钱菊英，医学博士，硕士生导师，主任医师，复旦大学附属中山医院心内科副主任，心导管室副主任，内科教研室副主任，上海医学会心血管学会委员兼秘书。   Qian Juying, MD, Co-Director of Department of Cardiology, Co-Director of Cardiac Catheterization Laboratory, Co-Director of Department of Internal Medicine Zhongshan Hospital, Fudan University Shanghai Institute of Cardiovascular Diseases

急性心肌梗死，转回原地   Paradigm Shift in Acute MI Comes Full Circle   （复旦大学附属中山医院 钱菊英 翻译）   要点： 在发现合适的治疗目标中数十年有争议且令人困惑的尝试   AMI的治疗并没有被清楚阐明，历史上关于治疗的争议也受其病因的确定而左右 在周二有关AMI的历史回顾中，德国Göttingen大学的Klaus Peter Rentrop解释了芝加哥的心血管病专家James B. Herrick是如何首先在20世纪早期提出冠状动脉血栓是导致心肌坏死的理论，但他的观念并没有被医学界所接纳。直到1959年，当有萌芽性的论文提出AMI溶栓治疗的可行性时，该理论仍被认为是有争议的。   FDA在1977年批准了溶栓治疗但没有把AMI列为适应证，该决定很大程度上是基于上世纪60年代动物研究的结果，该研究反驳了冠状动脉血栓诱致突发心肌梗死的看似有理的理论。   据Rentrop所述，当时普遍接受的结论是，冠状动脉血栓是心肌坏死后的结果而非原因。 结果或原因   Rentrop认为，“[William C.] Roberts的观点――心肌坏死是由于心肌的氧供和耗氧之间的不匹配所致――提出了通过降低氧耗而缩小心肌梗死面积的病理生理学原理，这是上世纪70年代的主要观点” 欧洲研究者启动了治疗冠状动脉内血栓的研究，集中于在AMI中使用链激酶。在这些研究中，1976年E.I.Chazov发表了一病例系列，报道了2例患者中冠状动脉内灌注链激酶，其中1例得到了再灌注。报道以俄文发表，很大程度上在西方仍不知道。 Rentrop表示，到上世纪70年代后期，Chazov后来又摈弃了他原先的理论，发表了AMI中使用透明质酸酶有阳性作用的研究，更符合当时主流思想的理论。 AMI和冠状动脉血栓 AMI是由冠状动脉内血栓所致的观念直至上世纪80年代早期才成为主流，1980年的Heart Disease教科书描述“溶栓治疗并不能一致性地改变AMI后的生存，尽管中度危险的患者可能受益”。 Rentrop说，在美国，晚至1979年，链激酶被提出用于预防微循环的血栓形成和降低后负荷，但“溶解闭塞性的冠状动脉血栓是不考虑的”。 当1977年Rentrop加入Göttingen大学时，研究已经在揭示有关AMI主流观点的方向进行。据Rentrop所述，他的导师D. Sinapius，Göttingen大学的病理学领袖，首选报道猝死和AMI患者中闭塞性血栓的发生率。尸解结果显示在心脏性猝死的40％病例中和死于AMI的80％病例中发现了闭塞性的血栓，证实了Herrick早先的理论。   随后的在体研究证实了AMI的闭塞性血栓发生率，其中包括Rentrop1978年的报道，显示经导丝再通血管可使急性冠状动脉闭塞减轻。 这个病例是个偶然事件，据Rentrop所述，在选择性心导管术中，一患者右冠状动脉的严重病变逐步进展成完全的闭塞。根据方案，可选择急症的搭桥手术，但Rentrop决定把导丝通过闭塞处以将血栓推到右冠状动脉的周围远端血管。   Rentrop说，“尝试取得成功，没有不良反应发生，患者立即稳定，随后进行了搭桥手术，并没有发生明显的心肌坏死。”   在1979年，Rentrop在AHA的年度会议上进行了在AMI患者中通过经腔内再通梗死血管限制心肌损伤的报告，开启了纤溶药物“世界范围内的复活” “纤溶治疗在欧洲已不再提倡”，Rentrop表示，“快速的再灌注是治疗目标。”   有关AMI病因的认识又回到了当初，由此，针对突然发生的心肌梗死的治疗也是如此。   （来源：www.tctmd.com）     Paradigm Shift in Acute MI Comes Full Circle Key Points: Decades of controversy confounded attempts at finding the appropriate target for therapy.   By TCT Daily Staff   Treatment for AMI has not always been clear cut, and historical controversy over treatment has hinged on determining its cause.   In an historical overview of AMI on Tuesday, Klaus Peter Rentrop, MD, of Göttingen University in Germany, explained how Chicago cardiologist James B. Herrick, MD, first advanced the theory in the early 20th century that coronary thrombosis causes myocardial necrosis, but his concept was not embraced by the medical community.   By 1959 the theory was still considered controversial when a seminal paper explored the feasibility of fibrinolysis in AMI.   The FDA approved thrombolytic therapy in 1977 but did not give an indication for AMI, a decision based largely on animal studies from the 1960s that had refuted the plausibility of coronary thrombosis precipitating sudden infarction.   The widely held conclusion at the time, according to Rentrop, was that coronary thrombosis is a consequence of myocardial necrosis, not a cause.   