Francis Roland C E, Höhne Claudia, Klein Adrian, Donaubauer Bernd, Kaisers Udo, Boemke Willehad
Department of Anesthesiology and Surgical Intensive Care Medicine, Experimental Anesthesia, Charité--Universitätsmedizin Berlin, Campus Virchow-Klinikum, Germany.
Exp Biol Med (Maywood). 2006 Jun;231(6):834-9.
The objective of this study was to investigate whether circulatory and hormonal changes during xenon plus remifentanil or isoflurane plus remifentanil anesthesia are altered by endothelin-A (ET(A)) receptor blockade. Eight beagle dogs were studied in four protocols (n = 7 each). After a 30-min awake period, anesthesia was induced with 8 mg/kg propofol, administered intravenously (iv), and maintained with either 0.8% +/- 0.01% (vol/vol) isoflurane plus 0.5 microg/kg/min remifentanil (Protocol 1) or 63% +/- 1% (vol/vol) xenon plus 0.5 microg/kg/min remifentanil (Protocol 2) for 1 hr. Protocols 3 and 4 were preceded by ET(A) blockade with ABT-627 (Atrasentan; iv bolus of 1 mg/kg, then 100 microg/kg/h continuously). Irrespective of Atrasentan administration, the mean arterial blood pressure (MAP) ranged between 92 and 96 mm Hg in the awake state and fell to 67 +/- 3 mm Hg in controls (mean +/- SEM) and to 64 +/- 2 mm Hg in the Atrasentan group during isoflurane plus remifentanil anesthesia, whereas MAP remained constant during xenon plus remifentanil anesthesia. A decrease in heart rate was observed during either kind of anesthesia, but bradycardia was most prominent during xenon plus remifentanil anesthesia. In the control groups, and in the Atrasentan-treated dogs, a decrease in cardiac output and an increase in systemic vascular resistance were more prominent during xenon plus remifentanil than during isoflurane plus remifentanil anesthesia. Hormonal alterations during anesthesia remained unaffected by ET(A) receptor blockade. Angiotensin II and vasopressin increased in all protocols, and adrenaline and noradrenaline concentrations rose only during xenon plus remifentanil anesthesia. We conclude that the hemodynamic and hormonal adaptation after xenon plus remifentanil and isoflurane plus remifentanil anesthesia does not depend on the endothelin system, because it is unaffected by ET(A) receptor inhibition. Therefore, the use of Atrasentan does not impair cardiovascular stability during xenon- or isoflurane-based anesthesia in our dog model. However, the way anesthesia is performed is of crucial importance for hemodynamic and hormonal reactions observed during research in animals because the release of vasopressin and catecholamines may be intensified by xenon plus remifentanil anesthesia.
本研究的目的是调查内皮素-A（ET(A)）受体阻断是否会改变氙气加瑞芬太尼或异氟烷加瑞芬太尼麻醉期间的循环和激素变化。八只比格犬按四种方案进行研究（每种方案n = 7）。在30分钟的清醒期后，静脉注射8mg/kg丙泊酚诱导麻醉，然后用0.8%±0.01%（体积/体积）异氟烷加0.5μg/kg/min瑞芬太尼（方案1）或63%±1%（体积/体积）氙气加0.5μg/kg/min瑞芬太尼（方案2）维持麻醉1小时。方案3和4在使用ABT-627（阿曲生坦；静脉推注1mg/kg，然后持续静脉输注100μg/kg/h）进行ET(A)阻断后进行。无论是否给予阿曲生坦，清醒状态下平均动脉血压（MAP）在92至96mmHg之间，在异氟烷加瑞芬太尼麻醉期间，对照组MAP降至67±3mmHg，阿曲生坦组降至64±2mmHg，而在氙气加瑞芬太尼麻醉期间MAP保持恒定。两种麻醉期间均观察到心率下降，但在氙气加瑞芬太尼麻醉期间心动过缓最为明显。在对照组和接受阿曲生坦治疗的犬中，与异氟烷加瑞芬太尼麻醉相比，氙气加瑞芬太尼麻醉期间心输出量下降和全身血管阻力增加更为明显。麻醉期间的激素变化不受ET(A)受体阻断的影响。所有方案中血管紧张素II和血管加压素均升高，仅在氙气加瑞芬太尼麻醉期间肾上腺素和去甲肾上腺素浓度升高。我们得出结论，氙气加瑞芬太尼和异氟烷加瑞芬太尼麻醉后的血流动力学和激素适应性不依赖于内皮素系统，因为它不受ET(A)受体抑制的影响。因此，在我们的犬模型中，使用阿曲生坦不会损害基于氙气或异氟烷的麻醉期间的心血管稳定性。然而，麻醉实施方式对于动物研究中观察到的血流动力学和激素反应至关重要，因为氙气加瑞芬太尼麻醉可能会加剧血管加压素和儿茶酚胺的释放。
