Isoproterenol-induced myocardial fibrosis in relation to myocyte necrosis

Journal Article · Fri Sep 01 00:00:00 EDT 1989 · Circulation Research; (USA)

DOI:https://doi.org/10.1161/01.RES.65.3.657· OSTI ID:5413125

Benjamin, I J; Jalil, J E; Tan, L B; Cho, K; Weber, K T; Clark, W A ^[1]

---

1. Michael Reese Hospital, Chicago, IL (USA)

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.

• OSTI ID: 5413125
• Journal Information: Circulation Research; (USA), Vol. 65:3; ISSN 0009-7330
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
FIBROBLASTS
CELL PROLIFERATION
MYOCARDIUM
PATHOLOGICAL CHANGES
SYMPATHOMIMETICS
BIOCHEMICAL REACTION KINETICS
AUTORADIOGRAPHY
DNA
DNA REPLICATION
DOSE-RESPONSE RELATIONSHIPS
FIBROSIS
HEART
MONOCLONAL ANTIBODIES
MYOSIN
NECROSIS
RATS
THYMIDINE
TRITIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
ANTIBODIES
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
BODY
CARDIOVASCULAR SYSTEM
CONNECTIVE TISSUE CELLS
DRUGS
GLOBULINS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
KINETICS
MAMMALS
MUSCLES
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PYRIMIDINES
REACTION KINETICS
RIBOSIDES
RODENTS
SOMATIC CELLS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques