Cirrhotic Cardiomyopathy Following Bile Duct Ligation in Rats—A Matter of Time?

• Main Authors: Arici, M. (Author), Braunschweig, T. (Author), Habigt, M.A (Author), Hein, M. (Author), Helmedag, M.J (Author), Klinge, U. (Author), Klinkenberg, A. (Author), Mechelinck, M. (Author), Theißen, A. (Author), Tolba, R.H (Author), Uhlig, M. (Author)
• Format: Article
• Language: English
• Published: MDPI 2023
• Subjects: bile duct ligation; chronic liver failure; cirrhotic cardiomyopathy; fibrosis; liver cirrhosis; mitochondropathy; myocardial failure; rodent model; second hit
• Online Access: View Fulltext in Publisher; View in Scopus

 Cirrhotic patients often suffer from cirrhotic cardiomyopathy (CCM). Previous animal models of CCM were inconsistent concerning the time and mechanism of injury; thus, the temporal dynamics and cardiac vulnerability were studied in more detail. Rats underwent bile duct ligation (BDL) and a second surgery 28 days later. Cardiac function was assessed by conductance catheter and echocardiography. Histology, gene expression, and serum parameters were analyzed. A chronotropic incompetence (Pd31 < 0.001) and impaired contractility at rest and a reduced contractile reserve (Pd31 = 0.03, Pdob-d31 < 0.001) were seen 31 days after BDL with increased creatine (Pd35, Pd42, and Pd56 < 0.05) and transaminases (Pd31 < 0.001). A total of 56 days after BDL, myocardial fibrosis was seen (Pd56 < 0.001) accompanied by macrophage infiltration (CD68: Pgroup < 0.001) and systemic inflammation (TNFα: Pgroup < 0.001, white blood cell count: Pgroup < 0.001). Myocardial expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) was increased after 31 (Pd31 < 0.001) and decreased after 42 (Pd42 < 0.001) and 56 days (Pd56 < 0.001). Caspase-3 expression was increased 31 and 56 days after BDL (Pd31 = 0.005; Pd56 = 0.005). Structural changes in the myocardium were seen after 8 weeks. After the second surgery (second hit), transient myocardial insufficiency with secondary organ dysfunction was seen, characterized by reduced contractility and contractile reserve. © 2023 by the authors.