PULMONARY CIRCULATORY DYSFUNCTION IN RATS WITH BILIARY-CIRRHOSIS - AN ANIMAL-MODEL OF THE HEPATOPULMONARY SYNDROME

We studied hypoxic pulmonary vasoconstriction (HPV) and pulmonary gas exchange in unanesthetized rats with biliary cirrhosis induced by chronic bile duct ligation (BDL) (5 to 6 wk) and compared pulmonary vascular reactivity in perfused lungs isolated from BDL and control rats. Awake, catheter-implanted, cirrhotic rats exhibited increased cardiac output, normal systemic and pulmonary arterial pressures, and decreased total systemic (TSR) and pulmonary (TPR) vascular resistances in comparison with those in sham-operated control rats. HPV was markedly depressed in cirrhotic rats (percent increase in TPR while breathing 8% O2: 42.3 +/- 13.7% in control and 0.9 +/- 3.6% in cirrhotic rats, p < 0.05), and this was associated with an increased AaPo2 (control rats, 15.7 +/- 1.1 mm Hg; cirrhotic rats, 23.1 +/- 1.9 mm Hg; p < 0.05). In contrast, the pulmonary pressor response to angiotensin II was intact, and the depression of HPV in cirrhotic rats was amellorated after anglotensin II infusion. These changes in cirrhotic rats were not due to the accompanying cholestasis since noncirrhotic rats with severe cholestasis had intact HPV and normal AaPo2. Lungs isolated from cirrhotic rats and perfused with blood from normal rats exhibited two patterns of response to hypoxia. In one group, HPV was blunted compared with that in control rats (change in pulmonary arterial perfusion pressure after 3% O2: control rats, 23.2 +/- 2.8 mm Hg; cirrhotic rats, 4.8 +/- 1.4 mm Hg; p < 0.01). Similar to the result in intact rat, angiotensin-II-induced vasoconstriction was preserved in lungs from cirrhotic rats, and HPV increased significantly after angiotensin II infusion (to 17.3 +/- 4.8 mm Hg). In the second group, baseline pulmonary arterial pressure progressively increased during normoxia, and this increase was attenuated by hypoxic ventilation (hypoxic vasodilation). We conclude that liver cirrhosis induces reversible depression of HPV and suggest that rats with chronic BDL provide a suitable animal model for studying the pulmonary circulatory alterations in the hepatopulmonary syndrome.