Retrograde Machine Perfusion for Long-Term Preservation of Canine Hearts

Abstracts Purpose: We attempt to determine if adult, single lung transplantation (SLT) could be safely performed in heavy smoking donors (HSD). Methods and Materials: The UNOS database was examined from 20052011 to determine if using HSD (420 pack years) provided mortality risk. Results: Of 3,704 SLT, 498 (13.4%) were from HSD. The two were similar in recipient age (60.6 vs 60.7 years, p¼0.20), male gender (61.3 vs 59.8%, p¼0.54), and ischemic time (4.1 vs 4.2 hrs, p¼0.11). Recipients of HSD had lower lung allocation score (39.7 vs 38.0, p¼0.02), less HLA mismatches (4.6 vs 4.5, p¼0.01), and higher Class I PRA (2.9 vs 3.8%, po0.001). Smoking donors were older (33.0 vs 41.3 years po0.001) and less likely male (62.5 vs 56.0%, p¼0.01). Recipients of HSD had longer length of stay (20.5 vs 23.0 days, po0.001). Freedom from bronchiolitis obliterans syndrome (p¼0.64) and median survival (1,516 vs 1,488 days, p¼0.10) were similar. Drop in FEV1 over time was less in the HSD group (p¼0.001). On multivariable analysis, HSD was not a predictor of mortality (HR: 1.15, 95%CI: 0.99-1.34, p¼0.07). Mortality was associated with recipient age, ischemic time, race mismatch, class I PRA, mechanical ventilation, and ECMO prior to transplantation. Conclusions: Single lung transplantation can be safely performed using HSD. 406 Extended Criteria Donors; a Safe Way To Expand the Lung Donor Pool? J. Somers,1 D. Ruttens,2 A. Stanzi,1 S.E. Verleden,2 E. Vandermeulen,2 A. Vaneylen,2 R. Vos,2 B. Vanaudenaerde,2 G.M. Verleden,2 D.E. Van Raemdonck.1 1Experimentele Thoraxheelkunde, Katholieke Universiteit Leuven, Leuven, Vlaams-Brabant, Belgium; 2Pneumologie, Katholieke Universiteit Leuven, Leuven, Vlaams-Brabant, Belgium. Purpose: Although the worldwide need to expand the lung donor pool, 75 % of multi-organ donors are discarded for lung transplantation (LTx). Herein, we report the outcome of liberalizing standard lung donor criteria. Methods and Materials: All effective heart-beating lung donors within our hospital network between 2000 and 2010 (n¼449) were classified as standard (SCD, n¼284) or extended (ECD, n¼149) criteria donors according to age (455years), P/F (o300mmHg) and the presence of chest x-ray abnormalities. With positive smoking status added as additional criterium, donors were reclassified as SCD (n¼166) or ECD (n¼212). Donor demographics were comparable between both groups. Time to extubation, ICU stay, pulmonary graft dysfunction (PGD) grades, acute and chronic rejection and survival in recipients were compared between groups. Results: Short-term outcome demonstrated significant differences in ICU stay (p¼0.03), PGD T12 (p¼0.003), T24 (p¼0.009) and T48

