Hemodynamic effects of acute and chronic administration of vapreotide in rats with cirrhosis.
The aim of this study was to assess the hemodynamic effects of acute and chronic administration of vapreotide, a somatostatin analog, in rats with intrahepatic portal hypertension induced by dimethylnitrosamine (DMNA) administration. Acute effects were evaluated at baseline and 30 min after placebo (N = 13) or vapreotide (8 /microg/kg/hr, N = 13) infusions in DMNA rats. Chronic hemodynamic effects were evaluated using subcutaneous implants for five weeks in anesthetized DMNA rats (placebo: N = 13, vapreotide: N = 13) and in sham rats (placebo: N = 10, vapreotide: N = 10). Hemodynamic measurements included splenorenal shunt blood flow (SRS BF) by the transit time ultrasound (TTU) method and cardiac output by the combined dilution-TTU method. Acute administration of vapreotide significantly decreased SRS BF (-17.3 +/- 19 vs - 1.1 +/- 14%, P < 0.05) and portal pressure (-8 +/- 9 vs 0 +/- 8%, p < 0.05) compared to placebo without systemic effects. Chronic administration of vapreotide significantly reduced the increase in SRS BF (2.4 +/- 1.5 vs 1.2 +/- 1.0 ml/min, P < 0.05) and cardiac index (50 +/- 15 vs 33 +/- 10 ml/min/100 g, P < 0.0001) while portal pressure and blood flow, and mean arterial pressure were not significantly changed compared to placebo. In conclusion, the acute administration of vapreotide decreased collateral circulation blood flow while chronic administration attenuated its development. Vapreotide seems to have a vasoconstrictive effect on collateral circulation.
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Nary
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Laboratoire HIFIH, UPRES EA 2170, Université d'Angers, France.
Moal
Frédéric
F
Oberti
Frédéric
F
Vuillemin
Eric
E
Calés
Paul
P
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000700:Analgesics; C051458:vapreotide; D013004:Somatostatin