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343
S162
Abstracts
The Journal of Heart and Lung Transplantation February 2006
single organ. As the lung appears to be the most robust NHBD organ, lung retrieval should be considered with all NHBD referrals. 343 ALLOCATION TO ZONE A STATUS 1A/1B HEART CANDIDATES BEFORE LOCAL STATUS 2 IS ASSOCIATED WITH REDUCED DEATHS IN ALL GEOGRAPHIC REGIONS IN THE U.S. R.T. Bustami,1 T.E. Hulbert-Shearon,2 A.M. Rodgers,1 S. Murray,2 K.P. McCullough,1 E.R. Garrity,3 R.M. Merion,2 1SRTR, URREA, Ann Arbor, MI; 2SRTR, University of Michigan, Ann Arbor, MI; 3 Loyola Cardiovascular Institute, Loyola University Medical Center, Maywood, IL Heart transplantation candidates in the US are currently prioritized by medical urgency status (1A, 1B, 2) within geographic areas (local OPO, Zone A, B and C). This study explored whether giving higher urgency status candidates enhanced access to donor organs would result in fewer deaths. Methods: The Thoracic Simulated Allocation Model (TSAM) was used to compare outcomes of (1) the current heart allocation system with (2) modified allocation to Zone A (⬍500 miles), for status 1A and 1B candidates before local status 2 candidates. For both (1) and (2), organs from adolescent (age 11–17) donors are offered to status 1A/1B pediatric (age ⬍ 18) candidates in Zone A ahead of adults at the same status. TSAM input for heart waitlist candidates in 2002 included waitlist and organ arrivals, status and removal data, and probability models for organ placement and post-transplant survival. Post-transplant survival was estimated using Cox models based on significant patient and donor characteristics. Results: Compared to current rules, TSAM predicted that prioritizing higher urgency status candidates within Zone A would result in 7% fewer total deaths, mostly due to a decrease in waitlist deaths (10%). A reduction in total deaths was predicted in each of the 11 regions, see table below. Compared to current rules, the modified system resulted in 353 (22%) more status 1A and 1B transplants, with a corresponding reduction in status 2 transplants. Post-transplant deaths were predicted to increase slightly but not significantly. Predicted Total Deaths: Current vs Modified System Region
Current System
Modified System
% Decrease
1 2 3 4 5 6 7 8 9 10 11 Total
27 112 100 86 134 25 76 60 79 79 100 878
25 106 89 80 127 23 69 56 74 75 95 819
7% 5% 11% 7% 5% 8% 9% 7% 6% 5% 5% 7%
Conclusion: Assignment of higher allocation priority to high urgency status candidates within Zone A is projected to considerably reduce overall deaths among heart transplant candidates and recipients. 344 NOVEL USE OF INHALED PERFLUOROCARBON TO ENHANCE DONOR LUNG PRESERVATION AND MINIMIZE ACUTE LUNG INJURY IN A SYNGENEIC RAT TRANSPLANT MODEL A.K. Singhal,1 M. Christofidou-Solomidou,2 C. Solomides,3 B.I. Goldman,3 S. Furukawa,1 1Department of Surgery, Temple University School of Medicine, Philadelphia, PA; 2Department of Medicine, University of Pennsylvania, Philadelphia, PA; 3 Department of Pathology, Temple University School of Medicine, Philadelphia, PA
Background: Decreases to pulmonary surfactant and/or changes to its composition are thought to play a crucial role in the pathogenesis of ischemia-reperfusion induced acute lung injury following lung transplantation. Inhaled perfluorocarbon (PFC) has been shown to prevent surfactant injury. Purpose: We investigated the novel use of PFC vapor ventilation to attenuate acute lung injury in a syngeneic rat model of left lung transplantation. Methods: Prior to harvest, all rats received an infusion of low potassium dextran (LPD) pulmoplegia and simultaneously ventilated with either oxygen alone (Control, n⫽7) or PFC saturated oxygen (PFC, N⫽6). The left lung from each rat was harvested and stored in LPD at 4 °C for 2 hours prior to transplant. At 24 hours after transplant, oxygenation (PaO2) was assessed in all rats and edema (microscopic and wet to dry weight ratios), oxidative injury (tissue malondialdehyde), and bronchoalveolar lavage cell counts in explanted transplanted lung. Results: One rat in each group expired. When compared to control, PaO2 in the PFC group was higher (227⫾68 vs 308⫾27 mm Hg, p⬍0.05) and demonstrated less microscopic edema, which was confirmed by wet/dry weight ratio (8.3⫾0.6 vs. 7.1⫾0.4, p⬍0.05). In the PFC group, there were trends toward both decreased oxidative injury (120⫾58 vs. 70⫾18 nanogm tissue malondialdehyde/ microgm protein, p⫽NS) and less cells in bronchoalveolar lavage eflluent (640⫾250 vs. 450⫾150 cells/ml, p⫽NS). Conclusions: The combination of PFC and LPD pulmoplegia preservation affords enhanced post transplant oxygenation, decreased pulmonary edema, and potentially decreases post transplant oxidative injury and cellular infiltrate. Thus, pretreatment of lungs with inhaled perfluorocarbon at lung harvest may improve post transplant outcomes. 