{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:00:00Z","timestamp":1779879600410,"version":"3.53.1"},"reference-count":74,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T00:00:00Z","timestamp":1682985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"B. Braun-Stiftung","award":["BBST-D-18-00022"],"award-info":[{"award-number":["BBST-D-18-00022"]}]},{"name":"Clinician Scientist \u201cStarter\u201d of RWTH Aachen University","award":["BBST-D-18-00022"],"award-info":[{"award-number":["BBST-D-18-00022"]}]},{"name":"ROTATION program of RWTH Aachen University","award":["BBST-D-18-00022"],"award-info":[{"award-number":["BBST-D-18-00022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 &lt; 0.001) and impaired contractility at rest and a reduced contractile reserve (Pd31 = 0.03, Pdob-d31 &lt; 0.001) were seen 31 days after BDL with increased creatine (Pd35, Pd42, and Pd56 &lt; 0.05) and transaminases (Pd31 &lt; 0.001). A total of 56 days after BDL, myocardial fibrosis was seen (Pd56 &lt; 0.001) accompanied by macrophage infiltration (CD68: Pgroup &lt; 0.001) and systemic inflammation (TNF\u03b1: Pgroup &lt; 0.001, white blood cell count: Pgroup &lt; 0.001). Myocardial expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1\u03b1) was increased after 31 (Pd31 &lt; 0.001) and decreased after 42 (Pd42 &lt; 0.001) and 56 days (Pd56 &lt; 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.<\/jats:p>","DOI":"10.3390\/ijms24098147","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T01:36:38Z","timestamp":1683077798000},"page":"8147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cirrhotic Cardiomyopathy Following Bile Duct Ligation in Rats\u2014A Matter of Time?"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6533-6515","authenticated-orcid":false,"given":"Moritz","family":"Uhlig","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9436-7353","authenticated-orcid":false,"given":"Marc","family":"Hein","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1445-608X","authenticated-orcid":false,"given":"Moriz A.","family":"Habigt","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 H.","family":"Tolba","sequence":"additional","affiliation":[{"name":"Institute for Laboratory Animal Science and Experimental Surgery, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9166-2912","authenticated-orcid":false,"given":"Till","family":"Braunschweig","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8914-7978","authenticated-orcid":false,"given":"Marius J.","family":"Helmedag","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Arici","sequence":"additional","affiliation":[{"name":"Luisenhospital, 52064 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Thei\u00dfen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Klinkenberg","sequence":"additional","affiliation":[{"name":"Luisenhospital, 52064 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Klinge","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8928-338X","authenticated-orcid":false,"given":"Mare","family":"Mechelinck","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Institute for Laboratory Animal Science and Experimental Surgery, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,2]]},"reference":[{"key":"ref_1","unstructured":"GBD 2017 Disease and Injury Incidence and Prevalence Collaborators (2018). 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