tion during SRL immunosuppression may be an important mechanism for the prevention of CAV. 492 New Tools for Tacrolimus (Tac) Dose Optimization in Lung Transplant Recipients during the First Post-Transplant Year: Preliminary Results of STIMMUGREP Study C. Monchaud 1,2 , M. Estenne 3 , M. Reynaud-Gaubert 4 , C. Pison 5 , M. Stern 6 , R. Kessler 7 , C. Dromer 8 , R. Guillemain 9 , A. Rousseau 1 , P. Marquet 1,2 1 Univ Limoges, Limoges, France; 2 CHU Limoges, Limoges, France; 3 Erasme University Hospital, Universite ´ Libre de Bruxelles, Brussels, Belgium; 4 Ho ˆpital Ste Marguerite, Marseille, France; 5 CHU Grenoble, Univ Grenoble, Grenoble, France; 6 Ho ˆpital Foch, Suresnes, France; 7 Ho ˆpitaux Universitaires de Strasbourg, Strasbourg, France; 8 Ho ˆpital du Haut-Le ´ve ˆque, CHU Bordeaux, Pessac, France; 9 Ho ˆpital Europe ´en Georges Pompidou, Assistance Publique-Ho ˆpitaux de Paris, Paris, France Purpose: The purposes of this study were to explain interpatient pharmacokinetic (PK) variability and create new tools for Tac dose adjustment in cystic fibrosis (CF) and non-CF lung transplant recipi- ents, to be used on the ISBA website (https://pharmaco.chu-limo- ges.fr/abis.htm) developed for the therapeutic drug monitoring (TDM) of immunosuppressants. Methods and Materials: In 120 lung transplant patients prospec- tively enrolled in the STIMMUGREP trial, full PK profiles (10-12 blood samples over 12 h) were collected at 2 or more of the following periods: between day 7 and day 14, month 1 (M1), M3 and M12. Tac whole blood levels were assayed by LC-MS/MS. Data were analyzed in 45 patients (33 CF) who were on Tac de novo and 25 patients shifted from cyclosporine to Tac during follow-up. We developed a Tac Bayesian estimator (BE) based on a population model built in NON- MEM®. CYP3A5*1/*3 genotype was investigated by allelic discrimi- nation. Results: The model was built in a population group (74 profiles) and the BE was validated in an independent group (68 profiles). Mean absorption time was found to be twice longer in CF than in non-CF patients. CYP3A5*1/*3 polymorphism significantly influenced Tac apparent oral clearance (Cl/F): Cl/F was approximately twice higher in CYP3A5 expressors (i.e., carrier of at least one CYP3A5*1 allele) than in non expressors. After inclusion of CF and CYP3A5 polymor- phism as covariates, Bayesian forecasting based on 3 blood samples obtained within the first 4 hours post-dose provided good estimation of Tac area-under-the-curve (AUC), with a mean bias of 3.212.0% (min: -13.8% - max: +51.1%). Bias was +20% in only 8.8% cases. Conclusions: The tools developed using the STIMMUGREP database provide an accurate prediction of Tac exposure in CF and non-CF lung transplant patients throughout the first year post-transplantation. They may allow routine Tac dose individualization and will be used in upcoming TDM clinical trials. 493 Ex-Vivo Repair of Donor Pig-Lungs Damaged by Aspiration S. Wipper, L. Janna, A. Dupree, C. Pahrmann, H. Reichenspurner, F.M. Wagner University Heart Center Hamburg, Hamburg, Germany Purpose: The aim of our study was to use our previously established reperfusion circuit to recondition lungs predamaged by aspiration of gastric acid and blood. Methods and Materials: Three study groups (n=6 each: I=control without aspiration, II=aspiration, III=aspiration+medical treatment with NO-ventilation, ACC, antibiotics and methylprednisolon) were perfused for 6hrs in our reperfusion circuit (rotary-pump, leucocyte- filter, heparin-coated deoxigenator, reservoir, priming erythrocyte- concentrate and Steen-solution 1:1, Hb5,5mg/dl) according to stan- dardized protocol. Respiratory and hemodynamic parameters were monitored