Development and Establishment of a New Therapeutic Strategy for Chronic Heart Failure due to Adenosine.

我们之前已经发现腺苷介导了对缺血和再灌注损伤的心脏保护作用。在本研究中，我们从基础和临床两个方面探讨了腺苷在缺血性和非缺血性心脏病中的作用。首先，我们检测了在缺血性和非缺血性心力衰竭中的基因表达，并检测了腺苷在基因表达中的作用。这是因为了解缺血心脏的病理生理机制对于保护心脏免受缺血和再灌注损伤是很重要的。然而，许多心脏病专家只研究了几种物质，一次使用Northern或Western印迹分析来阐明对患病心脏的药理作用。然而，许多物质同时对疾病心脏的病理生理起到作用。基因芯片技术是近年来发展起来的一种同时分析多种基因表达的新方法。我们进行了cdna阵列来检测有多少个基因是…，以及是什么基因。在使用和不使用腺苷受体抑制剂的情况下，使用cDNA阵列的患病心脏中的变化更大。心脏中许多基因的表达受缺血、机械和神经体液应激的调节。内源性腺苷调节了缺血心脏中这些调控基因的近一半。第二，我们评估了腺苷的前体ATP在限制急性心肌梗死患者梗死范围方面的效果。冠状动脉内注射三磷酸腺苷可以限制梗塞范围。第三，我们研究了腺苷在慢性心力衰竭中的作用，因为慢性心力衰竭是心血管疾病的最终常见终末期。我们用叙利亚仓鼠心力衰竭模型评价了心衰过程中外源性5‘-核苷酸酶的诱导过程。在慢性心力衰竭代偿期，失代偿期心衰患者外周血5‘-核苷酸酶活性升高，而失代偿期心力衰竭患者外周血5’-核苷酸酶活性降低。综上所述，我们揭示了腺苷对缺血性和非缺血性心力衰竭的有效治疗作用，为腺苷治疗慢性心力衰竭提供了新的思路。较少

We have previously revealed that adenosine mediates cardioprotection against ischemic and reperfusion injury. In the present study, we have been investigating the role of adenosine in ischemic and non- ischemic heart diseases from the basic and clinical aspects.First of all, we tested the gene expression in the ischemic and non- ischemic heart failure and we tested the role of adenosine in the gene expression. This is because it is important to know the pathophysiology of ischemic hearts to protect the hearts against ischemic and reperfusion injury. However, many cardiologists have investigated only a few substances once using Northern or Western blot analysis to clarify the pharmacological effect on the diseased hearts. However, many substances simultaneously contribute to the pathophysiology of diseased hearts. cDNA array technique has recently developed as a novel method to evaluate much gene expression at once. We performed cDNA array to examine how many and what kind of genes are … More changed in the diseased hearts using cDNA array with and without administration of an adenosine receptor inhibitor. Cardiac expression of many genes was regulated by ischemic, mechanical and neurohumoral stress. Endogenous adenosine modulated almost half of these regulated genes in the ischemic hearts.Second, we evaluated the effect of ATP, a precursor of adenosine, to limit the infarct size in the patients with acute myocardial infarction. Intracoronary injection of ATP was revealed to limit the infarct size.Third, we investigated the role of adenosine in chronic heart failure because chronic heart failure is the final common end- stage of cardiovascular diseases. We evaluated the process of induction of ecto- 5' -nucleotidase during the development of heart failure with the heart failure model of Syrian Hamster. At the compensatory period of chronic heart failure ecto- 5' -nucleotidase activity is enhanced, but ecto- 5'- nucleotidase activity was decreased in decompensated heart failure.Taken together, we have revealed that adenosine potently attenuates ischemic and non- ischemic heart failure, which may propose a new paradigm for the adenosine therapy of chronic heart failure. Less