56 Abstracts The Journal of Heart and Lung Transplantation January 1999 84 85 n=l,OOS). The median wait time in Group A was 439 days (95% C.I. of 405-467) vs. 780 days (724-869) in Group B. Conclusions: The waiting time for Group B was substantially longer than Group A. A nation-wide list allocating organs based solely on time would cause a dramatic reduction in lung transplants during the first 1 to 2 years at the sites where two-thirds of the procedures are currently performed. This could lead to the closing of many smaller centers regardless of their clinical outcomes. In addition, ischemia times and the geographic distribution of large centers could prevent ideal use of organs. The ramifications of the proposed changes in organ distribution should be investigated thoroughly prior to implementation. IMPROVED RESULTS FOR RETRANSPLANTATION IN ACUTE AND LATE PULMONARY GRAFT FAILURE W. I&ringer, K. Wiebe, M. Shiiber, U. Fmnke , J. Niedermeyer*, Th Wailers, A. Haverich, Div. of Thoracic and Cardiovascular Surgery, Div. of Pulmomary Medicine*, Hannover Medical School, 30623 Hannover, Germany Retransplantation of the lung is debated controversially, due to a shortage of donor organs and poor results reported. Out of 259 Patients (pts), who underwent lung or heart-lung transplantation at our institution since 1988, 21 pts (8.1 %) were re- transplanted for early, acute (9 pts) or chronic graft failure (12 pts) Retransplantation for acute pulmonary Eailure was performed 9-68 days following transplantation compared to 392-2288 days in late graft failure (bronchiolitis obliterans syndrome, BOS). Twelve of the 21 cases (mean age 36 (14-54)) underwent bilateral sequential pulmonary retmnsplantation. Prior to transplantation, 11 patients were mechanically ventilated. Actuarial survival for all primary lung transplants was 78 % at I year and 64 % at 5 years. For the 21 pts, who were retransplantated, postoperative mortality (90 days) was only 14,2 %, with 17 of 21 patients being discharged from hospital. Survival rates at I,2 and 5 years were 70%. 60% and 53 % respectively. Survival rates for retransplantlon in acute and chronic graft failure were comparable (67 % vs 73% at I yr, 53 vs 52 % at 5 yrs), but time spend in ICU different (62 vs 24 days). Causes of death in the 11 retransplants, who died were infection (4 pts), BOS (4 pts), cardiovascular failures (2 pts) and acute graft failure (Ipt). In contrast to primary transplantation, freedom from BOS (grade 1 or more) following retransplantation for late graft failure was reduced with 68.6 %, 42.2 %, 28.8 %and 28.8 %at 1,2,3 and 4 yrs respectively Retransplantation of the lung allows for acceptable results m carefully selected patients and should be considered as a therapeutical option in the management end-stage BOS. However accelerated reoccurrence of BOS has to be expected. T CELL ACTIVATION IN LEFT VENTRlCULAR ASSIST DEVICE (LVAD) RECIPIENTS OCCURS VIA A CD95-DEPENDENT PATHWAY, AND RESULTS IN LOSS OF THI CELLS AND HIGH LEVELS OF CIRCULATING IL-IO. J Ankersmit, M Schuster, N Edwards, E Burke, A Kocher, K Lietz, D Mancini, M Oz, S Itescu. Columbia University, New York, NY, 10032. We have previously shown that circulating T cells from LVAD recipients demonstrate an increased level of spontaneous T cell apoptosis in vivu. To investigate whether this heightened level of T cell apoptosis was a result of aberrant T cell activation via a CD95 (Fas)-mediated pathway, we measured the semm levels of CD95 (Fas) soluble cleavage products in these patients. The level of soluble CD95 (Fas) molecules was significantly higher in 20 LVAD recipients than in 20 NYHA heart failure controls (mean 2.0 &ml vs 0.6 n&l, p<O.O5). I l/20 (55%) of LVAD recipients had soluble CD95 levels greater than 2SD above the mean in controls, consistent with the high level of CD95 expression detected by immunofluorescence on T cells from LVAD patients. Since Thl T ceils are selectively susceptible to apoptosis via the CD95(Fas)-CD95ligand (FasL) pathway, we examined the relative expression of Thl and Tb2 cytokine profiles in LVAD recipients. In each of 12 heart failure controls, mRNA expression for both Thl cflokines (IL-2 and IFN-gamma) and Th2 cytokines (IL-IO and TGF-beta) was detected in peripheral blood T cells. In contrast, among 12 LVAD recipients mRNA for Th2 cytokines was uniformly detected whereas that for Thl cytokines was not detected in any individual. Since Tb2 type cytokines Induce B cell activation, and LVAD recipients demonstrate excessive B cell hypemeactivity in viva, we next investigated whether LVAD recipients had elevated circulating levels of IL-IO. The level of circulating IL-IO was significantly higher in 20 LVAD