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Effects of the V1a vasopressin agonist F‐180 on portal hypertension‐related bleeding in portal hypertensive rats
Author(s) -
Morales Josephine,
Moitinho Eduardo,
Abraldes Juan G.,
Fernández Mercedes,
Bosch Jaime
Publication year - 2003
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1016/j.hep.2003.09.023
Subject(s) - medicine , portal hypertension , vasopressin , terlipressin , placebo , shock (circulatory) , portal venous pressure , blood pressure , anesthesia , vein , agonist , hemodynamics , cardiology , receptor , cirrhosis , pathology , hepatorenal syndrome , alternative medicine
F‐180 is a new, long‐acting analog of vasopressin with a selective agonist effect on the vascular V1a receptors, with the advantage of having no effect on renal V2 receptors. F‐180 is approximately 20 times more powerful than terlipressin in reducing portal pressure and has less marked systemic effects. The present study investigated the effects of F‐180 on the outcome of portal hypertension‐related bleeding in hypovolemic rats. Partial portal vein‐ligated rats were subjected to portal hypertension‐related bleeding by sectioning a first‐order branch of the ileocolic vein. After hemodynamic stabilization, a second sectioning of the first‐order branch of the ileocolic vein section was performed in the already hypovolemic animals, and either F‐180 or placebo was administered. Blood transfusion was adjusted to maintain mean arterial pressure (MAP) γ > 80 mm Hg. The first section of a first‐order branch of the ileocolic vein induced a hemorrhage of similar severity in both groups of rats. After a 2nd sectioning of a first‐order branch of the ileocolic vein section, F‐180 was more effective than placebo in recovering shock (MAP, 21% ± 23% vs. 0% ± 13% in placebo; P < .05), preventing portal pressure (PP) increase during blood transfusion (PP: −1% ± 19% vs. 47% ± 65% in placebo; P = .07), reducing transfusion requirements (2.9 ± 3.3 mL vs. 11.2 ± 6.0 mL in placebo; P < .01), diminishing the magnitude of collected blood losses (5.1 ± 2.2 g vs. 12.7 ±7.7 g in placebo; P < .05), and decreasing the mortality from the portal hypertension‐related bleeding (10% vs. 60% in placebo; P < .05). In conclusion, in hypovolemic portal‐hypertensive rats during a portal hypertension‐related bleeding, F‐180 rapidly recovers arterial pressure and decreases transfusion requirements, blood losses, and mortality.