Document Detail

Hydroxyl radical production during myocardial ischemia and reperfusion in cats.
MedLine Citation:
PMID:  8770109     Owner:  NLM     Status:  MEDLINE    
We previously showed that generation of reactive oxygen species during myocardial ischemia and reperfusion stimulates cardiac sympathetic afferent nerve endings. We hypothesized that, in this feline model of brief ischemia and reperfusion, HO. is produced during ischemia and the rate and concentration of production of HO.during reperfusion is dependent on the duration of myocardial ischemia. Therefore, we evaluated the time dependency of production of HO. during reperfusion after 2, 5, and 10 min of reversible occlusion of the left anterior descending (LAD) coronary artery to induce ischemia in cats (n = 10). Blood samples collected from the coronary vein at 0.25, 1, 2, and 4 min after 2 min of ischemia revealed net cumulative rate of production of p-, m-, and o-tyrosine of 99 +/- 31, 10 +/- 5.1, and 0.8 +/- 0.2 nmol.min-1.g-1, respectively. After 5 min of ischemia, net cumulative rates of production of p-, m-, and o-tyrosine during reperfusion were 177 +/- 63, 74 +/- 26, and 1.6 +/- 0.8 nmol.min-1.g-1, respectively, whereas after 10 min of ischemia production rates were 153 +/- 42, 78 +/- 29, and 2.1 +/- 0.5 nmol.min-1.g-1, respectively. The highest rate of production of tyrosines was observed immediately after ischemia, perhaps indicating a washout of HO.-derived products that had accumulated in the myocardium during ischemia. To evaluate production of HO. during ischemia, deoxygenated saline (PO2 10 +/- 0.9 mmHg) containing phenylalanine was perfused into the ischemic coronary vascular bed through a cannula placed in the LAD (n = 16). Perfusate was collected from the coronary vein during the 10 min of ischemia. Net production of HO. during ischemia, measured by the production of p-, m-, and o-tyrosine, was 82 +/- 11, 6.6 +/- 0.4, and 1.7 +/- 0.3 nmol.min-1.g-1, respectively. Pretreatment with deferoxamine (10 mg/kg, n = 7) or dimethylthiourea (10 mg/kg, n = 6) decreased net production of HO. during ischemia and reperfusion. These results demonstrate that HO. is produced during brief ischemia and reperfusion, with the greatest amount being produced immediately after ischemia. Additionally, we show that the duration of brief ischemia determines the rate of production of HO. during reperfusion.
C A O'Neill; L W Fu; B Halliwell; J C Longhurst
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  271     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1996-10-30     Completed Date:  1996-10-30     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H660-7     Citation Subset:  IM    
Department of Internal Medicine, University of California, Davis 95616, USA.
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MeSH Terms
Deferoxamine / pharmacology
Free Radical Scavengers / pharmacology
Heart Ventricles
Hydroxyl Radical / metabolism*
Lactic Acid / biosynthesis
Myocardial Ischemia / metabolism*,  pathology
Myocardial Reperfusion*
Myocardium / metabolism*,  pathology
Organ Size
Siderophores / pharmacology
Thiourea / analogs & derivatives,  pharmacology
Grant Support
Reg. No./Substance:
0/Free Radical Scavengers; 0/Siderophores; 3352-57-6/Hydroxyl Radical; 50-21-5/Lactic Acid; 61805-96-7/1,3-dimethylthiourea; 62-56-6/Thiourea; 70-51-9/Deferoxamine

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