- Email: [email protected]
173: Normothermic Human Ex Vivo Lung Perfusion (EVLP) for Improved Assessment of Extended Criteria Donor Lungs for Transplantation
S126
Abstracts
this study was to investigate the influence of oxygen concentration and inflation pressure during ischemia on LIRI development. Methods and Materials: Male Sprague-Dawley rats (n⫽66) underwent 150 minutes left lung ischemia, by clamping the lung at: 1) Pressure (P) 5 cm H2O/0xygen (O) 0%; 2) P5/O30%; 3) P5/O100%; 4) P30/O0%; 5) P30/O30%; 6) P30/O100%. Animals were killed on day 2 postoperatively. Blood gas values were measured and lung compliance was recorded. Alveolar protein concentration and leukocyte infiltration (by flowcytometry) was assessed in broncho-alveolarlavage-fluid (BALf). Histological analysis was performed in 4 animals per group. Results: Clamping at a pressure of 30 cm H2O resulted in a significantly increased PaO2 and lung compliance, less diffuse alveolar damage on HE slides and less infiltration of CD4⫹- and CD8⫹lymphocytes and MHCII⫹-macrophages in the left BALf on day 2 as compared to clamping at a pressure of 5 cm H2O. Furthermore, the P5/O100 and P30/O100 groups demonstrated a lower PaO2 and decreased lung compliance as compared to respectively the P5/O30 and P30/O30 groups. Also, more CD8⫹-lymphocytes and MHCII⫹macrophages were found in the left BALf of the P5/O100 group than in the P5/O0 and P5/O30 groups. Conclusions: Preservation of the lung by high pressure inflation with 30% oxygen ameliorates LIRI. Prevention of (resorption) atelectasis may be the underlying mechanism and should therefore be avoided in clinical lung transplantation. 172 Recipient Hypertonic Saline Infusion Prevents Cardiac Allograft Dysfunction D. Ramzy, L.C. Tumiati, M. Badiwala, E. Tepperman, R. Sheshgiri, V. Rao Toronto General Hospital, Toronto, ON, Canada Purpose: Hypertonic saline(HTS) possess both potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and LV dysfunction following transplantation. Methods and Materials: Heart transplants were performed after 6 hours of ischemic storage. Recipient pigs were randomized to treatment with or without HTS(7.5% NaCl) prior to CPB. Coronary artery vasomotor function was assessed using a myograft apparatus to determine endothelial-dependent(Edep) and independent(Eind) relaxation following exposure to bradykinin(Bk) and sodium nitroprusside(SNP). LV performance was determined using pressure-volume loop analysis. Pulmonary IL-2, IL-6, TNF␣ and LV TNF␣ expression was measured. Plasma TNF␣ levels was assessed. Pulmonary and LV oxidative injury was also determined. Results: Weaning from CPB and LV performance after transplantation was improved in HTS-treated animals. Successful weaning from CPB was greater in the HTS treated hearts (8/8 vs. 2/8 p⬍0.05). There was improved LV functional recovery in HTS-treated animals as assessed by preload recruitable stroke work p⬍0.05. Treatment with HTS resulted in improved Edep and Eindep vasorelaxation compared to control (%maximum relaxation(Emax); Bk Emax:HTS; 60⫾8% vs. Con:37⫾11%, p⫽0.01; SNP Emax:HTS:77⫾5% vs. Con:62⫾2%, p⫽0.01). Pulmonary expression of IL-2, IL-6 and TNF␣ increased following transplantation while HTS therapy attenuated IL production (%increase from baseline; IL-2 Con:263⫾9% vs. HTS:65⫾14%; IL-6 Con:247⫾13% vs. HTS:55⫾17%; TNF␣ Con:203⫾79% vs. HTS:80⫾13% p⫽0.02). Transplantation increased plasma TNF␣ levels and LV TNF␣ expression while HTS prevented upregulation. HTS therapy significantly reduced pulmonary and LV oxidative injury. Conclusions: Recipient HTS pretreatment preserves allograft vasomotor and LV function. HTS therapy limited CPB induced injury as
The Journal of Heart and Lung Transplantation February 2009
evident by decreased pulmonary oxidative stress and IL levels. HTS may be a novel recipient intervention to prevent graft dysfunction. 173 Normothermic Human Ex Vivo Lung Perfusion (EVLP) for Improved Assessment of Extended Criteria Donor Lungs for Transplantation M. Cypel, J. Yeung, M. Liu, F. Chen, W. Karolak, K. Yasufuku, M. DePerrot, A. Pierre, T. Waddell, C.