Acute circulatory effects of doxorubicin in the conscious dog

Experimental work on the mechanisms of acute doxorubicin-induced cardiotoxicity may contribute to a better understanding of the clinical problem of cardiac failure after treatment with anthracycline derivatives. We studied aortic pressure and heart rate continuously for 1 h following a bolus injection of doxorubicin (1 mg/kg) in 7 dogs. In contrast with previous studies in intact animals, no anesthesia was used in order to eliminate possible interactions of doxorubicin with other drugs. One minute after doxorubicin injection a severe hypotension was observed, the average nadir in systolic and diastolic pressure being 62% and 42% of initial values. Surprisingly, the decrease in arterial blood pressure was not accompanied by cardiac acceleration. Doxorubicin, apparently interferes with the normal regulation of heart rate through the baroreceptor control system. Although several theories have been put forward regarding the mechanisms governing acute anthracycline cardiotoxicity, our knowledge of the phenomenon is still incomplete.