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Circulation, Vol 85, 1483-1490, Copyright © 1992 by American Heart Association
RH Charney, S Takahashi, M Zhao, EH Sonnenblick and C Eng
BACKGROUND. This study was performed to biochemically assess and quantify
the previously observed ultrastructural alterations in the collagen matrix
of stunned myocardium. METHODS AND RESULTS. The stunned myocardium was
produced in 13 mongrel dogs by a series of 12 coronary artery occlusions of
5 minutes followed by 10-minute reperfusion periods, with a final
reperfusion period of 90 minutes. Regional systolic function in the stunned
myocardium was 17% of control. Relative end-diastolic length in the stunned
region increased up to 8%. There was a nonuniform transmural loss of
collagen. Hydroxyproline in the stunned endocardium was not different from
control. The stunned midwall and epicardium demonstrated 12.5% (p less than
0.05) and 14.6% (p less than 0.005) decreases, respectively. All transmural
layers in the stunned myocardium had significant increases in collagenase
activity before procollagenase activation, averaging a 73.6% increase (p
less than 0.025). Complete activation of all procollagenase forms with
aminophenylmercuric acetate revealed no differences in fully activated
collagenase between the stunned and normal regions. The lysosomal enzymes,
elastase and cathepsin G, were not different between stunned and normal
zone tissue. These results would tend to exclude exogenous sources of
protease in the stunned myocardium at the 90- minute final reperfusion time
frame. Collagen fibers were isolated from the stunned and normal zone
tissue and underwent dansyl chloride reaction. Stunned collagen fibers had
9% greater dansyl labeling, suggesting greater numbers of exposed
N-terminal amino acid residues on the fiber and compatible with greater
enzymatic cleavage activity on the stunned collagen matrix. Tissue water
content was consistently greater in the stunned region compared to the
normal: a uniform transmural increase of approximately 1.7%. CONCLUSIONS.
The stunned myocardium is characterized by both systolic dysfunction and
diastolic expansion or dilatation. Endogenous procollagenase is activated
by the ischemic process leading to degradation of the extracellular matrix.
The underlying mechanisms may be relevant in ischemic enlargement of the
heart and cardiomyopathy.
ARTICLES
Collagen loss in the stunned myocardium
Department of Medicine, Albert Einstein College of Medicine, Bronx, N.Y. 10461.
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