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 less than 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 less than 0.1). Control subjects had marked increases in heart rate (+ 19% +/- 4%, p less than 0.01), cardiac index (+ 16% +/- 4%, p = 0.01) and arterial pressure (+ 10% +/- 3%, p less than 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 less than 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 administration caused a significant increase in portal pressure (from 18.1 +/- 1.1 to 19.0 +/- 1.2 mm Hg, p less than 0.01), as well as in azygos blood flow (from 0.54 +/- 0.03 to 0.64 +/- 0.04 L/min, + 19% +/- 4%, p less than 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.
Silva
G
G
Hepatic Hemodynamics Laboratory, Hospital Clínic i Provincial, University of Barcelona, Spain.
Navasa
M
M
Bosch
J
J
Chesta
J
J
Pilar Pizcueta
M
M
Casamitjana
R
R
Rivera
F
F
Rodés
J
J
D001401:Azygos Vein / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D005934:Glucagon / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D006503:Hepatic Veins / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D006975:Hypertension, Portal / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014690:Venous Pressure / Q000187:drug effects
D005934:Glucagon