{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T23:07:36Z","timestamp":1771024056486,"version":"3.50.1"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2000,1,4]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Cardiac performance is severely depressed in septic shock. Endotoxin has been implicated as the causative agent in Gram-negative sepsis, but similar abnormalities are encountered in Gram-positive sepsis. We investigated the influence of the major exotoxin of\n            <jats:italic>Staphylococcus aureus,<\/jats:italic>\n            staphylococcal \u03b1-toxin, in isolated perfused rat hearts.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014\u03b1-Toxin 0.25 to 1 \u03bcg\/mL caused a dose-dependent increase in coronary perfusion pressure that more than doubled. In parallel, we noted a decrease in left ventricular developed pressure and the maximum rate of left ventricular pressure rise (dP\/dt\n            <jats:sub>max<\/jats:sub>\n            ), dropping to a minimum of &lt;60% of control. These changes were accompanied by a liberation of thromboxane A\n            <jats:sub>2<\/jats:sub>\n            and prostacyclin into the coronary effluent. The release of creatine kinase, lactate dehydrogenase, potassium, and lactate did not surpass control heart values, and leukotrienes were also not detected. Indomethacin, acetylsalicylic acid, and the thromboxane receptor antagonist daltroban fully blocked the \u03b1-toxin\u2013induced coronary vasoconstrictor response and the decrease in left ventricular developed pressure and dP\/dt\n            <jats:sub>max<\/jats:sub>\n            , whereas the lipoxygenase inhibitor nordihydroguaiaretic acid, the platelet activating factor antagonist WEB 2086, and the \u03b1-adrenergic antagonist phentolamine were entirely ineffective. Inhibition of nitric oxide synthase even enhanced the \u03b1-toxin\u2013induced increase in coronary perfusion pressure and the loss in myocardial performance.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014Purified staphylococcal \u03b1-toxin provokes coronary vasoconstriction and loss in myocardial contractility. The responses appear to be largely attributable to the generation of thromboxane and are even enhanced when the endogenous nitric oxide synthesis is blocked. Bacterial exotoxins, such as staphylococcal \u03b1-toxin, may thus be implicated in the loss of cardiac performance encountered in Gram-positive septic shock.\n          <\/jats:p>","DOI":"10.1161\/01.cir.101.1.78","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"78-85","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":53,"title":["Staphylococcal \u03b1-Toxin Provokes Coronary Vasoconstriction and Loss in Myocardial Contractility in Perfused Rat Hearts"],"prefix":"10.1161","volume":"101","author":[{"given":"Ulf","family":"Sibelius","sequence":"first","affiliation":[{"name":"From the Department of Internal Medicine, Justus-Liebig-University, Giessen, and the II Department of Internal Medicine, Johannes-Gutenberg-University, Mainz (M.B.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Grandel","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Justus-Liebig-University, Giessen, and the II Department of Internal Medicine, Johannes-Gutenberg-University, Mainz (M.B.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Buerke","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Justus-Liebig-University, Giessen, and the II Department of Internal Medicine, Johannes-Gutenberg-University, Mainz (M.B.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doris","family":"Mueller","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Justus-Liebig-University, Giessen, and the II Department of Internal Medicine, Johannes-Gutenberg-University, Mainz (M.B.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ladislau","family":"Kiss","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Justus-Liebig-University, Giessen, and the II Department of Internal Medicine, Johannes-Gutenberg-University, Mainz (M.B.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Joachim","family":"Kraemer","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Justus-Liebig-University, Giessen, and the II Department of Internal Medicine, Johannes-Gutenberg-University, Mainz (M.B.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruediger","family":"Braun-Dullaeus","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Justus-Liebig-University, Giessen, and the II Department of Internal Medicine, Johannes-Gutenberg-University, Mainz (M.B.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner","family":"Haberbosch","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Justus-Liebig-University, Giessen, and the II Department of Internal Medicine, Johannes-Gutenberg-University, Mainz (M.B.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner","family":"Seeger","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Justus-Liebig-University, Giessen, and the II Department of Internal Medicine, Johannes-Gutenberg-University, Mainz (M.B.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friedrich","family":"Grimminger","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Justus-Liebig-University, Giessen, and the II Department of Internal Medicine, Johannes-Gutenberg-University, Mainz (M.B.), Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199305203282008"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-115-6-457"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","unstructured":"Kumar A Parrillo JE. 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