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Ex Vivo Lung Perfusion: Early Report of Brazilian Experience
Ex Vivo Lung Perfusion: Early Report of Brazilian Experience P.M. Pêgo-Fernandes, I.L. de Medeiros, A.W. Mariani, F.G. Fernandes, F.d.V. Unterpertinger, M.N. Samano, E.d.C. Werebe, M. Canzian, and F.B. Jatene ABSTRACT Introduction. Only about 15% of the potential candidates for lung donation are considered suitable for transplantation. A new method for ex vivo lung perfusion (EVLP) can be used to evaluate and recondition “marginal,” nonacceptable lungs. We have herein described an initial experience with ex vivo perfusion of 8 donor lungs deemed nonacceptable. Materials and Methods. After harvesting, the lungs were perfused ex vivo with Steen Solution, an extracellular matrix with high colloid osmotic pressure. A membrane oxygenator connected to the circuit received gas from a mixture of nitrogen and carbon dioxide, maintaining a normal mixed venous blood gas level in the perfusate. The lungs were gradually rewarmed, reperfused, and ventilated for evaluation through analyses of oxygenation capacity, pulmonary vascular resistance (PVR), lung compliance (LC), and biopsy. Results. The arterial oxygen pressure (with inspired oxygen fraction of 100%) increased from a mean of 206 mm Hg in the organ donor at the referring hospital to a mean of 498 mm Hg during the ex vivo evaluation. After 1 hour of EVLP, PVR varied from 440 –1454 dynes/sec/cm5; LC was in the range of 26 –90 mL/cmH2O. There was no histological deterioration after 10 hours of cold ischemia and 1 hour of EVLP. Conclusions. The ex vivo evaluation model can improve oxygenation capacity of “marginal” lungs rejected for transplantation. It has great potential to increase lung donor availability and, possibly, reduce time on the waiting list. UNG transplantation has shown increasing success, becoming the mainstay of therapy for selected patients with end-stage lung disease. Most of the donor lungs offered to transplantation teams are injured due to pulmonary complication during the brain-death process or in the intensive care unit (ICU) .1 Despite all the improvements in donor management and organ preservation, still only about 15% of potential candidate lungs are considered acceptable for transplantation.2 In São Paulo, Brazil, less than 5% of offered donor lungs are accepted by transplantation programs.3 Even with the use of “extended” and “marginal” donors, the rate of lung transplantations has stopped increasing in recent years, while the number of patients needing lung transplantation is increasing. The donor shortage results in more deaths on the waiting list.4,5 Thus, a strategy that could improve the quality and precision of assessment of nonacceptable donor lungs could have a major impact on reducing waiting time and mortality while on the list.
L
0041-1345/10/$–see front matter doi:10.1016/j.transproceed.2010.01.015 440
A new method for ex vivo lung evaluation has been developed recently by Steen and colleagues to assess the quality of lungs from a non– heart-beating donor.6 The method can also be used to recondition “marginal” and nonacceptable donor lungs. This study represented our initial experience with ex vivo lung perfusion (EVLP). It sought to evaluate the method’s feasibility for human lungs rejected for transplantation.
