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Endothelin-A Receptor Blockade Does Not Debilitate the Cardiovascular and Hormonal Adaptation to Xenon or Isoflurane Anesthesia in Dogs

Department of Anesthesiology and Surgical Intensive Care Medicine, Experimental Anesthesia, Charité—Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany

To whom requests for reprints should be addressed at ¹ Klinik für Anästhesiologie und operative Intensivmedizin, AG Experimentelle Anästhesie, Charité—Universitätsme-dizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail: roland.francis{at}charite.de

Abstract

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 µg/kg/min remifentanil (Protocol 1) or 63% ± 1% (vol/vol) xenon plus 0.5 µg/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 µg/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.

Key Words: cardiovascular • Atrasentan • renin-angiotensin system • vasopressin • catecholamines • beagle