Cardiovascular Toxicology

, Volume 10, Issue 2, pp 117–129

The Role of Lipophilic Bile Acids in the Development of Cirrhotic Cardiomyopathy


DOI: 10.1007/s12012-010-9069-8

Cite this article as:
Zavecz, J.H. & Battarbee, H.D. Cardiovasc Toxicol (2010) 10: 117. doi:10.1007/s12012-010-9069-8


Marked hemodynamic changes occur in humans and experimental animals with cirrhotic liver disease. In the heart, basal contractility, responsiveness to β-adrenoceptor activation, and excitation–contraction coupling (ECC) are negatively affected in models of cirrhosis and portal hypertension with portosystemic shunting (PVS), and comprise what has been called cirrhotic cardiomyopathy. These effects are accompanied by elevated circulating levels of bile acids. We investigated whether elevated bile acids act as a myocardial toxicant by exposing cardiac muscle in vitro to bile acids and compared these results with two models of cirrhotic cardiomyopathy with elevated bile acids: CCl4-induced cirrhosis and PVS. Cholic acid, a lipophilic bile acid, produced a decrease in basal cardiac contractility and responsiveness to β-adrenoceptor activation, both of which appeared to result from altered ECC. β-Adrenoceptor density and signaling were unaffected. Acutely, ursodeoxycholic acid, a more hydrophilic bile acid, had no effect. Cirrhosis produced a decrease in basal force, depressed β-adrenoceptor responsiveness, and altered ECC similar to cholic acid. However, cirrhosis also altered β-adrenoceptor signaling including decreases in cyclic AMP formation, expression of the stimulatory G protein, GS, and β-adrenoceptor density. Displacement of lipophilic bile acids by chronic administration of ursodeoxycholic acid to rats during the development of cirrhotic cardiomyopathy produced by PVS produced attenuation of the effect on ECC. These results suggest a possible role for lipophilic bile acids in some, but not all of the myocardial consequences of chronic portal vein stenosis and CCl4-induced cirrhosis.


Bile acidsCholic acidExcitation–contraction couplingCCl4-induced cirrhosisCirrhotic cardiomyopathyHeartPortal vein stenosisUrsodeoxycholic acid



Extracellular Ca2+ concentration


Excitation–contraction coupling


Krebs–Henseleit physiological salt solution


Portal vein stenosis


Ursodeoxycholic acid


Maximum rate of force development


Maximum rate of relaxation

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Pharmacology, Toxicology and NeuroscienceLouisiana State University Health Sciences CenterShreveportUSA
  2. 2.Department of Molecular and Cellular PhysiologyLouisiana State University Health Sciences CenterShreveportUSA