The Journal of Heart and Lung Transplantation
Volume 24, Issue 10 , Pages 1460-1467, October 2005

Report of the ISHLT Working Group on Primary Lung Graft Dysfunction Part III: Donor-Related Risk Factors and Markers

  • Marc de Perrot, MD

      Affiliations

    • Toronto General Hospital, Toronto, Ontario, Canada
    • Corresponding Author InformationReprint requests: Marc de Perrot, MD, Division of Thoracic Surgery, Toronto General Hospital, 9N-961, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada. Telephone: 416-340-6120. Fax: 416-340-4556.
    • ,
  • Robert S. Bonser, MSBCh (FRCS)

      Affiliations

    • Queen Elizabeth Hospital, Birmingham, UK
    • ,
  • John Dark, MB (FRCS)

      Affiliations

    • Freeman Hospital, Newcastle upon Tyne, UK
    • ,
  • Rosemary F. Kelly, MD

      Affiliations

    • University of Minnesota, Minneapolis, Minnesota
    • ,
  • David McGiffin, MD

      Affiliations

    • University of Alabama, Birmingham, Alabama
    • ,
  • Rebecca Menza, RN

      Affiliations

    • University of California, Berkeley, California
    • ,
  • Octavio Pajaro, MD, PhD

      Affiliations

    • Mayo Clinic Jacksonville, Jacksonville, Florida
    • ,
  • Stephan Schueler, MD

      Affiliations

    • Freeman Hospital, Newcastle upon Tyne, UK
    • ,
  • Geert M. Verleden, MD, PhD

      Affiliations

    • University Hospitals Leuven, Leuven, Belgium

Received 6 October 2004; received in revised form 7 February 2005; accepted 17 February 2005. published online 08 August 2005.

Article Outline

 

Primary graft dysfunction is the end result of a series of donor lung injuries before and after the declaration of brain death and during the transplant process, as well as in the recipient after reperfusion.1 Donor factors play an important role in the development of primary graft dysfunction after lung transplantation, but few clinical studies have analyzed their impact. Results have been hindered by variations in donor selection criteria and by use of different definitions of primary graft dysfunction between centers. The impact of donor factors, however, appears predominant during the initial 24 hours of reperfusion, whereas recipient factors seem more important thereafter.2 The impact of donor factors can be differentiated into those that are inherent to lung donor characteristics and those that are acquired at the time of death or later. This distinction is important because adequate donor management could potentially influence factors that are acquired at the time of death or subsequent to death.

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Inherent lung donor characteristics 

Age, smoking history, race, gender and underlying lung disease are inherent donor characteristics that may influence the quality of the lungs and potentially impact on recipient outcome. Christie and colleagues analyzed the impact of donor factors in a cohort study of 255 consecutive lung transplants and observed that several donor factors, including female gender, African American ethnicity and age, had an independent impact on the development of primary graft dysfunction.3 The difference seen in graft outcome with donor female gender has been observed in other organ transplantations and may be due to size discrepancies between donor and recipient, although other factors, such as gender-linked antigens, cannot be excluded. Because the mechanisms by which race and gender impact on outcome after lung transplantation remain speculative, they should not be used in the decision to accept or reject a donor lung.

Christie and colleagues found that donor age had an independent impact on the development of primary graft dysfunction after lung transplantation. Donor ages >45 years and <21 years were associated with a higher risk of primary graft dysfunction. Although the data for the young donors are equivocal, similar findings have been observed in the UNOS/ISHLT registry for older donors.4 Indeed, the combination of donor age >45 years and ischemic time >7 to 8 hours had a significant impact on 30-day mortality after lung transplantation, according to registry data.4 Some groups, however, have successfully used older donors if all other selection criteria were ideal.5, 6, 7, 8, 9 Hence, use of older donors most likely increases the risk of primary graft dysfunction, but the risk seems limited in the absence of other risk factors.

The impact of smoking history on primary graft dysfunction remains controversial. Although Oto and colleagues recently reported that a cumulative smoking history of >20 pack-years is associated with prolonged mechanical ventilation and ICU stay after lung transplantation, the incidence of death from non-specific graft failure was not significantly different between donors with a smoking history of >20 vs <20 pack-years.10 Unfortunately, these investigators did not directly report the impact of donor smoking history on the incidence of primary graft dysfunction. In their analysis, Christie and colleagues, observed that donor smoking history had no significant impact on primary graft dysfunction after lung transplantation. In the future, analysis in larger groups of patients will be necessary to quantify more precisely the impact that donor smoking history may play on the development of primary graft dysfunction.

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Acquired lung donor factors 

The occurrence of brain death, prolonged mechanical ventilation, bronchoaspiration, pneumonia, trauma, multiple blood transfusions or hemodynamic instability in the donor before the retrieval procedure can potentially contribute to lung injury and primary graft dysfunction.11

The deleterious effect of brain death on organ function has been increasingly recognized over the last few years.12 Brain death can induce disruption in homeostatic regulation, with profound disturbances in endocrine function, and an intense inflammatory reaction that may reduce the tolerance of the organs to handle a period of ischemia.13 Brain death has also been demonstrated experimentally to increase the risk of acute rejection and chronic graft dysfunction.14, 15 Clinically, Sommers and colleagues observed that recipients from donors with closed head injury had significantly lower oxygenation on arrival in the ICU than recipients from donors with other causes of death.2 Other groups, however, did not confirm this finding.3, 16

Biopsies from cadaveric kidney donors have been shown to have higher levels of inflammatory cytokines, adhesion molecules and human leukocyte antigen-DR (HLA-DR) than biopsies from living donors, and the expression of these markers on tubular cells before transplantation was associated with a higher incidence of primary graft dysfunction and early acute rejection.17, 18 Fisher and colleagues showed that interleukin-8 (IL-8) in lung bronchoalveolar lavage from 28 non-traumatic brain-dead donors was significantly higher than in healthy controls, and these IL-8 levels correlated with neutrophil infiltration in donor lung tissue.19

Several groups have begun to administer a bolus of steroids (methylprednisolone ∼15 mg/kg) after brain-death declaration to all potential lung donors to reduce the inflammatory reaction induced by brain death. The steroid bolus has been shown to improve arterial oxygen tension in the donor and also to be associated with an increased lung donor recovery rate as well as improved lung function in the recipient after transplantation.20, 21, 22

Hemodynamic instability with persistent low blood pressures can increase the risk of post-operative graft dysfunction after kidney and liver transplantation.23, 24 Prolonged hypotension before death has also been shown to be associated with significant deterioration in lung graft function after reperfusion in a rat model of non–heart-beating donor.25 Although not studied in clinical lung transplantation, similar findings are to be expected, because adequate blood pressure and stable hemodynamic parameters are important to maintain optimal oxygen delivery and energy metabolism in organ tissues.

Optimal filling pressures have not been analyzed in humans after brain-death declaration. However, experiments with brain-dead pigs have shown that the heart dilates rapidly and fails with a central venous pressure (CVP) of >9 mm Hg.26 A CVP of <10 mm Hg is usually recommended in clinical practice. However, caution must be taken with fluid resuscitation in brain-dead donors because excessive fluid administration can cause rapid deterioration in lung function, even if the CVP remains at <10 mm Hg.27 Excessive fluid administration can be detrimental to the lung, particularly if left-heart dysfunction has been demonstrated.

Persistent hypotension and hemodynamic instability from cardiac dysfunction are best managed with vasopressors. Dopamine is used as a first choice because of its potential vasodilative effect on renal and mesenteric blood flow. In addition, low-dose dopamine has recently been shown to improve lung edema in brain-dead donors.28 Although the data are limited, there is relatively strong evidence suggesting that epinephrine and norepinephrine should be replaced with vasopressin. Vasopressin has been shown to have a stabilizing effect on systemic blood pressure after brain death while also allowing for reduction or discontinuation of epinephrine and norepinephrine in most cadaveric donors.29, 30, 31 In addition, vasopressin improves maintenance of energy metabolism and is effective against diabetes insipidus, which occurs in 80% of brain-dead donors.32 Although dopamine and vasopressin are helpful in donor management, their impact on recipient outcome remains to be demonstrated.

Because pneumonia has been a major cause of early morbidity and mortality in lung transplant recipients, utilization of lungs from donors with a positive gram stain in tracheal secretions has initially been avoided. However, aggressive antibiotic treatment in donors and recipients has significantly reduced the incidence of recipient pneumonia, and recent series have shown that gram stain of donor tracheal aspirates does not correlate with recipient outcome.33 Positive gram stain of tracheal aspirates most likely does not indicate ongoing pneumonia, but simply a collection of purulent secretions in the upper airways. In contrast, positive cultures from donor bronchoalveolar lavage (BAL) may indicate ongoing pneumonia, be associated with lower oxygenation after reperfusion in the recipient, and lead to longer ICU stay as well as prolonged ventilation when compared to donors with negative BAL bacterial cultures.34 BAL cultures should be taken from all donors to aggressively adapt the anti-biotherapy post-operatively.

