161: Initial Topical Cooling Followed by Backtable Celsior Flush Perfusion Provides Excellent Early Graft Function in Porcine Single Lung Transplantation after 24 Hours of Cold Ischemia

161: Initial Topical Cooling Followed by Backtable Celsior Flush Perfusion Provides Excellent Early Graft Function in Porcine Single Lung Transplantation after 24 Hours of Cold Ischemia

S58 The Journal of Heart and Lung Transplantation, Vol 29, No 2S, February 2010 and red blood cell reduced glutathione (GSH) and NFK-B (p50) levels ...

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S58

The Journal of Heart and Lung Transplantation, Vol 29, No 2S, February 2010

and red blood cell reduced glutathione (GSH) and NFK-B (p50) levels were measured. Results: During the observation period the mean pulmonary artery pressure, oxygenation, airway pressure, and static lung compliance were significantly better in NAC compared to CON group. Extravascular lung water index was higher at all time points during the reperfusion in the CON group. BAL protein, nitrite/nitrate, NE, IL-8 levels at the end of the experiment were significantly higher in the CON compared to NAC group. Lung tissue reduced glutathione (GSH) levels were significantly higher in NAC compared to CON group. Red blood cell GSH levels were always higher in the NAC group during the reperfusion period compared to CON group. Quantitative rt-PCR in white blood cells for IL-8 was significantly higher in CON during the reperfusion period compared to NAC group (p⫽0.001). The amount of lung tissue NFK-B (p50) was significantly higher in CON compared to NAC (p⫽0.03). Conclusions: In this model, donor and recipient treatment with N-acetylcysteine effectively protected the lung from primary graft dysfunction after prolonged cold ischemia. 159 Transcriptional Signatures in Donor Lungs before and after Transplantation: A Functional Pathway Analysis of Donation after Cardiac Death (DCD) vs. Donation after Brain Death (DBD) C.H. Kang,1 M. Anraku,2 M. Cypel,2 J. Yeung,2 S. Gharib,3 A. Pierre,2 M. de Perrot,2 T. Waddell,2 M. Liu,2 S. Keshavjee.2 1Seoul National University Hospital, Seoul, Republic of Korea; 2Toronto General Hospital, Toronto, ON, Canada; 3University of Washington, Seattle, WA. Purpose: Lung donation after cardiac death (DCD) is a promising method to relieve the shortage of donor organs. We studied differential gene expression profiles in lungs from DCD and donation after brain death (DBD) before and after lung transplantation using functional pathway analysis. Methods and Materials: We performed microarray studies (Affymetrix Human Gene U-133 plus 2 GeneChip) on pre- and post-transplant lung tissues (n⫽ 35) from 7 DCD and 12 matched DBD patients. After preprocessing of expression data, Principal Component Analysis (PCA), significance analysis of microarray (SAM), and hierarchical clustering were performed to identify gene expression patterns and significantly regulated genes. We further applied Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) to the selected genes to determine functional significance and the genomic network relationship. Results: Gene expression profiles between DCD and DBD demonstrated clear distinction by PCA, particularly in the pre-transplant period (Figure 1). SAM and GSEA revealed 131 differentially regulated transcripts and 12 enriched gene sets in pre-transplant tissues. The gene sets enriched in DBD but not in DCD mapped to innate immunity, intracellular signaling, cytokine interaction, cell communication and apoptosis pathways.

Conclusions: Analysis of gene expression profiles in donor lungs indicate significant differences in pathway activation in DBD vs. DCD donor lungs. Less inflammatory features of DCD donor lungs support the safe application in lung transplantation of properly preserved DCD donor lungs.

