Hepatic cardiomyopathy, a special type of heart failure develops in up to 50% of patients
with cirrhosis and is a major determinant of survival. However, there is no reliable
model of hepatic cardiomyopathy in mice. Herein we aimed to characterize the detailed
hemodynamics of mice with bile-duct ligation (BDL)-induced liver fibrosis, by monitoring
echocardiography and intracardiac pressure-volume (PV) relationships and myocardial
structural alterations. Treatment of mice with a selective cannabinoid-2 receptor
(CB2 -R) agonist, known to attenuate inflammation and fibrosis, was used to explore
the impact of liver inflammation, fibrosis on cardiac function.BDL induced massive
inflammation (increased leukocyte infiltration, inflammatory cytokines and chemokines),
oxidative stress, microvascular dysfunction, and fibrosis in the liver. These pathological
changes were accompanied by impaired diastolic, systolic and macrovascular functions,
cardiac inflammation (increased MIP1, interleukin-1, P-selectin, CD45+ cells) and
oxidative stress (increased malondialdehyde, 3-nitrotyrosine and NADPH-oxidases).
CB2 -R up-regulation was observed both in livers and hearts of mice exposed to BDL.
CB2 -R activation markedly improved hepatic inflammation, impaired microcirculation,
fibrosis. CB2 -R activation also decreased serum TNF-alpha levels, and improved cardiac
dysfunction, myocardial inflammation and oxidative stress underlining the importance
of inflammatory mediators in the pathology of hepatic cardiomyopathy.We propose BDL-induced
cardiomyopathy in mice as a model for hepatic/cirrhotic cardiomyopathy. This cardiomyopathy,
similarly to cirrhotic cardiomyopathy in humans, is characterized by systemic hypotension,
impaired macro- and microvascular function accompanied by both systolic and diastolic
dysfunction. Our results indicate that the liver-heart inflammatory axis has a pivotal
pathophysiological role in the development of hepatic cardiomyopathy. Thus, controlling
liver and/or myocardial inflammation (e.g. with selective CB2-R agonists) may delay/prevent
the development of cardiomyopathy in severe liver disease. This article is protected
by copyright. All rights reserved.
