. Conclusion The myocardial protection effect of hyperpolarizing blood cardioplegia with pinacidil is superior to traditional hyperkalemic depolarizing cardioplegia.