Granfeldt Asger
Department of Anesthesiology, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark.
Dan Med J. 2012 Aug;59(8):B4496.
Cardiac arrest and acute myocardial infarction are leading causes of death in the middle-aged and elderly, whereas trauma primarily affects the younger segment of the population. The three conditions are all characterized by a period of reduced blood flow either regionally in the heart or globally, and treatment strategies target the restoration of normal blood flow. Paradoxically, reperfusion of ischemic tissue contributes to cellular injury in all three settings. Ischemic postconditioning initiated immediately at reperfusion was in 2003 introduced as a new potential treatment to limit injury following acute myocardial infarction. The aim of this dissertation was explore the mechanism of ischemic postconditioning during regional ischemia and test the effects of early pharmacological postconditioning using adenocaine in models of global I/R injury. In the first study, the mechanisms of postconditioning were explored. In a rat model of regional ischemia, it was demonstrated that postconditioning reduced infarct size. However when postconditioning was applied in already PMN-depleted rats, no further reduction in infarct size was observed. Furthermore, in a canine model of regional ischemia, postconditioning attenuated PMN superoxide production, implying that cardioprotection by postconditioning involves inhibition of PMNs. In the second study, treatment with adenocaine as pharmacological postconditioning during the immediate phase of cardiopulmonary resuscitation, attenuated early post-resuscitation myocardial dysfunction, augmented pulmonary and cardiac blood flow and reduced PMN superoxide production in a porcine model of cardiac arrest. In the third study, treatment with ALM/AL during the early phase of resuscitation was tested in a porcine model of hemorrhagic shock. Resuscitation with ALM/AL reduced fluid requirements during fluid resuscitation, transiently reduced whole body O2 consumption and improved cardiac and renal function. In conclusion, early intervention with either postconditioning or adenocaine attenuates I/R injury and organ dysfunction in animal models of acute myocardial infarction, cardiac arrest or hemorrhagic shock. Postconditioning and adenocaine may be promising new therapies for protection against I/R after acute myocardial infarction, cardiac arrest and hemorrhagic shock.
心脏骤停和急性心肌梗死是中老年人死亡的主要原因，而创伤主要影响年轻人群体。这三种情况的共同特征是心脏局部或全身血流减少一段时间，治疗策略旨在恢复正常血流。矛盾的是，缺血组织的再灌注在这三种情况下都会导致细胞损伤。2003年引入了在再灌注时立即启动的缺血后处理，作为限制急性心肌梗死后损伤的一种新的潜在治疗方法。本论文的目的是探讨局部缺血期间缺血后处理的机制，并在全身缺血/再灌注损伤模型中测试使用阿地卡因进行早期药物后处理的效果。在第一项研究中，探讨了后处理的机制。在大鼠局部缺血模型中，证明后处理可减小梗死面积。然而，当在已经耗尽中性粒细胞的大鼠中应用后处理时，未观察到梗死面积进一步减小。此外，在犬局部缺血模型中，后处理减弱了中性粒细胞超氧化物的产生，这意味着后处理的心脏保护作用涉及对中性粒细胞的抑制。在第二项研究中，在猪心脏骤停模型中，在心肺复苏的即刻阶段用阿地卡因进行药物后处理，可减轻复苏后早期心肌功能障碍，增加肺和心脏血流，并减少中性粒细胞超氧化物的产生。在第三项研究中，在猪失血性休克模型中测试了复苏早期用ALM/AL进行治疗的效果。用ALM/AL进行复苏可减少液体复苏期间的液体需求量，短暂降低全身耗氧量，并改善心脏和肾功能。总之，早期采用后处理或阿地卡因进行干预可减轻急性心肌梗死、心脏骤停或失血性休克动物模型中的缺血/再灌注损伤和器官功能障碍。后处理和阿地卡因可能是预防急性心肌梗死、心脏骤停和失血性休克后缺血/再灌注的有前景的新疗法。
