title: Cardiomyopathy reverses with recovery of liver injury, cholestasis and cholanemia in mouse model of biliary fibrosis.
abstract: BACKGROUND
  Triggers and exacerbants of cirrhotic cardiomyopathy (CC) are poorly understood, limiting treatment options in patients with chronic liver diseases. Liver transplantation alone reverses some features of CC, but the physiology behind this effect has never been studied.
  
  
  OBJECTIVE
  We aimed to determine whether reversal of liver injury and fibrosis in mouse affects cardiac parameters. The second aim was to determine whether cardiomyopathy can be induced by specifically increasing systemic bile acid (BA) levels.
  
  
  METHODS
  6-8 week old male C57BL6J mice were fed either chow (n = 5) or 3,5-diethoxycarbonyl-1,4-dihydroxychollidine (DDC) (n = 10) for 3 weeks. At the end of 3 weeks, half the mice in the DDC fed group were randomized to chow (the reversed [REV] group). Serial ECHOs and electrocardiographic analysis was conducted weekly for 6 weeks followed by liver tissue and serum studies. Hearts were analysed for key components of function and cell signalling. Cardiac physiological and molecular parameters were similarly analysed in Abcb11(-/-) mice (n = 5/grp) fed 0.5% cholic acid supplemented diet for 1 week.
  
  
  RESULTS
  Mice in the REV group showed normalization of biochemical markers of liver injury with resolution of electrocardiographic and ECHO aberrations. Catecholamine resistance seen in DDC group resolved in the REV group. Cardiac recovery was accompanied by normalization of cardiac troponin-T2 as well as resolution of cardiac stress response at RNA level. Cardiovascular physiological and molecular parameters correlated with degree of cholanemia. Cardiomyopathy was reproduced in cholanemic BA fed Abcb11(-/-) mice.
  
  
  CONCLUSIONS
  Cardiomyopathy resolves with resolution of liver injury, is associated with cholanaemia, and can be induced by BA feeding.
authors: Section of Pediatric Critical Care, Baylor College of Medicine, Houston, TX, USA.
authors: Moreshwar S
authors: MS
authors: Desai
authors: Zeena
authors: Z
authors: Eblimit
authors: Sundararajah
authors: S
authors: Thevananther
authors: Astrid
authors: A
authors: Kosters
authors: David D
authors: DD
authors: Moore
authors: Daniel J
authors: DJ
authors: Penny
authors: Saul J
authors: SJ
authors: Karpen
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000172:deficiency / Q000235:genetics; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002779:Cholestasis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D019826:Cholic Acid / Q000008:administration & dosage / Q000097:blood*; D004195:Disease Models, Animal; D004351:Drug Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011725:Pyridines / Q000494:pharmacology*; D020127:Recovery of Function; D015398:Signal Transduction; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: C530773:3,5-diethoxycarbonyl-1,4-dihydrocollidine; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C490549:Abcb11 protein, mouse; D000318:Adrenergic beta-Agonists; D015415:Biomarkers; D011725:Pyridines; D019826:Cholic Acid
keywords: bile acid-myocardial interaction; cardiac adaptation; cholanaemia; hepatic - cardiopathy; liver injury