345 EXOGENIC SURFACTANT THERAPY AS AN ADJUVANT THERAPY FOR LUNG PRESERVATION – EVALUATION OF THE OPTIMAL TIME POINT FOR INSTILLATION T. Wittwer,1 R. Nagib,1 M. Ochs,2 M. Vollroth,1 C. Muehlfeld,3 N. Madershahian,1 J. Groetzner,1 D. Vehre,1 T. Wahlers,1 1Dept. of Cardiothoracic and Vascular Surgery, Friedrich Schiller University, Jena, Germany; 2Institute of Anatomy, University of Bern, Bern, Switzerland; 3Dept. of Electron Microscopy, University of Goettingen, Goettingen, Germany Background: Optimal preservation of allograft function is still a major problem in lung transplantation. Ischemia/reperfusion-(I/R)injury results in alterations of endogenous surfactant integrity. Generally, application of exogenic surfactant has been shown to be effective in both prevention and therapy of I/R-injury. However systematic experimental studies on optimal timing of instillation of modern surfactant preparations (Curosurf®) are pending. Methods: In an extracorporeal rat model, all lungs (n⫽5/group) were preserved using antegrade Perfadex and stored for 4 hours of cold ischemia. In the 3 test groups, Curosurf was administered at different time points: prior to flush preservation (T1), following cold ischemia (T2), and during reperfusion (T3). Results were compared to controls (nS) without surfactant instillation. Postischemic lungs were reventilated and extracorporeally eperfused with xenogeneic blood. Oxygenation (paO2), hemodynamics (PAP) and inspiratory pressures (PIP) were monitored continuously. Intraalveolar edema was quantified stereologically. Statistics comprised different ANOVA models. Results: Oxygenation of T1 lungs was superior as compared to all other groups T2, T3 and nS (p ⬍ 0.02), while PAP- and PIP-values were comparable between Curosurf-treated groups. Stereology supported the oxygenation data with a clear tendency towards less intrapulmonary oedema in group T1.
Abstracts
The Journal of Heart and Lung Transplantation February 2006
single organ. As the lung appears to be the most robust NHBD organ, lung retrieval should be considered with all NHBD referrals. 343 ALLOCATION TO ZONE A STATUS 1A/1B HEART CANDIDATES BEFORE LOCAL STATUS 2 IS ASSOCIATED WITH REDUCED DEATHS IN ALL GEOGRAPHIC REGIONS IN THE U.S. R.T. Bustami,1 T.E. Hulbert-Shearon,2 A.M. Rodgers,1 S. Murray,2 K.P. McCullough,1 E.R. Garrity,3 R.M. Merion,2 1SRTR, URREA, Ann Arbor, MI; 2SRTR, University of Michigan, Ann Arbor, MI; 3 Loyola Cardiovascular Institute, Loyola University Medical Center, Maywood, IL Heart transplantation candidates in the US are currently prioritized by medical urgency status (1A, 1B, 2) within geographic areas (local OPO, Zone A, B and C). This study explored whether giving higher urgency status candidates enhanced access to donor organs would result in fewer deaths. Methods: The Thoracic Simulated Allocation Model (TSAM) was used to compare outcomes of (1) the current heart allocation system with (2) modified allocation to Zone A (⬍500 miles), for status 1A and 1B candidates before local status 2 candidates. For both (1) and (2), organs from adolescent (age 11–17) donors are offered to status 1A/1B pediatric (age ⬍ 18) candidates in Zone A ahead of adults at the same status. TSAM input for heart waitlist candidates in 2002 included waitlist and organ arrivals, status and removal data, and probability models for organ placement and post-transplant survival. Post-transplant survival was estimated using Cox models based on significant patient and donor characteristics. Results: Compared to current rules, TSAM predicted that prioritizing higher urgency status candidates within Zone A would result in 7% fewer total deaths, mostly due to a decrease in waitlist deaths (10%). A reduction in total deaths was predicted in each of the 11 regions, see table below. Compared to current rules, the modified system resulted in 353 (22%) more status 1A and 1B transplants, with a corresponding reduction in status 2 transplants. Post-transplant deaths were predicted to increase slightly but not significantly. Predicted Total Deaths: Current vs Modified System Region
Current System
Modified System
