title: Enhanced pulmonary function using dimethylthiourea for twelve-hour lung preservation.
abstract: Current preservation techniques for lung transplantation limit ischemic time to 6 hours. The purpose of this study was to evaluate the ability of dimethylthiourea, a low molecular weight free radical scavenger, to prolong this interval. An in vivo canine transplantation model was used to assess lung function. At harvest and after circulatory arrest, the donor lung was flushed with modified Euro-Collins solution (50 mL/kg). In a blinded fashion, dimethylthiourea (5 g) or saline solution was added to the flush solution at harvest and also infused (20 g over 2 hours) at reimplantation. Harvested lungs were stored for 12 hours at 4 degrees C. Allotransplantation was performed in recipient dogs ventilated with 40% O2. After 1 hour, the contralateral pulmonary artery was ligated, forcing the dog to be dependent on the transplanted lung. Twelve dogs were studied, with 6 randomly assigned to each treatment group in a blinded fashion. Measurements were recorded for 8 hours, keeping the inspired oxygen fraction constant at 0.40. All dimethylthiourea-treated dogs survived the observation period, whereas one third of the dogs that received saline solution died. Dimethylthiourea-treated dogs had significantly greater arterial oxygen tension and significantly less pulmonary vascular resistance compared with control animals. These results suggest that treatment of the lung with a free radical scavenger (dimethylthiourea) improves pulmonary function after reimplantation in a canine model after 12-hour hypothermic storage.
authors.affiliation: Division of Cardiothoracic Surgery, University of North Carolina School of Medicine, Chapel Hill.
authors.forename: C J
authors.initials: CJ
authors.lastname: Lambert
authors.forename: T M
authors.initials: TM
authors.lastname: Egan
authors.forename: F C
authors.initials: FC
authors.lastname: Detterbeck
authors.forename: B A
authors.initials: BA
authors.lastname: Keagy
authors.forename: B R
authors.initials: BR
authors.lastname: Wilcox
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D008168:Lung / Q000502:physiology*; D016040:Lung Transplantation; D009926:Organ Preservation / Q000379:methods; D010100:Oxygen / Q000097:blood; D011652:Pulmonary Circulation / Q000187:drug effects; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: C038983:1,3-dimethylthiourea; D013890:Thiourea; D010100:Oxygen