From the Heart Institute (InCor), Hospital das Clı´nicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. Supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Farmoterápica and Braile Biomédica. Address reprint requests to Paulo Manuel Pêgo Fernandes, Rua Dr. Enéas Carvalho de Aguiar, 44, 2° andar, bloco II, sala 09, São Paulo/SP, Brazil, 05403-000. E-mail: paulopego@incor. usp.br © 2010 Published by Elsevier Inc. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 42, 440 – 443 (2010)
EX VIVO LUNG PERFUSION
MATERIALS AND METHODS This study was conducted under the approval of our ethics committee. From March to July 2009, we evaluated nonacceptable lungs from brain-dead organ donors. Donor lung retrieval was performed according to current clinical practice. At harvest, the lungs were perfused through the pulmonary trunk with 60 ml/kg of cold Perfadex (Vitrolife, Gothenburg, Sweden) and subsequently stored at 4°C for 10 hours. After the period of cold static preservation, we initiated EVLP. The system consisted of a hard-shell reservoir, a centrifugal pump, a membrane oxygenator, and a heat exchanger (Braile Biomedica, São José do Rio Preto, Brazil). A flow probe and a temperature sensor were also included. The lungs were placed in a specifically designed lung enclosure (XVIVO, Vitrolife). The circuit was primed with 1.5 L of Steen Solution (Vitrolife AB), a buffered dextran-containing extracellular-type solution that includes human albumin to provide optimal colloid osmotic pressure. The pH in the solution was adjusted to a physiologic level with isotonic trometamol (Addex-THAM, Kabi, Sweden). A membrane oxygenator was used to deoxygenate the evaluation solution. Gas was supplied to the membrane oxygenator through 2 tanks, 1 with oxygen and the other with a special gas mixture of carbon dioxide (7%) and nitrogen (93%). The tank flow was adjusted until gas values resembling those of normal mixed venous blood were obtained in the evaluation solution, which recirculated in the system. The pulmonary artery was cannulated using a silastic cannula with a built-in pressure catheter (Vitrolife) for continuous measurements of pulmonary arterial pressure (PAP). The outflow perfusate from the pulmonary veins collected in the evaluation box was drained to the venous reservoir. An endotracheal tube inserted in the trachea was secured circumferentially with an umbilical tape (Fig 1). A low-flow perfusion (100 –150 mL/min) at 25°C was initiated through the lungs. Which were gradually warmed by increasing the temperature of the evaluation solution. When it reached 32°C (usually over 20 minutes), we started careful ventilation. In this moment we started the flow of the gas mixture to deoxygenate the inflow perfusate via the gas-exchange membrane. The pump flow was gradually increased but the PAP was never allowed to exceed 20 mm Hg. As a maintenance perfusate flow rate, we used 40% of estimate cardiac output (CO) to perfuse both lungs. CO was
Fig 1. Lungs positioned in the XVIVO chamber. Note the endotracheal cannula (white arrow) for ventilation and pulmonary artery cannula (black arrow) with a built-in pressure catheter.
441 estimated according to donor lung size: 3 ⫻ body surface area. When the temperature of the solution exiting the left atrium (LA) was 37°C, the ventilation was fixed to a tidal volume (TV) of 8 ml/kg, respiratory rate of 7 breaths/min, positive end-expiratory pressure (PEEP) of 5 cmH2O, and fraction of inspired oxygen (FiO2) of 100%. Recruitment maneuvers to a peak airway pressure of 25 cmH2O were used to recruit regions of lung atelectasis. When steady state was reached (usually after 60 minutes of perfusion), perfusate gases and hemodynamics were registered. The following variables were assessed: arterial oxygen partial pressure (PaO2), PaCO2, pulmonary vascular resistance (PVR ⫽ PAP ⫻ 80/pulmonary artery flow [dynes/sec/cm5]), and pulmonary compliance (PC ⫽ TV/airway plateau pressure ⫺ PEEP [mL/cmH2O]). Lung tissues samples from middle lobe were collected in 3 moments: immediately before harvest, after cold static preservation (10 hours), and after EVLP (1 hour). Samples were fixed in 10% buffered formalin for 24 hours, embedded in paraffin, sectioned in 5-m thickness, stained using hematoxylin and eosin (H&E), and examined for pathologic changes under light microscopy. A pulmonary pathologist evaluated midsagittal slices of lung sections to assess histopathological grading of acute lung injury using the following parameters: interstitial edema, intra-alveolar edema, arteriolar thickening, vascular thrombosis, hemorrhage, cell infiltration, intra-alveolar fibrin deposition, and necrosis. The severity of these findings was graded on a 4-point scale as follows: 0, absent; 1, mild; 2, moderate; and 3, severe. All data are expressed as mean ⫾ standard error of the mean. For functional data comparison before and after EVLP, Student paired-samples t test was performed. Comparison of acute lung injury scores between the 3 time points was performed using one-way analysis of variance (ANOVA) for repeated measures. Statistical analyses were performed using SPSS 17.0 (SPSS Inc., Chicago, Ill).
