Changes in Electrophysiology, Heart Rate Variability and Proteinuria in Clinical Dogs Treated with Doxorubicin Chemotherapy
Keywords:
dogs, doxorubicin, heart rate variability, proteinuria, QTcAbstract
The objective of the study was to evaluate the effects of doxorubicin (DOX) at the dose used in clinical practice (12-25 mg/m2 body surface area) on cardiac electrophysiology and proteinuria. Nine dogs with tumors were treated with 1st dose of DOX while 6 and 3 dogs were left for 2nd and 3rd doses, respectively. Measurements of blood chemistries, blood pressure, electrocardiography, heart rate variability and proteinuria were performed after the 1st, 2nd and 3rd doses of DOX. All data were obtained the day just before the next dose was introduced. Results showed that giving 1 to 3 doses of DOX did not alter serum CPK or AST. However, the BUN increased at the 3rd dose along with significant reduction in plasma albumin (p<0.05). The blood pressures decreased significantly (p<0.05) without heart rate acceleration at the 2nd dose, indicating impaired autonomic response. Electrocardiography demonstrated significant prolonged QTc (p<0.05) at the 2nd dose. Analysis of frequency domain power spectrum of heart rate variability showed increased low frequency (LF) and high frequency (HF) ratio (LF/HF) which suggested the enhancement of sympathetic over parasympathetic. Although proteinuria, which was mainly albumin, was minimal, it showed a dramatic increase as seen after the 1st dose of DOX treatment. These results suggest that routine screening using electrocardiography and proteinuria should be used for monitoring the cardiac and renal toxicities of DOX in dogs during anti-tumor treatment.