pre-harvest and hourly during reperfusion. Pre- and post- reperfusion wet-dry ratios were performed, histology evaluated by a semiquantitative score. Results: Compared to control (groupI) aspiration (groupII) resulted in decreasing pulmonary compliance (3115 vs. 467 ml/cmH2O), increase of PVR (1490412 vs. 1224544dynes), decrease of pulmo- nary oxygenation capacity(POC) (172115 vs. 37152mmHg), inter- stitial and intraalveolar edema formation and massive pulmonary cellular infiltration at study end-point. Macroscopically most lungs in Gr.II were massively edematous, heavy and hyperaemic, one lung even failed after 4hrs, while in groupI and III it was possible to sustain all lungs for 6hrs. Additional medical treatment (groupIII) improved pulmonary compliance (598ml/cmH2O) and PVR (585150dynes) significantly compared to groupI and II(p0.01), POC normalized at study end point (38345mmHg). Histology and wet-dry ratio con- firmed these results. After 6hrs of reperfusion 2/6 lungs in group II improved, but none reached transplantable status. In group III 4 organ blocks improved, of those two double and two further single lungs were in transplantable condition. Conclusions: Repair of aspiration damaged donor-lungs seems pos- sible by in-vitro-reperfusion with additional medical treatment in a significant percentage of cases. 494 Changing Trends in Infectious Complications among Heart Transplant Recipients F. Haddad 1 , T. Deuse 2 , F. Rosso 3 , M. Pham 1 , P. Khazanie 4 , H. Luikart 1 , H.A. Valantine 1 , S.A. Hunt 1 , T. Vu 1 , P.E. Oyer 2 , R.C. Robbins 2 , J.G. Montoya 31 Stanford University, Stanford, CA; 2 Stanford University, Stanford, CA; 3 Stanford University, Stanford, CA; 4 Stanford University, Stanford, CA Purpose: The objective of our study was to determine whether infectious complications in heart transplant patients have significantly changed over time, and if so, whether these changes have been influenced by the introduction of different immunosuppressive regi- mens and antimicrobial interventions. Methods and Materials: We analyzed the occurrence of various types of infections in 4 different cohorts of patients who underwent heart transplantation between 1978 and 2005 (672 patients). Each cohort corresponded to the use of a specific immunosuppressive regimen. The 1st cohort consisted of the pre-cyclosporine era (anti- thymocyte globulin or ATG followed by azathioprine and high doses of corticosteroids); the 2nd cohort consisted of the early cyclosporine era (ATG followed by cyclosporine and high doses of corticosteroids); the 3rd cohort was defined as the late cyclosporine era (cyclosporine, azathioprine, lower doses of corticosteroids, and trimethoprim-sulfa- methoxazole); and the last cohort corresponded to the introduction of newer immunosuppressants and induction agents (daclizumab followed by cyclosporine and mycophenolate mofetil) and more aggressive cytomegalovirus prophylaxis regimens. Results: The overall incidence of infections significantly decreased in the 4 cohorts from 3.35 episodes/patient, to 2.03, 1.35 and 0.60 in the more recent cohort (p0.001). There was a significant decrease in bacterial (p0.001), viral (p 0.001), fungal (p=0.009) and Pneumo- cystis infections (p0.001). A greater proportion of bacterial infec- tions in the recent eras were caused by Gram positive bacteria (28.6%, 31.4%, 51.0%, 67.6%, p=0.001). CMV infections but not Aspergillus infections occurred later after transplantation (8877 days, 84128, 224254, 304238, p 0.001). Conclusions: In the most recent era, immunosuppression and antimicrobial prophylaxis regimens continue to decrease the overall The Journal of Heart and Lung Transplantation Abstracts S237 Volume 28, Number 2S