Abstract
BackgroundFocal hepatic venous outflow obstruction frequently occurs after extended liver resection and leads to a portal hypertension, arterial hypoperfusion and parenchymal necrosis.In this study, we investigated the pharmacological modulation of liver perfusion and hepatic damage in a surgical model of hepatic outflow obstruction after extended liver resection by administration of 5 different drugs in comparison to an operative intervention, splenectomy.MethodsMale inbred Lewis rats (Lew/Crl) were subjected to right median hepatic vein ligation + 70% partial hepatectomy. Treatment consisted of a splenectomy or the application of saline, carvedilol or isosorbide-5-mononitrate (ISMN) (5 mg · kg−1 respectively 7,2 mg · kg−1 per gavage 12 h−1). The splenectomy was performed during operation. The effect of the treatments on hepatic hemodynamics were measured in non-operated animals, immediately after operation (n = 4/group) and 24 h after operation (n = 5/group). Assessment of hepatic damage (liver enzymes, histology) and liver cell proliferation (BrdU-immunohistochemistry) was performed 24 h after operation. Furthermore sildenafil (10 μg · kg−1 i.p. 12h−1), terlipressin (0.05 mg · kg−1 i.v. 12 h−1) and octreotide (10 μg · kg−1 s.c. 12 h−1) were investigated regarding their effect on hepatic hemodynamics and hepatic damage 24 h after operation (n = 4/group).ResultsCarvedilol and ISMN significantly decreased the portal pressure in normal non-operated rats from 11,1 ± 1,1 mmHg (normal rats) to 8,4 ± 0,3 mmHg (carvedilol) respectively 7,4 ± 1,8 mmHg (ISMN). ISMN substantially reduced surgery-induced portal hypertension from 15,4 ± 4,4 mmHg to 9,6 ± 2,3 mmHg. Only splenectomy reduced the portal flow immediately after operation by approximately 25%. No treatment had an immediate effect on the hepatic arterial perfusion. In all treatment groups, portal flow increased by approximately 3-fold within 24 h after operation, whereas hepatic arterial flow decreased substantially. Neither treatment reduced hepatic damage as assessed 24 h after operation. The distribution of proliferating cells appeared very similar in all drug treated groups and the splenectomy group.ConclusionTransient relative reduction of portal pressure did not result in a reduction of hepatic damage. This might be explained by the development of portal hyperperfusion which was accompanied by arterial hypoperfusion.
Highlights
Focal hepatic venous outflow obstruction frequently occurs after extended liver resection and leads to a portal hypertension, arterial hypoperfusion and parenchymal necrosis
The objective for this study was to investigate the modulation of hepatic hemodynamics after an extended hepatic resection by applying five clinically used drugs: We investigated the modulation of portal hemodynamics after an extended hepatic resection by applying the beta-blocker carvedilol, the nitrovasodilator isosorbide-5-mononitrate (ISMN), the vasopressin analogue terlipressin and the long-acting somatostatin analogue octreotide [11,12,13,14]
Hemodynamic measurement MAP remained stable throughout the operation in all animals and was not affected by the liver resection itself
Summary
Focal hepatic venous outflow obstruction frequently occurs after extended liver resection and leads to a portal hypertension, arterial hypoperfusion and parenchymal necrosis. Extended hepatic resection leads to a massive reduction of liver mass by 60 to 70%. The function of the remnant liver is determined by the optimal balance of blood inflow and outflow. The reduction of liver mass leads to an increase of portal venous flow, subsequently to portal hypertension and further to portal hyperperfusion [1, 2]. An extended liver resection with transection of the middle hepatic vein results in a focal hepatic venous outflow obstruction (FHOO). The obstruction leads to the formation of necrosis in the undrained tissue This results in an additional loss of functional liver mass in the remnant liver [4]
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