Systemic and splanchnic haemodynamic effects of sildenafil in an in vivo animal model of cirrhosis support for a risk in cirrhotic patients.
OBJECTIVE
Sildenafil is a selective inhibitor of the cGMP-specific phosphodiesterase type V (PDE-V) in the corpus cavernosum. PDE-V is also present in the mesenteric artery. Cirrhosis is complicated by a splanchnic vasodilation attributed to a local overproduction of nitric oxide (NO). As sildenafil potentiates the effects of NO, it may further decrease mesenteric vascular tone and increase portal venous blood flow. The aim is to evaluate the effects of sildenafil on the systemic and splanchnic haemodynamics in an experimental model of cirrhosis.


METHODS
Secondary biliary cirrhosis was induced in male Wistar rats by common bile duct ligation (CBDL, n=8); control rats were sham-operated (sham, n=7). The mean arterial pressure (MAP), portal venous pressure (PVP) and arterial mesenteric blood flow (MBF) were measured after intramesenteric (0.01-10 mg/kg) and after intravenous (i.v.) (0.01-10 mg/kg) administration of sildenafil.


RESULTS
Baseline PVP was significantly higher in CBDL than in sham rats, whereas baseline MAP tended to be lower and MBF tended to be higher in CBDL compared with sham rats. Both intramesenteric and i.v. injection of sildenafil significantly decreased MAP and increased MBF and PVP in a dose-dependent way. The decrease in MAP was significantly less important in CBDL than in sham rats. The increase in MBF was importantly lower in CBDL than in sham rats. PVP tended to increase more significantly in sham rats than in CBDL.


CONCLUSIONS
Sildenafil increases MBF and PVP and induces systemic hypotension. The effects are less pronounced in cirrhosis, suggesting vascular hyporesponsiveness to sildenafil. Although the rise in PVP in cirrhotic animals is smaller than in controls, it may present a risk for haemorrhagic complications. Further studies are necessary before prescribing sildenafil to patients with cirrhosis.
Colle
Isabelle
I
Department of Medicine, Ghent University Hospital, Ghent, Belgium. Isabelle.Colle@rug.ac.be
De Vriese
An S
AS
Van Vlierberghe
Hans
H
Lameire
Norbert H
NH
DeVos
Martine
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005355:Fibrosis / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006975:Hypertension, Portal / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D017082:Portal Pressure / Q000187:drug effects; D011687:Purines; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013152:Splanchnic Circulation / Q000187:drug effects*; D013450:Sulfones
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate