Dickerson R N, Lima J J, Kuhl D A, Brown R O, Hak L J
Department of Clinical Pharmacy, University of Tennessee, Memphis 38163, USA.
Pharmacotherapy. 1998 Jan-Feb;18(1):170-4.
We investigated the effect of endotoxemia on alpha1-adrenergic receptor-mediated smooth muscle contraction as measured by mean arterial pressure (MAP) in response to incremental doses of a vasopressor. Twelve male Sprague-Dawley rats were randomized to receive parenteral nutrition alone (PN) or in combination with a continuous infusion of endotoxin (PN-LPS) for 48 hours. Incremental doses of phenylephrine were given and peak MAP response was recorded. The endotoxin group had a decreased rise in MAP with the same dose of phenylephrine compared with the control group (59 +/- 14 and 99 +/- 12 mm Hg, respectively, p<0.001). However, the baseline MAP was higher in the endotoxin group (102 +/- 18 and 71 +/- 7 mm Hg, respectively, p<0.002). The overall maximum effect was the same for both groups (161 +/- 16 and 170 +/- 8 mm Hg, respectively, p=NS). These data indicate that sustained endotoxemia does not result in desensitization of alpha1-adrenergic responsiveness. Other mechanisms are responsible for the ineffectiveness of vasopressors during advanced sepsis.
我们通过测量平均动脉压（MAP）来研究内毒素血症对α1 - 肾上腺素能受体介导的平滑肌收缩的影响，该测量是针对递增剂量的血管加压药进行的。将12只雄性Sprague - Dawley大鼠随机分为两组，一组仅接受肠外营养（PN），另一组接受肠外营养并持续输注内毒素（PN - LPS），持续48小时。给予递增剂量的去氧肾上腺素，并记录MAP的峰值反应。与对照组相比，内毒素组在相同剂量去氧肾上腺素作用下MAP的升高幅度降低（分别为59±14和99±12 mmHg，p<0.001）。然而，内毒素组的基线MAP更高（分别为102±18和71±7 mmHg，p<0.002）。两组的总体最大效应相同（分别为161±16和170±8 mmHg，p =无显著性差异）。这些数据表明，持续性内毒素血症不会导致α1 - 肾上腺素能反应性脱敏。其他机制导致了晚期脓毒症期间血管加压药无效。
