Certain properties of the bleomycin analogs deglycobleomycin A2 and decarbamoylbleomycin A2 have been characterized. In common with bleomycin A2, both deglycobleomycin A2 and decarbamoylbleomycin A2 were found to mediate DNA degradation in the presence of Fe(II) + O2. Both analogs were found to have essentially the same sequence selectivity for DNA strand scission as bleomycin A2 when a 5'-[23P]-end-labeled linear duplex DNA derived from SV40 DNA was employed as a substrate. Product analysis for the three analogs was carried out by assay for malondialdehyde (precursors) after digestion of calf thymus DNA, and also by hplc analysis of the digestion products formed from the dodecanucleotide d(CGCTTTAAAGCG). All three Fe(II) X bleomycin A2 analogs produced the same products, albeit not in the same relative amounts.

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Milrinone (Inocor-Sanofi-Winthrop) represents a second generation phosphodiesterase inhibitor currently approved for intravenous administration in the treatment of decompensated congestive heart failure. By inhibiting Type III phosphodiesterase, milrinone increases intracellular cyclic adenosine monophosphate. This results in a positive inotropic effect on the heart and vasodilatation in the periphery. The hemodynamic consequences of this action produce left ventricular afterload reduction, with an increase in cardiac output and a reduction in total peripheral resistance. Unlike the sympathomimetic amines, milrinone produces no tolerance and possesses the distinct advantage of directly decreasing pulmonary vascular resistance. Short-term intermittent infusion by peripheral administration, continuous infusion, long-term therapy, and intermittent outpatient therapy was demonstrated to be safe, efficacious, and cost effective. It is hypothesized that intravenous milrinone, by producing biventricular afterload reduction, offers an efficacious, cost-effective tool for the treatment of decompensated heart failure.

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