PROGRESSION OF HEART FAILURE

截至1984年，据估计有200万患者发生心力衰竭。 仅在美国就有大约25万例新病例和20万例 每年的死亡人数。这些数字一直在稳步增长，并不断增加 高危老年人口的预期寿命和扩张。 尽管出现了更有效的治疗方法，但大多数患者，如果不是所有的患者， 继续屈从于这种疾病。缺血性心脏病是目前为止 最常见的导致心力衰竭的病因。严重丧失了生存能力 左心室(LV)心肌在大范围梗塞或 多发较小的梗塞，导致相当大的左心功能不全。 现在人们认识到，在国家和国家之间的过渡时期 代偿性左心功能不全与心脏失代偿和显性心脏 故障，左心室功能继续恶化，尽管没有 其他同时发生的临床事件。造成这种情况的因素是什么？ 左心功能进行性恶化不得而知。目前的建议 验证了左心功能进行性恶化的假设， 在此过渡期内，由于功能的逐渐丧失 残端持续变性和坏死所介导的心脏单位 存活的心肌细胞。拟议的研究也是为了测试 假设进行性退化和丧失的假说 剩余存活的心肌细胞是由反应性心肌细胞的发展引起的 间质纤维化是氧气扩散的屏障 毛细血管和胶原蛋白包裹心肌细胞。最后，研究 用来检验血管紧张素转换酶 抑制剂可防止或延缓左心功能进行性恶化 通过预防或减轻间质纤维化的发展。 这些相互关联的假说将在慢性阻塞性肺疾病的犬模型中进行检验。 冠状动脉内多个序贯病变所致的心力衰竭 微栓塞术。这是一种自发的犬科准备 远期左心功能恶化与反应性间质纤维化 停止冠状动脉微栓塞术，因此非常适合 对提议的假设进行详细的审问。揭开 负责从有偿向无偿过渡的机制(S) 失代偿性心力衰竭是发展中必不可少的有效 并针对特定的治疗方法，旨在预防或至少， 延缓了向明显心力衰竭的进展。

As of 1984, heart failure has been estimated to occur in 2 million patients in the United States alone with approximately 250,000 new cases and 200,000 deaths each year. These numbers have steadily increased with increasing life expectancy and expansion of the higher risk geriatric population. Despite the advent of more effective therapy, most, if not all patients, continue to succumb to this disease. Ischemic heart disease is by far the most common etiology leading to heart failure. Significant loss of viable left ventricular (LV) myocardium occurs after a large infarction or multiple smaller infarctions and results in considerable LV dysfunction. It is now recognized that during the transition period between a state of compensated LV dysfunction and cardiac decompensation and overt heart failure, lV function continues to deteriorate despite the absence of any additional concurrent clinical events. The factors responsible for this progressive worsening of LV function are not know. The present proposal tests the hypothesis that the progressive deterioration of LV function, during this transition period, results from progressive loss of functional cardiac units mediated by ongoing degeneration and necrosis of residual viable cardiomyocytes. The proposed studies are also designed to test the hypothesis that the hypothesis that the progressive degeneration and loss of residual viable cadiomyocytes result from the development of reactive interstitial fibrosis which acts as a barrier to oxygen diffusion between capillaries and the collagen encircled cardiomyocytes. Finally, studies are proposed to test the hypothesis that angiotensin converting enzyme inhibitors prevent or retard the progressive deterioration of LV function by preventing or attenuating the development of interstitial fibrosis. These interrelated hypotheses will be tested in a canine model of chronic heart failure produced by multiple sequential intracoronary microembolizations. This canine preparation manifests spontaneous deterioration of lV function and reactive interstitial fibrosis long-after cessation of coronary microembolizations and, therefore, is ideally suited for detailed interrogation of the proposed hypotheses. Uncovering the mechanism(s) responsible for the transition from compensated to decompensated heart failure is essential in the development of effective and target specific therapies aimed at preventing or, at the very least, retarding the progression toward overt heart failure.