Mansart Arnaud, Bollaert Pierre Edouard, Seguin Carole, Levy Bruno, Longrois Dan, Mallié Jean Pierre
Laboratoire de Néphrologie UPRES-JE, Faculté de Médecine, 54100 Vandoeuvre les Nancy, France.
Shock. 2003 Jan;19(1):38-44. doi: 10.1097/00024382-200301000-00008.
Recent findings in human septic shock suggest that glucocorticosteroids can limit and even reverse hemodynamic disturbances and dependence on catecholamines. In a rodent model of hypotensive and hypokinetic septic shock, we investigated the effects of early or late dexamethasone administration on hemodynamics, response to catecholamines, and cardiac beta-adrenergic signalling. As compared with sham-operated rats, the untreated septic rats displayed significant arterial hypotension and reduced aortic blood flow. However, in vivo pressor response to epinephrine and phenylephrine was not different among sham and septic animals. Conversely, the chronotropic response to isoproterenol was significantly attenuated in septic animals. Steroid-treated septic animals displayed complete reversal of hypotension, improvement in aortic blood flow, and reduced plasma lactate and nitrite/nitrate concentrations as compared with untreated septic animals. The number of myocardial beta-adrenergic receptors and in vivo isoproterenol-stimulated myocardial cAMP content were similar in sham and septic animals. Glucocorticosteroids, although not changing these patterns, significantly decreased the receptors affinity when administered late, but not early. In this model of septic shock, hemodynamic abnormalities may not be related to adrenergic receptor desensitization. That steroids can improve them suggests that they could act mainly distal to adrenergic receptors, for instance, on myocardial and vascular smooth fiber contraction properties through mechanisms probably including inducible nitric oxide synthase inhibition.
近期关于人类感染性休克的研究结果表明，糖皮质激素能够限制甚至逆转血流动力学紊乱以及对儿茶酚胺的依赖。在一个低血压和低动力性感染性休克的啮齿动物模型中，我们研究了早期或晚期给予地塞米松对血流动力学、对儿茶酚胺的反应以及心脏β-肾上腺素能信号传导的影响。与假手术大鼠相比，未治疗的感染性休克大鼠表现出显著的动脉低血压和主动脉血流量减少。然而，假手术组和感染性休克组动物对肾上腺素和去氧肾上腺素的体内升压反应并无差异。相反，感染性休克动物对异丙肾上腺素的变时反应显著减弱。与未治疗的感染性休克动物相比，接受类固醇治疗的感染性休克动物的低血压完全逆转，主动脉血流量改善，血浆乳酸和亚硝酸盐/硝酸盐浓度降低。假手术组和感染性休克组动物的心肌β-肾上腺素能受体数量以及体内异丙肾上腺素刺激的心肌环磷酸腺苷（cAMP）含量相似。糖皮质激素虽然不改变这些模式，但晚期给药（而非早期给药）时会显著降低受体亲和力。在这个感染性休克模型中，血流动力学异常可能与肾上腺素能受体脱敏无关。类固醇能够改善这些异常表明，它们可能主要作用于肾上腺素能受体的下游，例如，通过可能包括抑制诱导型一氧化氮合酶的机制，作用于心肌和血管平滑肌纤维的收缩特性。
