Kitakaze M, Hori M
Department of Internal Medicine and Therapeutics, Osaka University School of Medicine, Suita, Japan.
Heart Vessels. 1998;13(5):211-28. doi: 10.1007/BF03257244.
Prevention and attenuation of ischemia and reperfusion injury in patients with acute coronary syndrome are critically important for cardiologists. To save these patients from deleterious ischemic insults, there are three different strategies. The first strategy is to increase ischemic tolerance before the onset of myocardial ischemia; the second is to attenuate the ischemia and reperfusion injury when an irreversible process of myocardial cellular injury occurs; the third is to treat the ischemic chronic heart failure that is caused by acute myocardial infarction. Adenosine, which is known to be cardioprotective against ischemia and reperfusion injury, may merit being used for these three cardioprotection strategies. First of all, adenosine induces collateral circulation via induction of growth factors, and triggers ischemic preconditioning, both of which induce ischemic tolerance in advance. Secondly, endogenous adenosine may mediate the infarct size-limiting effect of ischemic preconditioning, and exogenous adenosine is known to attenuate ischemia and reperfusion injury. Thirdly, we also revealed that adenosine metabolism is changed in patients with chronic heart failure, and increases in adenosine levels may attenuate the severity of ischemic heart failure. Therefore, adenosine therapy may improve the pathophysiology of ischemic chronic heart failure. Taking these factors together, we hereby propose potential tools for cardioprotection attributable to adenosine in ischemic hearts, and we postulate the use of adenosine therapy before, during, and after the onset of acute myocardial infarction.
预防和减轻急性冠状动脉综合征患者的缺血再灌注损伤对心脏病专家至关重要。为了使这些患者免受有害的缺血性损伤,有三种不同的策略。第一种策略是在心肌缺血发作前提高缺血耐受性;第二种是在心肌细胞损伤的不可逆过程发生时减轻缺血再灌注损伤;第三种是治疗由急性心肌梗死引起的缺血性慢性心力衰竭。已知对缺血再灌注损伤具有心脏保护作用的腺苷,可能值得用于这三种心脏保护策略。首先,腺苷通过诱导生长因子诱导侧支循环,并触发缺血预处理,这两者均可预先诱导缺血耐受性。其次,内源性腺苷可能介导缺血预处理的梗死面积限制作用,并且已知外源性腺苷可减轻缺血再灌注损伤。第三,我们还发现慢性心力衰竭患者的腺苷代谢发生了变化,腺苷水平的升高可能会减轻缺血性心力衰竭的严重程度。因此,腺苷治疗可能会改善缺血性慢性心力衰竭的病理生理学。综合考虑这些因素,我们在此提出了缺血心脏中腺苷所致心脏保护的潜在工具,并推测在急性心肌梗死发作前、发作期间和发作后使用腺苷治疗。