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Ann Thorac Surg 1995;60:244
© 1995 The Society of Thoracic Surgeons
DR THOMAS M. EGAN (Chapel Hill, NC): What do you think the cardiac toxicity would be in vivo, and have you looked at that in any surviving rats that you have perfused?
DR PORT: There is evidence that glutathione may provide cardioprotection from agents such as doxorubicin. Therefore, there has been considerable hesitancy in using BSO, an inhibitor of glutathione, with systemic doxorubicin therapy. We have demonstrated in our model of isolated lung perfusion that there is very little systemic leak when perfusions are performed with doxorubicin. We have shown that the cardiac outputs of rats perfused with doxorubicin are preserved in comparison with intravenously treated animals. Doxorubicin isolated lung perfusion with BSO pretreatment is therefore an ideal treatment model.
DR FRANK A. BACIEWICZ (Detroit, MI): I enjoyed your paper. You have done previous studies at your institution with doxorubicin alone and showed almost no tumor in the lung. In this study did you select less than a maximum dose of doxorubicin so that tumor is present and a response can be seen with the BSO? If you used higher doses of doxorubicin, were there better results in concert with the BSO? Third, did you do a contralateral pneumonectomy to look at the toxicity in this model?
DR PORT: Our previous studies used much higher doses of doxorubicin for perfusions. In those studies we achieved a complete response to therapy. To assess the efficacy of BSO pretreatment, we needed to lower the dose of doxorubicin to the point where only a partial response was evident. In response to assessing local toxicity, we have not yet performed those experiments.
DR LARRY R. KAISER (Philadelphia, PA): I enjoyed your paper. You have done a lot with this model. You have treated with the BSO I believe at day 6 after injection of your tumor cells. I know the methylcholanthrene-induced sarcoma is quite an aggressive tumor. Do you have gross nodules that can be seen at day 7 when you did your isolated perfusion, or is there only microscopic disease at that point?
DR PORT: Gross disease is first evident by day 10.
DR KAISER: In how many days would the injection of tumor cells that you used here kill these animals if untreated?
DR PORT: Animals injected with this number of cells would succumb to disease by 21 days.
Related Article
Ann. Thorac. Surg. 1995 60: 239-243.
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