Ruffolo R R, Feuerstein G Z
Division of Pharmacological Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
Eur Heart J. 1998 Feb;19 Suppl B:B19-24.
Many pathophysiological processes are activated in patients with congestive heart failure, and several of these have been implicated in the progression of the disease. The most important processes to be activated in heart failure are the neurohormonal systems, which include the reninangiotensin system, the sympathetic nervous system and the endothelin system. In addition to the neurohormonal systems, the formation of reactive oxygen free radicals is increased in congestive heart failure. It has been proposed that the activation of neurohormonal pathways and the formation of oxygen free radicals ultimately lead to the activation of a family of transcription factors that are involved in cardiac and vascular remodelling which are hallmarks of congestive heart failure. In addition, the formation of oxygen free radicals has been implicated in the process of apoptosis, or programmed cell death, which may contribute to the continued loss of myocardial cells resulting in progressive decreases in left ventricular function, while at the same time contributing to the cardiac remodelling process which subsequently creates a pro-arrhythmic environment in the myocardium. Carvedilol is a novel multiple-action neurohormonal antagonist that has been shown to be effective in the management of congestive heart failure. Carvedilol also possesses a number of additional activities which may inhibit many of the chronic pathophysiological processes that are involved in the progression of congestive heart failure.
充血性心力衰竭患者体内多种病理生理过程被激活，其中一些与疾病进展有关。心力衰竭时被激活的最重要过程是神经激素系统，包括肾素 - 血管紧张素系统、交感神经系统和内皮素系统。除神经激素系统外，充血性心力衰竭时活性氧自由基的生成也会增加。有人提出，神经激素途径的激活和氧自由基的形成最终会导致一系列参与心脏和血管重塑的转录因子被激活，而心脏和血管重塑是充血性心力衰竭的标志。此外，氧自由基的形成与凋亡或程序性细胞死亡过程有关，这可能导致心肌细胞持续丢失，从而使左心室功能逐渐下降，同时也促进心脏重塑过程，随后在心肌中形成促心律失常环境。卡维地洛是一种新型的多效神经激素拮抗剂，已被证明在治疗充血性心力衰竭方面有效。卡维地洛还具有许多其他活性，可能会抑制许多参与充血性心力衰竭进展的慢性病理生理过程。
