Strasser R, Vogt A, Schaper W
Institut für Experimentelle Kardiologie der MPG Bad Nauheim.
Z Kardiol. 1996 Feb;85(2):79-89.
Short periods of ischemia render the myocardium more resistant to a subsequent prolonged coronary occlusion resulting in a reduction of infarct size. This cardioprotective mechanism has been called ischemic preconditioning. Acute myocardial ischemia results in a rapid decline of high energy phosphates. After short periods of ischemia the high energy phosphate levels are better preserved and the increase of lactate is slower during the prolonged subsequent ischemia in the preconditioned group compared to control. The duration of ischemia needed for induction of the protective effect is 2.5 min in dogs and 20 min in our swine model. In porcine myocardium the protection is lost about 1 h after induction and a renewal is not possible at that time, but is 24 h later. For rabbits or dogs, but not in pigs, a late protection 24 h after induction or preconditioning has been shown ("second window of protection"). Adenosine or adenosine A1 receptor agonists, muscarinic M2 receptor agonists, alpha 1-receptor agonists and bradykinin B2 receptor agonists as well as opening of the K+ATP-channel substitute for ischemia in the induction of protection. Activation of protein kinase C results in protection in rats and rabbits, but not in dogs or pigs. Inhibition of protein kinase C translocation or kinase activity results in a loss of the protection induced by preceding ischemia. After blockade of the K+ATP-channel the protection induced by adenosine A1 receptor activation is lost. Therefore opening of the K+ATP-channel is a prerequisite for induction of the protective effect. Inhibition of the inhibitory G-protein by pertussis toxin has been shown to result in a loss of protection, therefore the Gi-protein seems to be involved in the evolution of protection. In humans during coronary angioplasty anginal pain and lactate production during a second balloon occlusion is diminished without any change in the regional myocardial perfusion. This adaptation is inhibited by blockade of the K+ATP-channel or of the adenosine A1 receptor. Intermittent cross-clamping before a longer occlusion during open-heart surgery results in a better preservation of high energy phosphates compared to controls without preceding short ischemia. These observations support the hypothesis that ischemic preconditioning also occurs in humans. Angina pectoris preceding the myocardial infarction may have preconditioned the human heart against the subsequent myocardial infarction, but studies concerning the influence of angina pectoris on short-term outcome after thrombolysis are conflicting. In the future, ischemic preconditioning or preconditioning with drugs may prolong the duration of ischemia tolerated without necrosis and improve the prognosis of patients by reducing the infarct size.
短时间的缺血可使心肌对随后延长的冠状动脉闭塞产生更强的耐受性，从而减小梗死面积。这种心脏保护机制被称为缺血预处理。急性心肌缺血会导致高能磷酸化合物迅速减少。与对照组相比，在预处理组中，短时间缺血后，高能磷酸化合物水平能得到更好的维持，且在随后延长的缺血过程中乳酸的增加更为缓慢。在犬类动物中，诱导保护作用所需的缺血持续时间为2.5分钟，在我们的猪模型中为20分钟。在猪心肌中，诱导后约1小时保护作用消失，此时无法再次诱导产生保护作用，但24小时后可以。对于兔子或犬类动物，而非猪，诱导或预处理后24小时会出现延迟保护作用（“第二保护窗”）。腺苷或腺苷A1受体激动剂、毒蕈碱M2受体激动剂、α1受体激动剂和缓激肽B2受体激动剂以及开放K + ATP通道可替代缺血来诱导保护作用。蛋白激酶C的激活在大鼠和兔子中可产生保护作用，但在犬类或猪中则不然。抑制蛋白激酶C的易位或激酶活性会导致先前缺血诱导的保护作用丧失。阻断K + ATP通道后，腺苷A1受体激活所诱导的保护作用消失。因此，开放K + ATP通道是诱导保护作用的前提条件。已证明百日咳毒素抑制抑制性G蛋白会导致保护作用丧失，因此Gi蛋白似乎参与了保护作用的形成过程。在人类冠状动脉血管成形术中，第二次球囊闭塞期间的心绞痛和乳酸生成减少，而局部心肌灌注无任何变化。这种适应性变化会被K + ATP通道或腺苷A1受体的阻断所抑制。在心脏直视手术中，在较长时间闭塞之前进行间歇性交叉夹闭，与未进行短时间缺血预处理的对照组相比，能更好地维持高能磷酸化合物水平。这些观察结果支持了缺血预处理也发生在人类中的假说。心肌梗死之前的心绞痛可能已对人类心脏进行了预处理，使其对随后的心肌梗死产生耐受性，但关于心绞痛对溶栓后短期预后影响的研究结果相互矛盾。未来，缺血预处理或药物预处理可能会延长无坏死情况下可耐受的缺血持续时间，并通过减小梗死面积来改善患者的预后。
