Pyrrolidine dithiocarbamate reduces lung reperfusion injury

• Published in: The Journal of surgical research 2003-06, Vol.112 (1), p.12-18
• Main Authors: Long, Stewart M, Laubach, Victor E, Tribble, Curtis G, Kaza, Aditya K, Fiser, Steven M, Cassada, David C, Kern, John A, Kron, Irving L
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Female; Graft Survival - drug effects; HSP70; HSP70 Heat-Shock Proteins - metabolism; In Vitro Techniques; inflammation; ischemia; lung; Lung - metabolism; Lung Diseases - drug therapy; Lung Diseases - surgery; Lung Transplantation; Male; NF-kappa B - metabolism; NF-κB; pulmonary; Pyrrolidines - pharmacology; Rabbits; reperfusion injury; Reperfusion Injury - drug therapy; Thiocarbamates - pharmacology; transplant
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/S0022-4804(03)00139-2

Background. The inflammatory cascade has emerged as the primary mediator of reperfusion injury. Nuclear factor κB (NF-κB) is a rapid response transcription factor that activates genes responsible for the mediators of inflammation. Heat shock protein 70 (HSP70) has been shown to protect against lung injury. We hypothesized that the antioxidant pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB and upregulator of HSP70, would decrease lung injury after ischemia and reperfusion. Methods. Using our isolated, ventilated, blood-perfused rabbit lung model, all groups underwent lung harvest followed by 10-h storage (4°C) and blood reperfusion for 30 min. Group I lungs ( n = 5) served as controls. In group II lungs ( n = 5), both lung and blood donors received PDTC (100 mg/kg) intravenously 30 min before harvest. NF-κB activity was evaluated with electrophoretic mobility shift assay, and Western blot was performed for HSP70. Results. Group II demonstrated superior pulmonary function. Although HSP70 expression was somewhat elevated in group II lungs, NF-κB binding activity was not different between the groups. Conclusions. PDTC improves pulmonary function after ischemia and reperfusion in an isolated rabbit lung model. The improved function correlates with elevated HSP70 expression during initial reperfusion, independent of NF-κB activity.