Isolated lung perfusion with Adriamycin. A preclinical study.
Isolated in vivo single-lung perfusion with an Adriamycin-containing whole-blood perfusate was performed in three groups of dogs after establishing adequate controls. The procedure, performed through a left thoracotomy, was followed two weeks later by a contralateral pneumonectomy. Survival following pneumonectomy was used as the ultimate end point in assessing perfusion toxicity. Groups I and II had high mortality rates but provided valuable information concerning perfusion methods, venous drainage techniques, drug dosage schedules, and perfusate flow rates. The group III study consisted of five dogs perfused for 45 minutes at flow rates sufficient to maintain mean pulmonary artery pressure at 12-15 mm Hg. An initial Adriamycin (Adr) dosage of 0.5 micrograms/ml in the plasma perfusate resulted in mean peak Adr lung tissue levels of 3.8 +/- 1.06 micrograms/g. All animals survived right pneumonectomy 19 +/- 4 days later. Three dogs have been killed and histologic examination showed only mild focal pleural and subpleural interstitial fibrosis. Based on these studies it is concluded that isolated single-lung perfusion is a reproducibly safe technique and that a dosage of Adr has been identified which produces no apparent toxity in a large animal model. A clinical trial is currently in progress.
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000032:analysis; D008168:Lung / Q000032:analysis / Q000601:surgery; D008954:Models, Biological; D010477:Perfusion / Q000379:methods*; D011013:Pneumonectomy
D004317:Doxorubicin