Reduced in vivo high-energy phosphates precede adriamycin-induced cardiac dysfunction
M Y Maslov1, V P Chacko, G A Hirsch
1Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-6568, USA. mikhail.maslov@caritaschristi.org
Summary
Adriamycin (ADR) chemotherapy can cause heart damage by impairing energy metabolism before causing cardiac dysfunction. This study shows reduced high-energy phosphate (HEP) levels precede left ventricular (LV) issues in mice treated with ADR.
Area of Science:
- Biochemistry
- Cardiology
- Pharmacology
Background:
- Adriamycin (ADR) is a vital chemotherapy drug.
- ADR use is limited by cardiotoxicity.
- Cardiotoxicity may stem from impaired myocardial high-energy phosphate (HEP) metabolism.
Purpose of the Study:
- To test if cardiac energetics decline before left ventricular (LV) dysfunction in ADR-treated mice.
- To investigate the link between HEP metabolism and ADR-induced cardiomyopathy.
Main Methods:
- Mice received weekly ADR injections (5 mg/kg) for 5 weeks.
- Myocardial phosphocreatine-to-ATP ratio (PCr/ATP) measured using (31)P magnetic resonance spectroscopy.
- Left ventricular systolic and diastolic function assessed by magnetic resonance imaging.
Main Results:
- PCr/ATP significantly decreased at 6 weeks post-ADR, before changes in LV function.
- By 8 weeks, reduced PCr/ATP correlated with decreased ejection fraction and peak filling rate.
- These findings indicate impaired cardiac energetics precede LV dysfunction.
Conclusions:
- ADR administration impairs myocardial in vivo HEP metabolism.
- This metabolic impairment occurs before systolic or diastolic abnormalities.
- Impaired HEP metabolism is a likely contributor to ADR-induced myocardial dysfunction.
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