Document Detail


Matrix metalloproteinase inhibition during the development of congestive heart failure : effects on left ventricular dimensions and function.
MedLine Citation:
PMID:  10455065     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The development of congestive heart failure (CHF) is associated with left ventricle (LV) dilation and myocardial remodeling. The matrix metalloproteinases (MMPs) play a significant role in extracellular remodeling, and recent studies have demonstrated increased MMP expression and activity with CHF. Whether increased MMP activity directly contributes to the LV remodeling with CHF remains unknown. Accordingly, this study examined the effects of chronic MMP inhibition (MMPi) on LV size and function during the progression of CHF. Pigs were assigned to the following groups: (1) CHF, rapid pacing for 3 weeks at 240 bpm (n=12); (2) CHF/MMPi, rapid pacing and concomitant MMPi (PD166793, 20 mg/kg per day [n=10]), and (3) control (n=11). With pacing CHF, LV fractional shortening was reduced (19+/-1 versus 45+/-1%), and end-diastolic dimension increased (5.67+/-0.11 versus 3.55+/-0.05 cm), compared with baseline values (P<0.05). In the CHF/MMPi group, LV endocardial shortening increased (25+/-2%) and the end-diastolic dimension was reduced (4.92+/-0.17 cm) compared with CHF-only values (P<0.05). LV midwall shortening was reduced to a comparable degree in the CHF-only and CHF/MMPi groups. LV peak wall stress increased 3-fold with pacing CHF compared with controls and was significantly reduced in the CHF/MMPi group. LV myocardial stiffness was unchanged with CHF but was increased in the CHF/MMPi group. LV myocyte length was increased with pacing CHF compared with controls (180+/-3 versus 125+/-4 microm, P<0.05) and was reduced in the CHF/MMPi group (169+/-4 microm, P<0.05). Basal-state myocyte shortening velocity was reduced with pacing CHF compared with controls (33+/-2 versus 66+/-1 microm/s, P<0.05) and was unchanged in the CHF/MMPi group (31+/-2 microm/s). Using an ex vivo assay system, myocardial MMP activity was increased with pacing CHF and was reduced with chronic MMPi. In summary, concomitant MMPi with developing CHF limited LV dilation and reduced wall stress. These results suggest that increased myocardial MMP activity contributes to LV myocardial remodeling in developing CHF.
Authors:
F G Spinale; M L Coker; S R Krombach; R Mukherjee; H Hallak; W V Houck; M J Clair; S B Kribbs; L L Johnson; J T Peterson; M R Zile
Related Documents :
15991155 - Matrix, cytoskeleton, or myofilaments: which one to blame for diastolic left ventricula...
3969895 - Comparison of ventricular function after senning and jatene procedures for complete tra...
14981425 - Ultrasonic tissue characterization for patients with chagas' disease.
15773275 - One-year clinical experience with the acorn corcap cardiac support device: results of a...
11792335 - Utility and limitation of treadmill exercise echocardiography for detecting significant...
8996305 - Left atrial chamber and appendage function after internal atrial defibrillation: a pros...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation research     Volume:  85     ISSN:  0009-7330     ISO Abbreviation:  Circ. Res.     Publication Date:  1999 Aug 
Date Detail:
Created Date:  1999-09-21     Completed Date:  1999-09-21     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  364-76     Citation Subset:  IM    
Affiliation:
Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Collagenases / metabolism*
Down-Regulation
Electrophysiology
Heart Failure / enzymology*,  physiopathology
Heart Ventricles* / enzymology,  physiopathology
Swine
Ventricular Function, Left*
Grant Support
ID/Acronym/Agency:
HL-57952/HL/NHLBI NIH HHS; HL-59165/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
EC 3.4.24.-/Collagenases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Mitochondrial electron transport complex I is a potential source of oxygen free radicals in the fail...
Next Document:  Estradiol inhibits leukocyte adhesion and transendothelial migration in rabbits in vivo : possible m...