RESULTS
We evaluated 8 organ donors (3 men and 5 women) with a mean age of 50.2 years. Spontaneous intracerebral bleeding was the most frequent cause of death. Almost all donors were rejected for lung donation because of PaO2 values ⬍300 mm Hg with an FiO2 of 100% and PEEP of 5 cmH2O. Donor characteristics are shown in Table 1. The mean PaO2 obtained in the organ donor at the referring hospital was 206.04 mm Hg at a FiO2 of 100% with a PEEP of 5 cmH2O. At steady state, after EVLP the mean PaO2 was 498 mm Hg at a FiO2 of 100%. The difference between PaO2 in situ and PaO2 ex vivo was significant (P ⬍ .001; Fig 2). Table 2 shows individual changes in PaO2 values. The mean oxygen partial pressure in the inflow perfusate (PvO2) at steady state of EVLP (FiO2 100%) was 92.7 mm Hg, proving that the gas mixture applied to the gas-exchange membrane really “deoxygenated” the perfusate. During ex vivo evaluation the mean PVR was 788 dynes/ sec/cm5 (range, 440 –1454 dynes/sec/cm5) and the mean PC was 46.7 mL/cmH2O (range, 26.5–90 mL/cmH2O). Lung histology was preserved after 10 hours of cold ischemia and after 1 hour of EVLP. There was no significant difference between acute lung injury score at 3 times: 4.0 before harvest; 4.75 after cold ischemia; 4.75 after EVLP (P ⫽ .64; Fig 3).
442
PÊGO-FERNANDES, Table 1. Organ Donor Characteristics
Donor
Gender
Age (y)
1 2 3 4
F M F F
70 48 60 22
5 6 7 8
F M M F
41 74 26 61
Cause of Death
Reason for Refusal
ICB ICB ICB Anoxic encephalopathy SB ICB Head trauma ICB
Puder BGV Pneumonia Poor BGV Incompatible receptors Poor BGV Poor BGV Poor BGV Poor BGV
Time in Ventilator (d)
6 3 8 6 1 12 7 4
Abbreviations: F, female; M, male; ICB, intracerebral bleeding; SB, subarachnoid bleeding; BGV, blood gas values.
DISCUSSION
The donor shortage has resulted in an increasing number of deaths on the lung transplantation waiting list. Several methods to expand the current donor pool have been suggested, mainly, relaxation of previously strict donor criteria and use of “marginal” donor organs. Despite these measures, only about 15% of brainstem-dead organ donors have lungs suitable for transplantation. In this scenario EVLP becomes a new method allowing careful visual inspection of the explanted lungs as well as hemodynamic and ventilator measurements, to evaluate gas exchange. It also can be used to recondition nonacceptable lungs, as demonstrated by Steen et al, who transplanted 6 initially rejected donor lungs after EVLP reconditioning with good outcomes.7 In our study, 6 donors were rejected because of inadequate blood gas values. One was rejected because of extensive pneumonia and another because of the absence of a compatible recipient. With the ex vivo evaluation model, all lungs rejected with poor blood gas values met the blood gas criteria for acceptance (⬎400 mm Hg). There was no
Fig 2. Mean PaO2 after EVLP was significantly higher than mean PaO2 before harvesting (P ⬍ .001).