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Donor selection 

Clinical Markers 

The current criteria used to assess donor lungs are based on donor history, arterial blood gases, chest X-ray appearance, bronchoscopy findings and physical examination of the lung at the time of retrieval. These criteria have been reviewed in detail previously and are not the primary focus of this study.35 However, their accuracy in determining the risk of primary graft dysfunction after transplantation is not optimal. Primary graft dysfunction occasionally occurs in patients receiving lungs from ideal donors, whereas extended donors have been used without significant impairment in post-operative lung function.4, 5, 6, 7

Biologic Markers 

Because clinical factors are not accurate enough in predicting primary graft dysfunction after lung transplantation, some groups have focused on biologic markers as a predictor of outcome. As mentioned previously, kidney biopsies from cadaveric kidney donors appear to have significantly higher levels of inflammatory cytokines, adhesion molecules and HLA-DR than biopsies from living donors, and the expression of these markers on tubular cells before transplantation can be associated with a higher incidence of primary graft dysfunction and early acute rejection after transplantation.17, 18 In human lung transplantation, the chemokine IL-8 is upregulated in BAL and lung tissue from brain-dead donors and the level seems to correlate with the incidence of primary graft dysfunction after reperfusion.36, 37

Biologic markers should be accurate, provide rapid results, and be readily available for clinical use. Rapid, quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) may provide some of these advantages, such as measurement of cytokine levels within 1 hour after lung biopsy. The demonstration of tumor necrosis factor-alpha by RT-PCR in donor myocardium was found to predict post-operative right-heart dysfunction in recipients after heart transplantation.38 In clinical lung transplantation, the level of IL-6 measured by RT-PCR and the ratio of the pro-inflammatory cytokine, IL-6, to the anti-inflammatory cytokine, IL-10, was found to predict 30-day mortality and mortality from primary graft dysfunction, whereas no clinical factor did so in the same group of patients.39 In the future, rapid analysis of pro- and anti-inflammatory markers in lung parenchyma may be extremely useful to reduce the incidence of primary graft dysfunction by determining more precisely the type of lung suitable for transplantation or by influencing post-implantation management.

Lung Preservation 

Ischemia–reperfusion-induced lung injury plays a major role in the development of primary graft dysfunction. It is an inevitable step in the transplant process that may potentially add to other injuries occurring in the donor before the period of ischemia or in the recipient after reperfusion. Much of the experimental work over the past decade has focused on how to optimize the methods of lung preservation to reduce the impact of ischemia–reperfusion injury on post-transplant lung function. The temperature, volume and pressure of the preservation solution as well as inflation, temperature and oxygenation of the lung during storage have all been shown experimentally to impact on the quality of the lung after reperfusion. In addition, the type of lung preservation used and use of a retrograde flush have been shown experimentally and clinically to improve post-operative lung function. Some of these experiments are briefly reviewed in what follows.

Methods of Preservation 

The current clinical practice of lung preservation is a hypothermic pulmonary artery flush at 50 to 60 ml/kg, coupled with topical cold saline solution while ventilating the lungs.40 The lungs are then transported inflated, in a hypothermic (4°C) solution. The lungs are perfused via the pulmonary artery to uniformly cool the lung tissue and remove blood from the pulmonary vascular bed. Flushing prevents vessel thrombosis and insures uniform tissue cooling, which then decreases membrane damage from retained macrophages and neutrophils.41

Temperature of Preservation Solution 

Historically, hypothermia has been a major component of lung preservation and continues to play an important role.42 Hypothermia suppresses the activity of cellular degradative enzymes, which would otherwise lead to a rapid loss of cellular viability during ischemia at normothermic temperatures. Preservation of tissues at low temperatures reduces metabolic activity to such a level that cell viability can be maintained in the face of ischemia.43 Lung preservation at 4°C decreases the metabolic rate to 5% of the metabolic rate at 37°C.

Controversy remains regarding the optimal flush temperature for lung preservation. Small animal studies suggest that warmer preservation solution temperature would be better than 4°C.44, 45 However, ultrastructural analyses of human lung parenchyma at various time-points during the preservation period demonstrate minimal lung injury despite preservation at 4°C.46, 47 Hence, the known advantage of reduced metabolic activity at 4°C and technical ease of maintaining this temperature keeps the use of hypothermic perfusion flush temperature at 4°C the standard flushing temperature.

Volume of Preservation Solution 

The amount of flush solution required to adequately clear the blood from the lungs and optimize graft function is dependent on patient size and perfusion flow rates. Haverich and colleagues found that a solution volume of 60 ml/kg given at a high flow rate improved lung cooling and post-operative lung function.48 Although Steen and colleagues recommended volumes as high as 150 ml/kg, this has not been widely adopted as a significant improvement over 60 ml/kg.49 The infusion of 60 ml/kg of perfusate solution is sufficient to clear the lungs of blood and uniformly cool the lungs as well. If infused at a low perfusion pressure, the infusion requires only several minutes to complete.

