Scandinavian Cardiovascular Journal

ISSN: 1401-7431 (Print) 1651-2006 (Online) Journal homepage: http://www.tandfonline.com/loi/icdv20

Ventilation in situ after cardiac death improves pulmonary grafts exposed to 2 hours of warm ischemia Leif Pierre, Sandra Lindstedt & Richard Ingemansson To cite this article: Leif Pierre, Sandra Lindstedt & Richard Ingemansson (2015) Ventilation in situ after cardiac death improves pulmonary grafts exposed to 2 hours of warm ischemia, Scandinavian Cardiovascular Journal, 49:5, 293-298, DOI: 10.3109/14017431.2015.1052549 To link to this article: http://dx.doi.org/10.3109/14017431.2015.1052549

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Date: 06 November 2015, At: 04:10

Scandinavian Cardiovascular Journal, 2015; 49: 293–298

ORIGINAL ARTICLE

Ventilation in situ after cardiac death improves pulmonary grafts exposed to 2 hours of warm ischemia

LEIF PIERRE, SANDRA LINDSTEDT & RICHARD INGEMANSSON

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Department of Cardiothoracic Surgery, Skåne University Hospital, Lund, Lund University, Sweden

Abstract Background. The pulmonary donor pool would increase substantially if lungs could be donated after cardiac death (DCD). There have been ethical and legal obstacles since administration of heparin and cooling has to be done immediately after cardiac death. This study examines whether ventilation of DCD lungs without administering heparin or cooling the lungs after cardiac death could improve graft function. Method. Twelve donor pigs with a mean bodyweight of 70 kg were randomized into two groups. Six animals were ventilated in situ with 50% oxygen, 4 L/min, and 5 cm H2O in positive end-expiratory pressure or PEEP for 2 h after cardiac death. Six animals served as non-ventilated controls and were exposed to warm ischemia for 2 h. After 2 h, all lungs were harvested and flush perfused with Perfadex® solution and stored at 8°C for another 2 h. An ex vivo lung perfusion or EVLP circuit was used for evaluation. Results. Non-ventilated lungs developed pulmonary edema, and had highly impaired blood gas levels and a significantly increased weight. The ventilated lungs demonstrated excellent blood gas levels and unchanged weight. Conclusion. The increase in tolerable warm ischemic time in combination with avoiding heparinization and cooling might facilitate the use of DCD lungs for transplantation. Key words: DCD, lungs, ventilation in situ, warm ischemia

Introduction Since the first success in 1983, lung transplantation has become an established option for the treatment of patients with terminal lung disease (1). A considerable problem in clinical lung transplantation is the shortage of donor lungs. Only 20% of potential candidate lungs are being transplanted (2). The pulmonary donor pool would increase substantially if lungs could be safely transplanted from the donor after cardiac death (donated after cardiac death [DCD]) (3–7). According to Maastricht criteria, controlled donors are defined as those in whom cardiac arrest is expected after the withdrawal of life support, but before they are declared brain dead (Category 3), and those in whom cardiac arrest occurs after brain death (Category 4). Uncontrolled DCD lungs, Categories 1 and 2, are obtained donors who die in the prehospital environment or suffer unexpected cardiac arrest in the hospital (3,8). In DCD pulmonary grafts, tolerable warm ischemia after cardiac arrest is suggested to be limited to

1 h (4,9). If the warm ischemic time is to be extended beyond 1 h, protection of the pulmonary DCD graft inside the cadaver is necessary to minimize tissue degradation that will probably affect early and late graft functions after transplantation. In the present study, we ventilated the lungs in situ for 2 h without heparinization and without cooling of the lungs. A continued supply of oxygen might allow extension of the permissible ischemic time and provide better function in lungs harvested 2 h after cardiac arrest, thereby facilitating the use of DCD lungs for transplantation.

Material and methods Animal preparation Twelve Swedish landrace pigs were fasted overnight with free access to water. The study was approved by the Ethics Committee for Animal Research, Lund University, Sweden (No. M 172–11). All animals

Correspondence: Richard Ingemansson, MD, PhD, Department of Cardiothoracic Surgery, Skåne University Hospital, SUS, Lund, Lund University, SE-221 85 Lund, Sweden. Tel: ⫹46 46 173803. Fax: ⫹46 46 158635. E-mail: [email protected] (Received 20 January 2015 ; revised 28 April 2015 ; accepted 13 May 2015) ISSN 1401-7431 print/ISSN 1651-2006 online © 2015 Informa Healthcare DOI: 10.3109/14017431.2015.1052549

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received care according to the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes, as well as to the USA Principles of Laboratory Animal Care of the National Society for Medical Research, and the Guide for the Care and Use of Laboratory Animals. Premedication was performed with an intramuscular injection of xylazine (Rompun® vet. 20 mg/ml, Bayer AG, Leverkusen, Germany, 2 mg/kg) mixed with ketamine (Ketaminol® vet. 100 mg/ml, Farmaceutici Gellini S.p.A., Aprilia, Italy, 20 mg/kg) while the pigs were still in the stable. Peripheral i.v. access was then established in the ear. Oral intubation was performed using a 7.5-mm endotracheal tube after the induction of anesthesia with sodium thiopental (Pentothal, Abbott Laboratories, North Chicago, Illinois, USA) and pancuronium bromide (Pavulon, N.V. Organon, Oss, the Netherlands). Anesthesia was maintained by infusions of ketamine (Ketaminol® vet), midazolam (Midazolam Panpharma®, Oslo, Norway), and fentanyl (Leptanal®, Lilly, France). Fluid loss was compensated for by continuous infusion of Ringer’s acetate. Mechanical ventilation was established with a Siemens-Elema ventilator (Servo Ventilator 300, Siemens, Solna, Sweden). Preservation of the lungs Ventricular fibrillation was induced electrically. The animals were then randomized into two different groups. In the non-ventilation group, the animals were left untouched for 2 h at room temperature. In the ventilated group, the lungs were ventilated with an FiO2 of 0.5, a frequency of 15 breaths/min, a minute ventilation of 4 L/min, and 5 cm H2O in positive end-expiratory pressure (PEEP) for 2 h. Apart from the ventilation, the animals in this group were left untouched during the 2-h period at room temperature. Two hours after initiation of cardiac arrest, a median sternotomy was performed. The pulmonary artery was cannulated via the right ventricle with a 28F cannula secured with a purse-string suture placed in the outflow tract of the A. pulmonalis. The right and left pleurae were filled with ice slush to cool the lungs. The lungs were perfused antegradely with 4 L of cold Perfadex® solution (XVIVO Perfusion AB, Gothenburg Sweden) solution containing 1.0 ml of isotonic trometamol (Addex-THAM 3.3 mmol/ml, Fresenius Kabi AB Uppsala, Sweden), 2 ml of calcium chloride (0.45 mmol/ml), and 3 ml of nitroglycerin (5 mg/ml, BMM Pharma AB, Stockholm, Sweden) at a low perfusion pressure (⬍20 mmHg).

The lungs were harvested en bloc in a standard fashion, and weighed. A segment (~ 8 cm) of the descending aorta also was excised.The lungs, together with the aortic segment, were then immersed in cold Perfadex® solution and kept in cold storage at 8°C for 2 h. Ex Vivo lung perfusion Ex vivo lung perfusion (EVLP) was performed using the Medtronics Ex Vivo Lung Evaluation Set extracorporeal perfusion circuit by Medtronics (Medtronic AB, Kerkrade, the Netherlands; Ex Vivo Lung Evaluation Set). This system is not produced any longer; we use it only in experimental settings. The system was primed with STEEN solution™ (XVIVO Perfusion AB, Gothenburg Sweden) and 2 units of autologous blood, withdrawn previously from each donor. Imipenem (0.5 g, Tienam, Merck Sharp & Dohme, Sollentuna, Sweden), insulin (20 IU, Actrapid, Novo Nordisk, Bagsvaerd, Denmark), and heparin (10,000 IU, Leo Pharma, Malmö, Sweden) were added, and isotonic trometamol (Addex-Tham, Kabi, Sweden) was used to buffer the mixed solution to a temperature-adjusted pH of 7.4. Gas was supplied to the membrane oxygenator; first oxygen and CO2 were supplied during the reconditioning phase, and then 93% nitrogen and 7% CO2 were supplied during the evaluating phase, creating a normal venous blood gas in the perfusate to the pulmonary artery (in other words, the oxygenator was used to deoxygenate the perfusate). Before starting perfusion, the pulmonary artery was extended using the excised segment of the descending aorta to facilitate cannulation. The pulmonary artery cannula was then connected to the corresponding tube of the extracorporeal circuit, the air was removed, and the shunt of the circuit was clamped. An endotracheal tube was secured in the trachea with a cotton band and connected to the ventilator. The remnant of the left atrium was left open, preventing obstruction of the pulmonary outflow. Low-flow perfusion at 25°C was initiated through the lungs. The lungs were gradually warmed by increasing the temperature of the perfusate. When the temperature reached 32°C, ventilation was started with an FiO2 of 0.5 and a minute volume of 1 L/min, and no PEEP.The pump flow was gradually increased, but the pulmonary arterial pressure was never allowed to exceed 20 mmHg. With each 1°C increase in temperature, the ventilation was increased by a minute volume of 1 L. The technique is described earlier in detail (10,11).