160 Evaluation of the Lung Allocation Score in High Urgent and Urgent Lung Transplant Candidates in Eurotransplant J.M. Smits,1 G.D. Nossent,2 A.O. Rahmel,1 G. Laufer,3 J. Gottlieb.4 1 Eurotransplant, Leiden, Netherlands; 2UMCG, Groningen, Netherlands; 3 University Hospital, Vienna, Austria; 4Hannover Medical School, Hannover, Germany. Purpose: Investigate performance of the Lung Allocation Score (LAS) among the high urgent (HU) and urgent (U) transplant candidates in Eurotransplant (ET); and to identify useful additional parameters (LASplus) and their predictive capacities for lung transplant (LTx) survival benefit. Methods and Materials: All adult LTx candidates for whom a first HU or U request was made in ET in 2008 (N⫽316) were included. Patients were followed until LTx, death on the waiting list (WL), delisting or closure date i.e. April 1, 2009 occurred. Mean duration of post-transplant follow up was 220 days. Probabilities of death and of LTx were calculated using competing risk methodology, post- transplant survival rates were obtained by Kaplan-Meier estimates. The LASplus encompassed the following additional items: PAPm, RVPsys, pneumothorax with drain, extracorporal support, 6MWT x saturation, bilirubine, non-invasive ventilation (NIV), IV prostanoids, and coagulopathy. The LAS/ LASplus were decomposed into an urgency (WL death) and an outcome component (post-LTx survival) and both scores were dichotomized at their 50th percentile, yielding a high and low risk group. Results: Median age of the cohort was 48 y (23% emphysema, 29% fibrosis, 21% cystic fibrosis), 16% were intubated and 30% on NIV, 7% on extra-corporal support. Patients with a high risk LAS (⬎35) had a 11% chance of dying prior to transplantation, vs. 23% for those with a low risk LAS value (p⫽0.057) In contrast, the LASplus high risk (⬎⫽72) patients had a significant higher chance of dying on the waiting list (29%) compared to the LASplus low risk patients (8%) (p⫽⬍0.0001) The outcome component of the LASplus was significantly associated with post-LTx survival (⬍0.0001), no such effect was seen for the outcome component of the LAS (p⫽0.29). Conclusions: The LAS could not be used for a further risk stratification in this HU/U transplant candidate cohort. The addition of parameters improves its performance in critically ill patients in Eurotransplant. 161 Initial Topical Cooling Followed by Backtable Celsior Flush Perfusion Provides Excellent Early Graft Function in Porcine Single Lung Transplantation after 24 Hours of Cold Ischemia B. Gohrbandt,1 M. Avsar,1 G. Warnecke,1 S.P. Sommer,2 A. Haverich,1 M. Strueber.1 1Hannover Medical School, Hannover, Germany; 2 University Hospital of Wuerzburg, Wuerzburg, Germany. Purpose: Topical in situ cooling of the donor lungs is a technique potentially enabling the procurement of non-heart-beating donor lungs. Accordingly, we conducted experiments in the porcine lung transplantation model. Methods and Materials: 24 single lung transplants were performed in 4 groups of 6 animals each. Control LPD, control Celsior, topical cooling in-situ followed by LPD (exLPD) or Celsior (exCel) ex-situ flush were employed. All lungs were perfused antegrade with 1l solution at 4°C. Lungs were stored semi-inflated and immersed in preservation solution for 24 hours at 4°C. After transplantation, the right recipient bronchus and pulmonary artery were clamped and the animals remained dependent on the grafted lung. Results: 4 of 6 animals each in the LPD and Celsior groups and all 6 animals in both the exLPD and the exCel groups survived the 7 hours of reperfusion. The mean oxygenation index was favourably preserved in the exCel group at 7h after reperfusion (473⫾118 mmHg) over all other groups (LPD 341⫾225, Celsior 387⫾146, exLPD 327⫾166; P⬍0.0001, repeated-measures ANOVA). Pulmonary vascular resistance showed significantly lower values in Celsior and exCel groups (LPD 1310⫾620, Celsior 584⫾194, exLPD 1035⫾361, exCel 650⫾116 dyn*s⫺1*cm⫺5 at 7h after reperfusion; P⬍0.0001, repeated-measures ANOVA). Consistently, the wet-to-dry lung weight ratio also indicated better graft protection

