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Electrolyte and morphologic alterations of myocardium in adriamycin-treated rabbits
Abstract:
Rabbits receiving adriamycin (ADR) on a chronic schedule developed significant histopathologic, ultrastructural and tissue electrolyte alterations of the ventricular myocardium. Rabbits that developed clinicopathologic evidence of cardiomyopathy with ADR had histologic lesions of the myocardium, including perivascular fibrosis, interstitial fibrosis and edema and myocytolysis. Ultrastructurally, large vacuoles resembling distended sarcoplasmic reticulum displaced the contractile elements and mitochondria, which were diminished in number within affected myocytes. Frequently, mitochondria appeared as electron-dense structures surrounded by layers of membranes resembling myelin figures. In addition, rabbits with cardiomyopathy had marked elevations in ventricular Ca, Na and H(2)O concentrations. Serum electrolytes were not significantly elevated, but lactic dehydrogenase (LDH) and creatine phosphokinase (CPK) were significantly increased, indicative of a cardiomyopathy. Rabbits receiving ADR but not developing clinicopathologic evidence of heart failure also had significant elevations in ventricular Ca, Na and H(2)O. Rabbits with no cardiomyopathy had no increases either in serum electrolyte concentrations or CPK and LDH levels. These studies indicate that marked increases in ventricular tissue Ca precede and accompany morphologic evidence of chronic myocardial degeneration and may be instrumental in the development of the ADR-induced cardiomyopathy.
Insights
Adriamycin (ADR) causes chronic heart damage in rabbits, leading to cell changes and electrolyte imbalances. Increased calcium in heart tissue appears critical for developing ADR-induced cardiomyopathy.
Area of Science:
- Cardiology
- Toxicology
- Cell Biology
Background:
- Adriamycin (ADR) is a chemotherapy agent with known cardiotoxicity.
- Chronic ADR administration can lead to heart muscle damage (cardiomyopathy).
Purpose of the Study:
- To investigate the histopathologic, ultrastructural, and electrolyte changes in rabbit myocardium following chronic ADR exposure.
- To determine the role of tissue electrolytes, particularly calcium, in the development of ADR-induced cardiomyopathy.
Main Methods:
- Rabbits received chronic ADR treatment.
- Histopathologic and ultrastructural analyses of ventricular myocardium were performed.
- Tissue and serum electrolyte concentrations (Ca, Na, H2O), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) were measured.
Main Results:
- ADR-induced cardiomyopathy in rabbits showed perivascular/interstitial fibrosis, edema, and myocytolysis.
- Ultrastructural analysis revealed sarcoplasmic reticulum dilation and mitochondrial changes (diminished number, myelin figures).
- Marked increases in ventricular Ca, Na, and H2O were observed in rabbits with cardiomyopathy, preceding and accompanying morphologic damage. Elevated LDH and CPK also indicated cardiac injury.
Conclusions:
- Increased ventricular calcium concentrations precede and accompany morphologic evidence of chronic myocardial degeneration in ADR-treated rabbits.
- Elevated tissue calcium may play a crucial role in the pathogenesis of ADR-induced cardiomyopathy.
- Monitoring tissue electrolytes may aid in understanding and potentially mitigating ADR cardiotoxicity.