Superior protection in orthotopic rat lung transplantation with cyclic adenosine monophosphate and nitroglycerin–containing preservation solution Koichi.

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Presentation transcript:

Superior protection in orthotopic rat lung transplantation with cyclic adenosine monophosphate and nitroglycerin–containing preservation solution Koichi Kayano, MD, PhD, Koichi Toda, MD, Yoshifumi Naka, MD, PhD, Kenji Okada, MD, PhD, Mehmet C. Oz, MD, David J. Pinsky, MD The Journal of Thoracic and Cardiovascular Surgery Volume 118, Issue 1, Pages 135-144 (July 1999) DOI: 10.1016/S0022-5223(99)70152-2 Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig 1 Effect of preservation solution composition on pulmonary vascular resistance during lung harvest. After anesthesia, left atrium was vented and pulmonary artery was flushed with 30-mL volume of indicated preservation solution (4°C) at constant infusion pressure of 20 mm Hg. Flushing duration (in seconds) was measured as index of harvest pulmonary vascular resistance. EC, Euro-Collins solution; UW, University of Wisconsin solution; LPDG, low-potassium dextran glucose solution; CU, Columbia University solution; CU(–), Columbia University solution without db-cAMP and nitroglycerin. Compositions of these solutions are described in Table I. For each group N = 8. Boxes represent means; error bars indicate SEM. The Journal of Thoracic and Cardiovascular Surgery 1999 118, 135-144DOI: (10.1016/S0022-5223(99)70152-2) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig 2 Effect of preservation solution composition on arterial oxygenation after lung transplantation. Donor lungs were harvested and preserved with indicated solution for 6 hours at 4°C and transplanted orthotopically into strain-matched recipient. After transplantation native right pulmonary artery was ligated, and 30 minutes later (or just before recipient death), 200 μL left ventricular blood was obtained to determine arterial oxygenation. EC, Euro-Collins solution; UW, University of Wisconsin solution; LPDG, low-potassium dextran glucose solution; CU, Columbia University solution; CU(–) , Columbia University solution without db-cAMP and nitroglycerin. For each group N = 8. Boxes represent means; error bars indicate SEM. The Journal of Thoracic and Cardiovascular Surgery 1999 118, 135-144DOI: (10.1016/S0022-5223(99)70152-2) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig 3 Effect of preservation solution composition on PVR after lung transplantation. Experiments were performed as described in legend to Fig 2. PVR was calculated as described in text. EC, Euro-Collins solution; UW, University of Wisconsin solution; LPDG, low-potassium dextran glucose solution; CU, Columbia University solution; CU(–), Columbia University solution without db-cAMP and nitroglycerin. For each group N = 8. Boxes represent means; error bars indicate SEM. The Journal of Thoracic and Cardiovascular Surgery 1999 118, 135-144DOI: (10.1016/S0022-5223(99)70152-2) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig 4 Effect of preservation solution composition on graft neutrophil accumulation after lung transplantation. Experiments were performed as described in legend to Fig 2. Lungs were removed at 30 minutes after right pulmonary arterial ligation (or at recipient death if it preceded 30-minute time point), snap frozen in liquid nitrogen, and kept at –80°C until time of assay. Myeloperoxidase activity, as change in absorbance (ΔAbs) at 460 nm per minute, was used to quantify neutrophil accumulation. EC, Euro-Collins solution; UW, University of Wisconsin solution; LPDG, low-potassium dextran glucose solution; CU, Columbia University solution; CU(–), Columbia University solution without db-cAMP and nitroglycerin. For each group N = 8. Boxes represent means; error bars indicate SEM. The Journal of Thoracic and Cardiovascular Surgery 1999 118, 135-144DOI: (10.1016/S0022-5223(99)70152-2) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig 5 Effect of preservation solution composition on recipient TNF-α levels after lung transplantation. Experiments were performed as described in legend to Fig 2. Heparinized blood samples were taken from left ventricle at 30 minutes after right pulmonary arterial ligation (or at recipient death if it preceded 30-minute time point). After centrifugation to remove cellular elements, plasma was assayed for TNF-α by enzyme-linked immunosorbent assay. EC, Euro-Collins solution; UW, University of Wisconsin solution; LPDG, low-potassium dextran glucose solution; CU, Columbia University solution; CU(–), Columbia University solution without db-cAMP and nitroglycerin. For each group N = 8 blood samples assayed in duplicate. Boxes represent means; error bars indicate SEM. The Journal of Thoracic and Cardiovascular Surgery 1999 118, 135-144DOI: (10.1016/S0022-5223(99)70152-2) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig 6 Effect of preservation solution composition on recipient IL-1α levels after lung transplantation. Experiments were performed as described in legend to Fig 2. Heparinized blood samples were taken from left ventricle at 30 minutes after right pulmonary arterial ligation (or at recipient death if it preceded 30-minute time point). After centrifugation to remove cellular elements, plasma was assayed for IL-1α by enzyme-linked immunosorbent assay. For each group N = 8 blood samples assayed in duplicate. EC, Euro-Collins solution; UW, University of Wisconsin solution; LPDG, low-potassium dextran glucose solution; CU, Columbia University solution; CU(–) , Columbia University solution without db-cAMP and nitroglycerin. Boxes represent means; error bars indicate SEM. The Journal of Thoracic and Cardiovascular Surgery 1999 118, 135-144DOI: (10.1016/S0022-5223(99)70152-2) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig 7 Effect of preservation solution composition on recipient survival after lung transplantation. Experiments were performed as described in legend to Fig 2; after ligation of contralateral (right) pulmonary artery (PA), time was recorded until recipient death or until previously specified killing time at 30 minutes. Death was defined a priori as a pulmonary arterial flow of zero. Number of surviving recipients (numerator) and total number of transplantation experiments (denominator) are shown for each preservation solution. EC, Euro-Collins solution; UW, University of Wisconsin solution; LPDG, low-potassium dextran glucose solution; CU, Columbia University solution; CU(–), Columbia University solution without db-cAMP and nitroglycerin. Asterisk indicates P = .021 versus University of Wisconsin solution and low-potassium dextran glucose solution, P = .007 versus Euro-Collins solution. The Journal of Thoracic and Cardiovascular Surgery 1999 118, 135-144DOI: (10.1016/S0022-5223(99)70152-2) Copyright © 1999 Mosby, Inc. Terms and Conditions

