Platelet activating factor antagonist enhances lung preservation in a canine model of single lung allotransplantation.
Optimal techniques for lung preservation are yet to be defined. Platelet activating factor is a phospholipid released by a variety of cells and produces pulmonary abnormalities similar to posttransplantation pulmonary dysfunction. We investigated the strength of the effect of the platelet activating factor antagonist BN 52021 as compared with that of deferoxamine, an iron chelator previously shown to improve lung preservation. Differential lung function and pulmonary hemodynamics were used to assess preservation after a 6-hour period of cold ischemic storage in a modified canine model of left lung allotransplantation. Thirty size- and weight-matched mongrel male dogs were used for 15 transplant procedures randomized to one of three preservation techniques. The University of Wisconsin solution was used as the basic flush solution for all experimental animals. BN 52021 was added to the flush solution in one group (10 mg/kg, n = 5) and deferoxime in another group (10 mg/kg, n = 5). No additives were used for the control animals (n = 5). BN 52021 and deferoxime were administered to respective donor animals 30 minutes before organ harvesting (10 mg/kg) and to recipient animals 30 minutes before reperfusion (10 mg/kg). The pulmonary artery flush solution was administered (40 ml/kg) over 4 minutes. Recipient animals received double-lumen endotracheal tubes and were monitored with balloon-tipped, flow-directed catheters in both pulmonary arteries and dual-angle ultrasonic flow probes around each pulmonary artery. Solid-state high-fidelity micromanometers were used to measure pressures in the pulmonary artery, the left atrium, and the left ventricle. Systemic arterial, right and left pulmonary venous, and mixed venous blood samples were analyzed at 1, 2, 4, and 6 hours after transplantation. Pulmonary venous oxygen tension of the transplanted lung for the control group was 202 +/- 81 mm Hg versus 282 +/- 53 mm Hg for the BN 52021 group 6 hours after transplantation (p less than 0.05). Pulmonary vascular resistance of the transplanted lung for the control group was 319 +/- 54 dynes.sec.cm-5 versus 149 +/- 71 dynes.sec.cm-5 for the BN 52021 group (p less than 0.05). Proton magnetic resonance spectroscopy was performed on segments of upper and lower lobes of the native and transplanted lung from recipient animals to determine total lung water content. The BN 52021 group had a total lung water content of 57.3% as compared with 51.9% for the deferoxime group (p = not significant) and 88.6% for the control group (p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
Corcoran
P C
PC
Department of Surgery, Georgetown University Medical Center, Washington, D.C. 20007.
Wang
Y
Y
Katz
N M
NM
Rajan
S S
SS
Analouei
A R
AR
Foegh
M L
ML
Wallace
R B
RB
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology; D004224:Diterpenes; D004285:Dogs; D046934:Ginkgolides; D005978:Glutathione; D007328:Insulin; D007783:Lactones / Q000494:pharmacology*; D008168:Lung; D016040:Lung Transplantation / Q000502:physiology*; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011887:Raffinose; D015427:Reperfusion Injury / Q000517:prevention & control*; D012996:Solutions / Q000494:pharmacology; D014021:Tissue Preservation
D004224:Diterpenes; D046934:Ginkgolides; D007328:Insulin; D007783:Lactones; D019188:Organ Preservation Solutions; D010972:Platelet Activating Factor; D012996:Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; C045856:ginkgolide B; D005978:Glutathione; D003676:Deferoxamine; D000241:Adenosine; D011887:Raffinose