Influence of somatostatin and octreotide on liver microcirculation in an experimental mouse model of cirrhosis studied by intravital fluorescence microscopy.
OBJECTIVE
Chronic liver damage causes hepatic stellate cell (HSC) activation and contraction, leading to intrahepatic microvascular and structural changes. In vitro endothelin-1 (ET-1)-induced contraction of HSCs can be reduced by somatostatin (SST); however, intrahepatic in vivo effects have never been studied.


METHODS
Sinusoidal diameter was measured by intravital fluorescence microscopy in carbon tetrachloride (CCl(4)) and control mice before and after an intravenous (IV) bolus and after 0, 5, 10 and 15 min of an IV infusion of saline, 8 microg/kg/h SST or 8 microg/kg/h octreotide.


RESULTS
The baseline sinusoidal diameter in CCl(4) mice (3.01+/-0.05 microm) was significantly smaller than that in controls (4.37+/-0.06 microm). The sinusoidal diameter increased significantly in both groups after a bolus (27, 16% respectively) and following 5 min of SST IV infusion (28, 14% respectively). The percentage increase was significantly higher in CCl(4) mice as compared with controls. This dilatory effect continued for at least 15 min. SST did not influence the mean arterial blood pressure (MAP) and portal venous inflow. In none of the groups did octreotide or saline have any influence on sinusoidal diameters, MAP and portal venous inflow.


CONCLUSIONS
Sinusoidal diameter in cirrhotic mice is significantly smaller than that in controls. SST causes significant sinusoidal dilation following a bolus and for at least 15 min of IV infusion. Octreotide does not have any influence on liver sinusoids. These results demonstrate for the first time the in vivo dilatory effect of SST on liver sinusoids.
Vanheule
Eline
E
Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium. eline.vanheule@UGent.be
Geerts
Anja M
AM
Reynaert
Hendrik
H
Van Vlierberghe
Hans
H
Geerts
Albert
A
De Vos
Martine
M
Colle
Isabelle
I
D000818:Animals; D008099:Liver / Q000098:blood supply* / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000188:drug therapy*; D051379:Mice; D008833:Microcirculation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D015282:Octreotide / Q000494:pharmacology* / Q000627:therapeutic use; D013004:Somatostatin / Q000494:pharmacology* / Q000627:therapeutic use
D013004:Somatostatin; D015282:Octreotide