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Isoproterenol-induced myocardial fibrosis in relation to myocyte necrosis. Circ Res 1989 Sep;65(3):657-70

Date

09/01/1989

Pubmed ID

2527639

DOI

10.1161/01.res.65.3.657

Scopus ID

2-s2.0-0024416745   292 Citations

Abstract

Treatment of rats with the beta-adrenergic agonist isoproterenol results in cardiac hypertrophy, myocyte necrosis, and interstitial cell fibrosis. Our objectives in this study have been to examine whether hypertrophy and fibrosis occur in a compensatory and reparative response to myocyte loss or whether either process may be occurring independently of myocyte loss and thus be a reactive response to adrenergic hormone stimulation. We have examined this question by evaluating each of these responses in rats treated with different doses and forms of isoproterenol administration. Myocyte necrosis was evaluated using in vivo labeling with monoclonal antimyosin for identification of myocytes with permeable sarcolemma, which was indicative of irreversible injury. Myocardial fibrosis was evaluated by morphometric point counting of Gomori-stained tissue sections and by assessment of the stimulation of fibroblast proliferation by determination of increased levels of DNA synthesis. Stimulation of fibroblast DNA synthesis was determined from DNA specific radioactivities and radioautography after pulse labeling with [3H]thymidine. The evidence provided by this study suggests that the degree and timing of myocardial hypertrophy does not follow the course of myocyte loss and, thus, appears to be either a response to altered cardiac loading or a reactive response to beta-adrenergic hormone stimulation rather than a compensation for myocyte loss. Myocardial fibrosis, on the other hand, appears to be more closely related to myocyte necrosis with respect to collagen accumulation in the same areas of the heart, its dose-response relation to the amount of isoproterenol administered, and the timing of increased DNA synthesis, or fibroblast proliferation, after myocyte loss.

Author List

Benjamin IJ, Jalil JE, Tan LB, Cho K, Weber KT, Clark WA

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin




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

Animals
Antibodies, Monoclonal
Autoradiography
Cardiomegaly
DNA
DNA Replication
Fibrosis
Heart
Isoproterenol
Male
Myocardium
Myosins
Necrosis
Propranolol
Rats
Rats, Inbred Strains
Thymidine
Tritium
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a