F. Schneider et al., IN-VIVO EVIDENCE OF ENHANCED GUANYLYL CYCLASE ACTIVATION DURING THE HYPERDYNAMIC CIRCULATION OF ACUTE LIVER-FAILURE, Hepatology, 19(1), 1994, pp. 38-44
Nitric oxide and atrial natriuretic peptides are the main activators o
f guanylyl cyclases, which transform GTP into cyclic GMP and thereby c
ontribute to the decrease of vascular tone. To investigate the increas
e, if any, of plasma cyclic GMP concentrations in human patients with
hyperdynamic circulation resulting from acute liver failure and to asc
ertain 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 live
r transplantation and in normokinetic patients undergoing abdominal no
nseptic surgery. We also compared these data with those recorded in pa
tients with hyperkinetic shock resulting from gram-negative sepsis or
nitric oxide-independent vasomotor agent (carbamate) overdose. In all
these patients we simultaneously studied kidney function, platelet cou
nts and atrial natriuretic peptides. Patients with fulminant liver fai
lure had higher cyclic GMP concentrations than did control patients un
dergoing abdominal surgery (11.02 +/- 1.55 pmol . ml-1 vs. 1.77 +/- 0.
18 pmol . ml-1 p < 0.00 1). 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 f
ailure period to the posttransplantation period, although atrial natri
uretic peptide levels did not change significantly and kidney function
worsened. During the period of fulminant liver failure, cyclic GMP le
vels correlated with the decline in peripheral resistance but not with
other hemodynamic or biological data. With the improvement of periphe
ral resistance after the transplantation procedure, they did not furth
er correlate with systemic vascular resistance, only with creatininemi
a. Together these results suggest that guanylyl cyclase activation is
involved in the low vascular resistance observed during acute hepatoce
llular syndrome; furthermore, they indicate that particulate guanylyl
cyclase activation only partially explains the increase in cyclic GMP
observed during fulminant liver failure and put forward a role for sol
uble guanylyl cyclase activators such as nitric oxide.