心肌功能障碍是脓毒症常见的并发症，与患者死亡密切相关。研究表明，阻断α2A肾上腺素能受体（α2A-AR）能显著减轻脓毒症诱导的心肌功能障碍，降低脓毒症动物的死亡率。因此，右美托咪定（DEX）作为α2-AR激动剂类镇静剂，理论上可能会加重脓毒症心肌功能障碍。尽管有研究显示，复制脓毒症模型前或后1h给予DEX能抑制炎症反应、改善脓毒症动物的生存，但临床上，严重脓毒症或脓毒症休克患者已有器官功能障碍，时间上相当于CLP造模6 h后，那么CLP术后6 h给予DEX对脓毒症动物、特别是心肌功能，有何影响？目前缺乏研究。我们预实验发现DEX确实加重脂多糖诱导的心功能障碍，但机制并不清楚。本研究从心肌细胞、心脏成纤维细胞和血管内皮细胞α2A-AR和咪唑啉Ⅰ型受体、炎症、心肌钙代谢及线粒体功能方面，阐明DEX加重脓毒症心肌功能障碍的机制，对脓毒症心功能障碍患者合理选用镇静剂具有重要的临床指导意义。

Myocardial dysfunction is a common complication associated with increased morbidity and mortality in septic patients. Some studies have demonstrated that treatment of septic animals with α2A-adrenergic receptor (α2A-AR) antagonist attenuates myocardial dysfunction and significantly improves survival. According to these findings, we hypothesize that dexmedetomidine (DEX), an α2-AR agonist with sedative and analgesic properties used in the intensive care unit, may aggravate sepsis-induced myocardial dysfunction. Although some studies showed that administration of DEX before or 1 h after sepsis induction reduced the mortality rate and inhibited pro-inflammatory cytokine responses in sepsis, these are different from the clinical setting. In the clinic setting, the patients with severe sepsis and septic shock proceed to the development of one or multiple organ dysfunctions; this condition is similar to that of septic animals 6 h after sepsis induction. However, it is unclear whether administration of DEX 6 h after sepsis induction may affect survival and, particularly, myocardial dysfunction during sepsis. In order to test our hypothesis, we conducted a preliminary experiment and demonstrated that DEX administered 4 h post cecal ligation and puncture increased the mortality rate in rats and DEX treatment also enhanced lipopolysaccharide-induced myocardial dysfunction in isolated rat hearts, but the mechanisms by which DEX aggravated lipopolysaccharide-induced myocardial dysfunction are still unknown. In the present study, we used animal model of sepsis, isolated rat heart, cardiomyocytes, cardiac fibroblasts and endothelial cells to investigate the role of α2A-AR and imidazoline type-1 receptor signaling, cardiac inflammation as well as myocardial calcium regulation and mitochondrial function in the enhancing effects of DEX on sepsis-induced myocardial dysfunction. These investigations will further explain the molecular mechanisms for sepsis-triggered myocardial depression and provide the evidence for reasonable selection of sedative drugs in patients with septic myocardial dysfunction.