药物预处理与诱导超极化对离体心脏的保护研究

Myocardial protective effect of drug preconditioning and hyperpolarized arrest with pinacidil in isolated rabbit hearts

目的 探讨ATP敏感性钾通道开放剂 (KCOs)吡那地尔对Langendorff灌注兔心脏模型药物预处理与药物诱导超极化停跳的保护作用。 方法 离体兔心 40个 ,随机等分 5组。对比观察2种浓度吡那地尔在 4℃或 37℃全心缺血 40min ,复灌 2 0min的心肌组织腺苷酸含量 ,脂质过氧化物的变化 ,以及再灌注后 10、2 0min心功能恢复的情况。 结果 (1)心脏诱导停跳以 4℃超极化与药物预处理组迅速 ,37℃超极化组较为缓慢 ;再灌注后仅对照组心脏复跳较慢。 (2 )与对照组同期比较 ,经吡那地尔预处理以及超极化的心脏再灌注后心肌收缩力与左心室内压恢复较快 ,其中心肌收缩力的恢复更为显著 ;(3)再灌注后 ,对照组心肌ATP、总腺苷量、细胞能荷水平低于预处理与超极化组(P <0 0 5或 0 0 1) ,其中以 37℃预处理ATP含量较高 ;而经吡那地尔处理的 4组 ,丙二醛则不同程度的低于对照组。 结论 吡那地尔诱导心脏超极化停跳以及药物预处理 ,有助于降低心肌ATP的消耗 ,减少脂质过氧化物的形成 ,明显改善离体兔心脏缺血 /再灌注后期心功能。

Objective To study the myocard ial protective effect of drug preconditioning and hyperpolarized arrest indu ced by ATP sensitive potassium channel opener,pinacidil in isolated rabbit h earts. Methods 40 rabbits hearts were random ly divided into 5 groups (n=8 in each group): hypothermic hyperpolarized grou p (4 ℃, St.Thomas′ solution containing pinacidil 50 μmol/L, K + 5 mmol/L, LH group), normothermic hyperpolarized group (37 ℃,St Thomas′ solution cont aining pinacidil 50 μmol/L, K + 5 mmol/L, WH group), hyperkalemic contrast g roup (4 ℃,St.Thomas′ solution, K +16 mmol/L, group C), and preconditioning group [oxygenated pinacidil containing solution (10 μmol/L) for 15 min foll owing by re circulation 5 min and then adopted the same procedure as the grou p C after reclamping the aorta (St.Thomas'solution 4 ℃ or 37 ℃, LIP or WIP gr oup)]. The ischemic duration of all rabbits was 45 min, and the hearts were ob served for 30 min after recovery of infusion. Hemodynamics variables, level of lipid peroxide and adenine nucleotides of the myocardium (ATP,TAN and EC) were examined. Results In all groups except group C, myocardial contractility and heart rate reconvered quickly. The levels of m yocardial adenosine triphosphate (ATP), energy charge (EC) and total adeninenu cleotide(TAN)in the LH group or WH group, and LIP group or WIP group were muc h higher than those in the group C( P <0 05 or 0 01). The MDA level of t he group C was obviously higher than that of other groups. Conclu sion Drug preconditioning with ATP sensitive potassium channel opener pinacidil (10 μmol/L) may enhance myocardial protection effect against ischemia/reperfusion injury, regardless of hypothermia or normothermia. Myocard ial protective effect of hyperpolarized arrest induced by pinacidil (50 μmol/L) is superior to that of traditional hyperkalemic heart arrest in isolated rabbi t hearts perfused on a Langendorff apparatus.