title: Platelet activating factor antagonist enhances lung preservation.
abstract: Platelet activating factor (PAF) is a potent phospholipid mediator of the immune and inflammatory responses, which causes physiologic effects similar to post-transplant pulmonary dysfunction. This study investigates the hypothesis that the use of a specific PAF antagonist (PAFA), BN 52021, in canine lung transplantation improves lung preservation. Twelve pairs of canines underwent left lung allotransplantation after pulmonary artery flushing with modified Euro-Collins (EC) solution (40 ml/kg). The experimental group (N = 6) received EC with BN 52021 (10 mg/kg). BN 52021 was administered to donors prior to harvest and to recipients prior to reperfusion. The preservation interval was 20 hr and the study period was 12 hr post-transplant. Differential pulmonary function and hemodynamics were monitored, comparing the transplanted left lung and the native right lung. Recipients were ventilated on 100% O2. Administration of the platelet activating factor antagonist, BN 52021, was associated with improvement in transplant lung oxygenation, pulmonary vascular resistance, and compliance. At 12 hr, transplant lung pulmonary venous oxygen tension in the treatment group (EC + BN 52021) was 154 +/- 21 mm Hg versus 87 +/- 10 mm Hg in the control group (EC) (P less than 0.05). Pulmonary vascular resistance of the transplant lung at 12 hr was 146 +/- 24 Dynes.sec.cm-5 in the EC + BN 52021 group as compared to 320 +/- 51 Dynes.sec.cm-5 in the EC group (P less than 0.05). Dynamic pulmonary compliance of the transplant lung at 12 hr was 32 +/- 2.9 ml/cm H2O in the EC + BN 52021 group versus 13 +/- 2.0 ml/cm H2O in the EC group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery, Georgetown University Medical Center, Washington, D.C. 20007.
authors.forename: P C
authors.initials: PC
authors.lastname: Corcoran
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: N M
authors.initials: NM
authors.lastname: Katz
authors.forename: J D
authors.initials: JD
authors.lastname: St Louis
authors.forename: M L
authors.initials: ML
authors.lastname: Foegh
authors.forename: S S
authors.initials: SS
authors.lastname: Rajan
authors.forename: A R
authors.initials: AR
authors.lastname: Analouei
authors.forename: R B
authors.initials: RB
authors.lastname: Wallace
mesh_terms: D000818:Animals; D001834:Body Water; D004224:Diterpenes; D004285:Dogs; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008170:Lung Compliance; D016040:Lung Transplantation; D008297:Male; D009926:Organ Preservation; D010100:Oxygen / Q000097:blood; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D014655:Vascular Resistance
chemical_list: D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; C045856:ginkgolide B; D010100:Oxygen