{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:58:16Z","timestamp":1790625496475,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,1,14]],"date-time":"2013-01-14T00:00:00Z","timestamp":1358121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background\/Aims<\/jats:title><jats:p>Sepsis is a common complication of cirrhosis with a high mortality. Cirrhosis is associated with cardiac chronotropic and inotropic dysfunction, which is known as cirrhotic cardiomyopathy and might be linked to endotoxaemia. This study was aimed to explore the hypothesis that the inflammatory response induced by administration of low dose of lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>) exacerbates cardiac chronotropic dysfunction in cirrhotic rats; and if so, whether this is associated with altered cardiac toll\u2010like receptor expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cirrhosis was induced by surgical ligation of the bile duct in male Wister rats. Four weeks after bile duct ligation or sham surgery, the subjects were given intraperitoneal injection of either saline or <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> (0.1\u00a0mg\/kg). Five hours after <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> injection, the atria were isolated and spontaneously beating rate and chronotropic responsiveness to \u03b2\u2010adrenergic stimulation was assessed using standard organ bath. The expression of toll\u2010like receptor 4 (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4) was assessed the atria using immunohistochemistry as well as quantitative <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> injection could induce a significant hypo\u2010responsiveness to adrenergic stimulation in sham\u2010operated rats. However, in cirrhotic rats, the chronotropic responses did not change after acute injection of <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>. Immunohistochemical study showed that <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 is mainly expressed in the myocardium in control atria and its expression is markedly decreased in myocardial layer following chronic bile duct ligation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data showed that cirrhosis is associated with development of tolerance to cardiac chronotropic effect of <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> in rats and this might be caused by altered localization of <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>4 in myocardium.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12039","type":"journal-article","created":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T08:16:58Z","timestamp":1352362618000},"page":"368-374","source":"Crossref","is-referenced-by-count":16,"title":["Cirrhosis is associated with development of tolerance to cardiac chronotropic effect of endotoxin in rats"],"prefix":"10.1111","volume":"33","author":[{"given":"Farahnaz","family":"Jazaeri","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed M.","family":"Tavangar","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Ghazi\u2010Khansari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad R.","family":"Khorramizadeh","sequence":"additional","affiliation":[{"name":"Department of Immunology School of Medicine Tehran University of Medical Sciences Tehran 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