Haemodynamic and hormonal changes during haemorrhage in conscious dogs treated with an endothelin-A receptor antagonist.

This study compares the haemodynamic and hormonal responses during haemorrhage of conscious dogs pre-treated with an endothelin-A (ET-A) receptor inhibitor. The dogs were studied in two different randomized groups: the control group and a group that was given the ET-A receptor antagonist ABT-627 (as a bolus of 1 mg x kg of body weight(-1) followed by 0.01 mg x kg body weight(-1) x min(-1) intravenously). The time-course was the same for both groups: after a 1 h baseline period (pre-haemorrhage), blood (25 ml x kg of body weight(-1)) was withdrawn within 5 min. Haemodynamics were continuously recorded and hormone levels measured after 1 h (post-haemorrhage). Thereafter, the blood withdrawn was retransfused within 5 min and haemodynamics again observed for 1 h (post-retransfusion). In ABT-627-treated dogs, the decrease in mean arterial pressure from 87+/-3 to 64+/-3 mmHg (P<0.05 versus pre-haemorrhage), and cardiac output from 2.1+/-0.1 to 1.3+/-0.1 l x min(-1) (P<0.05 versus pre-haemorrhage) and the increase in systemic vascular resistance from 3286+/-174 to 4211+/-230 dyn.s.cm(-5) (P<0.05 versus pre-haemorrhage) during acute haemorrhage are comparable with controls. During haemorrhage in controls, vasopressin levels increased from 0+/-0 to 13+/-2 pg x ml(-1) (P<0.05 versus pre-haemorrhage), angiotensin II levels increased from 9+/-1 to 28+/-9 pg x ml(-1) (P<0.05 versus pre-haemorrhage) and adrenaline levels increased from 134+/-22 to 426+/-74 pg x ml(-1) (P<0.05 versus pre-haemorrhage) whereas noradrenaline levels did not change (approx. 200 pg x ml(-1)). In ABT-627-treated dogs, vasopressin levels increased from 0.2+/-0.0 to 22.2+/-6.1 pg x ml(-1) (P<0.05 versus pre-haemorrhage and P<0.05 versus control), angiotensin II levels increased from 8+/-1 to 37+/-8 pg x ml(-1) (P<0.05 versus pre-haemorrhage), noradrenaline levels increased from 147+/-16 to 405+/-116 pg x ml(-1) (P<0.05 versus pre-haemorrhage) and adrenaline levels did not change (200 pg x ml(-1)) during haemorrhage. We conclude from our results that dogs receiving the selective ET-A inhibitor ABT-627 seem to show a different hormonal response after haemorrhage compared with controls, displaying considerably higher noradrenaline concentrations. Independent of ET-A receptor inhibition, cardiac output during haemorrhage was maintained within the control range. This may indicate that the organism is defending blood flow (cardiac output) over blood pressure during haemorrhage, and that this defence strategy is not compromised by ET-A receptor inhibition.