{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T20:26:35Z","timestamp":1773260795704,"version":"3.50.1"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2005,8,2]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Lipoteichoic acid (LTA) represents a major virulence factor in gram-positive sepsis.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            In the present study we perfused isolated rat hearts for 180 minutes with highly purified LTA from\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            . A progressive decline of left ventricular contractile function paralleled by the expression of myocardial tumor necrosis factor-\u03b1 (TNF-\u03b1) mRNA and protein as well as the release of TNF-\u03b1 into the perfusate was observed in LTA-perfused hearts. Employment of an anti\u2013TNF-\u03b1 antibody completely prevented the loss in contractile function. When CD14, a prominent pathogen recognition receptor, was blocked by a specific antibody, induction of TNF-\u03b1 mRNA and protein release as well as the associated cardiodepression was diminished in response to LTA. Synthesis of TNF-\u03b1 protein was located to interstitial cells of LTA-challenged hearts as detected by immunohistochemistry. Besides progressive cardiodepression, coronary perfusion pressure (CPP) was moderately increased in LTA-perfused hearts. This was accompanied by the release of thromboxane A\n            <jats:sub>2<\/jats:sub>\n            (TXA\n            <jats:sub>2<\/jats:sub>\n            ) into the perfusate and the induction of cyclooxygenase (Cox)-2 mRNA and protein in the myocardium. Blocking of TXA\n            <jats:sub>2<\/jats:sub>\n            by the nonspecific Cox inhibitor indomethacin, the thromboxane receptor antagonist daltroban, or the selective Cox-2 inhibitor NS-398 prevented the increase in CPP.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            LTA causes cardiac depression by activating myocardial TNF-\u03b1 synthesis via CD14 and induces coronary vascular disturbances by activating Cox-2\u2013dependent TXA\n            <jats:sub>2<\/jats:sub>\n            synthesis. These phenomena may contribute to cardiac depression in gram-positive sepsis.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.104.503938","type":"journal-article","created":{"date-parts":[[2005,7,26]],"date-time":"2005-07-26T00:43:54Z","timestamp":1122338634000},"page":"691-698","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Mechanisms of Cardiac Depression Caused by Lipoteichoic Acids From\n            <i>Staphylococcus aureus<\/i>\n            in Isolated Rat Hearts"],"prefix":"10.1161","volume":"112","author":[{"given":"Ulrich","family":"Grandel","sequence":"first","affiliation":[{"name":"From the Departments of Internal Medicine (U.G., M. Hopf, K.H., M. Heep, S.P., R.T.S., W.S., F.G., U.S.) and Pathology (L.F., R.M.B.), Justus Liebig University, Giessen; Department of Internal Medicine, Martin Luther University, Halle-Wittenberg (M.B.); and Department of Biochemical Pharmacology, University of Konstanz, Konstanz (S.M., T.H.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hopf","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (U.G., M. Hopf, K.H., M. Heep, S.P., R.T.S., W.S., F.G., U.S.) and Pathology (L.F., R.M.B.), Justus Liebig University, Giessen; Department of Internal Medicine, Martin Luther University, Halle-Wittenberg (M.B.); and Department of Biochemical Pharmacology, University of Konstanz, Konstanz (S.M., T.H.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Buerke","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (U.G., M. Hopf, K.H., M. Heep, S.P., R.T.S., W.S., F.G., U.S.) and Pathology (L.F., R.M.B.), Justus Liebig University, Giessen; Department of Internal Medicine, Martin Luther University, Halle-Wittenberg (M.B.); and Department of Biochemical Pharmacology, University of Konstanz, Konstanz (S.M., T.H.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Hattar","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (U.G., M. Hopf, K.H., M. Heep, S.P., R.T.S., W.S., F.G., U.S.) and Pathology (L.F., R.M.B.), Justus Liebig University, Giessen; Department of Internal Medicine, Martin Luther University, Halle-Wittenberg (M.B.); and Department of Biochemical Pharmacology, University of Konstanz, Konstanz (S.M., T.H.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Heep","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (U.G., M. Hopf, K.H., M. Heep, S.P., R.T.S., W.S., F.G., U.S.) and Pathology (L.F., R.M.B.), Justus Liebig University, Giessen; Department of Internal Medicine, Martin Luther University, Halle-Wittenberg (M.B.); and Department of Biochemical Pharmacology, University of Konstanz, Konstanz (S.M., T.H.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludger","family":"Fink","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (U.G., M. Hopf, K.H., M. Heep, S.P., R.T.S., W.S., F.G., U.S.) and Pathology (L.F., R.M.B.), Justus Liebig University, Giessen; Department of Internal Medicine, Martin Luther University, Halle-Wittenberg (M.B.); and Department of Biochemical Pharmacology, University of Konstanz, Konstanz (S.M., T.H.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer M.","family":"Bohle","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (U.G., M. Hopf, K.H., M. Heep, S.P., R.T.S., W.S., F.G., U.S.) and Pathology (L.F., R.M.B.), Justus Liebig University, Giessen; Department of Internal Medicine, Martin Luther University, Halle-Wittenberg (M.B.); and Department of Biochemical Pharmacology, University of Konstanz, Konstanz (S.M., T.H.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siegfried","family":"Morath","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (U.G., M. Hopf, K.H., M. Heep, S.P., R.T.S., W.S., F.G., U.S.) and Pathology (L.F., R.M.B.), Justus Liebig University, Giessen; Department of Internal Medicine, Martin Luther University, Halle-Wittenberg (M.B.); and Department of Biochemical Pharmacology, University of Konstanz, Konstanz (S.M., T.H.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Hartung","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (U.G., M. Hopf, K.H., M. 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