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Differential cardiotoxic electrocardiographic response to doxorubicin treatment in conscious versus anesthetized mice
Anna Warhol1, Sharon A George1, Sofian N Obaid1
1Department of Biomedical Engineering, The George Washington University, Washington, DC, USA.
Introduction:
Doxorubicin (DOX), an anticancer drug used in chemotherapy, causes significant cardiotoxicity. This study aimed to investigate the effects of DOX on mouse cardiac electrophysiology, in conscious versus anesthetized state.
Methods:
Male and female C57BL/6 mice were injected with saline, 20 or 30 mg/kg DOX. ECGs were recorded 5 days post-injection in conscious and isoflurane anesthetized states. ECGs were analyzed using a custom MATLAB software to determine P, PR, QRS, QTc, and RR intervals as well as heart rate variability (HRV).
Results:
ECGs from the same mouse demonstrated P wave and QTc shortening as well as PR and RR interval prolongation in anesthetized versus conscious saline-treated mice. ECG response to DOX was also modulated by anesthesia. DOX treatment induced significant ECG modulation in female mice alone. While DOX20 treatment caused decrease in P and QRS durations, DOX30 treatment-induced QTc and RR interval prolongation in anesthetized but not in conscious female mice. These data suggest significant sex differences and anesthesia-induced differences in ECG response to DOX. HRV measured in time and frequency domains, a metric of arrhythmia susceptibility, was increased in DOX20-treated mice compared to saline.
Conclusions:
This study for the first time identifies that the ECG response to DOX is modulated by anesthesia. Furthermore, this response demonstrated stark sex differences. These findings could have significant implications in clinical diagnosis of DOX cardiotoxicity.
Insights
Anesthesia significantly alters electrocardiogram (ECG) responses to doxorubicin (DOX), a chemotherapy drug, with notable sex differences observed in mice. These findings impact clinical diagnosis of DOX cardiotoxicity.
Area of Science:
- Cardiology
- Pharmacology
- Translational Medicine
Background:
- Doxorubicin (DOX) is a vital chemotherapy agent with known cardiotoxicity.
- Understanding DOX-induced cardiac electrophysiological changes is crucial for patient management.
Purpose of the Study:
- To investigate the impact of anesthesia on doxorubicin's effects on mouse cardiac electrophysiology.
- To identify potential sex-based differences in these responses.
Main Methods:
- Male and female mice received saline or doxorubicin (20 or 30 mg/kg).
- Electrocardiograms (ECGs) were recorded in conscious and isoflurane-anesthetized states 5 days post-injection.
- ECG intervals (P, PR, QRS, QTc, RR) and heart rate variability (HRV) were analyzed.
Main Results:
- Anesthesia altered ECG parameters (P, QTc shortening; PR, RR prolongation) in saline-treated mice.
- Doxorubicin's ECG effects were modulated by anesthesia, particularly in female mice.
- DOX treatment increased arrhythmia susceptibility (HRV) in female mice.
Conclusions:
- Anesthesia significantly modifies electrocardiogram responses to doxorubicin.
- Significant sex differences exist in doxorubicin-induced cardiac electrophysiological changes.
- Findings have implications for diagnosing doxorubicin cardiotoxicity in clinical settings.