DCD lungs exposed to warm ischemia Lung evaluation Blood gases were analyzed at the end of the EVLP procedure with FiO2 of 1.0, 0.5, and 0.21, respectively. The lungs were then weighed before and after the EVLP procedure. The pulmonary arterial branches were macroscopically studied for thrombotic material by opening the arteries as far distally as possible.

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Calculations and statistics Calculations and statistical analysis were performed using GraphPad 4.0 software. Statistical analysis was performed using one-way analysis of variance or ANOVA and Bonferroni’s multiple comparison tests, comparing all groups. Significance was defined as p ⬍ 0.05 (*), p ⬍ 0.01 (**), p ⬍ 0.001 (***), and p ⬎ 0.05 (not significant, n.s.). The results are presented as mean and standard error of the mean (SEM).

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Table I. Two hours of warm ischemia. Non-ventilation Ventilation Mean ⫾ SEM Mean ⫾ SEM FiO2 ⫽ 1.0

PvCO2 PvO2 PaCO2 PaO2 FiO2 ⫽ 0.5 PvCO2 PvO2 PaCO2 PaO2 FiO2 ⫽ 0.21 PvCO2 PvO2 PaCO2 PaO2

4.3 ⫾ 0.1 6.8 ⫾ 0.2 3.9 ⫾ 0.1 9.6 ⫾ 0.8 4.3 ⫾ 0.2 6.1 ⫾ 0.1 4.0 ⫾ 0.1 7.6 ⫾ 0.3 4.5 ⫾ 0.1 6.0 ⫾ 0.1 4.0 ⫾ 0.2 6.2 ⫾ 0.2

4.4 ⫾ 0.2 7.7 ⫾ 0.7 3.7 ⫾ 0.1 71.2 ⫾ 2.7 3.6 ⫾ 0.3 6.8 ⫾ 0.2 3.5 ⫾ 0.2 30.0 ⫾ 0.8 3.8 ⫾ 0.1 6.6 ⫾ 0.2 3.4 ⫾ 0.1 13.9 ⫾ 0.7

p value n.s ⬍ 0.050 n.s ⬍ 0.001 n.s n.s n.s ⬍ 0.001 n.s n.s ⬍ 0.050 ⬍ 0.001

FiO2, Inspired oxygen fraction; PvCO2, venous carbon dioxide partial pressure; PvO2, venous oxygen partial pressure; PaCO2, arterial carbon dioxide partial pressure; PaO2, arterial oxygen partial pressure.

the EVLP (n.s). Comparing the two groups, the ventilated group showed significantly lower pulmonary graft weight after the EVLP compared with the non-ventilated group (p ⬍ 0.001) (Figure 1).

Results Study groups

Macroscopic appearance

No significant differences were observed in animal weight in the two groups (68 ⫾ 1 kg in the nonventilated group and 72 ⫾ 3 kg in the ventilated group, p ⬎ 0.05). No anatomical anomalies, signs of infection, or malignancy were found in any of the animals at autopsy.

No thrombotic material was observed in either of the groups. This indicates that it is not necessary to administer heparin in pigs to avoid thrombosis in

Arterial and venous blood gases during EVLP At an FiO2 of 1.0, the PaO2 was 71.2 ⫾ 2.7 kPa in the ventilated group and 9.6 ⫾ 0.8 kPa (p ⬍ 0.001) in the non-ventilated group. At a FiO2 of 0.5, the PaO2 was 30.0 ⫾ 0.8 kPa in the ventilated group and 7.6 ⫾ 0.3 kPa (p ⬍ 0.001) in the non-ventilated group. At a FiO2 of 0.21, the PaO2 was 13.9 ⫾ 0.7 kPa in the ventilated group and 6.2 ⫾ 0.2 kPa (p ⬍ 0.001) in the non-ventilated group. The arterial and venous blood gases at 1.0, 0.5, and 0.21 FiO2 are presented in Table I.