S155 (p¼0.03) but not for time to extubation (p¼0.28). No significant differences were seen in long-term outcome like acute rejection (p¼0.84), chronic rejection (p¼0.18) and 10-year survival (p¼0.33, Figure A). Adding donor smoking status resulted in similar findings. Significant differences remained in short-term outcome like PGD T12(p¼0.001), T24(p¼0.001) and T48(p¼0.001), extubation time (p¼0.04), ICU stay (p¼0.02) was observed. While no differences were found for long-term outcome as acute rejection (P¼0.85), chronic rejection (p¼0.54) and survival (p¼0.72, Figure B). Conclusions: Although, transplanting ECD lungs has an impact on the early post-operative outcome after LTx, even more pronounced for lungs from smokers, liberalization of lung donor criteria did not negatively influence long-term outcome after LTx. 407 Tissue Evaluation of Donor Lungs Preserved with the Organ Care System (OCS) Device: Experience of Padova F. Calabrese,1 M. Schiavon,1 F. Lunardi,1 N. Nannini,1 G. Marulli,1 S. Nicotra,1 P. Feltracco,2 G. Di Gregorio,2 M. Loy,1 F. Rea.1 1 Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy; 2Department of Pharmacology and Anesthesiology, University of Padova, Padova, Italy. Purpose: The success of organ transplantation can be attributed to many factors but ultimately depends upon retrieval and preservation techniques to maintain the quality of an organ. Donor lungs are usually flushed and preserved at cold temperatures before transplantation. Even if this method is able to reduce the organ damages during transport, significant lung alteration occur with a time-dependent mechanism. Organ Care System (OCS) Lung is the first portable normothermic donor lung perfusion device that combine preservation, assessment and transport of donor lung thus reducing these ischemic damage. Our aim was to evaluate tissue alterations in donor lungs preserved with the standard procedure and with the new normothermic device. Methods and Materials: Six donor lungs for each preservation technique were evaluated in a period between December 2011 and November 2012. In all lungs two biopsies (at least of 2 cmq) were performed one during back-table after cold retrograde perfusion and the other during transplantation after blood reperfusion to assess ischemic-reperfusion alterations. Different histological categories of lung injury were considered and quantified: intraalveolar edema, hemorrhage and capillary congestion. Moreover apoptosis was also evaluated by using the terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling. Results: No significant morphological difference were observed in terms of: intraalveolar edema, capillary congestion, and intraalveolar hemorrhage. OCS lung donors showed less leucocyte margination and significant less apoptosis both at cold ischemia time and after reperfusion. Conclusions: Our study based on the evaluation of principal tissue changes supports the beneficial effect of OCS devise against transplantassociated cold ischemia/reperfusion injury. 408 Retrograde Machine Perfusion for Long-Term Preservation of Canine Hearts M.L. Cobert, S. Brant, L.M. West, M.E. Jessen, M. Peltz. Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Purpose: Most machine perfusion preservation strategies utilize antegrade delivery of perfusate or blood through the ascending aorta but this technique is potentially limited by aortic valve incompetence. We hypothesize that retrograde machine perfusion preservation through the coronary sinus avoids this issue and allows for recovery of donor hearts after long-term storage. Methods and Materials: Canine hearts were procured after cardioplegic arrest with 1 liter University of Wisconsin Machine Perfusion Solution (UWMPS) and preserved for 12 hours in UWMPS by either

S156

Group Static Retrograde Perfusion

The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2013 410

Total Ischemic Time (min)

PRSW (mm Hg)

CK (IU/mL)

836⫾10 840⫾17

17⫾11 59⫾6

21439⫾5798 9123⫾716

Data are mean⫾SEM;

-po.05 vs Static Group

conventional static storage (Static group, n¼4) at 0-4oC or retrograde % machine perfusion through the coronary sinus (RP group, n¼4) at 5oC. Myocardial oxygen consumption (MVO2) and lactate accumula% were monitored in perfused hearts. Donor hearts were implanted tion into recipient animals and reperfused for six hours. The preload recruitable stroke work (PRSW) was determined hourly. Total CK was measured at the end of each experiment. Results: RP hearts maintained stable MVO2 over the 12 hour preservation interval. Lactate accumulation was low in RP hearts. All RP hearts separated from cardiopulmonary bypass (CPB). All static storage hearts either did not separate from CPB or required a return to CPB by the end of the six hour reperfusion interval (po.05). The slope of the PRSW in RP hearts was increased compared the static storage group (po.05) and did not differ from baseline values. There was a trend towards greater CK release in static storage hearts (p¼.09). Conclusions: Retrograde machine perfusion can preserve donor hearts for long intervals. Cardiac function after implantation was not different from baseline function suggesting excellent myocardial protection. A retrograde machine perfusion strategy appears promising for safely extending the donor ischemic interval and improving results of heart transplantation. 409 Donor Hearts Not Offered or Rejected for Transplantation – A Lost Opportunity? J.M. DiMaio, M. Morse, W.A. Teeter, M.L. Cobert, L.M. West, M.E. Jessen, M. Peltz. Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX. Purpose: Heart transplantation remains the most effective therapy for end-stage heart failure but is limited by the scarcity of available donors. Even among standard criteria donors, cardiac donor conversion rates are less than 50% suggesting that a number of potentially acceptable hearts are not transplanted. We evaluated a series of donor hearts not placed and assessed their suitability for transplantation. Methods and Materials: 33 donor hearts either rejected or not offered for transplantation and tissue donation were procured in an organ procurement organization approved research protocol from 1/2008 to 2/2012. Clinical data from these research donors were reviewed to determine whether hearts were potentially acceptable or unacceptable. To be deemed acceptable, donors had to be less than 55 years of age with a satisfacory functional evaluation (echocardiography, cardiac catheterization) and/or intraoperative assessment by the procuring surgeon. Donors with recent IV drug use were considered unacceptable. Results: 16 hearts were considered acceptable and 17 hearts were considered unacceptable. Among donors 50 years of age or younger, 14/18 were considered acceptable. Acceptable cardiac donors were younger (36⫾3 vs 53⫾4 years, po.01) and also were more likely to have available functional data (81 vs 24%, po.01). Chest trauma and positive donor blood cultures occurred more frequently in unacceptable donors (po.05). Ejection fraction (58⫾4% acceptable vs 54⫾5% unacceptable), donor height (170⫾3cm acceptable vs 170⫾3cm unacceptable) and donor weight (83⫾4 kg acceptable vs 76⫾5 kg unacceptable) were not different among groups. Only 7 of 33 hearts were offered for transplantation. Among these, the three most frequent reasons for rejection were donor age/quality, size, and social history. Conclusions: In this selected cohort, nearly half of the hearts rejected or not offered for donation were potentially suitable for transplantation. These data suggest a significant number of acceptable donor hearts are not transplanted.

Ex-Vivo Perfusion of Human Donor Hearts Reduces Cold Ischemia Time M. Deng,2 E. Soltesz,3 E. Hsich,4 Y. Naka,5 D. Mancini,5 F. Esmailian,6 J. Kobashigawa,6 M. Camacho,7 D. Baran,8 J. Madsen,9 P. LePrince,10 A. Ardehali.1 1Department of Surgery, Division of Cardiothoracic Surgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA; 2Department of Medicine, Division of Cardiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA; 3Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH; 4Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH; 5 Department of Surgery, New York Presbyterian Hospital/Columbia Medical Center, New York, NY; 6Cedars-Sinai Heart Institute, CedarsSinai Medical Center, Los Angeles, CA; 7Department of Cardiothoracic Surgery, Barnabas Health Heart Center of Newark Beth Isreal Medical Center, Newark, NJ; 8Department of Heart Failure and Transplant, Barnabas Health Heart Center of Newark Beth Isreal Medical Center, Newark, NJ; 9Department of Surgery, Cardiac Surgery, Massachusetts General Hospital, Boston, MA; 10Department of Surgery, Groupe Hospitalier Pitie-Salpetriere, Paris, France. Purpose: Cold ischemia is an obligatory part of solid organ transplantation. Prolonged cold ischemia time (CIT) in heart transplantation can impact early allograft function and may be associated with chronic rejection. CIT beyond 6 hours is associated with increased recipient mortality based on ISHLT/UNOS database. Ex-vivo organ perfusion (Organ Care System (OCS)) maintains the donor hearts in a warm, beating state and reduces CIT. The purpose of this study is to compare CIT of donor hearts preserved on ice vs. on OCS. Methods and Materials: PROCEED II is an FDA approved prospective, randomized, international multi-center study that is designed to compare OCS to cold static preservation of the donor hearts during transport. As of 10/01/12, 79 patients had been enrolled into this study. 40 patients were randomized to cold static preservation arm (control group); 39 patients were randomized to OCS (OCS group). Results: Table 1 compares the cross clamp time and CIT for the OCS and Control groups.There is a statistically significant increase in possible cross clamp time (po0.05) with a concurrent significantly decreased CIT (po0.05). No donor heart was discarded due to technical issues related to OCS instrumentation or preservation.

Cross Clamp Vs. CIT for the OCS and Control Groups OCS Group - mean ⫾ SD (range) Total Cross Clamp Time (min) OCS Group Explantation and Instrumentation Time (min) OCS Group Implantation Time (min) Total CIT (min)

Control Group - mean ⫾ SD (range)

329 ⫾ 79 (149-543) 180 ⫾ 66 (36-312) 29 ⫾ 7 (16-50)

N/A

80 ⫾ 23 (43-142)

N/A

109 ⫾ 26 (62-169)

180 ⫾ 66 (36-312)

Conclusions: Ex vivo perfusion of donor hearts on OCS reduces CIT by nearly 40% when compared to the control group. Reduction in CIT may improve short and long term heart allograft function. 411 Is Lactate Level during Warm Perfusion a Predictor for Post Transplant Outcomes? M. Deng,2 E. Soltesz,3 E. Hsich,4 Y. Naka,5 D. Mancini,5 F. Esmailian,6 J. Kobashigawa,6 M. Camacho,7 D. Baran,8 J. Madsen,9 P. LePrince,10 A. Ardehali.1 1Department of Surgery, Division of Cardiothoracic Surgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA; 2Department of Medicine, Division of Cardiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA; 3Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, OH; 4Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH; 5 Department of Surgery, New York Presbyterian Hospital/Columbia Medical Center, New York, NY; 6Cedars-Sinai Heart Institute,