Why the study?
Does pretreatment with chelating agents (EDTA or ICRF 159) prevent adriamycin- or daunomycin-induced increases in coronary perfusion pressure in isolated dog hearts?
Does pretreatment with chelating agents (EDTA or ICRF 159) prevent adriamycin- or daunomycin-induced increases in coronary perfusion pressure in isolated dog hearts?
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Chelation with EDTA or ICRF 159 prevents anthracycline-induced increases in coronary vascular resistance and alters their metabolism in isolated dog hearts, suggesting a potential mechanism to reduce cardiotoxicity.
In the isolated, blood-perfused dog heart daunomycin (50 mg) or adriamy-cin (50 mg) induced significant increases in coronary perfusion pressure. This effect appeared to be related to the conversion of the parent compounds to aglycone metabolites similar to daunomycinone. Pretreatment of the heart with agents blocking the vasoactive actions of epinephrine, histamine, serotonin or acetylcholine did not prevent the alteration in coronary vascular resistance. In contrast, 100 mg of either EDTA or ICRF 159 prevented the marked increase in perfusion pressure and reduced the formation of aglycone metabolites. Chelation is a common property of the 2 agents suggesting that removal of certain cations may alter metabolism and reduce the toxicity of adriamycin and daunomycin.
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Herman et al. (1972) studied this question.
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