Pyrrolidine dithiocarbamate reduces lung reperfusion injury.
BACKGROUND
The inflammatory cascade has emerged as the primary mediator of reperfusion injury. Nuclear factor kappaB (NF-kappaB) 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-kappaB 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 degrees 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-kappaB 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-kappaB 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-kappaB activity.
Long
Stewart M
SM
Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia Health System, Charlottesville, Virginia 22908-1359, USA.
Laubach
Victor E
VE
Tribble
Curtis G
CG
Kaza
Aditya K
AK
Fiser
Steven M
SM
Cassada
David C
DC
Kern
John A
JA
Kron
Irving L
IL
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000188:drug therapy* / Q000601:surgery; D016040:Lung Transplantation; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy*; D013859:Thiocarbamates / Q000494:pharmacology*
D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid