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Systemic and splanchnic haemodynamic effects of sildenafil in an in vivo animal model of cirrhosis support for a risk in cirrhotic patients

Isabelle Colle (UGent) , An De Vriese (UGent) , Hans Van Vlierberghe (UGent) , Norbert Lameire (UGent) and Martine De Vos (UGent)
(2004) LIVER INTERNATIONAL. 24(1). p.63-68
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Abstract
Objectives: 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. Conclusion: 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.
Keywords
cirrhosis, sildenafil, portal hypertension, splanchnic, haemodynamic, PORTAL HYPERTENSIVE-RATS, ISOLATED AORTIC RINGS, NITRIC-OXIDE, HYPERPOLARIZING FACTOR, ERECTILE DYSFUNCTION, LIVER-CIRRHOSIS, ENDOTHELIUM, RELAXATION, MEN, RESPONSES

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Chicago
Colle, Isabelle, An De Vriese, Hans Van Vlierberghe, Norbert Lameire, and Martine De Vos. 2004. “Systemic and Splanchnic Haemodynamic Effects of Sildenafil in an in Vivo Animal Model of Cirrhosis Support for a Risk in Cirrhotic Patients.” Liver International 24 (1): 63–68.
APA
Colle, Isabelle, De Vriese, A., Van Vlierberghe, H., Lameire, N., & De Vos, M. (2004). Systemic and splanchnic haemodynamic effects of sildenafil in an in vivo animal model of cirrhosis support for a risk in cirrhotic patients. LIVER INTERNATIONAL, 24(1), 63–68.
Vancouver
1.
Colle I, De Vriese A, Van Vlierberghe H, Lameire N, De Vos M. Systemic and splanchnic haemodynamic effects of sildenafil in an in vivo animal model of cirrhosis support for a risk in cirrhotic patients. LIVER INTERNATIONAL. 2004;24(1):63–8.
MLA
Colle, Isabelle, An De Vriese, Hans Van Vlierberghe, et al. “Systemic and Splanchnic Haemodynamic Effects of Sildenafil in an in Vivo Animal Model of Cirrhosis Support for a Risk in Cirrhotic Patients.” LIVER INTERNATIONAL 24.1 (2004): 63–68. Print.
@article{348849,
  abstract     = {Objectives: 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.
Conclusion: 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.},
  author       = {Colle, Isabelle and De Vriese, An and Van Vlierberghe, Hans and Lameire, Norbert and De Vos, Martine},
  issn         = {1478-3231},
  journal      = {LIVER INTERNATIONAL},
  keywords     = {cirrhosis,sildenafil,portal hypertension,splanchnic,haemodynamic,PORTAL HYPERTENSIVE-RATS,ISOLATED AORTIC RINGS,NITRIC-OXIDE,HYPERPOLARIZING FACTOR,ERECTILE DYSFUNCTION,LIVER-CIRRHOSIS,ENDOTHELIUM,RELAXATION,MEN,RESPONSES},
  language     = {eng},
  number       = {1},
  pages        = {63--68},
  title        = {Systemic and splanchnic haemodynamic effects of sildenafil in an in vivo animal model of cirrhosis support for a risk in cirrhotic patients},
  url          = {http://dx.doi.org/10.1111/j.1478-3231.2004.00892.x},
  volume       = {24},
  year         = {2004},
}

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