Bloor B C, Stead S W, Snipper D M, Flacke W E
Department of Anesthesiology, University of California, Los Angeles 90024-1778.
J Cardiovasc Pharmacol. 1989 Mar;13(3):398-404. doi: 10.1097/00005344-198903000-00007.
The relationship between halothane concentration and tachyphylaxis to sodium nitroprusside (SNP) was studied in a rabbit model. Three groups of six rabbits (groups A, B, and C) were anesthetized with halothane at 0.75, 1.0, and 1.25 vol% end-tidal, respectively. SNP-induced hypotension was maintained for 135 min or until a cumulative total dose of 12 mg/kg had been infused (defined as "marked tachyphylaxis"). Plasma norepinephrine (NE), epinephrine (EPI) levels, and plasma renin activity (PRA) were measured. Initial mean arterial pressure (MAP) (72 +/- 2 mm Hg), heart rate (325 +/- 12 beats/min), and the amount of SNP required to induce 40% hypotension (19 +/- 4 micrograms/kg/min) did not differ significantly among the three groups. In group A, five out of six animals exhibited "marked tachyphylaxis." In group B, only one animal showed "marked tachyphylaxis"; the remaining five required a dose rate of 104 +/- 38 micrograms/kg/min at 135 min to maintain a 40% reduction in MAP. In group C, none of the animals showed "marked tachyphylaxis"; the dose rate of SNP required after 135 min was 29 +/- 14 micrograms/kg/min. In all groups, SNP dose rate was found to best correlate (p less than 0.0005, r = 0.79) with NE levels and not with PRA or arterial blood pH. This implies that reflex sympathetic activation is the measured mediator of SNP tachyphylaxis. Halothane blunted the tachyphylaxis (sympathetic response) to SNP-induced hypotension at higher concentrations.
在兔模型中研究了氟烷浓度与对硝普钠（SNP）快速耐受性之间的关系。三组兔子，每组6只（A组、B组和C组），分别用呼气末浓度为0.75%、1.0%和1.25%体积分数的氟烷麻醉。将SNP诱导的低血压维持135分钟，或直至累计总剂量达到12mg/kg（定义为“明显快速耐受性”）。测量血浆去甲肾上腺素（NE）、肾上腺素（EPI）水平以及血浆肾素活性（PRA）。三组的初始平均动脉压（MAP）（72±2mmHg）、心率（325±12次/分钟）以及诱导40%低血压所需的SNP量（19±4μg/kg/分钟）无显著差异。A组6只动物中有5只表现出“明显快速耐受性”。B组只有1只动物表现出“明显快速耐受性”；其余5只在135分钟时需要104±38μg/kg/分钟的剂量率来维持MAP降低40%。C组没有动物表现出“明显快速耐受性”；135分钟后所需的SNP剂量率为29±14μg/kg/分钟。在所有组中，发现SNP剂量率与NE水平的相关性最佳（p<0.0005，r = 0.79），而与PRA或动脉血pH无关。这意味着反射性交感神经激活是所测得的SNP快速耐受性的介质。在较高浓度时，氟烷减弱了对SNP诱导的低血压的快速耐受性（交感反应）。
