SWINE LUNGS EXPRESSING HUMAN COMPLEMENT-REGULATORY PROTEINS ARE PROTECTED AGAINST ACUTE PULMONARY DYSFUNCTION IN A HUMAN PLASMA PERFUSION MODEL

Pulmonary transplantation is currently limited by the number of suitab le cadaver donor lungs, For this reason, pulmonary xenotransplantation is currently being Investigated, Objective: Our goal was to assess th e role of complement in pulmonary xenograft dysfunction. Methods: The pulmonary function of swine expressing human decay accelerating factor and human CD59 (n = 6) was compared with that of the lungs from nontr ansgenic (control) swine (n = 6) during perfusion with human plasma, R esults: After 2 hours of perfusion, the pulmonary vascular resistance was 1624 +/- 408 dynes . sec . cm(-5) in central lungs and 908 +/- 68 dynes . sec . cm(-5) in transgenic lungs (p < 0.05), Central lungs had a venous oxygen tension of 271 +/- 23 mm Hg with a ratio of venous ox ygen tension to inspired oxygen fraction of 452 +/- 38 at 2 hours of p erfusion; transgenic lungs had a venous oxygen tension of 398 +/- 11 m m Hg and a ratio of venous oxygen tension to inspired oxygen fraction of 663 +/- 18 (p < 0.05), Control lungs showed a decrease of 79.8% +/- 3.7% in static pulmonary compliance by 2 hours, versus a 12.0% +/- 8. 1% decrease by the transgenic lungs (p < 0.05), The control lungs also developed 561.7 +/- 196.2 ml of airway edema over 2 hours, in contras t to 6.5 +/- 1.7 ml in transgenic lungs (p < 0.05), Conclusion: Lungs from swine expressing human decay accelerating factor and human CD59 f unctioned better than nontransgenic swine lungs when perfused with hum an plasma, These results suggest that complement activation is involve d in producing acute pulmonary xenograft dysfunction and demonstrate t hat lungs from swine expressing human decay accelerating factor and hu man CD59 are protected against pulmonary injury when perfused with hum an plasma.