| Coronary constriction and consequent cardiodepression in pulmonary embolism are mediated by pulmonary big endothelin and enhanced in early endothelial dysfunction. | |
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MedLine Citation:
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PMID: 9504580 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: Myocardial ischemia plays a central role in the development of right ventricular failure after acute pulmonary embolism. This study investigates whether pulmonary mediators act specifically on coronary tone and cardiac contractile function in acute pulmonary microembolization and whether such effects are altered in the case of early systemic atherosclerosis. We employ a novel model of serial perfusion in which an isolated rabbit heart is perfused with the effluent of the same animal's isolated lung. DESIGN: Controlled experiment using isolated organs. SETTING: Experimental laboratory. SUBJECTS: Male New Zealand White rabbits (controls). Age-matched, male Watanabe rabbits (hypercholesterolemic, development of accelerated atherosclerosis). INTERVENTIONS: Seven isolated control and seven isolated Watanabe hearts were perfused with the saline effluent of the same animal's isolated lung. After the assessment of the baseline data, the lungs were gradually embolized with glass beads measuring 100 microm in diameter to induce an increase in mean pulmonary arterial pressure from 6 to 8 mm Hg, at baseline, up to 25 mm Hg. MEASUREMENTS AND MAIN RESULTS: Pulmonary embolization to 25 mm Hg evoked a coronary constriction, measured as coronary flow decrease to 89 +/- 7% of the baseline value in controls. In the Watanabe group, coronary constriction was significantly enhanced, compared with controls, with coronary flow decreasing to 76 +/- 6% of the baseline value. In both groups, coronary constriction was followed by a deterioration in cardiac contractile performance. This cardiodepression was significantly deeper in Watanabe hearts with respect to both maximum ventricular pressures and maximum rates of pressure development and decline. Coronary constriction and cardiodepression were prevented by coronary infusion of the nonselective endothelin antagonist PD-145065, the endothelinA antagonists A-127722 and BQ-123, and the endothelin-converting enzyme inhibitor phosphoramidon. Concentration of big endothelin in pulmonary effluent increased from 5.6 +/- 0.3 pmol/L in controls and 5.6 +/- 0.2 pmol/L in the Watanabe group, at baseline, to 8.8 +/- 0.4 pmol/L in controls and 8.9 +/- 0.4 pmol/L in the Watanabe group, at 25 mm Hg pulmonary arterial pressure. Endothelin was not detectable at any time during the experiment in pulmonary effluent. The coronary gradient, calculated as a difference in concentration between coronary and pulmonary effluent, was negative for big endothelin and positive for endothelin in both groups. CONCLUSIONS: We have demonstrated that an increase in pulmonary release of big endothelin occurs during lung embolism, which, in turn, results in coronary constriction and consequent cardiodepression. This action of big endothelin is based on its local coronary conversion into endothelin. In addition, coronary endothelial dysfunction, attributed to early systemic atherosclerosis, was shown to represent a specific risk factor in these events. |
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Authors:
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T Dschietzig; M Laule; K Alexiou; K Schrör; G Baumann; K Stangl |
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: 26 ISSN: 0090-3493 ISO Abbreviation: Crit. Care Med. Publication Date: 1998 Mar |
Date Detail:
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Created Date: 1998-03-26 Completed Date: 1998-03-26 Revised Date: 2009-11-19 |
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: 510-7 Citation Subset: AIM; IM |
Affiliation:
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Medizinische Klinik und Poliklinik I, Charité, Humboldt-Universität, Berlin, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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6-Ketoprostaglandin F1 alpha
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metabolism Animals Arteriosclerosis / complications, physiopathology Aspartic Acid Endopeptidases / antagonists & inhibitors Coronary Circulation* Endothelin-1 Endothelins / antagonists & inhibitors, physiology* Endothelium, Vascular / physiopathology* Glycopeptides / pharmacology Male Metalloendopeptidases Myocardial Contraction* Oligopeptides / pharmacology Peptides, Cyclic / pharmacology Protein Precursors / physiology* Pulmonary Embolism / complications, physiopathology* Pyrrolidines / pharmacology Rabbits Receptors, Endothelin / antagonists & inhibitors Thromboxane B2 / metabolism Vasoconstriction* |
| Chemical | |
Reg. No./Substance:
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0/A 127722; 0/Endothelin-1; 0/Endothelins; 0/Glycopeptides; 0/Oligopeptides; 0/Peptides, Cyclic; 0/Protein Precursors; 0/Pyrrolidines; 0/Receptors, Endothelin; 136553-81-6/cyclo(Trp-Asp-Pro-Val-Leu); 153049-49-1/PD 145065; 36357-77-4/phosphoramidon; 54397-85-2/Thromboxane B2; 58962-34-8/6-Ketoprostaglandin F1 alpha; EC 3.4.23.-/Aspartic Acid Endopeptidases; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.71/endothelin-converting enzyme |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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