Faculty Collaboration Database

Early short-term treatment with doxycycline modulates postinfarction left ventricular remodeling. Circulation 2003 Sep 23;108(12):1487-92

Date

09/04/2003

Pubmed ID

12952845

DOI

10.1161/01.CIR.0000089090.05757.34

Scopus ID

2-s2.0-0141839055 (requires institutional sign-in at Scopus site)   126 Citations

Abstract

BACKGROUND: Myocardial infarction (MI) is associated with early metalloproteinase (MMP) activation and extracellular matrix (ECM) degradation. We hypothesized that preserving the original ECM of the infarcted left ventricle (LV) by use of early short-term doxycycline (DOX) treatment preserves cardiac structure and function.

METHODS AND RESULTS: LV morphometry and function were measured in 3 groups of rats (sham, MI, and MI+DOX). DOX (30 mg/kg per day) was given orally 48 hours before and 48 hours after MI. Rats were examined at 2 and 4 weeks after MI. By 4 weeks, DOX significantly decreased (P<0.05 versus MI) the heart weight to body weight ratio, myocyte cross-sectional area, and internal LV diameter, whereas it preserved anterior wall thickness within the infarct. Collagen/muscle area fraction did not change in the region of the infarct/scar. Parallel left shifts (versus MI) were observed in pressure-volume relationships of DOX MI rats at all pressures. DOX treatment also shifted passive epicardial strains within the scar area toward normal values. No differences were observed in LV end-diastolic or peak systolic pressures, peak positive or negative LV dP/dt, or isovolumic relaxation rates. Assessment of LV global MMP and MMP-2/9 activities 1 hour after MI using fluorescent probes yielded significant differences with DOX.

CONCLUSIONS: Brief, early MMP inhibition after MI yields preservation of LV structure and global as well as scar area passive function, supporting the concept that preserving the original ECM early after coronary occlusion lessens ventricular remodeling.

Author List

Villarreal FJ, Griffin M, Omens J, Dillmann W, Nguyen J, Covell J

Author

Michael O. Griffin MD, PhD Associate Professor in the Radiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Body Weight
Disease Models, Animal
Disease Progression
Doxycycline
Drug Administration Schedule
Enzyme Activation
Extracellular Matrix
Heart
Hemodynamics
Male
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinases
Myocardial Infarction
Organ Size
Rats
Rats, Sprague-Dawley
Time Factors
Ventricular Function, Left
Ventricular Remodeling