Pressure of Preservation Solution Infusion 

The optimal pulmonary artery pressure for infusion is controversial. Sasaki and colleagues observed that flushing pressures of 10 to 15 mm Hg achieved significantly better lung function than infusions at pressures of 20 and 25 mm Hg.50 The high pulmonary artery pressures noted during the flush with Euro-Collins solution and the improvement in lung function with the addition of prostaglandins also suggest that the optimal perfusion pressure should be in the lower range to maximize graft function after transplantation.51

Inflation or Ventilation 

Experimental and clinical studies clearly support the importance of ventilation during lung procurement and inflation during storage.41, 52 However, over-distension of the lung by either static inflation, high tidal volume or high positive end-expiratory pressure (PEEP) can be detrimental to the lungs, and hyperinflation during storage can increase the pulmonary capillary filtration coefficient.53 Lung inflation during storage should be limited to 50% of the total lung capacity or to an airway pressure of 10 to 15 cm H2O to avoid barotraumas.54, 55

Storage Temperature 

The ideal temperature for lung storage remains unclear. In the process of lung transportation, hypothermia is used to decrease cellular metabolic activity and preserve lung function. However, it can also compound injury due to ischemia–reperfusion. Tissue edema as a result of hypothermia is due to decreased ATPase activity.56 ATPase-dependent ion balance in the cell becomes disrupted, alters cellular function, and leads to membrane disruption, followed by cell death. The ATPase activity is temperature-dependent and tissue-specific.56 In the lung, hypothermia results in increased extravascular fluid and pulmonary vasoconstriction. This contributes to diminished oxygen exchange and increased pulmonary vascular resistance after reperfusion. Several animal studies have shown that pulmonary function after 12 to 24 hours of storage is superior if the lungs are preserved at 10°C instead of 4°C or 15°C.57 However, in clinical lung transplantation, parenchymal injury is dependent on multiple factors, making it difficult to determine the precise contribution from hypothermia alone. In addition, lungs preserved at 10°C require a greater amount of metabolic substrate and the risk of lung injury can increase extremely rapidly if the temperature rises above 10°C during preservation. Hence, given the logistics of transportation and the inconclusive experimental data regarding optimal storage temperature, 4°C continues to be the most common temperature for lung storage.

Oxygenation 

The lung has the ability to remain in aerobic conditions during preservation if it is inflated with oxygen.58 This remains true even under conditions of hypothermia.59 However, there is a fine line between oxygen requirements for metabolic purposes, and excessive concentrations leading to free-radical production even before reperfusion. In fact, oxygen-free-radical–mediated injury has been shown to occur before reperfusion when rabbit lungs were stored at 10°C, and inflated with 100% oxygen.60 This correlates with the finding in rat lungs that there is an oxygen-dependent injury taking place during the ischemic phase.61 As a result, the most common clinical practice is ventilation and lung inflation with an Fio2 of 0.30 to 0.50.

Preservation Solutions 

There has been a recent trend toward the use of low-potassium solutions (extracellular), such as Perfadex (Vitrolife, Goteborg, Sweden), for lung preservation. Low-potassium dextran solution has been introduced in the clinical arena after a significant amount of experimental work illustrated its benefits.49, 62 Low-potassium dextran (LPD) is the only preservation solution developed specifically for lung preservation. Other low-potassium solutions include Wallwork’s solution and Celsior. Celsior contains the anti-oxidants mannitol, glutathione, glutamate and histidine as well as lactobionate. A modified cold blood solution as proposed by Wallwork and colleagues includes the addition of heparin and lactated Ringer solution to the blood.

The key components of LPD are the dextran and low-potassium concentration. Dextran-40 in the LPD solution functions as an oncotic agent, tending to keep water in the intravascular compartment, and thereby decreasing interstitial edema formation. It also reduces the aggregation of erythrocytes and circulating thrombocytes, which may improve the microcirculation and reduce cellular activation. The low-potassium concentration maintains normal pulmonary artery pressures during infusion. A further development is a dextran–glucose-based extracellular solution.63, 64 The addition of glucose is designed to support aerobic metabolism and maintain cell integrity during prolonged ischemia. Perfadex is an LPD–glucose solution that is now clinically available worldwide.

The addition of glucose to a lung preservation solution takes advantage of the unique aspect of lung physiology in transplantation. That is, the inflated lung has the ability to supply oxygen to its parenchyma even during storage. A lung flushed with 1% glucose added to LPD solution and stored for >24 hours was found to be associated with continued normal glucose metabolism in the lung.63 Analyzing lung tissue, the investigators found that tissue glucose, glucose-6-phosphate and lactate levels rose in a parallel fashion, indicating the presence of glycolysis in response to glucose in the LPD solution.

Clinical reports from 6 centers have compared the effect of Perfadex with an historical control group of lungs preserved with Euro-Collins.65, 66, 67, 68, 69, 70 Five centers showed significantly better lung function on arrival in the ICU and a trend toward lower 30-day mortality with Perfadex. An additional report demonstrated that, after adjustment for graft ischemic time, extracellular-type preservation solutions were associated with a decreased incidence of primary graft dysfunction after lung transplantation when compared with intracellular-type preservation solutions.71

