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 (ETA) blockade on the haemodynamic and hormonal responses to haemorrhage in dogs anaesthetized with xenon/remifentanil (X/R) or isoflurane/remifentanil (I/R). Study design Prospective experimental randomized controlled study. Animals Six female Beagle dogs, 13.4 ± 1.3 kg. Methods Animals were anaesthetized with remifentanil 0.5 μg 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 cmH2O (I/R, ns) and from 8 ± 1 to 5 ± 1 cmH2O (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 and clinical relevance Selective ETA receptor blockade with atrasentan did not impair the haemodynamic and hormonal compensation of acute haemorrhage during X/R or I/R anaesthesia in dogs.