Document Detail

Hydrogen peroxide causes cardiac dysfunction independent from its effects on matrix metalloproteinase-2 activation.
MedLine Citation:
PMID:  17612643     Owner:  NLM     Status:  MEDLINE    
Hydrogen peroxide (H2O2) causes cardiac dysfunction through multiple mechanisms. As oxidative stress can activate matrix metalloproteinases (MMPs) and, in particular, MMP-2 activity is associated with oxidative stress injury in the heart, we hypothesized that MMP-2 activation by H2O2 in isolated rat hearts contributes to cardiac dysfunction in this model. Isolated working rat hearts were perfused at 37 degrees C with a recirculating Krebs-Henseleit buffer+/-5 mmol/L pyruvate, known to protect hearts from oxidative stress. H2O2 (300 micromol/L) was added as a single bolus after 20 min of equilibration, and cardiac function was monitored for 60 min. MMPs activities in both the heart and perfusate samples were assessed by gelatin zymography. Tissue high energy phosphates were analysed by HPLC. The actions of 2 MMP inhibitors, doxycycline (75 micromol/L) or Ro 31-9790 (3 micromol/L), were also assessed. H2O2 at 300 micromol/L produced a rapid decline in cardiac mechanical function, which was maximal at 5 min. A peak in perfusate MMP-2 activity was also observed at 5 min. The deleterious effect of H2O2 on cardiac function was abolished by pyruvate but not by the MMPs inhibitors. This study suggests that in intact hearts, H2O2 induces contractile dysfunction independent of MMPs activation.
Hernando León; Norma Bautista-López; Jolanta Sawicka; Richard Schulz
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  85     ISSN:  0008-4212     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:    2007 Mar-Apr
Date Detail:
Created Date:  2007-07-06     Completed Date:  2007-10-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  341-8     Citation Subset:  IM    
Department of Pediatrics, Cardiovascular Research Group, 4-62 Heritage Medical Research Centre, University of Alberta, Edmonton, AB T6G 2S2, Canada.
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MeSH Terms
Antioxidants / pharmacology
Coronary Circulation / drug effects
Doxycycline / pharmacology
Heart / drug effects*,  physiology,  physiopathology
Hydrogen Peroxide / toxicity*
Hydroxamic Acids / pharmacology
Matrix Metalloproteinase 2 / antagonists & inhibitors,  metabolism*
Phosphates / metabolism
Pyruvic Acid / pharmacology
Rats, Sprague-Dawley
Reg. No./Substance:
0/Antioxidants; 0/Hydroxamic Acids; 0/Phosphates; 0/Ro 31-9790; 127-17-3/Pyruvic Acid; 564-25-0/Doxycycline; 7722-84-1/Hydrogen Peroxide; EC Metalloproteinase 2; EC protein, rat

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