DE
MEDEIROS, MARIANI ET AL
Table 2. PaO2 (mm Hg) Measured In Situ in Each Organ Donor Before Harvesting the Lung and After EVLP Donor
PaO2 In Situ (FiO2 100%)
PaO2 Ex Vivo (FiO2 100%)
1 2 3 4 5 6 7 8 Mean ⫾ SEM
92.0 365.6 179.9 350.0 100.0 286.0 216.8 58.0 206.04 ⫾ 42.16
457.0 463.0 515.0 489.0 458.0 548.0 507.0 547.0 498.0 ⫾ 13.27
deterioration in lung structure as demonstrated by histopathological analysis. Wierup et al used the same method to evaluate 6 lung donors rejected for transplantation.8 After EVLP, the PaO2 was ⬎400 mm Hg in 3 cases, between 300 and 400 mm Hg in 2 cases, and below ⬍300 mm Hg in 1 case. The mean PVR was 400 dynes/sec/cm5, whereas our cases had a mean PVR of 788 dynes/sec/cm5, which can be explained by the fact that our cases had longer cold ischemia time (10 hours vs 7 hours) and we included organ donors with pneumonia and with more time on mechanical ventilation (6 days vs 2 days). This new method enables us to evaluate lungs ex vivo without edema formation. The most important observation is that the reperfusion may be carefully controlled at normothermia with an adequate perfusion solution at a pressure of ⬍20 mm Hg. The high colloid osmotic pressure of Steen Solution allows mobilization and removal of interstitial and alveolar fluid. It also enables inspection of the whole lungs, and consequently reexpansion of persistent atelectatic lung areas by means of manual ventilation and manipulation.8 We believe that EVLP has great potential to increase lung donor availability and, possibly, reduce waiting time and on list mortality. These new strategies for prolonged normothermic ex vivo perfusion may be used for ex vivo
Fig 3. There was no histological deterioration after EVLP. Lung injury score was the same in the 3 time points (P ⫽ .64).
EX VIVO LUNG PERFUSION
assessment, treatment, and even more sophisticated pharmacologic or molecular therapeutic repair of injured donor lungs.9 REFERENCES 1. De Perrot M, Snell GI, Babcock WD, et al: Strategies to optimize the use of currently available lung donors. J Heart Lung Transplant 23:1127, 2004 2. Botha P, Trivedi D, Weir CJ, et al: Extend donor criteria in lung transplantation: impact on organ allocation. J Thorac Cardiovasc Surg 131:1154, 2006 3. Pêgo-Fernandes PM, Samano MN, Junqueira JJM, et al: Lung donor profile in the state of São Paulo, Brazil, in 2006. J Bras Pneumol 34:497, 2008
443 4. Costa da Silva F Jr, JE Afonso Jr, Pêgo-Fernandes PM, et al: São Paulo lung transplantation waiting list: patient characteristics and predictors of death. Transplant Proc 41:927, 2009 5. Feltrim MIZ, Rozanski A, Borges ACS, et al: The quality of life of patients on the lung transplantation waiting list. Transplant Proc 40:819, 2008 6. Steen S, Sjoberg T, Pierre L, et al: Transplantation of lungs from a non-heart-beating donor. Lancet 357:825, 2001 7. Ingemansson R, Eyjolfsson A, Mared L, et al: Clinical transplantation of initially rejected donor lungs after reconditioning ex vivo. Ann Thorac Surg 87:255, 2009 8. Wierup P, Haraldsson A, Nilsson F, et al: Ex vivo evaluation of nonacceptable donor lungs. Ann Thorac Surg 81:460, 2006 9. Cypel M, Yeung JC, Hirayama S, et al: Technique for prolonged normothermic ex vivo lung perfusion. J Heart Lung Transplant 27:1319, 2008
L
0041-1345/10/$–see front matter doi:10.1016/j.transproceed.2010.01.015 440
A new method for ex vivo lung evaluation has been developed recently by Steen and colleagues to assess the quality of lungs from a non– heart-beating donor.6 The method can also be used to recondition “marginal” and nonacceptable donor lungs. This study represented our initial experience with ex vivo lung perfusion (EVLP). It sought to evaluate the method’s feasibility for human lungs rejected for transplantation.
