Document Detail


Mechanisms for blockade of in vivo activator production in the ischemic intestine and multi-organ failure.
MedLine Citation:
PMID:  11092684     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
H Mitsuoka; G W Schmid-Schönbein
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  14     ISSN:  1073-2322     ISO Abbreviation:  Shock     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2001-03-06     Completed Date:  2001-05-31     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  522-7     Citation Subset:  IM    
Affiliation:
Department of Bioengineering and The Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla 92093-0412, USA.
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MeSH Terms
Descriptor/Qualifier:
Allopurinol / 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:
3HL 43026/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
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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