Endothelin causes portal and pulmonary hypertension in porcine
endotoxemic shock.
Yamamoto, S., H. P. Burman, C. P. O'donnell, P. A. Cahill, J. L.
Robotham.
Department of Anesthesiology and Critical Care Medicine, The Johns
Hopkins Medical Institutions, Baltimore, MD 21287 and Department of
Surgery, Georgetown University Medical Center, Washington, DC
20007
APStracts 3:0376H, 1996.
A porcine model of endotoxemic shock was used to test the hypothesis
that endothelins (ET) mediate the sustained increases in portal and
pulmonary vascular resistances. Anesthetized pigs (N=18) were
instrumented and pretreated with: 1) saline as a control; 2)
indomethacin (IDM), a cyclooxygenase (COX) inhibitor; or 3)
IDM+bosentan (BOS), a mixed ET receptor antagonist; and then were
treated with endotoxin to produce shock and followed for 240 min.
Global and regional hemodynamic parameters, and plasma levels of ET-1
and thromboxane B2 (TxB2), were measured. The results show that: 1)
ET is independently responsible for the sustained increase in
pulmonary vascular resistance; 2) ET and COX products combine to
increase portal venous resistance; 3) ET independently reduces
cardiac output and attenuates or negates global systemic arterial
vasodilation (presumptively mediated by nitric oxide) while
exhibiting regional differences, having little if any influence on
the gut arterial bed. When considered with our prior study of nitric
oxide regulation of the same beds in endotoxemic shock (J Appl
Physiol 78: 1319-1329, 1995), the similarities between the portal
venous and pulmonary arterial beds suggest that these two beds
reflect phenomena occurring in microvascular/venous beds in multiple
organs. The overall results suggest a dynamic balance exists between
NO and ET regulating arterial and microvascular/venous vasomotor
activity during the evolution of endotoxemic shock.
Received 26 April 1996; accepted in final form 8 August 1996.
APS Manuscript Number H369-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996