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J Hepatol. 2016 Apr;64(4):834-42. doi: 10.1016/j.jhep.2015.12.003. Epub 2015 Dec 11.

Enoxaparin reduces hepatic vascular resistance and portal pressure in cirrhotic rats.

Author information

1
Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Barcelona, Spain.
2
Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
3
Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
4
Centro de Investigación Médica Aplicada (CIMA), Division of Hepatology and Gene Therapy, Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
5
Hemotherapy and Hemostasis Department, Hospital Clínic, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
6
Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. Electronic address: jcgarcia@clinic.cat.

Abstract

BACKGROUND & AIMS:

Increased hepatic vascular resistance due to fibrosis and elevated hepatic vascular tone is the primary factor in the development of portal hypertension. Heparin may decrease fibrosis by inhibiting intrahepatic microthrombosis and thrombin-mediated hepatic stellate cell activation. In addition, heparin enhances eNOS activity, which may reduce hepatic vascular tone. Our study aimed at evaluating the effects of acute, short-, long-term and preventive enoxaparin administration on hepatic and systemic hemodynamics, liver fibrosis and nitric oxide availability in cirrhotic rats.

METHODS:

Enoxaparin (1.8 mg/kg subcutaneously), or its vehicle, was administered to CCl4-cirrhotic rats 24h and 1h before the study (acute), daily for 1 week (short-term) or daily for 3 weeks (long-term) and to thioacetamide-cirrhotic rats daily for 3 weeks with/without thioacetamide (preventive/long-term, respectively). Mean arterial pressure, portal pressure, portal blood flow, hepatic vascular resistance and molecular/cellular mechanisms were evaluated.

RESULTS:

No significant changes in hemodynamic parameters were observed in acute administration. However, one-week, three-week and preventive treatments significantly decreased portal pressure mainly due to a decrease in hepatic vascular resistance without significant changes in mean arterial pressure. These findings were associated with significant reductions in liver fibrosis, hepatic stellate cell activation, and desmin expression. Moreover, a reduction in fibrin deposition was observed in enoxaparin-treated rats, suggesting reduced intrahepatic microthrombosis.

CONCLUSION:

Enoxaparin reduces portal pressure in cirrhotic rats by improving the structural component of increased liver resistance. These findings describe the potentially beneficial effects of enoxaparin beyond the treatment/prevention of portal vein thrombosis in cirrhosis, which deserve further investigation.

KEYWORDS:

Anticoagulation; Cirrhosis; Hepatic stellate cells; Low molecular weight heparin; Portal hypertension

PMID:
26686269
DOI:
10.1016/j.jhep.2015.12.003
[Indexed for MEDLINE]

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