Repetitive administration of the anthracycline antineoplastic doxorubicin in man or experimental animals produce a dose-related cardiomyopathy that may culminate in severe cardiac dysfunction, overt heart failure, or death. We propose (a) to study the cardiovascular effects of long-term doxorubicin administration in dogs equipped with totally implantable telemetry devices and (b) to use the derived information to test a cardioprotective strategy that is based on the hypothesis that cardiac damage is mediated, at least in part, by the release of vasoactive amines (histamine and catecholamines). The first goal of this investigation is to elucidate the manner in which the heart of the intact conscious animal with normal cardiovascular reflexes responds to long-term doxorubicin administration, and to correlate functional changes accompanying the onset of cardiomyopathy and failure with structural changes in the heart. Specific physiological and pharmacological interventions will be employed to characterize serial changes in sympathetic and parasympathetic control mechanisms and the inotropic responsiveness of the heart. Animals on a long-term dosing regimen of doxorubicin combines with histaminic (diphenhydramine and cimetidine) and adrenergic (phentolamine and propranolol) blockade will then be evaluated using the same experimental interventions, and the success of the cardioprotective strategy will be judged on the basis of deviation from the failure profile. This research is important not only because it will provide clinically useful information regarding an important antineoplastic drug, but also because it will permit us to evaluate a heart failure model that is based on a chemically induced myopathy and to demonstrate the usefulness of totally implantable telemetry instrumentation in conducting cardiovascular studies that require weeks and months to complete.