Retrograde Flush 

Retrograde flush, which refers to the administration of flush solution through the left atrial appendage or the pulmonary veins, and drainage through the pulmonary artery, has been described for lung and heart–lung transplantation. The technique adds the potential advantages of flushing both the bronchial and pulmonary vessels, and of limiting the effect of pulmonary arterial vasoconstriction on the distribution of the flush solution. Experimentally, a retrograde flush has been found to improve lung preservation when compared with an anterograde flush.72 This effect was attributed to more effective clearance of red blood cells within the capillaries, better distribution of the flush solution along the tracheobronchial tree, and less severe impairment of surfactant function. However, despite the retrograde flush, pre-treatment with prostaglandin E1 was still helpful in improving pulmonary dynamic compliance after reperfusion.73 After these results were published, several groups have adopted a combined procedure with an anterograde flush through the pulmonary artery, followed by a retrograde flush through each of the pulmonary veins in situ with the lungs still ventilated. Venuta and colleagues completed a study of 14 patients demonstrating that the addition of a retrograde flush to an anterograde flush was associated with improved lung function after transplantation when compared with an anterograde-only flush.74 A retrograde flush was also shown to help remove blood clots from the distal pulmonary artery bed that are occasionally seen in cadaveric lung donors.75, 76

Ischemic Time 

Although prolonged ischemic time has been shown by some investigators to have an impact on the occurrence of primary graft dysfunction, its role may have become less important with improvement in lung preservation methods.77, 78, 79 Recently, ischemic times of up to 10 or even 12 hours have been successfully reported with optimal donors, and ischemic times of 6 to 8 hours are usually considered reasonable.1 Ueno and colleagues reported a series of 74 patients undergoing bilateral lung transplants for indications other than primary pulmonary hypertension and Eisenmenger syndrome, and observed that ischemic times of >8 hours were associated with lower oxygenation in the recipient during the first 24 hours of reperfusion.80 A large review from the international registry on 5,052 lung transplant recipients has also shown an increased 30-day mortality with cold ischemic times of >7 to 8 hours and donors >45 years of age.4 However, most of these studies were performed with intracellular preservation solutions such as Euro-Collins, which have been shown to be less efficient than extracellular preservation solutions. Hence, currently, prolonged ischemia should probably be seen as an additional risk factor, but not as a direct cause of primary graft dysfunction.

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Conclusions 

Donor factors should be differentiated into those that are inherent to lung donor characteristics and those that are acquired at the time of brain death or thereafter. Inherent lung donor characteristics, such as age and smoking history, can potentially increase the risk of post-operative lung dysfunction. However, improvement in donor management and lung preservation techniques over the past decade have helped to expand the number of lungs available for transplantation and to reduce the risk of primary graft dysfunction. Currently, primary graft dysfunction is more likely to be the end result of a series of insults to the lungs than to be due to a single factor only. In the future, the development of a multi-institutional database prospectively collecting demographic data from lung donors, length of ischemic time and recipient’s conditions will help to stratify the impact that each of these factors may have on outcome after lung transplantation. This information as well as the potential development of biologic markers could be extremely helpful to further expand the lung donor pool without increasing the risk of primary graft dysfunction.