Fig 8 A, Effect of preservation time on arterial oxygenation after lung transplantation. Grafts were preserved in Columbia University solution at 4°C for indicated durations, after which they were transplanted orthotopically into strain-matched recipients. At 30 minutes after ligation of native right pulmonary artery or at recipient death, 200 μL blood was sampled from left ventricle for blood gas analysis. N = 8, N = 8, N = 3, N = 3, and N = 6 transplants for preservation durations of 6, 9, 12, 15, and 18 hours, respectively. B, Effect of preservation time on PVR after lung transplantation. Grafts were preserved in Columbia University solution at 4°C for indicated durations, after which they were transplanted orthotopically into strain-matched recipients. At 30 minutes after ligation of native right pulmonary artery or at recipient death, PVR was measured as described in legend to Fig 3. N = 8, N = 8, N = 3, N = 3, and N = 6 transplants for preservation durations of 6, 9, 12, 15, and 18 hours, respectively. C, Effect of preservation time on graft neutrophil accumulation after lung transplantation. Grafts were preserved in Columbia University solution at 4°C for indicated durations, after which they were transplanted orthotopically into strain-matched recipients. At 30 minutes after ligation of native right pulmonary artery or at recipient death, lung tissue was obtained and myeloperoxidase activity was measured as described in the legend to Fig 4. N = 8, N = 8, N = 3, N = 3, and N = 6 transplants for preservation durations of 6, 9, 12, 15, and 18 hours, respectively. D, Effect of preservation time on recipient survival after lung transplantation. Grafts were preserved in Columbia University solution at 4°C for indicated durations, after which they were transplanted orthotopically into strain-matched recipients. Immediately after transplantation native (right) pulmonary artery was ligated, and time until recipient death was recorded. Survivals at 30 minutes are shown. N = 8, N = 8, N = 3, N = 3, and N = 6 transplants for preservation durations of 6, 9, 12, 15, and 18 hours, respectively. The Journal of Thoracic and Cardiovascular Surgery 1999 118, 135-144DOI: (10.1016/S0022-5223(99)70152-2) Copyright © 1999 Mosby, Inc. Terms and Conditions