Abstracts in the exCel group (LPD 8.1⫾0.8, Celsior 8.4⫾0.8, exLPD 7.5⫾1.0, exCel 3.1⫾0.9; P⬍0.0001, ANOVA). Conclusions: Initial topical cooling followed by backtable perfusion is a feasible technique for pulmonary graft preservation providing excellent post-transplant function, whereas Celsior revealed improved results in this setting. This technique could advance non-heart beating donation. 162 The Obligation To Say Thank-You J. Poole,1 M. Shildrick,2 P. McKeever,3 H. Ross,4 O. Mauthner,4 E. De Luca,4 S. Abbey.5 1Ryerson University, Toronto, ON, Canada; 2 Queen’s University Belfast, Belfast, Ireland; 3Bloorview Kids Rehab, Toronto, ON, Canada; 4University Health Network–Toronto General Hospital, Toronto, ON, Canada; 5University Health Network–Toronto General Hospital, Toronto, ON, Canada. Purpose: Common clinical practice encourages heart transplant recipients (HTR) to write a thank-you letter to the donor family. Our national policy dictates that letters are written anonymously and bureaucratic structures are in place to both facilitate and vet any exchange of correspondence between donor family and recipient to ensure this. This study explores HTR experiences of writing a thank-you letter. Methods and Materials: Focused open-ended interviews were conducted in a non-clinical setting with 27 medically stable HTR [70% male, mean age 53 ⫾ 13.8yrs; mean time since transplant 4.06 ⫾ 2.4yrs]. 25 interviews were audio/video-taped to capture voice and body language, and were transcribed verbatim. NVivo8 qualitative software was used to code language, bodily gesture, volume and tone in keeping with our phenomenologically informed method. Results: Participants found it difficult to write anonymously and still find the right words to communicate their feelings. Of 25 interpretable interviews 18 patients wrote a donor letter (3 ghostwritten, 2 by wife, 1 by daughter) of whom 11 demonstrated distress/disturbance with the process e.g. ‘I must have done half a dozen different drafts before I finally did it’, ‘much more emotional experience than what I anticipated’. 5 confirmed a response from the donor and one patient was uncertain. 5 did not write a letter (all of whom demonstrated distress/disturbance) ‘ I mean, I got life, they lost a life’, ‘I’ve written a thank-you letter 15,000 times in my mind’, ‘to know that they still have somebody in their family’. 2 denied any knowledge of letter writing process. Conclusions: Writing the donor family thank-you letter is not a neutral experience for HTR, despite assumptions among healthcare professionals. HTR conveyed a yearning to connect with the donor family and expressed significant distress/disturbance when correspondence with the donor family failed. This contradicts the conventional biomedical discourse that the transplanted heart is a depersonalised spare part. Better support mechanisms or revision with regard to this common transplant practice are needed. 163 Predictors and Outcomes Associated with Quality of Life (QOL) in Family Caregivers to Cardiothoracic Transplant Recipients M.A. Dew,1 L. Myaskovsky,2 A.J. DeVito Dabbs,3 A.F. DiMartini,4 Y. Toyoda,5 R. Zomak,6 R.L. Kormos.5 1University of Pittsburgh School of Medicine, Pittsburgh, PA; 2University of Pittsburgh School of Medicine, Pittsburgh, PA; 3University of Pittsburgh School of Nursing, Pittsburgh, PA; 4University of Pittsburgh School of Medicine, Pittsburgh, PA; 5University of Pittsburgh Medical Center, Pittsburgh, PA; 6University of Pittburgh Medical Center, Pittsburgh, PA. Purpose: Improvements in cardiothoracic transplant (CTT) recipients’ care, combined with healthcare economic factors, have led to shorter hospital stays and extended patient life expectancies, thus placing increased caregiving responsibility on families. Because transplant programs rely on family caregivers to assist with patient recovery, we examined the effects of such burden on caregivers and whether any decrements in caregiver well-being affected patient outcomes. Methods and Materials: In 302 consecutive CTT recipients, 269 (lung n⫽154, heart n⫽115) had a family caregiver who agreed to enroll. Care-