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References 

  1. de Perrot M , Liu M , Waddell TK , Keshavjee S . Ischemia–reperfusion induced lung injury . Am J Respir Crit Care Med . 2003;167:490–511
  2. Sommers KE , Griffith BP , Hardesty RL , Keenan RJ . Early lung allograft function in twin recipients from the same donor (risk factor analysis) . Ann Thorac Surg . 1996;62:784–790
  3. Christie JD , Kotloff RM , Pochettino A , et al.   Clinical risk factors for primary graft failure following lung transplantation . Chest . 2003;124:1232–1241
  4. Novick RJ , Bennett LE , Meyer DM , Hosenpud JD . Influence of graft ischemic time and donor age on survival after lung transplantation . J Heart Lung Transplant . 1999;18:425–431
  5. Sundaresan S , Semenkovich J , Ochoa L , et al.   Successful outcome of lung transplantation is not compromised by the use of marginal donor lungs . J Thorac Cardiovasc Surg . 1995;109:1075–1079
  6. Bhorade SM , Vigneswaran W , McCabe MA , Garrity ER . Liberalization of donor criteria may expand the donor pool without adverse consequence in lung transplantation . J Heart Lung Transplant . 2000;19:1199–1204
  7. Gabbay E , Williams TJ , Griffiths AP , et al.   Maximizing the utilization of donor organs offered for lung transplantation . Am J Respir Crit Care Med . 1999;160:265–271
  8. Pierre AF , Sekine Y , Hutcheon MA , Waddell TK , Keshavjee SH . Marginal donor lungs (a reassessment) . J Thorac Cardiovasc Surg . 2002;123:421–428
  9. de Perrot M , Waddell TK , Shargall Y , et al.   Lung transplantation with donors 60 years of age and older . J Heart Lung Transplant . 2003;22(suppl):S87
  10. Oto T , Griffiths AP , Levvey B , et al.   A donor history of smoking affects early but not late outcome in lung transplantation . Transplantation . 2004;78:599–606
  11. de Perrot M , Weder W , Patterson GA , Keshavjee S . Strategies to increase limited donor resources . Eur Respir J . 2004;23:477–482
  12. Avlonitis VS , Fisher AJ , Kirby JA , Dark JH . Pulmonary transplantation (the role of brain death in donor lung injury) . Transplantation . 2003;75:1928–1933
  13. Bittner HB , Kendall SW , Chen EP , Craig D , Van Trigt P . The effects of brain death on cardiopulmonary hemodynamics and pulmonary blood flow characteristics . Chest . 1995;108:1358–1363
  14. Wilhelm MJ , Pratschke J , Beato F , et al.   Activation of the heart by donor brain death accelerates acute rejection after transplantation . Circulation . 2000;102:2426–2433
  15. Pratschke J , Wilhelm MJ , Laskowski I , et al.   Influence of donor brain death on chronic rejection of renal transplants in rats . J Am Soc Nephrol . 2001;12:2474–2481
  16. Waller DA , Thompson AM , Wrightson WN , et al.   Does the mode of donor death influence the early outcome of lung transplantation? A review of lung transplantation from donors involved in major trauma . J Heart Lung Transplant . 1995;14:318–321
  17. Schwarz C , Regele H , Steininger R , et al.   The contribution of adhesion molecule expression in donor kidney biopsies to early allograft dysfunction . Transplantation . 2001;71:1666–1670
  18. Koo DD , Welsh KI , McLaren AJ , et al.   Cadaver versus living donor kidneys (impact of donor factors on antigen induction before transplantation) . Kidney Int . 1999;56:1551–1559
  19. Fisher AJ , Donnelly SC , Hirani N , et al.   Enhanced pulmonary inflammation in organ donors following fatal non-traumatic brain injury . Lancet . 1999;353:1412–1413
  20. Follette DM , Rudich SM , Babcock WD . Improved oxygenation and increased lung donor recovery with high-dose steroid administration after brain death . J Heart Lung Transplant . 1998;17:423–429
  21. McElhinney DB , Khan JH , Babcock WD , Hall TS . Thoracic organ donor characteristics associated with successful lung procurement . Clin Transplant . 2001;15:68–71
  22. Wigfield CH , Golledge HD , Shenton BK , Kirby JA , Dark JH . Ameliorated reperfusion injury in lung transplantation after reduction of brain death induced inflammatory graft damage in the donor . J Heart Lung Transplant . 2002;21:57
  23. Lucas BA , Vaughn WK , Spees EK , Sanfilippo F . Identification of donor factors predisposing to high discard rates of cadaver kidneys and increased graft loss within one year posttransplantation—SEOPF 1977–1982. South-Eastern Organ Procurement Foundation . Transplantation . 1987;43:253–258
  24. Busuttil RW , Goldstein LI , Danovitch GM , Ament ME , Memsic LD . Liver transplantation today . Ann Intern Med . 1986;104:377–389
  25. Tremblay LN , Yamashiro T , DeCampos KN , et al.   Effect of hypotension preceding death on the function of lungs from donors with nonbeating hearts . J Heart Lung Transplant . 1996;15:260–268
  26. Wicomb WN , Cooper DK , Lanza RP , Novitzky D , Isaacs S . The effects of brain death and 24 hours’ storage by hypothermic perfusion on donor heart function in the pig . J Thorac Cardiovasc Surg . 1986;91:896–909
  27. Pennefather SH , Bullock RE , Dark JH . The effect of fluid therapy on alveolar arterial oxygen gradient in brain-dead organ donors . Transplantation . 1993;56:1418–1422
