Department of Anesthesiology, Critical Care and Pain Medicine, Saarland University Medical Center, Homburg (Saar), Germany.
Shock. 2013 Aug;40(2):129-35. doi: 10.1097/SHK.0b013e31829c361d.
Dobutamine is recommended for the treatment of sepsis-related circulatory failure in international guidelines. Furthermore, dobutamine has been demonstrated to improve liver function and hepatic perfusion after experimental hemorrhagic shock. Yet, it is unknown whether dobutamine may also induce hepatoprotective effects in sepsis. This study was designed to investigate the effect of dobutamine on survival, hepatic function, and microcirculation after polymicrobial sepsis in rat. Under general anesthesia, male Sprague-Dawley rats (n = 25/group) underwent pretreatment with dobutamine (10 μg/kg per minute) in the presence or absence of β1-receptor antagonist esmolol (500 μg/kg per minute), esmolol alone, or vehicle for 6 h, before induction of sepsis (cecal ligation and incision [CLI]). Sham-operated animals were treated likewise but underwent no CLI. Five hours after CLI, either liver function was assessed by plasma disappearance rate of indocyanine green (n = 5/group), or intravital microscopy was performed (n = 5/group) for evaluation of hepatic perfusion index and hepatic integrity (as propidium iodide-stained cells per field). Alternatively, survival time after induction of CLI was monitored under general anesthesia (n = 15/group). Compared with controls, dobutamine pretreatment significantly improved plasma disappearance rate of indocyanine green (13.8% ± 4.1% vs. 20.6% ± 4.6%; P = 0.029), hepatic perfusion index (275.0 ± 126.1 vs. 703.5 ± 177.4 pL/s per mm; P < 0.001), hepatocellular injury (22.2 ± 6.7 vs. 6.4 ± 3.1 cells per field; P < 0.001), and survival time (326 ± 20 vs. 603 ± 41 min; P < 0.001). Coadministration of esmolol abolished the protective effect of dobutamine completely. Our results indicate that pretreatment with dobutamine may improve survival, liver function, and hepatic microcirculation after polymicrobial sepsis in rat via β1-adrenoceptor activation. Dobutamine could therefore play a relevant role for hepatoprotection under septic conditions.
多巴酚丁胺在国际指南中被推荐用于治疗与脓毒症相关的循环衰竭。此外，多巴酚丁胺已被证明可改善实验性失血性休克后肝功能和肝灌注。然而，尚不清楚多巴酚丁胺是否也可在脓毒症中诱导肝保护作用。本研究旨在探讨多巴酚丁胺对大鼠多微生物脓毒症后生存、肝功能和微循环的影响。在全身麻醉下，雄性 Sprague-Dawley 大鼠（每组 n = 25）在诱导脓毒症（盲肠结扎和切开术 [CLI]）前 6 小时接受多巴酚丁胺（10μg/kg/分钟）预处理，同时给予β1-受体拮抗剂艾司洛尔（500μg/kg/分钟），单独给予艾司洛尔或载体。假手术组动物接受同样处理，但不进行 CLI。CLI 后 5 小时，通过评估吲哚菁绿（ICG）的血浆清除率来评估肝功能（每组 n = 5），或进行活体显微镜检查（每组 n = 5）以评估肝灌注指数和肝完整性（碘化丙啶染色细胞数/视野）。或者，在全身麻醉下监测 CLI 诱导后的生存时间（每组 n = 15）。与对照组相比，多巴酚丁胺预处理显著改善 ICG 的血浆清除率（13.8%±4.1%比 20.6%±4.6%；P = 0.029），肝灌注指数（275.0±126.1 比 703.5±177.4 pL/s/每 mm；P < 0.001），肝细胞损伤（22.2±6.7 比 6.4±3.1 个细胞/视野；P < 0.001）和生存时间（326±20 比 603±41 分钟；P < 0.001）。同时给予艾司洛尔完全消除了多巴酚丁胺的保护作用。我们的结果表明，通过β1-肾上腺素能受体激活，多巴酚丁胺预处理可改善大鼠多微生物脓毒症后的生存、肝功能和肝微循环。因此，多巴酚丁胺在脓毒症条件下可能对肝保护具有重要作用。