From the Heart Institute (InCor), Hospital das Clı´nicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. Supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Farmoterápica and Braile Biomédica. Address reprint requests to Paulo Manuel Pêgo Fernandes, Rua Dr. Enéas Carvalho de Aguiar, 44, 2° andar, bloco II, sala 09, São Paulo/SP, Brazil, 05403-000. E-mail: paulopego@incor. usp.br © 2010 Published by Elsevier Inc. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 42, 440 – 443 (2010)
EX VIVO LUNG PERFUSION
MATERIALS AND METHODS This study was conducted under the approval of our ethics committee. From March to July 2009, we evaluated nonacceptable lungs from brain-dead organ donors. Donor lung retrieval was performed according to current clinical practice. At harvest, the lungs were perfused through the pulmonary trunk with 60 ml/kg of cold Perfadex (Vitrolife, Gothenburg, Sweden) and subsequently stored at 4°C for 10 hours. After the period of cold static preservation, we initiated EVLP. The system consisted of a hard-shell reservoir, a centrifugal pump, a membrane oxygenator, and a heat exchanger (Braile Biomedica, São José do Rio Preto, Brazil). A flow probe and a temperature sensor were also included. The lungs were placed in a specifically designed lung enclosure (XVIVO, Vitrolife). The circuit was primed with 1.5 L of Steen Solution (Vitrolife AB), a buffered dextran-containing extracellular-type solution that includes human albumin to provide optimal colloid osmotic pressure. The pH in the solution was adjusted to a physiologic level with isotonic trometamol (Addex-THAM, Kabi, Sweden). A membrane oxygenator was used to deoxygenate the evaluation solution. Gas was supplied to the membrane oxygenator through 2 tanks, 1 with oxygen and the other with a special gas mixture of carbon dioxide (7%) and nitrogen (93%). The tank flow was adjusted until gas values resembling those of normal mixed venous blood were obtained in the evaluation solution, which recirculated in the system. The pulmonary artery was cannulated using a silastic cannula with a built-in pressure catheter (Vitrolife) for continuous measurements of pulmonary arterial pressure (PAP). The outflow perfusate from the pulmonary veins collected in the evaluation box was drained to the venous reservoir. An endotracheal tube inserted in the trachea was secured circumferentially with an umbilical tape (Fig 1). A low-flow perfusion (100 –150 mL/min) at 25°C was initiated through the lungs. Which were gradually warmed by increasing the temperature of the evaluation solution. When it reached 32°C (usually over 20 minutes), we started careful ventilation. In this moment we started the flow of the gas mixture to deoxygenate the inflow perfusate via the gas-exchange membrane. The pump flow was gradually increased but the PAP was never allowed to exceed 20 mm Hg. As a maintenance perfusate flow rate, we used 40% of estimate cardiac output (CO) to perfuse both lungs. CO was
Fig 1. Lungs positioned in the XVIVO chamber. Note the endotracheal cannula (white arrow) for ventilation and pulmonary artery cannula (black arrow) with a built-in pressure catheter.
441 estimated according to donor lung size: 3 ⫻ body surface area. When the temperature of the solution exiting the left atrium (LA) was 37°C, the ventilation was fixed to a tidal volume (TV) of 8 ml/kg, respiratory rate of 7 breaths/min, positive end-expiratory pressure (PEEP) of 5 cmH2O, and fraction of inspired oxygen (FiO2) of 100%. Recruitment maneuvers to a peak airway pressure of 25 cmH2O were used to recruit regions of lung atelectasis. When steady state was reached (usually after 60 minutes of perfusion), perfusate gases and hemodynamics were registered. The following variables were assessed: arterial oxygen partial pressure (PaO2), PaCO2, pulmonary vascular resistance (PVR ⫽ PAP ⫻ 80/pulmonary artery flow [dynes/sec/cm5]), and pulmonary compliance (PC ⫽ TV/airway plateau pressure ⫺ PEEP [mL/cmH2O]). Lung tissues samples from middle lobe were collected in 3 moments: immediately before harvest, after cold static preservation (10 hours), and after EVLP (1 hour). Samples were fixed in 10% buffered formalin for 24 hours, embedded in paraffin, sectioned in 5-m thickness, stained using hematoxylin and eosin (H&E), and examined for pathologic changes under light microscopy. A pulmonary pathologist evaluated midsagittal slices of lung sections to assess histopathological grading of acute lung injury using the following parameters: interstitial edema, intra-alveolar edema, arteriolar thickening, vascular thrombosis, hemorrhage, cell infiltration, intra-alveolar fibrin deposition, and necrosis. The severity of these findings was graded on a 4-point scale as follows: 0, absent; 1, mild; 2, moderate; and 3, severe. All data are expressed as mean ⫾ standard error of the mean. For functional data comparison before and after EVLP, Student paired-samples t test was performed. Comparison of acute lung injury scores between the 3 time points was performed using one-way analysis of variance (ANOVA) for repeated measures. Statistical analyses were performed using SPSS 17.0 (SPSS Inc., Chicago, Ill).