-W. Chow, M. Hutcheon, C. Chaparro, L.G. Singer, S. Keshavjee University of Toronto, Toronto, ON, Canada Purpose: Expected Completion Date: March 2009. Sponsor of the trial: VITROLIFE. Summary of Objectives: 1) To examine the feasibility and safety of ex vivo perfusion of extended criteria donor lungs prior to transplantation and 2) To determine if ex vivo evaluation of extended donor lungs prior to the decision of transplantation will increase utilization rates and improve outcomes after lung transplantation. Methods and Materials: Lungs (n⫽22) from brain dead and nonheart-beating donors that do not meet the ISHLT standard lung donor guidelines and meet study inclusion criteria (Bilateral lung transplantation, donor age ⱕ 60 years, donor PaO2/FiO2 ⱕ 300mmHg, poor oxygenation and/or poor lung compliance as the primary reason for unsuitability) are flushed antegrade and retrograde with Perfadex® and stored at 40C. The lungs are transferred to our center according to standard practice and subsequently placed in an ex vivo circuit (Toronto XVIVOTM System) and perfused normothermically with Steen SolutionTM for 2 to 4h for physiologic re-assessment. With respect to the decision for lung utilization, those organs with a delta pO2 (⌬ pO2 ⫽ Pulmonary vein pO2 - pulmonary artery pO2) during ex vivo perfusion assessment ⬎ 400mmHg, are considered transplantable. Lungs are excluded for transplantation: if ⌬ pO2 ⬍ 400mmHg or if they demonstrate ⬎10% deterioration in any of the following functional parameters: pulmonary vascular resistance (PVR), dynamic compliance or airway pressures. Lungs are also excluded for transplantation if they are deemed unsuitable based on the clinical judgment of the lung transplant surgeon. Endpoints: Primary endpoints: ISHLT PGD scores in the first 72h and recipient mortality at 30 days. Secondary endpoints: 1. Length of ICU stay, 2. Length of intubation, 3. Need for extra-corporeal membrane oxygenator (ECMO), 4. Inflammatory cytokines/biomarkers before and after ex vivo perfusion and after LTx (in samples prospectively collected to be retrospectively analyzed). 174 Maintenance of Human Heart Oxidative Metabolism after 12 Hour Perfusion Preservation M. Cobert, M. Peltz, L. West, M.E. Jessen University of Texas Southwestern Medical Center at Dallas, Dallas, TX Purpose: Perfusion preservation with oxygenated preservation solution may extend the storage interval and permit utilization of marginal donor hearts. We previously evaluated a perfusion device (LifeCradle®, Organ Transport Systems, Inc.) in a large animal model and demonstrated improved post-transplantation ventricular function, reduced apoptosis, and reduced lactate accumulation. We applied the same preservation strategy to rejected hearts from human donors to evaluate device performance in a human model. Methods and Materials: Human hearts unsuitable for transplantation (n⫽9) were obtained from potential donors throughout our local organ procurement organization. Explanted hearts (n⫽8) were flushed with University of Wisconsin Machine Perfusion Solution, connected to the perfusion device and perfused at 10 mL/100g/min at
Abstracts
this study was to investigate the influence of oxygen concentration and inflation pressure during ischemia on LIRI development. Methods and Materials: Male Sprague-Dawley rats (n⫽66) underwent 150 minutes left lung ischemia, by clamping the lung at: 1) Pressure (P) 5 cm H2O/0xygen (O) 0%; 2) P5/O30%; 3) P5/O100%; 4) P30/O0%; 5) P30/O30%; 6) P30/O100%. Animals were killed on day 2 postoperatively. Blood gas values were measured and lung compliance was recorded. Alveolar protein concentration and leukocyte infiltration (by flowcytometry) was assessed in broncho-alveolarlavage-fluid (BALf). Histological analysis was performed in 4 animals per group. Results: Clamping at a pressure of 30 cm H2O resulted in a significantly increased PaO2 and lung compliance, less diffuse alveolar damage on HE slides and less infiltration of CD4⫹- and CD8⫹lymphocytes and MHCII⫹-macrophages in the left BALf on day 2 as compared to clamping at a pressure of 5 cm H2O. Furthermore, the P5/O100 and P30/O100 groups demonstrated a lower PaO2 and decreased lung compliance as compared to respectively the P5/O30 and P30/O30 groups. Also, more CD8⫹-lymphocytes and MHCII⫹macrophages were found in the left BALf of the P5/O100 group than in the P5/O0 and P5/O30 groups. Conclusions: Preservation of the lung by high pressure inflation with 30% oxygen ameliorates LIRI. Prevention of (resorption) atelectasis may be the underlying mechanism and should therefore be avoided in clinical lung transplantation. 172 Recipient Hypertonic Saline Infusion Prevents Cardiac Allograft Dysfunction D. Ramzy, L.C. Tumiati, M. Badiwala, E. Tepperman, R. Sheshgiri, V. Rao Toronto General Hospital, Toronto, ON, Canada Purpose: Hypertonic saline(HTS) possess both potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and LV dysfunction following transplantation. Methods and Materials: Heart transplants were performed after 6 hours of ischemic storage. Recipient pigs were randomized to treatment with or without HTS(7.5% NaCl) prior to CPB. Coronary artery vasomotor function was assessed using a myograft apparatus to determine endothelial-dependent(Edep) and independent(Eind) relaxation following exposure to bradykinin(Bk) and sodium nitroprusside(SNP). LV performance was determined using pressure-volume loop analysis. Pulmonary