Petersen John W, Felker G Michael
Division of Cardiovascular Medicine, Duke University Medical Center, Durham, NC, USA.
Crit Care Med. 2008 Jan;36(1 Suppl):S106-11. doi: 10.1097/01.CCM.0000296273.72952.39.
Impaired cardiac contractility is a fundamental component of the heart failure syndrome, initiating the cycle of vasoconstriction, neurohormonal and inflammatory activation, and adverse ventricular remodeling that leads to heart failure progression. Based on this core paradigm, drugs that increase cardiac contractility (positive inotropes) are theoretically appealing as a heart failure therapy, and such agents have been extensively investigated in both acute and chronic heart failure. Although these agents clearly improve cardiac output, their use in heart failure has consistently been associated with increased myocardial oxygen demand, cardiac arrhythmias, and mortality in a variety of clinical settings. Based on these data, the routine use of inotropes as heart failure therapy is not indicated in either the acute or chronic setting. Inotropes may be a necessary evil in a subset of acute heart failure patients, such as those with acute heart failure decompensation in the setting of clinically evident hypoperfusion or shock, or as a bridge to more definitive treatment, such as revascularization or cardiac transplantation. Currently available inotropes, such as dobutamine and milrinone, act (directly or indirectly) by increasing cyclic adenylate monophosphate and therefore intracellular calcium flux. Whether newer inotropes with differing mechanisms of action will realize the potential clinical benefits of inotropic therapy without the risk remains a subject of ongoing investigation.
心脏收缩功能受损是心力衰竭综合征的一个基本组成部分，启动了血管收缩、神经激素和炎症激活以及不良心室重塑的循环，进而导致心力衰竭进展。基于这一核心范式，增强心脏收缩力的药物（正性肌力药）在理论上作为心力衰竭治疗手段具有吸引力，并且这类药物已在急性和慢性心力衰竭中得到广泛研究。尽管这些药物明显改善心输出量，但在各种临床情况下，它们用于心力衰竭治疗一直与心肌需氧量增加、心律失常和死亡率升高相关。基于这些数据，无论是在急性还是慢性情况下，均不建议常规使用正性肌力药作为心力衰竭治疗手段。在一部分急性心力衰竭患者中，如那些在临床上明显存在灌注不足或休克情况下出现急性心力衰竭失代偿的患者，或者作为通向更确定性治疗（如血运重建或心脏移植）的桥梁，正性肌力药可能是一种无奈之选。目前可用的正性肌力药，如多巴酚丁胺和米力农，通过增加环磷酸腺苷，从而增加细胞内钙通量（直接或间接）发挥作用。具有不同作用机制的新型正性肌力药能否在无风险的情况下实现正性肌力治疗的潜在临床益处，仍是一个正在研究的课题。