RESULTS
We evaluated 8 organ donors (3 men and 5 women) with a mean age of 50.2 years. Spontaneous intracerebral bleeding was the most frequent cause of death. Almost all donors were rejected for lung donation because of PaO2 values ⬍300 mm Hg with an FiO2 of 100% and PEEP of 5 cmH2O. Donor characteristics are shown in Table 1. The mean PaO2 obtained in the organ donor at the referring hospital was 206.04 mm Hg at a FiO2 of 100% with a PEEP of 5 cmH2O. At steady state, after EVLP the mean PaO2 was 498 mm Hg at a FiO2 of 100%. The difference between PaO2 in situ and PaO2 ex vivo was significant (P ⬍ .001; Fig 2). Table 2 shows individual changes in PaO2 values. The mean oxygen partial pressure in the inflow perfusate (PvO2) at steady state of EVLP (FiO2 100%) was 92.7 mm Hg, proving that the gas mixture applied to the gas-exchange membrane really “deoxygenated” the perfusate. During ex vivo evaluation the mean PVR was 788 dynes/ sec/cm5 (range, 440 –1454 dynes/sec/cm5) and the mean PC was 46.7 mL/cmH2O (range, 26.5–90 mL/cmH2O). Lung histology was preserved after 10 hours of cold ischemia and after 1 hour of EVLP. There was no significant difference between acute lung injury score at 3 times: 4.0 before harvest; 4.75 after cold ischemia; 4.75 after EVLP (P ⫽ .64; Fig 3).
442
PÊGO-FERNANDES, Table 1. Organ Donor Characteristics
Donor
Gender
Age (y)
1 2 3 4
F M F F
70 48 60 22
5 6 7 8
F M M F
41 74 26 61
Cause of Death
Reason for Refusal
ICB ICB ICB Anoxic encephalopathy SB ICB Head trauma ICB
Puder BGV Pneumonia Poor BGV Incompatible receptors Poor BGV Poor BGV Poor BGV Poor BGV
Time in Ventilator (d)
6 3 8 6 1 12 7 4
Abbreviations: F, female; M, male; ICB, intracerebral bleeding; SB, subarachnoid bleeding; BGV, blood gas values.
DISCUSSION
The donor shortage has resulted in an increasing number of deaths on the lung transplantation waiting list. Several methods to expand the current donor pool have been suggested, mainly, relaxation of previously strict donor criteria and use of “marginal” donor organs. Despite these measures, only about 15% of brainstem-dead organ donors have lungs suitable for transplantation. In this scenario EVLP becomes a new method allowing careful visual inspection of the explanted lungs as well as hemodynamic and ventilator measurements, to evaluate gas exchange. It also can be used to recondition nonacceptable lungs, as demonstrated by Steen et al, who transplanted 6 initially rejected donor lungs after EVLP reconditioning with good outcomes.7 In our study, 6 donors were rejected because of inadequate blood gas values. One was rejected because of extensive pneumonia and another because of the absence of a compatible recipient. With the ex vivo evaluation model, all lungs rejected with poor blood gas values met the blood gas criteria for acceptance (⬎400 mm Hg). There was no
Fig 2. Mean PaO2 after EVLP was significantly higher than mean PaO2 before harvesting (P ⬍ .001).