S59 giver interviews assessed multiple QOL domains, caregiving burden and psychosocial factors at 2-, 7- and 12-months post-CTT. Patient health status data were drawn from patient interviews and medical records. Mixed effects modeling and regression analyses examined caregiver QOL levels and predictors. Survival analysis determined whether caregiver QOL at 12 months post-CTT predicted patient survival time. Results: Caregivers’ average emotional and social QOL exceeded normative levels at all time points. Physical functioning and bodily pain worsened over the year (p⬍ .01; p⬍.05 respectively). Caregiver optimism at initial assessment predicted QOL in all domains. Greater caregiver burden predicted poorer physical and emotional QOL. Poorer family support predicted poorer emotional and social QOL (all p’s⬍.001). There were no differences by type of transplant. Controlling for patients’ physical functional status at 12 months post-CTT, caregivers’ perceptions that their own health was poorer independently increased patient mortality risk during the next 8 years (p⬍.05): for each 10 point drop on the 100-point health perceptions scale in caregivers, patient mortality risk increased by 20%. Conclusions: Educational and counseling programs for transplant families must address the potential for caregiver QOL to decline in the aftermath of the transplant, and develop strategies to prevent such decline and its potential impact on CTT recipients. 164 The Relationships among Satisfaction with Heart Transplant on Quality of Life (QOL) Outcomes 5 to 10 Years after Heart Transplantation(HT) C. White-Williams,1 K.L. Grady,2 E. Wang,3 D.C. Naftel,4 J.K. Kirklin,5 S. Myers,6 B. Rybarczyk,7 J.B. Young,8 J. Czerr,9 D. Pelegrin,10 J. Kobashigawa,11 J. Chait,12 A. Heroux,13 R. Higgins.14 1University of Alabama at Birmingham, Birmingham, AL; 2Northwestern Memorial Hospital, Chicago, IL; 3Northwestern Memorial Hospital, Chicago, IL; 4 University of Alabama at Birmingham, Birmingham, AL; 5University of Alabama at Birmingham, Birmingham, AL; 6University of Alabama at Birmingham, Birmingham, AL; 7Virginia Commonwealth University, Richmond, VA; 8The Cleveland Clinic, Cleveland, OH; 9The Cleveland Clinic, Cleveland, OH; 10The Cleveland Clinic, Cleveland, OH; 11UCLA Medical Center, Los Angeles, CA; 12UCLA Medical Center, Los Angeles, CA; 13Loyola University Medical Center, Maywood, IL; 14Rush University Medical Center, Chicago, IL. Purpose: Information regarding perceived satisfaction with HT and its relationship with quality of life (QOL) outcomes and other variables 5 to 10 years (yrs) after HT is unknown. The purposes of this longitudinal study were to examine demographic, physiologic, and psychosocial characteristics and their relationship to satisfaction with HT, and to identify predictors of satisfaction with HT. Methods and Materials: Data were collected from 555 HT pts (78% male, 88% white, mean age 53.8yrs) at 4 U.S. sites using the following instruments: HT Rating Scale, Sickness Impact Profile, HT Symptom Checklist, HT Stressor Scale, QOL Index, Cardiac Depression Scale, and chart review. Statistical analyses included t-tests, Pearson correlations, and multivariate regression. Results: Perceived satisfaction with HT [Mean⫽9.6 (1⫽not satisfied, 10⫽very satisfied)] remained stable from 5 to 10 yrs after HT. At 5 and 10 yrs post HT, there were no differences in satisfaction with HT by gender, race, or education. However, at 10 yrs post HT, older pts were more satisfied with HT (p⫽.003). Married pts were more satisfied with HT at both 5 and 10 yrs (p⬍.0001). At 5 yrs, pts with less renal dysfunction (p⫽.04), fewer psychological symptoms (p⫽.02), less rejection (p⫽.02), less coronary disease (p⫽.02) were more satisfied with HT while at 10 yrs, pts with fewer cardiac symptoms (p⬍.0001), fewer oncology symptoms (p⫽.009), less infection (p⫽.006) were more satisfied with HT. At 5 yrs post HT, predictors of more satisfaction with HT were better overall QOL and less overall stress (R2⫽0.36, p⫽.02). Conclusions: Most pts 5 to 10 yrs post HT were very satisfied with HT. Being married and having fewer co-morbidities and symptoms were associated with more satisfaction long-term after HT. Better QOL and less stress were predictors of more satisfaction with HT. It is important for clinicians to identify pts at risk for poor satisfaction with HT and to develop interventions that will facilitate improved satisfaction after HT.