  28. Ware LB , Fang X , Wang Y , et al.   Selected contribution (mechanisms that may stimulate the resolution of alveolar edema in the transplanted human lung) . J Appl Physiol . 2002;93:1869–1874
  29. Pennefather SH , Bullock RE , Mantle D , Dark JH . Use of low dose arginine vasopressin to support brain-dead organ donors . Transplantation . 1995;59:58–62
  30. Iwai A , Sakano T , Uenishi M , et al.   Effects of vasopressin and catecholamines on the maintenance of circulatory stability in brain-dead patients . Transplantation . 1989;48:613–617
  31. Chen JM , Cullinane S , Spanier TB , et al.   Vasopressin deficiency and pressor hypersensitivity in hemodynamically unstable organ donors . Circulation . 1999;100(suppl 19):244–246
  32. Washida M , Okamoto R , Manaka D , et al.   Beneficial effect of combined triiodothyronine and vasopressin administration on hepatic energy status and systemic hemodynamics after brain death . Transplantation . 1992;54:44–49
  33. Weill D , Dey GC , Hicks RA , et al.   A positive donor gram stain does not predict outcome following lung transplantation . J Heart Lung Transplant . 2002;21:555–558
  34. Avlonitis VS , Krause A , Luzzi L , et al.   Bacterial colonization of the donor lower airways is a predictor of poor outcome in lung transplantation . Eur J Cardiothorac Surg . 2003;24:601–607
  35. Orens JB , Boehler A , de Perrot M , et al.   A review of lung transplant donor acceptability criteria . J Heart Lung Transplant . 2003;22:1183–1200
  36. de Perrot M , Sekine Y , Fischer S , et al.   Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation . Am J Respir Crit Care Med . 2002;165:211–215
  37. Fisher AJ , Donnelly SC , Hirani N , et al.   Elevated levels of interleukin-8 in donor lungs is asociated with early graft failure after lung transplantation . Am J Respir Crit Care Med . 2001;163:259–265
  38. Birks EJ , Owen VJ , Burton PB , et al.   Tumor necrosis factor-alpha is expressed in donor heart and predicts right ventricular failure after human heart transplantation . Circulation . 2000;102:326–331
  39. Kaneda H , Gutierrez C , de Perrot M , et al.   Preimplantation multiple cytokine mRNA expression analysis in donor lung grafts predicts survival after lung transplantation in humans . J Heart Lung Transplant . 2004;23(suppl):S49
  40. Hopkinson DN , Bhabra MS , Hooper TL . Pulmonary graft preservation (a worldwide survey of current clinical practice) . J Heart Lung Transplant . 1998;17:525–531
  41. Veith FJ , Sinha SBP , Graves JS , Boley SJ , Dougherty JC . Ischemic tolerance of the lung (the effects of ventilation and inflation) . J Thorac Cardiovasc Surg . 1971;61:804–810
  42. Baldwin JC , Frist WH , Starkey TD , et al.   Distant graft procurement for combined heart and lung transplantation using pulmonary artery flush and simple topical hypothermia for graft preservation . Ann Thorac Surg . 1987;43:670–673
  43. Pegg DE . Organ preservation . Surg Clin N Am . 1986;66:617–632
  44. Wang LS , Nakamol K , Hsieh CM , Miyoshi S , Copper JD . Influence of temperature of flushing solution on lung preservation . Ann Thorac Surg . 1993;55:711–715
  45. Albes JM , Fischer F , Bando T , et al.   Influence of the perfusate temperature on lung preservation (is there an optimum?) . Eur Surg Res . 1997;29:5–11
  46. Fehrenbach H , Riemann D , Wahlers T , et al.   Scanning and transmission electron microscopy of human donor lungs (fine structure of the pulmonary parenchyma following preservation and ischemia) . Acta Anal (Basel) . 1994;151:220–231
  47. Muller C , Hoffman H , Bittmann L , et al.   Hypothermic storage alone in lung preservation for transplantation (a metabolic, light microscopic, and functional analysis after 18 hours of preservation) . Transplantation . 1997;63:625–630
  48. Haverich A , Aziz S , Scott WG , Jamieson SW , Shumway NE . Improved lung preservation using Euro-Collins solution for flush-perfusion . Thorac Cardiovasc Surg . 1986;34:368–376
  49. Steen S , Sjoberg T , Massa G , Ericsson L , Lindberg L . Safe pulmonary preservation for 12 hours with low-potassium-dextran solution . Ann Thorac Surg . 1993;55:434–440
  50. Tanaka H , Chiba Y , Sasaki M , Matsukawa S , Muraoka R . Relationship between flushing pressure and nitric oxide production in preserved lungs . Transplantation . 1998;65:460–464
  51. Puskas JD , Cardoso PF , Mayer E , et al.   Equivalent eighteen-hour lung preservation with low-potassium dextran or Euro-Collins solution after prostaglandin E1 infusion . J Thorac Cardiovasc Surg . 1992;104:83–89
  52. Badellino MM , Morganroth ML , Grum CM , et al.   Hypothermia or continuous ventilation decreases ischemia–reperfusion injury in an ex vivo rat lung model . Surgery . 1989;105:752–760
  53. Haniuda M , Hasegawa S , Shiraishi T , et al.   Effects of inflation volume during lung preservation on pulmonary capillary permeability . J Thorac Cardiovasc Surg . 1996;112:85–93
  54. DeCampos KN , Keshavjee S , Liu M , Slutsky AS . Optimal inflation volume for hypothermic preservation of rat lungs . J Heart Lung Transplant . 1998;17:599–607
