Kushnir Alexander, Marks Andrew R
Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Adv Pharmacol. 2010;59:1-30. doi: 10.1016/S1054-3589(10)59001-X.
According to the American Heart Association it is estimated that the United States will spend close to $39 billion in 2010 to treat over five million Americans suffering from heart failure. Patients with heart failure suffer from dyspnea and decreased exercised tolerance and are at increased risk for fatal ventricular arrhythmias. Food and Drug Administration -approved pharmacologic therapies for heart failure include diuretics, inhibitors of the renin-angiotensin system, and β-adrenergic receptor antagonists. Over the past 20 years advances in the field of ryanodine receptor (RyR2)/calcium release channel research have greatly advanced our understanding of cardiac physiology and the pathogenesis of heart failure and arrhythmias. Here we review the key observations, controversies, and discoveries that have led to the development of novel compounds targeting the RyR2/calcium release channel for treating heart failure and for preventing lethal arrhythmias.
根据美国心脏协会的估计，2010年美国将花费近390亿美元来治疗超过500万心力衰竭患者。心力衰竭患者会出现呼吸困难和运动耐量下降，并且发生致命性室性心律失常的风险增加。美国食品药品监督管理局批准的用于治疗心力衰竭的药物疗法包括利尿剂、肾素-血管紧张素系统抑制剂和β-肾上腺素能受体拮抗剂。在过去20年里，兰尼碱受体（RyR2）/钙释放通道研究领域的进展极大地推进了我们对心脏生理学以及心力衰竭和心律失常发病机制的理解。在此，我们回顾了一些关键的观察结果、争议点以及发现，这些促成了针对RyR2/钙释放通道开发新型化合物以治疗心力衰竭和预防致命性心律失常。
