Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, USA.
Crit Care Med. 2012 Jun;40(6):1957-60. doi: 10.1097/CCM.0b013e31824e0fe5.
To compare the effects on von Willebrand factor release of the mixed vasopressin type 1a and type 2 receptor agonist arginine vasopressin and the selective vasopressin type 1a receptor agonist FE 202158, [Phe2,Ile3,Hgn4,Orn(iPr)8]vasopressin, at doses required for the treatment of septic shock.
Prospective, randomized, controlled laboratory experiment.
University animal research facility.
Twenty-four chronically instrumented sheep.
After a 5-day recovery from instrumentation, sheep were randomly assigned to receive a single intravenous bolus of the selective vasopressin type 2 receptor agonist desmopressin (1 nmol·kg(-1)) or continuous intravenous infusions of arginine vasopressin (3 pmol·kg(-1)·min(-1)), the selective vasopressin type 1a receptor agonist FE 202158 (10 pmol·kg(-1)·min(-1)), or vehicle (0.9% NaCl) (n = 6 each).
The von Willebrand factor antigen activity relative to hemoglobin concentration (vWF:Ag/Hb ratio) was measured at different time points during the 120-min study period. Maximal vWF:Ag/Hb ratio expressed as percentage of baseline level was significantly increased compared to vehicle-infused animals (3 ± 2%) in the desmopressin (40 ± 6%, p < .001) and arginine vasopressin groups (25 ± 4%, p < .001). The ratio for the FE 202158 group was not statistically different from the sham group (9 ± 2%, p = .208). Notably, maximal vWF:Ag/Hb ratio was lower in the FE 202158 than the arginine vasopressin group (p < .005).
Unlike the mixed vasopressin type 1a receptor/vasopressin type 2 receptor agonist arginine vasopressin, the selective vasopressin type 1a receptor agonist FE 202158 does not release von Willebrand factor. Because von Willebrand factor is involved in coagulatory and inflammatory pathways during septic shock, future studies should clarify the role of the vasopressin type 2 receptor-mediated von Willebrand factor increase by arginine vasopressin and the potential benefit of selective vasopressin type 1a receptor-agonists like FE 202158.
比较混合血管加压素 1a 型和 2 型受体激动剂精氨酸血管加压素和选择性血管加压素 1a 型受体激动剂[Phe2，Ile3，Hgn4，Orn（iPr）8]血管加压素在治疗感染性休克所需剂量下对血管性血友病因子释放的影响。
前瞻性、随机、对照实验室实验。
大学动物研究设施。
24 只慢性仪器化绵羊。
仪器操作后 5 天恢复期，绵羊随机接受单次静脉推注选择性血管加压素 2 型受体激动剂去氨加压素（1 nmol·kg（-1））或连续静脉输注精氨酸加压素（3 pmol·kg（-1）·min（-1）），选择性血管加压素 1a 型受体激动剂 FE 202158（10 pmol·kg（-1）·min（-1））或载体（0.9%NaCl）（每组 6 只）。
在 120 分钟研究期间的不同时间点测量血管性血友病因子抗原活性相对于血红蛋白浓度（vWF：Ag/Hb 比值）。与载体输注动物（3 ± 2%）相比，去氨加压素（40 ± 6%，p <.001）和精氨酸加压素组（25 ± 4%，p <.001）的最大 vWF：Ag/Hb 比值明显升高。FE 202158 组的比值与假手术组无统计学差异（9 ± 2%，p =.208）。值得注意的是，FE 202158 组的最大 vWF：Ag/Hb 比值低于精氨酸加压素组（p <.005）。
与混合血管加压素 1a 型受体/血管加压素 2 型受体激动剂精氨酸加压素不同，选择性血管加压素 1a 型受体激动剂 FE 202158 不会释放血管性血友病因子。由于血管性血友病因子在感染性休克期间参与凝血和炎症途径，未来的研究应阐明精氨酸加压素介导的血管加压素 2 型受体增加的血管性血友病因子增加的作用，以及 FE 202158 等选择性血管加压素 1a 型受体激动剂的潜在益处。
