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

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.

Get full access to this article

View all access options for this article.

References

Colson P, Ryckwaert F, Coriat P. Renin angiotensin system antagonists and anesthesia. Anesth Analg 89:1143–1155, 1999.

Ryckwaert F, Colson P. Hemodynamic effects of anesthesia in patients with ischemic heart failure chronically treated with angiotensin-converting enzyme inhibitors. Anesth Analg 84:945–949, 1997.

Pagel PS, Farber NE, Warltier DC. Cardiovascular Pharmacology. In: Miller RD, Ed. Anesthesia (5th ed.) New York: Churchill Livingstone, Vol 1:pp96–124, 2000.

Morelli A, Tritapepe L, Rocco M, Conti G, Orecchioni A, De Gaetano A, Picchini U, Pelaia P, Reale C, Pietropaoli P. Terlipressin versus norepinephrine to counteract anesthesia-induced hypotension in patients treated with renin-angiotensin system inhibitors: effects on systemic and regional hemodynamics. Anesthesiology 102:12–19, 2005.

Channick RN, Sitbon O, Barst RJ, Manes A, Rubin LJ. Endothelin receptor antagonists in pulmonary arterial hypertension. J Am Coll Cardiol 43(12 Suppl S):62S–67S, 2004.

Cotter G, Kaluski E, Stangl K, Pacher R, Richter C, Milo-Cotter O, Perchenet L, Kobrin I, Kaplan S, Rainisio M, Frey A, Neuhart E, Vered Z, Dingemanse J, Torre-Amione G. The hemodynamic and neuro-hormonal effects of low doses of tezosentan (an endothelin A/B receptor antagonist) in patients with acute heart failure. Eur J Heart Fail 6:601–609, 2004.

Teerlink JR, McMurray JJ, Bourge RC, Cleland JG, Cotter G, Jondeau G, Krum H, Metra M, O’Connor CM, Parker JD, Torre-Amione G, Van Veldhuisen DJ, Frey A, Rainisio M, Kobrin I. Tezosentan in patients with acute heart failure: design of the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Study (VERITAS). Am Heart J 150:46–53, 2005.

Lynch C 3rd, Baum J, Tenbrinck R. Xenon anesthesia. Anesthesiology 92:865–868, 2000.

Rossaint R, Reyle-Hahn M, Schulte Am Esch J, Scholz J, Scherpereel P, Vallet B, Giunta F, Del Turco M, Erdmann W, Tenbrinck R, Hammerle AF, Nagele P. Multicenter randomized comparison of the efficacy and safety of xenon and isoflurane in patients undergoing elective surgery. Anesthesiology 98:6–13, 2003.

10.

Hettrick DA, Pagel PS, Kersten JR, Tessmer JP, Bosnjak ZJ, Georgieff M, Warltier DC. Cardiovascular effects of xenon in isoflurane-anesthetized dogs with dilated cardiomyopathy. Anesthesiology 89: 1166–1173, 1998.

11.

Marx T, Froeba G, Wagner D, Baeder S, Goertz A, Georgieff M. Effects on haemodynamics and catecholamine release of xenon anaesthesia compared with total i.v. anaesthesia in the pig. Br J Anaesth 78:326–327, 1997.

12.

Luttropp HH, Romner B, Perhag L, Eskilsson J, Fredriksen S, Werner O. Left ventricular performance and cerebral haemodynamics during xenon anaesthesia. A transoesophageal echocardiography and trans-cranial Doppler sonography study. Anaesthesia 48:1045–1049, 1993.

13.

Ishiguro Y. Cardiovascular effects of xenon. Int Anesthesiol Clin 39: 77–84, 2001.

14.

Committee on Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. Washington, DC: Institute of Laboratory Animal Resources. National Research Council, Department of Health and Human Services. National Academy of Sciences, 1996.

15.

Francis RC, Höhne C, Kaczmarczyk G, Boemke W. Effect of angiotensin II and endothelin-1 receptor blockade on the haemodynamic and hormonal changes after acute blood loss and after retransfusion in conscious dogs. Acta Physiol Scand 180:319–328, 2004.

16.

Schaffer JP. Modified sequentially rejective multiple test procedures. J Am Statist Assoc 81:826–831, 1986.

17.

Spieker LE, Mitrovic V, Noll G, Pacher R, Schulze MR, Muntwyler J, Schalcher C, Kiowski W, Lüscher TF. Acute hemodynamic and neurohumoral effects of selective ET_A receptor blockade in patients with congestive heart failure. J Am Coll Cardiol 35:1745–1752, 2000.

18.

Opgenorth TJ, Wessale JL, Dixon DB, Adler AL, Calzadilla SV, Padl RJ, Wu-Wong JR. Effects of endothelin receptor antagonists on the plasma immunoreactive endothelin-1 level. J Cardiovasc Pharmacol 36(5 Suppl 1):292–296, 2000.

19.

Davis JO, Freeman RH. Mechanisms regulating renin release. Phys Rev 56:1–56, 1976.

20.

Kienbaum P, Heuter T, Michel MC, Peters J. Racemic ketamine decreases muscle sympathetic activity but maintains the neural response to hypotensive challenges in humans. Anesthesiology 92:94–101, 2000.

21.

Hüneke R, Fassl J, Rossaint R, Luckhoff A. Effects of volatile anesthetics on cardiac ion channels. Acta Anaesthesiol Scand 48:547–561, 2004.

22.

Gruss M, Bushell TJ, Bright DP, Lieb WR, Mathie A, Franks NP. Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Mol Pharmacol 65:443–452, 2004.

23.

de Sousa SL, Dickinson R, Lieb WR, Franks NP. Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon. Anesthesiology 92:1055–1066, 2000.