Document Detail

Sodium-hydrogen exchange inhibition and beta-blockade additively decrease infarct size.
MedLine Citation:
PMID:  17307470     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Perioperative myocardial infarction adversely affects survival after cardiac operations. In animal studies Na+/H+ exchange inhibitors protect hearts against ischemia-reperfusion injury, but human trials have failed to consistently show beneficial effects. The aim of this study was to investigate whether the combination of the Na+/H+ exchange inhibitor cariporide and the beta-blocker metoprolol additively protects hearts from severe ischemia-reperfusion injury. METHODS: Isolated Langendorff-perfused rat hearts were randomly assigned to a vehicle-treated control group, or groups with 10-minute preischemia infusions of cariporide (10 micromol/L), metoprolol (10 micromol/L), or both cariporide and metoprolol. The hearts were then subjected to 20 minutes of global ischemia followed by 60 minutes of reperfusion. At the end of reperfusion, the hearts were randomly assigned to undergo either infarct size measurements or left ventricular mitochondrial function analyses. RESULTS: The combination of cariporide and metoprolol limited infarct size significantly compared with control group or cariporide alone (5% +/- 1% versus 58% +/- 9% or 38.4% +/- 4% of risk zone; p < 0.05). Cariporide alone did not reduce infarct size significantly as compared with the control group. As compared with the control group, cariporide and metoprolol decreased mitochondrial calcium content (6.4 +/- 1.2 versus 10.2 +/- 1.1 nmol/mg protein; p < 0.05), and increased respiratory control ratio (9.5 +/- 0.6 versus 5.3 +/- 0.7; p < 0.05). However, hearts treated with cariporide or metoprolol alone did not show significant improvement in mitochondrial calcium content (7.8 +/- 1.2 and 7.8 +/- 1.5 nmol/mg protein) or respiratory control ratio (5.0 +/- 0.7 and 7.3 +/- 0.7). CONCLUSIONS: The combination of cariporide and metoprolol additively limits infarct size after severe ischemia-reperfusion injury in an isolated rat heart model. Infarct size reduction occurs in association with protection from increased mitochondrial calcium content after reperfusion.
Peipei Wang; Corinne Zaragoza; William Holman
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  83     ISSN:  1552-6259     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-19     Completed Date:  2007-03-30     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1121-7     Citation Subset:  AIM; IM    
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
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MeSH Terms
Adrenergic beta-Antagonists / pharmacology*
Calcium / metabolism
Drug Combinations
Guanidines / pharmacology*
Heart / physiopathology
Heart Ventricles
Metoprolol / pharmacology*
Mitochondria, Heart / metabolism
Mitochondrial Proteins / metabolism
Myocardial Contraction
Myocardial Infarction / pathology*
Myocardial Reperfusion Injury / metabolism,  physiopathology,  prevention & control
Oxygen Consumption / drug effects
Rats, Sprague-Dawley
Severity of Illness Index
Sodium-Hydrogen Antiporter / antagonists & inhibitors*
Sulfones / pharmacology*
Grant Support
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Drug Combinations; 0/Guanidines; 0/Mitochondrial Proteins; 0/Sodium-Hydrogen Antiporter; 0/Sulfones; 0/cariporide; 37350-58-6/Metoprolol; 7440-70-2/Calcium
Comment In:
Ann Thorac Surg. 2007 Mar;83(3):1128   [PMID:  17307471 ]

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