Korean J Pathol.  2001 Jun;35(3):189-195.

Cardiac Myocyte Cell Death in Isoproterenol-Induced Cardiac Hypertrophy in Rats

• Kim SK
• Chang ES
• Kwon GY

Abstract

BACKGROUND: Although cardiac hypertrophy contributes to cardiac failure, the underlying mechanism has not yet been precisely determined. This study was planned in order to determine the pathogenesis of heart failure following cardiac hypertrophy induced by -adrenergic stimulation.
METHODS
The extent of cardiac hypertrophy was assessed after administrating isoproterenol (ISO, 5 mg/kg) intraperitoneally for 6 hours, 1, 3, 5, 7 and 10 days. The hematoxylin-eosin, Masson's trichrome and phosphotungstic acid hematoxylin stains along with immunohistochemical stainings for proliferating cell nuclear antigen and Ki-67 were performed in the paraffin-embedded left ventricle sections. Apoptosis was assessed by DNA laddering and terminal deoxynucleotidyl transferase TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay. TUNEL positive myocytes and some nonmyocytes appeared in the subepicardium at 6 hours after ISO administration. The localization of these cells was shifted to the subendocardium within 24 hours, and the TUNEL positive cells were seen throughout the myocardium on the 5th day after ISO treatment. Necrotic myocyte death occurred on the 3rd day of ISO administration in the subendocardium, and initial pericellular fibrosis was followed and increased thereafter, with replacement fibrosis accompanied by further necrotic myocyte cell death.
CONCLUSIONS
Our data showed that ISO treatment induced apoptotic myocyte death and superimposed necrotic myocyte death with subsequent fibrosis. The observed cardiac myocyte death may reflect myocardial dysfunction.

Keyword

Isoproterenol; Hypertrophy; Left ventricle; Apoptosis

MeSH Terms

Animals
Apoptosis
Cardiomegaly*
Cell Death*
Coloring Agents
DNA
DNA Nucleotidylexotransferase
Fibrosis
Heart Failure
Heart Ventricles
Hematoxylin
Hypertrophy
In Situ Nick-End Labeling
Isoproterenol
Muscle Cells
Myocardium
Myocytes, Cardiac*
Phosphotungstic Acid
Proliferating Cell Nuclear Antigen
Rats*
Coloring Agents
DNA
DNA Nucleotidylexotransferase
Hematoxylin
Isoproterenol
Phosphotungstic Acid
Proliferating Cell Nuclear Antigen