Systemic hypotension and decreased pressor response in dogs with chronic bile duct ligation
Article first published online: 7 DEC 2005
Copyright © 1986 American Association for the Study of Liver Diseases
Volume 6, Issue 4, pages 595–600, July/August 1986
How to Cite
Bomzon, A., Rosenberg, M., Gali, D., Binah, O., Mordechovitz, D., Better, O. S., Greig, P. D. and Blendis, L. M. (1986), Systemic hypotension and decreased pressor response in dogs with chronic bile duct ligation. Hepatology, 6: 595–600. doi: 10.1002/hep.1840060408
- Issue published online: 7 DEC 2005
- Article first published online: 7 DEC 2005
- Manuscript Accepted: 20 FEB 1986
- Manuscript Received: 3 OCT 1984
- Binational German Science Foundation in cooperation
- National Council for Research and Development, Israel
- H. K. Detweiler Travel Fellowship of the Royal College of Physicians
- Surgeons of Canada
- Stanley Vineberg Fellowship of the Technion Faculty of Medicine, Israel
Vascular instability as defined by systemic hypotension and unresponsiveness to endogenous or exogenous vasoactive substances is a feature of both patients and experimental animals with obstructive jaundice. In this study, we have attempted to dissect the possible mechanisms for these abnormalities using both in vivo and in vitro methods. In vivo cumulative pressor responses (Rmax) to intravenous and intraarterial infusions of norepinephrine and angiotensin II and to intravenous infusion of angiotensin I were studied pre- and postoperatively in chronic bile duct-ligated dogs and compared to sham-operated dogs. Preoperatively, the pressor responses to the cumulative infusion of six doses of vasoactive substances in the pre-sham operated and prechronic bile duct-ligated dogs were not significantly different. Postoperatively, in the sham-operated dogs, there was no significant change in systemic blood pressure at 1 and 3 weeks, and only in isolated instances were significantly different pressor responses found compared to the preoperative result. In chronic bile duct-ligated dogs, the mean systemic blood pressure fell significantly from 117.2 ± 3.1 to 107.2 ± 3.0 mm Hg (p < 0.01) at 1 week and remained significantly lower at 3 weeks [109.7 ± 2.6 mm Hg (p < 0.05)]. The Rmax to intravenous, but not intraarterial norepinephrine, was significantly decreased. In contrast, the Rmax to both intravenous and intraarterial angiotensin II infusions were significantly depressed at both 1 and 3 weeks. Similarly, the response to intravenous angiotensin I was significantly depressed.
Cardiac output rose moderately in two sham-operated dogs from an average of 3.1 to 3.5 liters per min by 3 weeks associated with a decrease of 14.8% in peripheral vascular resistance. In chronic bile duct-ligated dogs, it rose from 2.9 to 3.6 liters per min associated with a 33% drop in peripheral vascular resistance. There was no evidence of a metabolic acidosis or hypovolemia in the chronic bile duct-ligated dogs.
In vitro, using isolated helically cut arterial strips, we found that in chronic bile duct-ligated dogs, the mean cumulative contractile response (Rmax) to the addition of angiotensin II to the organ bath (1,571 ± 695 mg) was significantly lower than that from sham-operated controls (3,683 ± 380 mg). In contrast with norepinephrine, there was no significant difference between arterial strips from chronic bile duct-ligated and sham-operated dogs, thus confirming the in vivo results.
In conclusion, the reduced pressor responsiveness to vasoactive substances in this animal model of chronic liver disease is associated with evidence of systemic vasodilation and appears to be multifactorial in origin. With angiotensin II, there is a peripheral and possibly a central defect, whereas with norepinephrine it appears to be a central or cardiopulmonary effect. A better understanding of the mechanism of these changes may help in the management of circulatory abnormalities in patients with obstructive jaundice.