Monti E, Piccinini F, Villani F, Favalli L
Cancer Chemother Pharmacol. 1986;18(3):289-91. doi: 10.1007/BF00273406.
A single administration of adriamycin (DXR) 6.0 mg/kg i.v. to rats brings about a biphasic impairment of the maximal myocardial contractile performance, measured as dF/dt of ex vivo isolated atria incubated in the presence of calcium concentrations varying up to 12 mM. The initial impairment of the contractile performance peaks 1 week after DXR administration and recovers within 3 weeks (acute phase of cardiotoxicity). After this time and up to the end of the observation period (8 weeks after treatment), delayed cardiotoxicity occurs, showing a progressive and irreversible impairment of the contractile performance of the atria. This behaviour parallels the previously shown ECG and morphological abnormalities. Tissue determinations of DXR showed that the drug is present in myocardium during the acute phase of cardiotoxicity, while the metabolite adriamycinol is not detectable 1 week after DXR administration. These data show that the presence of DXR and/or metabolites in heart muscle is not necessary for the delayed form of cardiotoxicity to become apparent and suggest that this form of cardiotoxicity is related to a mechanism different from that involved in acute cardiotoxicity.
给大鼠静脉注射一次阿霉素（DXR）6.0mg/kg，会导致最大心肌收缩性能出现双相损害，该性能通过在高达12mM的不同钙浓度下孵育的离体心房的dF/dt来测量。收缩性能的初始损害在给予DXR后1周达到峰值，并在3周内恢复（心脏毒性急性期）。在此之后直至观察期结束（治疗后8周），出现迟发性心脏毒性，表现为心房收缩性能进行性且不可逆的损害。这种行为与先前显示的心电图和形态学异常相似。DXR的组织测定表明，在心脏毒性急性期心肌中存在该药物，而在给予DXR 1周后无法检测到代谢产物阿霉素醇。这些数据表明，心肌中存在DXR和/或代谢产物对于迟发性心脏毒性的显现并非必要，并提示这种形式的心脏毒性与急性心脏毒性所涉及的机制不同。
