Peritonitis induces rat cardiac myocytes to promote polymorphonuclear leukocyte emigration and activate endothelial cells: Effect of lipopolysaccharide pretreatment

OBJECTIVEPeritonitis induced by cecal ligation and perforation results in inflammation and dysfunction of the rat myocardium, an organ remote from the locus of infection. This peritonitis-induced pathology can be prevented by pretreating these animals with lipopolysaccharide before cecal ligation and perforation. In the present study, we assessed a) whether cardiomyocytes obtained from rats subjected to cecal ligation and perforation could induce polymorphonuclear leukocyte transendothelial migration, b) whether these cardiomyocytes could activate endothelial cells (increased proadhesive phenotype), and c) whether these responses could be attenuated by lipopolysaccharide pretreatment. DESIGNProspective animal study. SETTINGExperimental animal laboratory. SUBJECTSMale Sprague Dawley rats. INTERVENTIONSLipopolysaccharide pretreated and nonpretreated rats were subjected to cecal ligation and perforation or to laparotomy. Myocytes were isolated 6 hrs after surgery and used for in vitro experiments. MEASUREMENTS AND MAIN RESULTS Myocytes isolated from cecal ligation and perforation rats promoted migration of polymorphonuclear leukocytes across a rat endothelial cell monolayer, an effect prevented by platelet activating factor receptor antagonists. Myocytes isolated from these animals also increased surface level expression of intercellular adhesion molecule-1 on rat endothelial cells, an effect also prevented by platelet activating factor receptor antagonists. Myocytes isolated from rats pretreated with lipopolysaccharide and then subjected to cecal ligation and perforation did not a) promote polymorphonuclear leukocyte transendothelial migration or b) increase intercellular adhesion molecule-1 surface expression on endothelial cells. CONCLUSIONSOur findings indicate that induction of peritonitis results in a systemic response that induces cardiac myocytes to become proinflammatory (i.e., these myocytes produce chemotactic factors and activate endothelial cells). This effect of cecal ligation and perforation is abrogated by pretreating animals with lipopolysaccharide before induction of peritonitis.