| Beneficial effects of BAY u3405, a novel thromboxane A2 receptor antagonist, in splanchnic artery occlusion shock. | |
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MedLine Citation:
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PMID: 7878075 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Splanchnic artery occlusion shock was induced in male anaesthetized rats by clamping the splanchnic artery for 45 min. The arteries were then released and survival rate, mean survival time, mean arterial blood pressure, plasma levels of thromboxane B2 and 6-keto-PGF1 alpha, macrophage phagocytosis activity and plasma levels of myocardial depressant factor were evaluated. In addition, the neutrophilic infiltrate was quantified in the ileum and lung using a myeloperoxidase (MPO) assay. Sham splanchnic-artery-occlusion-shocked rats were used as controls. Splanchnic-artery-occlusion-shocked rats died within 93 +/- 7 min, while all sham-shocked animals survived more than 3 h. Splanchnic artery occlusion shock caused changes in mean arterial blood pressure, significantly increased the plasma levels of thromboxane B2 (7.5 +/- 1.3 ng/ml; p < 0.001 vs. sham), 6-keto-PGF1 alpha (8.9 +/- 1.7 ng/ml; p < 0.001 vs. sham) and myocardial depressant factor (114 +/- 11 U/ml), and reduced macrophage phagocytosis. Furthermore, MPO activity was significantly elevated (0.12 +/- 0.03 x 10(-3) and 1.8 +/- 0.5 x 10(-3) U/g protein in the ileum and lung, respectively) 70 min after starting reperfusion. Administration of BAY u3405, a novel thromboxane A2 receptor antagonist (30 mg/kg i.v., 30 min before occlusion), significantly increased survival time (187 +/- 3.7 min) and survival rate, improved mean arterial blood pressure, reduced the plasma levels of myocardial depressant factor (54 +/- 3 U/ml), partially restored macrophage phagocytosis and lowered MPO activity in both the ileum and the lung. Our data are consistent with an involvement of thromboxane A2 in splanchnic artery occlusion shock and suggest that BAY u3405 might be of benefit in low-flow states such as circulatory shock. |
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Authors:
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P Canale; F Squadrito; D Altavilla; M Ioculano; G M Campo; G Squadrito; G Urna; A Sardella; A P Caputi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Pharmacology Volume: 49 ISSN: 0031-7012 ISO Abbreviation: Pharmacology Publication Date: 1994 Dec |
Date Detail:
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Created Date: 1995-04-03 Completed Date: 1995-04-03 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0152016 Medline TA: Pharmacology Country: SWITZERLAND |
Other Details:
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Languages: eng Pagination: 376-85 Citation Subset: IM |
Affiliation:
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Institute of Pharmacology, School of Medicine, University of Messina, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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6-Ketoprostaglandin F1 alpha
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blood Animals Arterial Occlusive Diseases / drug therapy*, mortality, physiopathology Blood Pressure / physiology Carbazoles / pharmacology*, therapeutic use Macrophages / physiology Male Myocardial Depressant Factor / blood Peroxidase / metabolism Phagocytosis / physiology Rats Rats, Sprague-Dawley Receptors, Thromboxane / antagonists & inhibitors* Shock / drug therapy*, physiopathology Splanchnic Circulation / drug effects* Sulfonamides / pharmacology*, therapeutic use Survival Rate Thromboxane A2 / antagonists & inhibitors* Thromboxane B2 / blood |
| Chemical | |
Reg. No./Substance:
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0/Carbazoles; 0/Myocardial Depressant Factor; 0/Receptors, Thromboxane; 0/Sulfonamides; 116649-85-5/ramatroban; 54397-85-2/Thromboxane B2; 57576-52-0/Thromboxane A2; 58962-34-8/6-Ketoprostaglandin F1 alpha; EC 1.11.1.7/Peroxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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