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Detection of antineoplastic agent induced cardiotoxicity by 31P NMR of perfused rat hearts
Abstract:
Development of dose dependent chronic irreversible cardiotoxicity is a key problem encountered in chemotherapy with adriamycin. Here it has been demonstrated that infusion of this agent produced distinct and largely irreversible changes in levels of phosphate metabolites and substantial acidosis that are detected by 31P NMR of the Langendorf perfused heart. Administration of the antioxidant, butylated hydroxytoluene minimizes these spectral changes but does not substantially diminish the antineoplastic activity of adriamycin. Bisantrene (CL 216,942), a noncardiotoxic anthracene with antineoplastic activity, produces only minor perturbations of the 31P spectrum of the perfused rat heart. These studies demonstrate the potential utility of employing 31P NMR to monitor acute or chronic cardiotoxicity in the perfused rat heart and for developing noninvasive in vivo NMR techniques for monitoring cardiotoxicity in experimental animals and humans.
Insights
Adriamycin chemotherapy causes irreversible heart damage by altering phosphate metabolites. Antioxidants reduce these changes without affecting cancer treatment efficacy, suggesting NMR can monitor heart toxicity.
Area of Science:
- Biochemistry
- Cardiology
- Oncology
Background:
- Adriamycin chemotherapy can cause dose-dependent, irreversible cardiotoxicity, a significant clinical challenge.
- Understanding the biochemical mechanisms of adriamycin-induced cardiotoxicity is crucial for developing safer treatments.
Purpose of the Study:
- To investigate the effects of adriamycin on cardiac phosphate metabolites and acidosis using 31P NMR.
- To evaluate the protective role of the antioxidant butylated hydroxytoluene against adriamycin cardiotoxicity.
- To assess the cardiotoxicity profile of bisantrene, a non-cardiotoxic anthracene derivative.
Main Methods:
- Utilized 31P Nuclear Magnetic Resonance (NMR) spectroscopy on Langendorff-perfused rat hearts.
- Administered adriamycin and monitored changes in phosphate metabolites and acidosis.
- Investigated the effects of butylated hydroxytoluene and bisantrene on cardiac 31P NMR spectra.
Main Results:
- Adriamycin infusion induced significant, largely irreversible changes in cardiac phosphate metabolites and acidosis, detectable by 31P NMR.
- Butylated hydroxytoluene administration minimized these spectral changes but did not compromise adriamycin's anti-cancer activity.
- Bisantrene, a non-cardiotoxic agent, caused only minor perturbations in the 31P NMR spectrum.
Conclusions:
- 31P NMR is a valuable tool for monitoring acute and chronic cardiotoxicity in perfused rat hearts.
- This technique holds potential for developing noninvasive in vivo NMR methods to assess cardiotoxicity in preclinical and clinical settings.
- Findings support the development of strategies to mitigate adriamycin-induced cardiotoxicity while preserving its therapeutic benefits.