Pulmonary graft weight In the non-ventilated group, the weight of the pulmonary graft was 650 ⫾ 33 g before the EVLP and 1167 ⫾ 69 g after the EVLP (p ⬍ 0.001). In the ventilated group, the weight of the pulmonary graft was 687 ⫾ 9 g before the EVLP and 707 ⫾ 12 g after

Figure 1. Mean lung weight (⫾ SEM) after EVLP of lungs exposed to 2 h of warm ischemia. The ventilated group received ventilation of the lungs during the warm ischemic period while the nonventilated group did not. Significance was defined as p ⬍ 0.05 (*), p ⬍ 0.01 (**), p ⬍ 0.001 (***), and p ⬎ 0.05 (not significant, n.s.).

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pigs kept at room temperature. A fulminant lung edema was present in all the lungs from the nonventilated group. Furthermore, three out of six lungs in this group were hepatized in the lower lobes bilaterally.

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Comment We have earlier reported the results of the first six double-lung transplantations performed in the world with donor lungs that were rejected for transplantation by the Scandiatransplant, Eurotransplant, and the UK transplant organizations due to poor arterial oxygen tension (12). The EVLP method, which has been described in detail previously (10,12–14), has been suggested as a novel method of differentiating between “good” and “poor” pulmonary grafts in this suboptimal population. EVLP also serves as an excellent method of evaluating lung function in DCD lungs (15–18). Currently, the majority of clinical lung transplant programs harvest lungs from brain-dead donors or HBD. Lately, strategies have evolved to increase the size of the pulmonary donor pool by using DCD lungs. In 1991, Egan et al. (4) showed that canine cadaver lungs harvested 1 h after cessation of circulation (“l-hour” lungs) could produce adequate gas exchange for survival. “Two-hour” cadaver lung recipients did less well, and only 1 of 4 animals receiving a “4-hour” cadaver lung survived the observation period. Steen et al. successfully transplanted the first uncontrolled DCD lung in modern history in the year 2000, where the donor lung was exposed to 1 h of warm ischemia (19). These findings suggest that lung tissue may remain viable for a sufficient period to allow safe postmortem harvesting for transplantation. The tolerable warm ischemia after cardiac arrest seems to be limited to 1 h (4,9,19). If the warm ischemic time is to be extended beyond 1 h, protection of the pulmonary DCD graft inside the cadaver is necessary to minimize tissue degradation by anaerobic catabolic processes that will affect early and late graft function after transplantation. An efficient technique of organ preservation in the cadaver also helps to extend the pre-explantation interval, thereby providing sufficient time for the transplantation team to organize family consent and organ retrieval. Harvesting organ with such a short notice and without family consensus has been a major reason why DCD lung transplantation programs are struggling with ethical dilemmas. The lung is unique among solid organs because it does not rely on vascular perfusion for cellular respiration. Respiration can occur directly across

the pulmonary gas interface, and gas exchange processes are entirely passive. Therefore, one would expect that the metabolic requirements of lung tissue should be low and that the lung might tolerate considerable periods of ischemia. This knowledge has led to the suggestion that ventilation might be a reliable option to preserve aerobic metabolism of pulmonary cells after cardiac arrest (20,21). Egan et al. were first to examine pulmonary cell viability in cadaveric rats by using a trypan blue vital dye exclusion method (22). In their report, at 12 h after death, 77% of cells in non-ventilated lungs were not viable compared with only 26% in oxygen-ventilated lungs, and 71% in nitrogen-ventilated lungs. These values were comparable to 69%, 19%, and 70%, respectively, from a study made by Van Raemdonck et al. on rabbit lungs (23). A complementary ultrastructural study by Egan et al. showed significant attenuation of damage to intracellular organelles in pulmonary parenchymal cells from cadaveric rat lungs ventilated with oxygen up to 8 h after death when compared with non-ventilated lungs (24). Besides these morphologic and ultra-structural studies, there is also biochemical evidence that tissue degradation can be prevented when oxygen is supplied to the lungs through the air (25,26). The ideal preservation method during the warm ischemic period in the DCD remains unclear. However, in the present study, we compare DCD lungs exposed to 2 h of warm ischemia, where six of the lungs were ventilated with 50% oxygen, a minute ventilation of 4 L/min, and a PEEP of 5 cm H2O. The other six lungs served as controls and were not ventilated. None of the donor animals received heparin (27). All the lungs were evaluated in the EVLP system after completed 8C storage for 2 h. All the lungs that were not ventilated developed severe pulmonary edema and had poor blood gas levels and a highly significantly increased lung weight compared with the ventilated lungs. The ventilated lungs showed excellent blood gas levels, and unchanged lung weight after EVLP, indicating good lung function (Table I, Figure 1). Specific values for expectable donor lungs (blood gases, weight, and macroscopical appearance) are the same in pigs and humans. We speculate that cellular respiration can continue in the absence of circulation to the lung. Although perfusion remains necessary for a continued supply of metabolic substrates and for the removal of metabolic by-products, there is probably an interval in which there is sufficient availability of substrate as well as a sufficiently low concentration of toxic by-products to permit cellular viability in the presence of a stagnant blood pool. We believe this time could be extended from one to two hours if the lung is ventilated during the warm ischemic period.

