Endothelin receptor subtype A blockade does not affect the haemodynamic recovery from haemorrhage during xenon/remifentanil or isoflurane/remifentanil anaesthesia in dogs.
OBJECTIVE
To test the compensatory role of endothelin-1 when acute blood loss is superimposed on anaesthesia, by characterizing the effect of systemic endothelin receptor subtype A (ET(A)) blockade on the haemodynamic and hormonal responses to haemorrhage in dogs anaesthetized with xenon/remifentanil (X/R) or isoflurane/remifentanil (I/R).


METHODS
Prospective experimental randomized controlled study.


METHODS
Six female Beagle dogs, 13.4 +/- 1.3 kg.


METHODS
Animals were anaesthetized with remifentanil 0.5 microg kg(-1) minute(-1) plus either 0.8% isoflurane (I/R) or 63% xenon (X/R), with and without (Control) the systemic intravenous endothelin receptor subtype A antagonist atrasentan (four groups, n = 6 each). After 60 minutes of baseline anaesthesia, the dogs were bled (20 mL kg(-1)) over 5 minutes and hypovolemia was maintained for 1 hour. Continuous haemodynamic monitoring was performed via femoral and pulmonary artery catheters; vasoactive hormones were measured before and after haemorrhage.


RESULTS
In Controls, systemic vascular resistance (SVR), vasopressin and catecholamine plasma concentrations were higher with X/R than with I/R anaesthesia at pre-haemorrhage baseline. The peak increase after haemorrhage was higher during X/R than during I/R anaesthesia (SVR 7420 +/- 867 versus 5423 +/- 547 dyne seconds cm(-5); vasopressin 104 +/- 23 versus 44 +/- 6 pg mL(-1); epinephrine 2956 +/- 310 versus 177 +/- 99 pg mL(-1); norepinephrine 862 +/- 117 versus 195 +/- 33 pg mL(-1), p < 0.05). Haemorrhage reduced central venous pressure from 3 +/- 1 to 1 +/- 1 cm H(2)O (I/R, ns) and from 8 +/- 1 to 5 +/- 1 cm H(2)O (X/R, p < 0.05), but did not reduce mean arterial pressure, nor cardiac output. Atrasentan did not alter the haemodynamic and hormonal response to haemorrhage during either anaesthetic protocol.


CONCLUSIONS
Selective ET(A) receptor blockade with atrasentan did not impair the haemodynamic and hormonal compensation of acute haemorrhage during X/R or I/R anaesthesia in dogs.
Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany. roland.francis@charite.de
Roland C E
RC
Francis
Claudia
C
Höhne
Adrian
A
Klein
Udo X
UX
Kaisers
Philipp A
PA
Pickerodt
Willehad
W
Boemke
D000758:Anesthesia / Q000379:methods / Q000662:veterinary*; D000769:Anesthesia, Inhalation / Q000379:methods / Q000662:veterinary; D000771:Anesthesia, Intravenous / Q000379:methods / Q000662:veterinary; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D000818:Animals; D000077868:Atrasentan; D016063:Blood Loss, Surgical / Q000503:physiopathology / Q000662:veterinary; D002395:Catecholamines / Q000097:blood; D004283:Dog Diseases / Q000503:physiopathology*; D004285:Dogs; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006470:Hemorrhage / Q000503:physiopathology / Q000662:veterinary*; D007530:Isoflurane; D009638:Norepinephrine / Q000097:blood; D010880:Piperidines; D011759:Pyrrolidines / Q000494:pharmacology*; D000077208:Remifentanil; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014667:Vasopressins / Q000097:blood; D014978:Xenon
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D002395:Catecholamines; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010880:Piperidines; D011759:Pyrrolidines; D014667:Vasopressins; D014978:Xenon; D007530:Isoflurane; D000077208:Remifentanil; D000077868:Atrasentan; D009638:Norepinephrine; D004837:Epinephrine