HEMODYNAMIC-EFFECTS OF GLUCAGON IN PORTAL-HYPERTENSION

It has been suggested that glucagon contributes to the pathogenesis of portal hypertension by increasing portal blood flow. This study examined this issue by assessing the hemodynamic effects of a pharmacological dose of glucagon (1 mg, intravenously) in patients with cirrhosis and portal hypertension (n = 10) and in subjects without significant liver disease (controls = n = 5). Patients with cirrhosis had much higher glucagon levels than control subjects (875 ± 167 vs. 186 ± 25 pg/ml, p < 0.01) and showed blunted hemodynamic responses after glucagon administration. This occurred despite greater circulating glucagon levels, probably because of a significant prolongation of the plasma half‐life of exogenously administered glucagon (4.9 ± 0.4 vs. 2.7 ± 0.1 min, p < 0.1). Control subjects had marked increases in heart rate (+19% ± 4%, p < 0.01), cardiac index (+16% ± 4%, p = 0.01) and arterial pressure (+ 10% ± 3%, p < 0.05), but corresponding changes in patients with cirrhosis (+ 7% ± 1%, +6% ± 1%, and +6% ± 2%, respectively) were significantly less pronounced (p = 0.05), and there was a negative correlation between basal glucagon levels and the response of heart rate to glucagon injection (r = ‐0.804, p < 0.001). Resistance to the systemic effects of glucagon in cirrhosis may thus be caused by a down‐regulation of vascular glucagon receptors. In addition, glucagon adminstration caused a significant increase in portal pressure (from 18.1 ± 1.1 to 19.0 ± 1.2 mm Hg, p < 0.01), as well as in azygos blood flow (from 0.54 ± 0.03 to 0.64 ± 0.04 L/min, +19% ± 4%, p < 0.02), reflecting increased portocollateral blood flow. These findings are consistent with the hypothesis that glucagon is one of the factors contributing to the splanchnic vasodilatation and increased portal pressure of cirrhosis. Copyright © 1990 American Association for the Study of Liver Diseases