title: Antagonisation of platelet activating factor--a new therapeutic concept for improvement of organ quality in lung preservation.
abstract: The release of platelet activating factor (PAF) is thought to be one of the most important pathophysiological pathways in the development of ischemic lung injury. We investigated the use of a PAF antagonist (PAF-a) in a canine model in reducing PAF-mediated pulmonary dysfunction following lung preservation and transplantation. Twelve combined heterotopic heart and orthotopic left lung allotransplantations were performed after 6 h of cold ischemia. Following administration of prostacyclin (PGI2), Euro-Collins solution (EC) was used for pulmonary artery flush in all donors, while in six animals the PAF-a, WEB 2170 BS, was administered to the donor (0.15 mg/kg for 30 min), to the storage solution (0.3 mg/kg) and to the recipient during reperfusion for a total of 6 h (0.3 mg/kg per h) EC/PAF-a). In all donors myocardial preservation was achieved using St. Thomas Hospital solution. Postoperatively, cardiorespiratory function was evaluated separately for donor and recipient organs at an FiO2 of 0.4 for a maximum of 12 h. The quality of lung preservation was assessed by means of postoperative oxygenation (pO2), pulmonary artery pressure (PAP) and pulmonary vascular resistance index (PVRI). In the EC/PAF-a group, pO2 of the donor lung was significantly elevated (P < 0.01) and PVRI was significantly lower (P < 0.05) when compared to the EC group, while PAP showed no significant differences between both groups and throughout the entire postoperative course. We concluded that a significant improvement in the current clinical standard for lung preservation could be obtained by the application of WEB 2170 BS in combination with EC flush as demonstrated by improved oxygenation and lower PVRI of the transplantated organs.
authors: Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Federal Republic of Germany.
authors: S W
authors: SW
authors: Hirt
authors: T
authors: T
authors: Wahlers
authors: M
authors: M
authors: Jurmann
authors: L
authors: L
authors: Dammenhayn
authors: R
authors: R
authors: Rohde
authors: A
authors: A
authors: Haverich
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D001794:Blood Pressure; D002122:Calcium Chloride / Q000494:pharmacology*; D002314:Cardioplegic Solutions / Q000494:pharmacology; D004285:Dogs; D006321:Heart; D016041:Heart-Lung Transplantation / Q000379:methods* / Q000502:physiology; D008168:Lung; D008274:Magnesium / Q000494:pharmacology*; D023421:Models, Animal; D009926:Organ Preservation / Q000379:methods; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011189:Potassium Chloride / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000517:prevention & control*; D012129:Respiratory Function Tests; D012965:Sodium Chloride / Q000494:pharmacology*; D014655:Vascular Resistance
chemical_list: D001639:Bicarbonates; D002314:Cardioplegic Solutions; D010972:Platelet Activating Factor; C041711:St. Thomas' Hospital cardioplegic solution; D012965:Sodium Chloride; D011189:Potassium Chloride; D008274:Magnesium; D002122:Calcium Chloride