Consequence or cause   "[William C.] Roberts’ view — that myocardial necrosis is caused by a mismatch between myocardial oxygen supply and demand — provided the pathophysiological rationale for limiting the infarct size by reduction of oxygen demand, the dominating concept of the 1970s," Rentrop said.   European researchers initiated trials of therapies to treat coronary thrombosis, concentrating on streptokinase use in AMI.   Among these studies was a case series published in 1976 by E.I. Chazov, MD, who reported use of intracoronary streptokinase infusion in two patients, with reperfusion resulting in one.   The report was published in Russian and remained largely unknown in the West. Chazov later rejected his original theory and, by the late 1970s, had published research on the positive effects of hyaluronidase in AMI – a theory more in line with mainstream thinking, Rentrop said.   AMI and coronary thrombosis   The idea that AMI caused coronary thrombosis dominated until the early 1980s.   The 1980 textbook Heart Disease stated that "fibrinolytic therapy does not unequivocally alter survival after AMI, although medium-risk patients may be benefited."   As late as 1979 in the United States, streptokinase was touted for prevention of thrombus formation in the microcirculation and for reduction of afterload, but "lysis of an occlusive coronary thrombus was not considered," Rentrop said.   When Rentrop joined Göttingen University in 1977, studies were already underway to trump the prevailing consensus about AMI.   According to Rentrop, his mentor D. Sinapius, MD, head of pathology at Göttingen, was the first to report the frequency of occlusive thrombi in sudden death and AMI.   A postmortem pathological examination found occlusive thrombi in 40% of cases of sudden cardiac death and in 80% of deaths due to AMI, confirming Herrick’s original theory.   Further in vivo investigations confirmed the frequency of occlusive thrombi in AMI. Included among these was a 1978 report by Rentrop on the relief of an acute coronary occlusion by guidewire recanalization.   That case turned out to be a fortuitous accident. According to Rentrop, a severe RCA lesion in a patient progressed to complete occlusion during an elective catheterization.   Per protocol, emergency bypass surgery was an option, but Rentrop decided to push the thrombus into the periphery of the RCA advancing a guidewire across the occlusion.   "The attempt succeeded without adverse effects. The patient stabilized immediately, underwent bypass surgery, and did not sustain significant myocardial necrosis," Rentrop said.   In 1979, Rentrop presented a talk on limitation of myocardial injury by transluminal recanalization of the infarct vessel in AMI at the AHA annual meeting, kicking off a "worldwide renaissance" in fibrinolytic medicine.   "Fibrinogenolysis was no longer cited in Europe," Rentrop said. "Rapid reperfusion was the goal."   Beliefs about the etiology of AMI had shifted back to where they began and, as a result, so did therapy aimed at treating sudden-onset infarct.   （source：www.tctmd.com）