LIVER DISEASE

Hepatic venous dysregulation contributes to blood volume pooling in cirrhotic rats

Y Li, H Liu, S A Gaskari, D-M McCafferty, S S Lee

Liver Unit, GI Research Group, University of Calgary, Calgary, Canada

Correspondence to:
Dr S S Lee
3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada; samlee{at}ucalgary.ca

Background and aims: In cirrhosis, despite increased total blood volume, the circulation behaves as if it were volume depleted, a phenomenon termed "decreased effective circulating volume". As the gut/liver veins are the major blood reservoir, this suggests hepatosplanchnic venous pooling. We therefore aimed to elucidate the vasoactive responses of the hepatic veins in cirrhosis.

Methods: Cirrhosis was induced by chronic bile duct ligation in rats. The in vivo responses of postsinusoidal venules and sinusoids to vasoactive drugs, 20% haemorrhage, and 20% mannitol (volume expansion) were examined by intravital microscopy. In isolated perfused livers, change in liver weight was measured as an index of the hepatic vascular volume response.

Results: Blood volume was significantly increased in cirrhotic rats. In the cirrhotic hepatic vasculature, constrictive responses to norepinephrine and haemorrhage were blunted compared with controls. In contrast, the dilatory responses to the nitric oxide (NO) donor sodium nitroprusside and volume expansion were enhanced. Both constrictive and dilatory abnormalities were reversed by the NO synthase inhibitor N-nitro-L-arginine methyl ester.

Conclusions: The hepatic sinusoidal and venous bed of cirrhotic rats showed an enhanced dilatory capacity to buffer volume increases but inadequately constricted in response to volume depletion or catecholamines. Both abnormalities may contribute to volume pooling and are mediated by NO.

Abbreviations: BDL, bile duct ligated; L-NAME, N-nitro-L-arginine methyl ester; NE, norepinephrine; NO, nitric oxide; NOS, nitric oxide synthase; SNP, sodium nitroprusside; PCV, packed cell volume; IVC, inferior vena cava

Keywords: cirrhosis; nitric oxide; sinusoid; postsinusoidal venule; intravital microscopy

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