IL-2, IL-6, TNF␣ and LV TNF␣ expression was measured. Plasma TNF␣ levels was assessed. Pulmonary and LV oxidative injury was also determined. Results: Weaning from CPB and LV performance after transplantation was improved in HTS-treated animals. Successful weaning from CPB was greater in the HTS treated hearts (8/8 vs. 2/8 p⬍0.05). There was improved LV functional recovery in HTS-treated animals as assessed by preload recruitable stroke work p⬍0.05. Treatment with HTS resulted in improved Edep and Eindep vasorelaxation compared to control (%maximum relaxation(Emax); Bk Emax:HTS; 60⫾8% vs. Con:37⫾11%, p⫽0.01; SNP Emax:HTS:77⫾5% vs. Con:62⫾2%, p⫽0.01). Pulmonary expression of IL-2, IL-6 and TNF␣ increased following transplantation while HTS therapy attenuated IL production (%increase from baseline; IL-2 Con:263⫾9% vs. HTS:65⫾14%; IL-6 Con:247⫾13% vs. HTS:55⫾17%; TNF␣ Con:203⫾79% vs. HTS:80⫾13% p⫽0.02). Transplantation increased plasma TNF␣ levels and LV TNF␣ expression while HTS prevented upregulation. HTS therapy significantly reduced pulmonary and LV oxidative injury. Conclusions: Recipient HTS pretreatment preserves allograft vasomotor and LV function. HTS therapy limited CPB induced injury as
The Journal of Heart and Lung Transplantation February 2009
evident by decreased pulmonary oxidative stress and IL levels. HTS may be a novel recipient intervention to prevent graft dysfunction. 173 Normothermic Human Ex Vivo Lung Perfusion (EVLP) for Improved Assessment of Extended Criteria Donor Lungs for Transplantation M. Cypel, J. Yeung, M. Liu, F. Chen, W. Karolak, K. Yasufuku, M. DePerrot, A. Pierre, T. Waddell, C.-W. Chow, M. Hutcheon, C. Chaparro, L.G. Singer, S. Keshavjee University of Toronto, Toronto, ON, Canada Purpose: Expected Completion Date: March 2009. Sponsor of the trial: VITROLIFE. Summary of Objectives: 1) To examine the feasibility and safety of ex vivo perfusion of extended criteria donor lungs prior to transplantation and 2) To determine if ex vivo evaluation of extended donor lungs prior to the decision of transplantation will increase utilization rates and improve outcomes after lung transplantation. Methods and Materials: Lungs (n⫽22) from brain dead and nonheart-beating donors that do not meet the ISHLT standard lung donor guidelines and meet study inclusion criteria (Bilateral lung transplantation, donor age ⱕ 60 years, donor PaO2/FiO2 ⱕ 300mmHg, poor oxygenation and/or poor lung compliance as the primary reason for unsuitability) are flushed antegrade and retrograde with Perfadex® and stored at 40C. The lungs are transferred to our center according to standard practice and subsequently placed in an ex vivo circuit (Toronto XVIVOTM System) and perfused normothermically with Steen SolutionTM for 2 to 4h for physiologic re-assessment. With respect to the decision for lung utilization, those organs with a delta pO2 (⌬ pO2 ⫽ Pulmonary vein pO2 - pulmonary artery pO2) during ex vivo perfusion assessment ⬎ 400mmHg, are considered transplantable. Lungs are excluded for transplantation: if ⌬ pO2 ⬍ 400mmHg or if they demonstrate ⬎10% deterioration in any of the following functional parameters: pulmonary vascular resistance (PVR), dynamic compliance or airway pressures. Lungs are also excluded for transplantation if they are deemed unsuitable based on the clinical judgment of the lung transplant surgeon. Endpoints: Primary endpoints: ISHLT PGD scores in the first 72h and recipient mortality at 30 days. Secondary endpoints: 1. Length of ICU stay, 2. Length of intubation, 3. Need for extra-corporeal membrane oxygenator (ECMO), 4. Inflammatory cytokines/biomarkers before and after ex vivo perfusion and after LTx (in samples prospectively collected to be retrospectively analyzed). 174 Maintenance of Human Heart Oxidative Metabolism after 12 Hour Perfusion Preservation M. Cobert, M. Peltz, L. West, M.E. Jessen University of Texas Southwestern Medical Center at Dallas, Dallas, TX Purpose: Perfusion preservation with oxygenated preservation solution may extend the storage interval and permit utilization of marginal donor hearts. We previously evaluated a perfusion device (LifeCradle®, Organ Transport Systems, Inc.) in a large animal model and demonstrated improved post-transplantation ventricular function, reduced apoptosis, and reduced lactate accumulation. We applied the same preservation strategy to rejected hearts from human donors to evaluate device performance in a human model. Methods and Materials: Human hearts unsuitable for transplantation (n⫽9) were obtained from potential donors throughout our local organ procurement organization. Explanted hearts (n⫽8) were flushed with University of Wisconsin Machine Perfusion Solution, connected to the perfusion device and perfused at 10 mL/100g/min at