  55. Kayano K , Toda K , Naka Y , Pinsky DJ . Identification of optimal conditions for lung graft storage with Euro-Collins solution by use of a rat orthotopic lung transplant model . Circulation . 1999;100(suppl):257–261
  56. Martin DR , Scott DF , Downes GL , Belzer FO . Primary cause of unsuccessful liver and heart preservation (cold sensitivity of the ATPase system) . Ann Surg . 1972;175:111–117
  57. Wang LS , Yoshikawa K , Miyoshi S , et al.   The effect of ischemic time and temperature on lung preservation in a simple ex vivo rabbit model used for functional assessment . J Thorac Cardiovasc Surg . 1989;98:333–342
  58. De Leyn PRJ , Lerut TE , Scheinemakers HH , et al.   Effect of inflation on adenosine triphosphate catabolism and lactate production during normothermic lung ischemia . Ann Thorac Surg . 1993;55:1073–1079
  59. Date H , Matsumura A , Manchester JK , et al.   Changes in alveolar oxygen and carbon dioxide concentration and oxygen consumption during lung preservation . J Thorac Cardiovasc Surg . 1993;105:492–501
  60. Heiniuda M , Dresler CM , Mizuta T , Cooper JD , Patterson GA . Free radical–mediated vascular injury in lungs preserved at moderate hypothermia . Ann Thorac Surg . 1995;60:1376–1381
  61. Fisher AB , Dodia C , Tan Z , Ayene I , Eckenhoff RG . Oxygen-dependent lipid peroxidation during lung ischemia . J Clin Invest . 1991;88:674–679
  62. Keshavjee SH , Yamazaki F , Cardoso PF , et al.   A method for safe twelve-hour pulmonary preservation . J Thorac Cardiovasc Surg . 1989;98:529–534
  63. Date H , Matsumura A , Manchester JK , et al.   Evaluation of lung metabolism during successful twenty-four hour canine lung preservation . J Thorac Cardiovasc Surg . 1993;105:480–491
  64. Wagner FM , Jamieson SW , Fung J , et al.   A new concept for successful long-term pulmonary preservation in a dog model . Transplantation . 1995;59:1530–1536
  65. Fischer S , Matte-Martyn A , de Perrot M , et al.   Low-potassium dextran preservation solution improves lung function after human lung transplantation . J Thorac Cardiovasc Surg . 2001;121:594–596
  66. Struber M , Wilhelmi M , Harringer W , et al.   Flush perfusion with low potassium dextran solution improves early graft function in clinical lung transplantation . Eur J Cardiothorac Surg . 2001;19:190–194
  67. Muller C , Furst H , Reichenspurner H , et al.   Lung procurement by low-potassium dextran and the effect on preservation injury. Munich Lung Transplant Group . Transplantation . 1999;68:1139–1143
  68. Aziz TM , Pillay TM , Corris PA , et al.   Perfadex for clinical lung procurement (is it an advance?) . Ann Thorac Surg . 2003;75:990–995
  69. Rega F , Verleden G , Vanhaecke J , Daenen W , Van Raemdonck D . Switch from Euro-Collins to Perfadex for pulmonary graft preservation resulted in superior outcome in transplant recipient . J Heart Lung Transplant . 2003;22(suppl):S111
  70. Rabanal JM , Ibanez AM , Mons R , et al.   Influence of preservation solution on early lung function (Euro-Collins vs Perfadex) . Transplant Proc . 2003;35:1938–1939
  71. Thabut G , Vinatier I , Brugiere O , et al.   Influence of preservation solution on early graft failure in clinical lung transplantation . Am J Respir Crit Care Med . 2001;164:1204–1208
  72. Struber M , Hohlfeld JM , Kofidis T , et al.   Surfactant function in lung transplantation after 24 hours of ischemia (advantage of retrograde flush perfusion for preservation) . J Thorac Cardiovasc Surg . 2002;123:98–103
  73. Chen CZ , Gallagher RC , Ardery P , et al.   Retrograde flush and cold storage for twenty-two to twenty-five hours lung preservation with and without prostaglandin E1 . J Heart Lung Transplant . 1997;16:658–666
  74. Venuta F , Rendina EA , Bufi M , et al.   Preimplantation retrograde pneumoplegia in clinical lung transplantation . J Thorac Cardiovasc Surg . 1999;118:107–114
  75. Fischer S , Gohrbandt B , Meyer A , et al.   Should lungs from donors with severe acute pulmonary embolism be accepted for transplantation? The Hannover experience . J Thorac Cardiovasc Surg . 2003;126:1641–1643
  76. Nguyen DQ , Salerno CT , Bolman RM , Park SJ . Pulmonary thromboembolectomy of donor lungs prior to lung transplantation . Ann Thorac Surg . 1999;67:1787–1789
  77. Thabut G , Vinatier I , Stern JB , et al.   Primary graft failure following lung transplantation (predictive factors of mortality) . Chest . 2002;121:1876–1882
  78. Fiser SM , Kron IL , Long SM , et al.   Influence of graft ischemic time on outcomes following lung transplantation . J Heart Lung Transplant . 2001;20:1291–1296
  79. Gammie JS , Stukus DR , Pham SM , et al.   Effect of ischemic time on survival in clinical lung transplantation . Ann Thorac Surg . 1999;68:2015–2020
  80. Ueno T , Snell GI , Williams TJ , et al.   Impact of graft ischemic time on outcomes after bilateral sequential single-lung transplantation . Ann Thorac Surg . 1999;67:1577–1582

PII: S1053-2498(05)00134-8

doi:10.1016/j.healun.2005.02.017

The Journal of Heart and Lung Transplantation
Volume 24, Issue 10 , Pages 1460-1467, October 2005

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