Journal article
Prolonged administration of a dithiol antioxidant protects against ventricular remodeling due to ischemia-reperfusion in mice
American journal of physiology. Heart and circulatory physiology, Vol.295(3), pp.H1303-H1310
09/01/2008
DOI: 10.1152/ajpheart.01143.2007
PMCID: PMC2544508
PMID: 18689493
Abstract
The prolonged production of reactive oxygen species due to ischemia-reperfusion (I/R) is a potential cause of the pathological remodeling that frequently precedes heart failure. We tested the ability of a potent dithiol antioxidant, bucillamine, to protect against the long-term consequences of I/R injury in a murine model of myocardial infarction. After transiently occluding the left anterior descending coronary artery for 30 min, saline or bucillamine (10 mu g/g body wt) was injected intravenously as a bolus within the first 5 min of reperfusion. The antioxidant treatment continued with daily subcutaneous injections for 4 wk. There were no differences in infarct sizes between bucillamine-and saline-treated animals. After 4 wk of reperfusion, cardiac hypertrophy was decreased by bucillamine treatment (ventricular weight-to-body weight ratios: I/R + saline, 4.5 +/- 0.2 mg/g vs. I/R + bucillamine, 4.2 +/- 0.1 mg/g; means +/- SE; P < 0.05). Additionally, the hearts of bucillamine-treated mice had improved contractile function (echocardiographic measurement of fractional shortening) relative to saline controls: I/R + saline, 32 +/- 3%, versus I/R + bucillamine, 41 +/- 4% (P < 0.05). Finally, I/R-induced injury in the saline-treated mice was accompanied by a fetal pattern of gene expression determined by ribonuclease protection assay that was consistent with pathological cardiac hypertrophy and remodeling [increased atrial natriuretic peptide, beta-myosin heavy chain (MHC), skeletal alpha-actin; decreased sarco(endo) plasmic reticulum Ca2+ ATPase 2a, and alpha-MHC-to-beta-MHC ratio]. These changes in gene expression were significantly attenuated by bucillamine. Therefore, treatment with a dithiol antioxidant for 4 wk after I/R preserved ventricular function and prevented the abnormal pattern of gene expression associated with pathological cardiac remodeling.
Details
- Title: Subtitle
- Prolonged administration of a dithiol antioxidant protects against ventricular remodeling due to ischemia-reperfusion in mice
- Creators
- S. Kelly Ambler - University of Colorado DenverYvonne K. Hodges - University of Colorado DenverGayle M. Jones - University of Colorado DenverCarlin S. Long - University of Colorado DenverLawrence D. Horwitz - University of Colorado Denver
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.295(3), pp.H1303-H1310
- Publisher
- Amer Physiological Soc
- DOI
- 10.1152/ajpheart.01143.2007
- PMID
- 18689493
- PMCID
- PMC2544508
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Number of pages
- 8
- Grant note
- R01HL066399 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) HL-55291; HL-66399; HL-79160 / National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 09/01/2008
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984656604002771
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