Daş G, Vernunft A, Görs S, Kanitz E, Weitzel J M, Brüssow K-P, Metges C C
J Anim Sci. 2016 Dec;94(12):5182-5191. doi: 10.2527/jas.2016-1018.
Experimental setups for physiological research, in which acute operative interventions need to be performed, can require inclusion of general anesthesia (GA), which may interfere or confound with the effects of the experimental factors of interest on measured variables. It was recently shown that the most commonly used sedatives/anesthetics in pigs (e.g., ketamine, xylazine, azaperone) affect physiological responses and thus the primary metabolic readouts have the potential to be confounded. To extend the search for a physiologically-friendly anesthesia regime for such studies, we investigated effects of GA induced by propofol (Prop) or pentobarbital (Pent) or propofol plus isoflurane (Prop + Isof) on plasma concentrations of commonly measured metabolites and hormones. In 2 experimental runs, 6 female pigs fitted with jugular vein catheters were used. Fasted pigs received either no drug (CON) or anesthetized rotationally either with Prop, Pent or Prop + Isof on different days, separated with washout periods of sufficient length (2 to 3 d). Six-h profiles of glucose, lactate, non-esterified fatty acids (NEFA), triglycerides (TG), cholesterol, urea as well as hormones including glucagon, insulin and cortisol were determined. Concentrations of cholesterol, urea and glucagon remained unaffected by any of the treatments ( > 0.05). Pent tended to increase cortisol from 30 to 90 min after drug administration. Glucose and lactate concentrations were increased ( < 0.05) by Prop and Pent within the first hour of GA ( < 0.05). Propofol and Pent reduced NEFA concentrations, which were more pronounced during the last 2 h of the studied period. Triglyceride concentrations were increased by all 3 agents within the first 45 min with Prop containing treatments exerting a stronger effect than Pent. Our data suggest that GA with Prop and particularly with Pent adulterate plasma metabolite and hormone profiles of pigs acutely, and thus has the potential to confound the effects of experimental factors of interest. Although Prop + Isof anesthesia did not differ from the controls, providing a physiologically-friendly GA, both single and the isoflurane-combined treatment of Prop induced hypertriglyceridemia due to the lipid adjuvant of the Prop drugs. It is concluded that readouts obtained under GA may be influenced both by physiological adulterations as response to anesthesia as well as by artifacts due to accompanying ingredients of the drug formulations.
在需要进行急性手术干预的生理学研究实验设置中，可能需要使用全身麻醉（GA），这可能会干扰或混淆感兴趣的实验因素对测量变量的影响。最近有研究表明，猪中最常用的镇静剂/麻醉剂（如氯胺酮、赛拉嗪、阿扎哌隆）会影响生理反应，因此主要的代谢读数有可能被混淆。为了进一步寻找适用于此类研究的生理友好型麻醉方案，我们研究了丙泊酚（Prop）、戊巴比妥（Pent）或丙泊酚加异氟烷（Prop + Isof）诱导的全身麻醉对常见测量代谢物和激素血浆浓度的影响。在2次实验中，使用了6头装有颈静脉导管的雌性猪。禁食的猪要么不接受药物（CON），要么在不同日期轮流接受Prop、Pent或Prop + Isof麻醉，期间有足够长的洗脱期（2至3天）。测定了葡萄糖、乳酸、非酯化脂肪酸（NEFA）、甘油三酯（TG）、胆固醇、尿素以及包括胰高血糖素、胰岛素和皮质醇在内的激素的6小时变化曲线。胆固醇、尿素和胰高血糖素的浓度不受任何处理的影响（>0.05）。戊巴比妥给药后30至90分钟，皮质醇有升高趋势。丙泊酚和戊巴比妥在全身麻醉的第一小时内使葡萄糖和乳酸浓度升高（<0.05）。丙泊酚和戊巴比妥降低了NEFA浓度，在研究期的最后2小时更为明显。所有3种药物在最初45分钟内均使甘油三酯浓度升高，含丙泊酚的处理比戊巴比妥的作用更强。我们的数据表明，丙泊酚尤其是戊巴比妥诱导的全身麻醉会急性改变猪的血浆代谢物和激素谱，因此有可能混淆感兴趣的实验因素的影响。虽然丙泊酚加异氟烷麻醉与对照组无差异，提供了一种生理友好型全身麻醉，但由于丙泊酚药物的脂质佐剂作用，丙泊酚单一治疗以及与异氟烷联合治疗均诱导了高甘油三酯血症。结论是，在全身麻醉下获得的读数可能既受作为对麻醉反应的生理改变影响，也受药物制剂伴随成分引起的假象影响。
