title: Effect of inhaled tacrolimus on ischemia reperfusion injury in rat lung transplant model.
abstract: OBJECTIVE
  Systemic tacrolimus therapy has been shown to protect against lung ischemia-reperfusion injury in animal models. We sought to investigate on a functional and cellular level if inhaled nanoparticle tacrolimus administered to the donor lung before procurement could similarly attenuate ischemia-reperfusion injury after lung transplant.
  
  
  METHODS
  An isogenic orthotopic rat model of single left lung transplant was used. Donor animals were pretreated with inhaled tacrolimus (treatment group) or inhaled lactose (controls) before lung procurement. Lung grafts were subjected to 3 hours of cold ischemia followed by 4 hours of reperfusion after graft implantation. Recipient animal arterial blood gas measurement and isograft wet to dry weight ratios were obtained. Macrophage, neutrophil, and T-cell accumulation and activation in lung isografts, including γδ T-cell, T-helper, and cytotoxic T-cell subtypes were analyzed by flow cytometry. Tacrolimus levels were measured in the lung isograft using liquid chromatography/mass spectrometry. Isograft cytokine levels were measured with commercial enzyme-linked immunosorbent assay and microbead array kits.
  
  
  RESULTS
  Oxygenation in treatment group animals was significantly higher than in controls. The presence of macrophages, neutrophils, and all T-cell subtypes in the isografts as well as isograft levels of inflammatory cytokines were all less in the treatment group versus controls, although no single variable achieved statistical significance.
  
  
  CONCLUSIONS
  Inhaled nanoparticle tacrolimus treatment of lung donors is associated with an attenuation of ischemia-reperfusion injury on a functional and cellular level in lung transplant.
authors.affiliation: Department of Cardiothoracic Surgery, University of Texas Health Science Center in San Antonio, San Antonio, Tex. Electronic address: Bayer@uthscsa.edu.
authors.forename: Johanna
authors.initials: J
authors.lastname: Bayer
authors.forename: Nitin A
authors.initials: NA
authors.lastname: Das
authors.forename: Clinton E
authors.initials: CE
authors.lastname: Baisden
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Rani
authors.forename: Daniel T
authors.initials: DT
authors.lastname: DeArmond
authors.forename: Jay I
authors.initials: JI
authors.lastname: Peters
authors.forename: Scott B
authors.initials: SB
authors.lastname: Johnson
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001784:Blood Gas Analysis; D002633:Chemotaxis / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016040:Lung Transplantation / Q000009:adverse effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D053758:Nanoparticles; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: 12; 38; 38.1; 9; CD; IRI; clusters of differentiation; ischemia-reperfusion injury