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DCD lungs exposed to warm ischemia This will give the transplantation team sufficient time to organize family consent and organ retrieval. Including the cooled storage time of 2 h and the EVLP time, the transplantation team will have about 5–6 h to call in and prepare the recipient. The procedure will be less invasive than, for example, topical cooling inside the deceased where four thoracic tubes must be inserted and connected to a cooling source (19). The present study also demonstrated that administration of heparin before death is not mandatory for prevention of intraluminal distal obstruction by clots in the pulmonary vasculature. We speculate that the anticoagulant factors produced by the pulmonary vascular endothelium may in conjunction with warm ischemia prevent intravascular plugging within the pulmonary parenchyma. The findings in the present study allow us to make all necessary arrangements for clinical transplantations. Furthermore, we can avoid administration of heparin and insertion of cooling drainage which have been former ethical issues.

Limitations of the study The study was performed on lungs of healthy 70-kg pigs and not on human DCD lungs.

Conclusions Ventilation in situ of DCD lungs appears to increase the tolerable period of ischemia from one to at least two hours in lungs exposed to warm ischemia. We also conclude that it is not necessary to heparinize the donor as long as the lungs are kept inside the animal. It may be realistic to consider using DCD lungs to expand the human pulmonary donor pool using the above-described technique. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

References 1. Dilling DF, Glanville AR. Advances in lung transplantation: The year in review. J Heart Lung Transplant. 2011; 30:247–51. 2. Punch JD, Hayes DH, LaPorte FB, McBride V, Seely MS. Organ donation and utilization in the United States, 1996–2005. Am J Transplant. 2007;7:1327–38. 3. Dominguez-Gil B, Haase-Kromwijk B, Van Leiden H, Neuberger J, Coene L, Morel P, et al. Current situation of donation after circulatory death in European countries. Transpl Int. 2011;24:676–86.

