Hemodynamic Effects of Glucagon in Portal Hypertension

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Abstract
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.