In vivo evidence of enhanced guanylyl cyclase activation during the hyperdynamic circulation of acute liver failure.
Nitric oxide and atrial natriuretic peptides are the main activators of guanylyl cyclases, which transform GTP into cyclic GMP and thereby contribute to the decrease of vascular tone. To investigate the increase, if any, of plasma cyclic GMP concentrations in human patients with hyperdynamic circulation resulting from acute liver failure and to ascertain whether guanylyl cyclase activation is involved in the decline of systemic vascular resistance that occurs in this pathophysiological condition, we simultaneously recorded hemodynamic data and cyclic GMP levels in patients with fulminant liver failure before and after liver transplantation and in normokinetic patients undergoing abdominal nonseptic surgery. We also compared these data with those recorded in patients with hyperkinetic shock resulting from gram-negative sepsis or nitric oxide-independent vasomotor agent (carbamate) over-dose. In all these patients we simultaneously studied kidney function, platelet counts and atrial natriuretic peptides. Patients with fulminant liver failure had higher cyclic GMP concentrations than did control patients undergoing abdominal surgery (11.02 +/- 1.55 pmol.ml-1 vs. 1.77 +/- 0.18 pmol.ml-1, p < 0.001). At similar heart-loading conditions these concentrations were lower than those in gram-negative septic shock (18.2 +/- 1.35 pmol.ml-1, p < 0.05) but higher than those in carbamate-induced shock (3.6 +/- 0.7 pmol.ml-1, p < 0.01). In addition, cyclic GMP concentrations significantly decreased from the fulminant liver failure period to the posttransplantation period, although atrial natriuretic peptide levels did not change significantly and kidney function worsened.(ABSTRACT TRUNCATED AT 250 WORDS)
Schneider
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F
Service de Réanimation Médicale, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, France.
Lutun
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P
Boudjema
K
K
Wolf
P
P
Tempé
J D
JD
D000293:Adolescent; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000097:blood; D001775:Blood Circulation; D002219:Carbamates / Q000009:adverse effects; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism*; D006439:Hemodynamics; D006501:Hepatic Encephalopathy / Q000097:blood / Q000201:enzymology / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D017114:Liver Failure, Acute / Q000097:blood / Q000201:enzymology / Q000503:physiopathology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011446:Prospective Studies; D012769:Shock / Q000139:chemically induced; D012772:Shock, Septic / Q000201:enzymology / Q000503:physiopathology; D014655:Vascular Resistance
D002219:Carbamates; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D006152:Cyclic GMP