DE
MEDEIROS, MARIANI ET AL
Table 2. PaO2 (mm Hg) Measured In Situ in Each Organ Donor Before Harvesting the Lung and After EVLP Donor
PaO2 In Situ (FiO2 100%)
PaO2 Ex Vivo (FiO2 100%)
1 2 3 4 5 6 7 8 Mean ⫾ SEM
92.0 365.6 179.9 350.0 100.0 286.0 216.8 58.0 206.04 ⫾ 42.16
457.0 463.0 515.0 489.0 458.0 548.0 507.0 547.0 498.0 ⫾ 13.27
deterioration in lung structure as demonstrated by histopathological analysis. Wierup et al used the same method to evaluate 6 lung donors rejected for transplantation.8 After EVLP, the PaO2 was ⬎400 mm Hg in 3 cases, between 300 and 400 mm Hg in 2 cases, and below ⬍300 mm Hg in 1 case. The mean PVR was 400 dynes/sec/cm5, whereas our cases had a mean PVR of 788 dynes/sec/cm5, which can be explained by the fact that our cases had longer cold ischemia time (10 hours vs 7 hours) and we included organ donors with pneumonia and with more time on mechanical ventilation (6 days vs 2 days). This new method enables us to evaluate lungs ex vivo without edema formation. The most important observation is that the reperfusion may be carefully controlled at normothermia with an adequate perfusion solution at a pressure of ⬍20 mm Hg. The high colloid osmotic pressure of Steen Solution allows mobilization and removal of interstitial and alveolar fluid. It also enables inspection of the whole lungs, and consequently reexpansion of persistent atelectatic lung areas by means of manual ventilation and manipulation.8 We believe that EVLP has great potential to increase lung donor availability and, possibly, reduce waiting time and on list mortality. These new strategies for prolonged normothermic ex vivo perfusion may be used for ex vivo
Fig 3. There was no histological deterioration after EVLP. Lung injury score was the same in the 3 time points (P ⫽ .64).
EX VIVO LUNG PERFUSION
assessment, treatment, and even more sophisticated pharmacologic or molecular therapeutic repair of injured donor lungs.9 REFERENCES 1. De Perrot M, Snell GI, Babcock WD, et al: Strategies to optimize the use of currently available lung donors. J Heart Lung Transplant 23:1127, 2004 2. Botha P, Trivedi D, Weir CJ, et al: Extend donor criteria in lung transplantation: impact on organ allocation. J Thorac Cardiovasc Surg 131:1154, 2006 3. Pêgo-Fernandes PM, Samano MN, Junqueira JJM, et al: Lung donor profile in the state of São Paulo, Brazil, in 2006. J Bras Pneumol 34:497, 2008
443 4. Costa da Silva F Jr, JE Afonso Jr, Pêgo-Fernandes PM, et al: São Paulo lung transplantation waiting list: patient characteristics and predictors of death. Transplant Proc 41:927, 2009 5. Feltrim MIZ, Rozanski A, Borges ACS, et al: The quality of life of patients on the lung transplantation waiting list. Transplant Proc 40:819, 2008 6. Steen S, Sjoberg T, Pierre L, et al: Transplantation of lungs from a non-heart-beating donor. Lancet 357:825, 2001 7. Ingemansson R, Eyjolfsson A, Mared L, et al: Clinical transplantation of initially rejected donor lungs after reconditioning ex vivo. Ann Thorac Surg 87:255, 2009 8. Wierup P, Haraldsson A, Nilsson F, et al: Ex vivo evaluation of nonacceptable donor lungs. Ann Thorac Surg 81:460, 2006 9. Cypel M, Yeung JC, Hirayama S, et al: Technique for prolonged normothermic ex vivo lung perfusion. J Heart Lung Transplant 27:1319, 2008