硫氮卓酮对失血性休克犬心脏的保护作用及其机制

Beneficial Effects of Diltiazem on Myocardium in Canine Hemorrhagic Shock

杂种犬１１只，股动脉放血使平均动脉压（ＭＡＰ）维持在６．０ｋＰａ９０ｍｉｎ，回输全部血液，继续观察１５０ｍｉｎ。休克３０ｍｉｎ时，硫氮 酮（ＤｉｌｔｉａｚｅｍＤｉｌ）组（ｎ＝６）输入Ｄｉｌ［４０ｍｇ／（ｋｇ·ｍｉｎ）］，共１５ｍｉｎ，总液体量３ｍｌ／ｋｇ。休克组（ｎ＝５）于相同时间输入等量生理盐水。实验结果显示：Ｄｉｌ组在２１０ｍｉｎ和２４０ｍｉｎ时ＭＡＰ明显高于休克组，而±ｄｐ／ｄｔｍａｘ则从１２０ｍｉｎ始显著高于休克组。电镜下休克组心肌肌原纤维和线粒体均呈不同程度损伤性改变，而Ｄｉｌ组心肌超微结构基本正常。实验结果还显示，Ｄｉｌ组心肌组织中脂质过氧化产物丙二醛（ＭＤＰ）含量和黄嘌呤氧化酶（ＸＯ）活性明显低于休克组，而超氧化物歧化酶（ＳＯＤ）活性显著高于休克组。上述结果表明，硫氮 酮具有抗休克和保护心肌作用，其机制可能与其防止细胞内钙超载，抑制脂质过氧化有关。

The role of diltiazem on myocardial contractility, ultrastructure and lipid peroxidation in a hemorrhagic shock model were studied. Anesthetized mongrel dogs were rapidly bled to a mean arterial pressure(MAP) of 6.0 kPa (45 mmHg) and maitained at that level for 90 min followed by resuscitation with all shed blood. At 30 min into hemorrhagic shock diltiazem[40 μg/(kg·min),n=6] or same volume of saline(3 ml/kg,n=5) was infused intravenously over 15 min. At the end of experiment(240 min after hemorrhage and resuscitation) the dogs were euthanized by pentobarbital overdose and myocardial samples were obtained and analyzed. The results demonstrated: Resuscitation with shed blood alone did not restore the MAP and left venticular dp/dtmax completely, Diltiazem treatment significantly facilitated the normalization of MAP and left ventricular dp/dtmax and also remarkably ameliorated myocardial ultrastructure damage. Further more , myocardial of diltiazem treatment dogs exhibited less malonyldialdehyde, lower xanthine oxidative activity and higher activity of superoxide dismutase as compared with those of control dogs. These data suggest that diltiazem has a beneficial effect on myocardium of dogs with hemorrhagic shock, which is associated with its calcium channel blockade and antioxidant activity.