Document Detail

Alteration in myocardial prostaglandin D synthase expression in pressure overload-induced left ventricular remodeling in rats.
MedLine Citation:
PMID:  22228706     Owner:  NLM     Status:  MEDLINE    
We hypothesized that acute pharmacological blockade of cyclooxygenase-2 (COX-2) using nimesulide (Nime) would prevent maladaptive changes in left ventricular (LV) structure and function secondary to abdominal aortic coarctation-induced pressure overload (PO). In vivo LV chamber dimension and function were assessed by pressure/volume admittance catheter at 14 days' postsurgery in three groups (n ≥ 6/group): sham-operated (Sham); untreated PO; and selective COX-2 inhibitor nimesulide-treated PO (PO + Nime; 25 mg/kg/d). Treatment was initiated 24 h prior to surgical induction of PO. Relative to Sham, there was a marked increase in LV mass index in the PO groups (2.2 ± 0.01 mg/g versus 2.9 ± 0.10 mg/g Sham versus PO, PO+Nime: 2.5 ± 0.03 mg/g). End diastolic volume, an indicator of chamber size, was significantly decreased in the PO animals compared with Sham (202 ± 17μL versus 143 ± 16 μL Sham versus PO, PO + Nime: 226 ± 9 μL). Collagen levels in PO rats assessed by hydroxyproline analysis were significantly elevated relative to Sham values. Nimesulide treatment attenuated: (1) the increase in LV mass index; (2) the reduction in end diastolic volume; and (3) the PO-induced increase in myocardial collagen. In summary, acute COX-2 inhibition with nimesulide attenuated the maladaptive changes in the LV after PO. Acknowledging the clinical failure of chronic COX-2 inhibitor use, we propose that acute treatment with COX-2 inhibition during the initial stages of cardiac remodeling can be beneficial in maintaining the normal cardiac structure and function during PO.
Krishna T Nagalla; Monica Gole; Mario A Claudino; Jason D Gardner; David B Murray
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-06
Journal Detail:
Title:  Experimental biology and medicine (Maywood, N.J.)     Volume:  237     ISSN:  1535-3699     ISO Abbreviation:  Exp. Biol. Med. (Maywood)     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-12     Completed Date:  2012-02-27     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  100973463     Medline TA:  Exp Biol Med (Maywood)     Country:  England    
Other Details:
Languages:  eng     Pagination:  24-30     Citation Subset:  IM    
Department of Pharmacology, University of Mississippi, University, MS 38677, USA.
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MeSH Terms
Aortic Coarctation / physiopathology
Collagen / metabolism
Cyclooxygenase 2 / metabolism
Cyclooxygenase 2 Inhibitors / administration & dosage*
Heart / physiopathology
Heart Diseases / drug therapy*,  pathology,  physiopathology
Heart Ventricles / metabolism
Intramolecular Oxidoreductases / metabolism*
Lipocalins / metabolism*
Myocardium / metabolism,  pathology
Rats, Sprague-Dawley
Sulfonamides / administration & dosage*
Ventricular Function, Left
Ventricular Remodeling / drug effects*
Reg. No./Substance:
0/Cyclooxygenase 2 Inhibitors; 0/Lipocalins; 0/Sulfonamides; 51803-78-2/nimesulide; 9007-34-5/Collagen; EC 2; EC 5.3.-/Intramolecular Oxidoreductases; EC R2 D-isomerase

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