Rudiger Alain, Singer Mervyn
Bloomsbury Institute of Intensive Care Medicine, Wolfson Institute for Biomedical Research and Department of Medicine, University College London, UK.
Crit Care Med. 2007 Jun;35(6):1599-608. doi: 10.1097/01.CCM.0000266683.64081.02.
To review mechanisms underlying sepsis-induced cardiac dysfunction in general and intrinsic myocardial depression in particular.
MEDLINE database.
Myocardial depression is a well-recognized manifestation of organ dysfunction in sepsis. Due to the lack of a generally accepted definition and the absence of large epidemiologic studies, its frequency is uncertain. Echocardiographic studies suggest that 40% to 50% of patients with prolonged septic shock develop myocardial depression, as defined by a reduced ejection fraction. Sepsis-related changes in circulating volume and vessel tone inevitably affect cardiac performance. Although the coronary circulation during sepsis is maintained or even increased, alterations in the microcirculation are likely. Mitochondrial dysfunction, another feature of sepsis-induced organ dysfunction, will also place the cardiomyocytes at risk of adenosine triphosphate depletion. However, clinical studies have demonstrated that myocardial cell death is rare and that cardiac function is fully reversible in survivors. Hence, functional rather than structural changes seem to be responsible for intrinsic myocardial depression during sepsis. The underlying mechanisms include down-regulation of beta-adrenergic receptors, depressed postreceptor signaling pathways, impaired calcium liberation from the sarcoplasmic reticulum, and impaired electromechanical coupling at the myofibrillar level. Most, if not all, of these changes are regulated by cytokines and nitric oxide.
Integrative studies are needed to distinguish the hierarchy of the various mechanisms underlying septic cardiac dysfunction. As many of these changes are related to severe inflammation and not to infection per se, a better understanding of septic myocardial dysfunction may be usefully extended to other systemic inflammatory conditions encountered in the critically ill. Myocardial depression may be arguably viewed as an adaptive event by reducing energy expenditure in a situation when energy generation is limited, thereby preventing activation of cell death pathways and allowing the potential for full functional recovery.
全面回顾脓毒症诱导的心脏功能障碍，尤其是心肌固有抑制的潜在机制。
MEDLINE数据库。
心肌抑制是脓毒症中公认的器官功能障碍表现。由于缺乏普遍接受的定义且未开展大型流行病学研究，其发生率尚不确定。超声心动图研究表明，40%至50%的脓毒性休克持续患者会出现心肌抑制，定义为射血分数降低。脓毒症时循环血容量和血管张力的变化不可避免地会影响心脏功能。尽管脓毒症期间冠状动脉循环得以维持甚至增加，但微循环仍可能发生改变。线粒体功能障碍是脓毒症诱导的器官功能障碍的另一个特征，也会使心肌细胞面临三磷酸腺苷耗竭的风险。然而，临床研究表明，心肌细胞死亡很少见，幸存者的心脏功能可完全恢复。因此，功能而非结构变化似乎是脓毒症期间心肌固有抑制的原因。潜在机制包括β-肾上腺素能受体下调、受体后信号通路抑制、肌浆网钙释放受损以及肌原纤维水平的电机械偶联受损。这些变化大多（如果不是全部的话）受细胞因子和一氧化氮调节。
需要进行综合研究以区分脓毒症性心脏功能障碍各种潜在机制的主次。由于这些变化中的许多与严重炎症而非感染本身有关，对脓毒症性心肌功能障碍的更好理解可能有益地扩展到危重病患者中遇到的其他全身炎症性疾病。心肌抑制可以说是一种适应性事件，通过在能量生成受限的情况下减少能量消耗，从而防止细胞死亡途径的激活，并允许完全功能恢复的可能性。