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4. Egan TM, Lambert CJ, Jr., Reddick R, Ulicny KS, Jr., Keagy BA, Wilcox BR. A strategy to increase the donor pool: Use of cadaver lungs for transplantation. Ann Thorac Surg. 1991;52:1113–20. 5. Cypel M, Yeung JC, Keshavjee S. Novel approaches to expanding the lung donor pool: Donation after cardiac death and ex vivo conditioning. Clin Chest Med. 2011;32:233–44. 6. Bolys R, Ingemansson R, Sjoberg T, Steen S. Vascular function in the cadaver up to six hours after cardiac arrest. J Heart Lung Transplant. 1999;18:582–6. 7. De Vleeschauwer S, Van Raemdonck D, Vanaudenaerde B, Vos R, Meers C, Wauters S, et al. Early outcome after lung transplantation from non-heart-beating donors is comparable to heart-beating donors. J Heart Lung Transplant. 2009;28:380–7. 8. Kootstra G, Daemen JH, Oomen AP. Categories of nonheart-beating donors. Transplant Proc. 1995;27:2893–4. 9. Van Raemdonck DE, Jannis NC, De Leyn PR, Flameng WJ, Lerut TE. Warm ischemic tolerance in collapsed pulmonary grafts is limited to 1 hour. Ann Surg. 1998;228:788–96. 10. Lindstedt S, Eyjolfsson A, Koul B, Wierup P, Pierre L, Gustafsson R, et al. How to recondition ex vivo initially rejected donor lungs for clinical transplantation: Clinical experience from Lund University Hospital. J Transpl. 2011;2011:754383. 11. Lindstedt S, Pierre L, Ingemansson R. A short period of ventilation without perfusion seems to reduce atelectasis without harming the lungs during ex vivo lung perfusion. J Transplant. 2013;2013:729286. 12. Ingemansson R, Eyjolfsson A, Mared L, Pierre L, Algotsson L, Ekmehag B, et al. Clinical transplantation of initially rejected donor lungs after reconditioning ex vivo. Ann Thorac Surg. 2009;87:255–60. 13. Steen S, Ingemansson R, Eriksson L, Pierre L, Algotsson L, Wierup P, et al. First human transplantation of a nonacceptable donor lung after reconditioning ex vivo. Ann Thorac Surg. 2007;83:2191–4. 14. Pierre L, Lindstedt S, Hlebowicz J, Ingemansson R. Is it possible to further improve the function of pulmonary grafts by extending the duration of lung reconditioning using ex vivo lung perfusion? Perfusion. 2013;28:322–7. 15. Cypel M, Yeung JC, Hirayama S, Rubacha M, Fischer S, Anraku M, et al. Technique for prolonged normothermic ex vivo lung perfusion. J Heart Lung Transplant. 2008;27: 1319–25. 16. Cypel M, Yeung JC, Liu M, Anraku M, Chen F, Karolak W, et al. Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med. 2011;364:1431–40. 17. Wallinder A, Ricksten SE, Silverborn M, Hansson C, Riise GC, Liden H, et al. Early results in transplantation of initially rejected donor lungs after ex vivo lung perfusion: a casecontrol study. Eur J Cardiothorac Surg. 2014;45:40–4. 18. Machuca TN, Cypel M. Ex vivo lung perfusion. J Thorac Dis. 2014;6:1054–62. 19. Steen S, Sjoberg T, Pierre L, Liao Q, Eriksson L, Algotsson L. Transplantation of lungs from a non-heart-beating donor. Lancet. 2001;357:825–9. 20. Ulicny KS, Jr., Egan TM, Lambert CJ, Jr., Reddick RL, Wilcox BR. Cadaver lung donors: Effect of preharvest ventilation on graft function. Ann Thorac Surg. 1993;55:1185–91. 21. Greco R, Cordovilla G, Sanz E, Benito J, Criado A, Gonzalez M, et al. Warm ischemic time tolerance after ventilated nonheart-beating lung donation in piglets. Eur J Cardiothorac Surg. 1998;14:319–25. 22. D’Armini AM, Roberts CS, Griffith PK, Lemasters JJ, Egan TM. When does the lung die? I. Histochemical evidence of pulmonary viability after “death”. J Heart Lung Transplant. 1994;13:741–7.

298

L. Pierre et al.

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23. Kuang JQ, Van Raemdonck DE, Jannis NC, De Leyn PR, Verbeken EK, Flameng WJ, et al. Pulmonary cell death in warm ischemic rabbit lung is related to the alveolar oxygen reserve. J Heart Lung Transplant. 1998;17:406–14. 24. Alessandrini F, D’Armini AM, Roberts CS, Reddick RL, Egan TM. When does the lung die? II. Ultrastructural evidence of pulmonary viability after “death”. J Heart Lung Transplant. 1994;13:748–57. 25. D’Armini AM, Tom EJ, Roberts CS, Henke DC, Lemasters JJ, Egan TM. When does the lung die? Time course of high

energy phosphate depletion and relationship to lung viability after “death”. J Surg Res. 1995;59:468–74. 26. De Leyn PR, Lerut TE, Schreinemakers HH, Van Raemdonck DE, Mubagwa K, Flameng W. Effect of inflation on adenosine triphosphate catabolism and lactate production during normothermic lung ischemia. Ann Thorac Surg. 1993;55:1073–8. 27. Lindstedt S, Pierre L, Hlebowicz J, Ingemansson R. Heparin does not seem to improve the function of pulmonary grafts for lung transplantation. Scand Cardiovasc J. 2013;47:307–13.

Ventilation in situ after cardiac death improves pulmonary grafts exposed to 2 hours of warm ischemia.

The pulmonary donor pool would increase substantially if lungs could be donated after cardiac death (DCD). There have been ethical and legal obstacles...
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