Höhne Claudia, Vogler Pia, Frerking Ilka, Francis Roland C E, Swenson Erik R, Kaczmarczyk Gabriele, Boemke Willehad
Clinic of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum, Charité, Humboldt-University of Berlin, Germany.
Anesthesiology. 2004 Apr;100(4):885-93. doi: 10.1097/00000542-200404000-00019.
The objective of this study was to determine whether endothelin-A receptor blockade (ETAB) impairs hemodynamic and hormonal regulation compared with controls and angiotensin II receptor blockade (AT1B) during hypotensive hemorrhage in dogs under isoflurane-nitrous oxide anesthesia.
Six dogs were studied in four protocols: (1) control experiments (controls); (2) ETA blockade using ABT-627 (ETAB); (3) AT1 blockade using losartan (AT1B); and (4) combined AT1B and ETAB (AT1B + ETAB). After a 30-min awake period, isoflurane-nitrous oxide anesthesia was established (1.3 minimum anesthetic concentration). After 60 min of anesthesia, 20 ml blood/kg body weight was withdrawn within 5 min, and the dogs were observed for another hour. Thereafter, the blood was retransfused, and the dogs were observed for a final hour.
Anesthesia: Cardiac output decreased in all protocols, whereas mean arterial pressure decreased more in AT1B and AT1B + ETAB than in controls and ETAB. Hemorrhage: After 60 min, cardiac output had decreased less in controls than in all other protocols. Mean arterial pressure decreased more during ETAB than in controls, but most severely during AT1B and AT1B + ETAB. Angiotensin II increased further only in controls and ETAB, whereas vasopressin and catecholamines increased similarly in all protocols. Retransfusion: Mean arterial pressure remained below controls in all protocols but was lowest when the AT1 receptor was blocked. Cardiac output fully recovered in all but the ETAB protocol.
ETAB impairs long-term hemodynamic regulation after hemorrhage and retransfusion during anesthesia despite an activation of vasoconstrictive hormones. This suggests that endothelins have a role in long-term cardiovascular regulation. AT1B impairs both short- and long-term blood pressure regulation during anesthesia and after hemorrhage.
本研究的目的是确定在异氟烷 - 氧化亚氮麻醉下的犬类低血压性出血过程中，与对照组和血管紧张素 II 受体阻断（AT1B）相比，内皮素 - A 受体阻断（ETAB）是否会损害血流动力学和激素调节。
六只犬按照四个方案进行研究：（1）对照实验（对照组）；（2）使用 ABT - 627 进行 ETA 阻断（ETAB）；（3）使用氯沙坦进行 AT1 阻断（AT1B）；（4）联合 AT1B 和 ETAB（AT1B + ETAB）。在 30 分钟的清醒期后，建立异氟烷 - 氧化亚氮麻醉（1.3 最低麻醉浓度）。麻醉 60 分钟后，在 5 分钟内抽出 20 毫升/千克体重的血液，然后观察犬类 1 小时。此后，进行输血，并再观察犬类 1 小时。
麻醉：在所有方案中的心输出量均下降，而平均动脉压在 AT1B 和 AT1B + ETAB 组中比对照组和 ETAB 组下降得更多。出血：60 分钟后，对照组的心输出量下降幅度小于所有其他方案。平均动脉压在 ETAB 组中比对照组下降得更多，但在 AT1B 和 AT1B + ETAB 组中下降最为严重。仅在对照组和 ETAB 组中血管紧张素 II 进一步升高，而在所有方案中血管加压素和儿茶酚胺的升高情况相似。输血：在所有方案中平均动脉压均低于对照组，但在 AT1 受体被阻断时最低。除 ETAB 方案外，所有方案的心输出量均完全恢复。
尽管血管收缩激素被激活，但 ETAB 在麻醉期间出血和输血后会损害长期血流动力学调节。这表明内皮素在长期心血管调节中起作用。AT1B 在麻醉期间和出血后会损害短期和长期血压调节。