% Decrease
1 2 3 4 5 6 7 8 9 10 11 Total
27 112 100 86 134 25 76 60 79 79 100 878
25 106 89 80 127 23 69 56 74 75 95 819
7% 5% 11% 7% 5% 8% 9% 7% 6% 5% 5% 7%
Conclusion: Assignment of higher allocation priority to high urgency status candidates within Zone A is projected to considerably reduce overall deaths among heart transplant candidates and recipients. 344 NOVEL USE OF INHALED PERFLUOROCARBON TO ENHANCE DONOR LUNG PRESERVATION AND MINIMIZE ACUTE LUNG INJURY IN A SYNGENEIC RAT TRANSPLANT MODEL A.K. Singhal,1 M. Christofidou-Solomidou,2 C. Solomides,3 B.I. Goldman,3 S. Furukawa,1 1Department of Surgery, Temple University School of Medicine, Philadelphia, PA; 2Department of Medicine, University of Pennsylvania, Philadelphia, PA; 3 Department of Pathology, Temple University School of Medicine, Philadelphia, PA
Background: Decreases to pulmonary surfactant and/or changes to its composition are thought to play a crucial role in the pathogenesis of ischemia-reperfusion induced acute lung injury following lung transplantation. Inhaled perfluorocarbon (PFC) has been shown to prevent surfactant injury. Purpose: We investigated the novel use of PFC vapor ventilation to attenuate acute lung injury in a syngeneic rat model of left lung transplantation. Methods: Prior to harvest, all rats received an infusion of low potassium dextran (LPD) pulmoplegia and simultaneously ventilated with either oxygen alone (Control, n⫽7) or PFC saturated oxygen (PFC, N⫽6). The left lung from each rat was harvested and stored in LPD at 4 °C for 2 hours prior to transplant. At 24 hours after transplant, oxygenation (PaO2) was assessed in all rats and edema (microscopic and wet to dry weight ratios), oxidative injury (tissue malondialdehyde), and bronchoalveolar lavage cell counts in explanted transplanted lung. Results: One rat in each group expired. When compared to control, PaO2 in the PFC group was higher (227⫾68 vs 308⫾27 mm Hg, p⬍0.05) and demonstrated less microscopic edema, which was confirmed by wet/dry weight ratio (8.3⫾0.6 vs. 7.1⫾0.4, p⬍0.05). In the PFC group, there were trends toward both decreased oxidative injury (120⫾58 vs. 70⫾18 nanogm tissue malondialdehyde/ microgm protein, p⫽NS) and less cells in bronchoalveolar lavage eflluent (640⫾250 vs. 450⫾150 cells/ml, p⫽NS). Conclusions: The combination of PFC and LPD pulmoplegia preservation affords enhanced post transplant oxygenation, decreased pulmonary edema, and potentially decreases post transplant oxidative injury and cellular infiltrate. Thus, pretreatment of lungs with inhaled perfluorocarbon at lung harvest may improve post transplant outcomes. 345 EXOGENIC SURFACTANT THERAPY AS AN ADJUVANT THERAPY FOR LUNG PRESERVATION – EVALUATION OF THE OPTIMAL TIME POINT FOR INSTILLATION T. Wittwer,1 R. Nagib,1 M. Ochs,2 M. Vollroth,1 C. Muehlfeld,3 N. Madershahian,1 J. Groetzner,1 D. Vehre,1 T. Wahlers,1 1Dept. of Cardiothoracic and Vascular Surgery, Friedrich Schiller University, Jena, Germany; 2Institute of Anatomy, University of Bern, Bern, Switzerland; 3Dept. of Electron Microscopy, University of Goettingen, Goettingen, Germany Background: Optimal preservation of allograft function is still a major problem in lung transplantation. Ischemia/reperfusion-(I/R)injury results in alterations of endogenous surfactant integrity. Generally, application of exogenic surfactant has been shown to be effective in both prevention and therapy of I/R-injury. However systematic experimental studies on optimal timing of instillation of modern surfactant preparations (Curosurf®) are pending. Methods: In an extracorporeal rat model, all lungs (n⫽5/group) were preserved using antegrade Perfadex and stored for 4 hours of cold ischemia. In the 3 test groups, Curosurf was administered at different time points: prior to flush preservation (T1), following cold ischemia (T2), and during reperfusion (T3). Results were compared to controls (nS) without surfactant instillation. Postischemic lungs were reventilated and extracorporeally eperfused with xenogeneic blood. Oxygenation (paO2), hemodynamics (PAP) and inspiratory pressures (PIP) were monitored continuously. Intraalveolar edema was quantified stereologically. Statistics comprised different ANOVA models. Results: Oxygenation of T1 lungs was superior as compared to all other groups T2, T3 and nS (p ⬍ 0.02), while PAP- and PIP-values were comparable between Curosurf-treated groups. Stereology supported the oxygenation data with a clear tendency towards less intrapulmonary oedema in group T1.