| Leukotriene-mediated coronary vasoconstriction and loss of myocardial contractility evoked by low doses of Escherichia coli hemolysin in perfused rat hearts. | |
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MedLine Citation:
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PMID: 12626969 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: hemolysin has been implicated as an important pathogenic factor in extraintestinal infections including sepsis. We investigated the effects of coronary administration of hemolysin on cardiac function in isolated rat hearts perfused at constant flow. DESIGN: Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Isolated hearts from male Wistar rats. INTERVENTIONS: Isolated hearts were perfused with purified hemolysin for 60 min. MEASUREMENTS AND MAIN RESULTS: Low concentrations of the toxin in the perfusate (0.1-0.2 hemolytic units/mL) caused a dose-dependent coronary vasoconstriction with a marked increase in coronary perfusion pressure, which was paralleled by a decrease in left ventricular developed pressure (and the maximum rate of left ventricular pressure increase). Moreover, 0.2 hemolytic units/mL hemolysin evoked ventricular fibrillation within 10 mins of toxin application. These events were accompanied by the liberation of leukotrienes (LTC4, LTD4, LTE4, and LTB4), thromboxane A2, prostaglandin I2, and the cell necrosis markers lactate dehydrogenase and creatine kinase into the recirculating perfusate. The lipoxygenase inhibitor MK-886 fully blocked the toxin-induced coronary vasoconstrictor response and the loss of myocardial contractility and reduced the release of lactate dehydrogenase and creatine kinase. In contrast to this, the cyclooxygenase inhibitor indomethacin was entirely ineffective. In addition, hemolysin elicited an increase in heart weight and left ventricular end-diastolic pressure, the latter again being suppressed by MK-886. CONCLUSIONS: Low doses of hemolysin cause strong coronary vasoconstriction, linked with loss of myocardial performance, release of cell injury enzymes, and electrical instability, with all events being largely attributable to toxin-elicited leukotriene generation in the coronary vasculature. Bacterial exotoxins such as hemolysin thus may be implicated in the cardiac abnormalities encountered in septic shock. |
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Authors:
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Ulf Sibelius; Ulrich Grandel; Michael Buerke; Ladislau Kiss; Pascal Klingenberger; Martina Heep; Emmanoyil Bournelis; Werner Seeger; Friedrich Grimminger |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Critical care medicine Volume: 31 ISSN: 0090-3493 ISO Abbreviation: Crit. Care Med. Publication Date: 2003 Mar |
Date Detail:
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Created Date: 2003-03-10 Completed Date: 2003-04-11 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0355501 Medline TA: Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 683-8 Citation Subset: AIM; IM |
Affiliation:
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Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Coronary Circulation Coronary Vessels / physiopathology* Disease Models, Animal* Dose-Response Relationship, Drug Escherichia coli* Escherichia coli Infections / complications* Exotoxins / adverse effects* Heart Failure / immunology, microbiology*, physiopathology Hemolysin Proteins / adverse effects* Indoles / pharmacology Leukotrienes / physiology* Lipoxygenase Inhibitors / pharmacology Male Myocardial Contraction* Prospective Studies Rats Shock, Septic / immunology, microbiology*, physiopathology Vasoconstriction* Ventricular Dysfunction, Left / immunology, microbiology, physiopathology Ventricular Fibrillation / immunology, microbiology*, physiopathology Ventricular Pressure |
| Chemical | |
Reg. No./Substance:
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0/Exotoxins; 0/Hemolysin Proteins; 0/Indoles; 0/Leukotrienes; 0/Lipoxygenase Inhibitors; 118414-82-7/L 663536 |
| Comments/Corrections | |
Comment In:
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Crit Care Med. 2003 Mar;31(3):971-3
[PMID:
12627015
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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