recipients than in 20 88 87 NYHA heart failure controls (mean 13.4 pgiml vs I .8 pg/ml, p<O.OS). l3/20 (65%) LVAD recipients had circulating IL-IO levels greater than 2SD above the mean in controls. Together, these results indicate that the high levels of T cell apoptosis in LVAD recipients occurs via a CD95-dependent pathway, and that the subsequent selective loss of Thl cells results in unopposed ThZ activity with high levels of circulating Th2 cytokines. This mechanism is likely to account for the excessive B cell hyperreactivity and antibody production in LVAD recipients. T CELL APOPTOSIS AND DEFECTS IN CELLULAR IMMUNITY INDUCED BY EXPOSURE TO BIOMATERIALS: IMPLICATIONS FOR LEFT VENTRlCULAR ASSIST DEVICE (LVAD) IMPLANTATION. .I Ankersmit, M Schuster, S Shah, K Olson, A Lehman, I M&w, A Kocher, K Lie& S Modak, N Edwards, M Oz, S Itescu. We have previously shown that LVAD recipients demonstrate defects in cellular immunity in viva which result in a high incidence of fungal and other systemic infections. Since LVAD recipients also demonstrate aberrant CD95 (Fas>mediated T cell activation, we investigated whether high levels of T cell apoptosis were present in these patients. In 12 LVAD recipients, T cell expression of phosphatidylserine, a marker of T cell apoptosis, was increased compared with 20 NYHA heart failure controls (39% vs 7%, p<O.OOl), and CD4 T cells from LVAD recipients had greater susceptibility to activation-induced cell death (p<O.O5). To investigate whether excessive T cell apoptosis and defects in T cell immunity were a direct result of T cell exposure to broadly- used polymeric biomaterials, we studied the effects of polyurethane (LVAD membrane), polyethylene terephtbalate (DACRON), and polytetmfluoroethylene (PTFE) on proliferative activities and apoptosis of T cells from healthy controls. Following culture of normal T cells with LVAD, DACRON and PTFE biomaterials, T cell proliferative responses to mixed lymphocyte culture (MLC) were reduced by means of 79%, 86%. and 13%, respectively, and to PHA stimulation by means of 70%, 82%, and 15%, respectively. Silicone, used as a negative control, inhibited stimulation to MLC by 22% and to PHA by 24%. Next, T cells from healthy controls were cultured for 24 hours with each biomaterial and apoptosis was measured by TUNEL technique, with single strand breaks in DNA detected in a microplate reader at 450 Nm. T cells cultured with LVAD or DACRON, but not PTFE, demonstrated DNA fragmentation which was over 3SD higher than that observed with medium alone (p<o.OS). This was confvmed by autoradiography of in-situ end-labeled DNA showing characteristic fragmentation patterns in cultured T cells. Together, these results demonstrate that certain biomaterials are not biologically inert, but instead possess properties which induce apoptosis in human T cells. These properties may account for the high levels of in viva apoptosis observed in LVAD recipients, and the high incidence of defects in cell-mediated immunity. PROFILE OF SOLUBLE COAGULANT AND INFLAMMATORY MARKERS DURING LONG-TERM LEFT VENTRICULAR ASSIST DEVICE SUPPORT P.A. Fedalen. C.A. Fisher, S. Furukawa, A. Eibidakis, D. Ramasamy, R. Vattikutl. V. Jeevanandam, Temple University Health Sciences Center, Philadelphia, PA Since the need for donor hearts outweighs organ availability, interest has hamed cm the TCI He&Mat& left venbicular assist device (LVAD) for pennan+ support in patients with end-stage heart failure. Previous work by tis labomtory has demonstrated activation of platelets and increased coagulation and tibrinolysis in the immediate peri-implantation period. To further extend these observaticms we studied these LVAD recipients for 6 weeks into the pc&operative period. Seven patients undergoing LVAD im@ntation were compared with 8 patients undergoing comnary artery bypass grafting (CABG) to control for the effwis of cardiopulmonary bypass. All patients were started on aspirin within the first postopemtive week. Platelet activation, determined’by the release of platelet factor 4, was similar in the two groups. Thrombin-antithrombin (TAT) III levels, a marker fw thrombin generation, were consistently higher in the LVAD PopuIation with a significant difference noted in the sixth postopzmtive week. Fibrinolytic activity, demonstrated by increased levels of plasmin-x2 antiplasmin (PAP), was observed only m the LVAD cohort. Markers for intlammalion (C3a, IL-6, IL-S, elastase, TNF-a) showed no significant differences between the two gmups. 0 7.5 9.7 0.13 398 722 o.b8 7 22 0:19 *1* 21 +59 *147 *I 210 1 11 27 0.09 169 658 0.01 136 365 0.1x *I *5 -20 353 237 ,113 42 5.6 25 0.05 592 2227 0.03 8 35 0.08 +l t2 +47 t498 *I +7 ‘values x&EM; **p value