title: Protective effect of a nebulized beta2-adrenoreceptor agonist in warm ischemic-reperfused rat lungs.
abstract: BACKGROUND
  It seems inevitable that non-beating-heart donors will be utilized to resolve the shortage of donors for clinical lung transplantation. The control of warm ischemia-reperfusion injury is crucial in manipulating non-beating-heart donors. We hypothesized that nebulization of a beta2-adrenoreceptor agonist, salmeterol xinafoate (SLM), during warm ischemia would increase lung tissue cyclic adenosine monophosphate (cAMP) levels, resulting in lung protection.
  
  
  METHODS
  Two studies were conducted. The first investigated the effect of SLM nebulization during ischemia on pulmonary ischemia-reperfusion injury, using an isolated rat lung-perfusion model. The heart-lung block was excised with cannulation of the pulmonary artery and vein, exposed to 55 minutes of ischemia at 37 degrees C, and subsequently reperfused for 60 minutes. Several parameters were measured during reperfusion. In the second study, to measure changes in lung tissue cAMP levels during warm ischemia with or without SLM nebulization, rat lungs were harvested and exposed to 60 minutes of warm ischemia with ventilation.
  
  
  RESULTS
  Salmeterol xinafoate nebulization significantly decreased the pulmonary shunt fraction, airway resistance, and pulmonary vascular resistance. It also inhibited pulmonary edema throughout the reperfusion period. Lung tissue cAMP was effectively maintained by SLM nebulization at the end of reperfusion. Myeloperoxidase activity in the lungs was decreased significantly by SLM nebulization. Lung tissue cAMP levels decreased during the 60 minutes of warm ischemia, but increased with SLM nebulization (p < 0.01).
  
  
  CONCLUSIONS
  Our results confirmed that SLM nebulization during warm ischemia maintained lung tissue cAMP levels, resulting in the alleviation of pulmonary warm ischemia-reperfusion injury.
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Kyoto, Japan.
authors.forename: Fengshi
authors.initials: F
authors.lastname: Chen
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takuji
authors.initials: T
authors.lastname: Fujinaga
authors.forename: Jitian
authors.initials: J
authors.lastname: Zhang
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamakawa
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Omasa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakai
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Hanaoka
authors.forename: Toru
authors.initials: T
authors.lastname: Bando
authors.forename: Hiromi
authors.initials: H
authors.lastname: Wada
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Fukuse
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D000242:Cyclic AMP / Q000032:analysis; D004734:Energy Metabolism; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D000068299:Salmeterol Xinafoate; D014655:Vascular Resistance / Q000187:drug effects; D052096:Warm Ischemia
chemical_list: D000318:Adrenergic beta-Agonists; D000336:Aerosols; D000068299:Salmeterol Xinafoate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D009195:Peroxidase; D000420:Albuterol