| Mechanisms for blockade of in vivo activator production in the ischemic intestine and multi-organ failure. | |
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MedLine Citation:
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PMID: 11092684 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Our recent results indicate that pancreatic enzymes in the ischemic intestine are involved in the production of in vivo activators, which stimulate cells in the cardiovascular system and initiate multiple organ failure. Since the intestine is a rich source of xanthine oxidase (XO), we investigated whether XO may be involved in the production of circulating activators in shock. The small intestine was perfused with saline (SAL group), a broad acting pancreatic enzyme inhibitor, ANGD (ANGD group), allopurinol (ALLOP group), or a combination of ANGD and allopurinol (ANGD + ALLOP group). 100 min of splanchnic arterial occlusion was followed by 120 min of reperfusion. Leukocytes from asymptomatic volunteers were incubated with plasma from experimental animals, and the fractions of pseudopod positive cells were counted as an indicator for the activator. ANGD served to preserve the arterial blood pressure (MAP) close to its control values (96.6 +/- 6.2 % in ANGD versus 60.9 +/- 6.2 % in SAL, 120 min after reperfusion, P < 0.05). In line with our previous experiments, ANGD decreased the formation of activator (30.5 +/- 4.8% in SAL versus 7.3 +/- 1.6 % in ANGD, 120 min after reperfusion, P< 0.05). Although allopurinol inhibited the XO in the small intestine, no protection from early indicators of multi-organ injury was detected. The recovery of MAP and reduced levels of plasma activator achieved in the ANGD + ANGD group was similar to those in the ALLOP group. These results indicate that XO may not serve as a significant source for plasma derived activators in an acute phase of shock after severe intestinal ischemia. |
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Authors:
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H Mitsuoka; G W Schmid-Schönbein |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 14 ISSN: 1073-2322 ISO Abbreviation: Shock Publication Date: 2000 Nov |
Date Detail:
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Created Date: 2001-03-06 Completed Date: 2001-05-31 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 522-7 Citation Subset: IM |
Affiliation:
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Department of Bioengineering and The Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla 92093-0412, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Allopurinol
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pharmacology Animals Bile / secretion Blood Pressure / drug effects Duodenum / blood supply*, pathology Guanidines / pharmacology Intestinal Mucosa / drug effects, pathology, physiopathology Ischemia / pathology, physiopathology* Leukocytes / physiology* Male Multiple Organ Failure / pathology, physiopathology* Neutrophils / physiology* Protease Inhibitors / pharmacology Rats Rats, Wistar Xanthine Dehydrogenase / metabolism Xanthine Oxidase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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3HL 43026/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Guanidines; 0/Protease Inhibitors; 315-30-0/Allopurinol; 81525-10-2/nafamostat; EC 1.17.1.4/Xanthine Dehydrogenase; EC 1.17.3.2/Xanthine Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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