Ischemia-reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndrome

Fiser, Steven M.; Tribble, Curtis G.; Long, Susan K. De; Kaza, Aditya K.; Kern, John A.; Jones, David R.; Robbins, Mark D.; Krön, Irving L.

doi:10.1016/s0003-4975(01)03606-2

Cited by 240 publications

(178 citation statements)

References 26 publications

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“…Life-threatening IR injury occurs in up to 20% of transplants and results in primary graft dysfunction with a mortality rate of up to 60% (1,2). Moreover, by up-regulating the expression of the MHC II molecules, IR injury seems also to predispose to acute (3,4) and chronic rejection (5,6).…”

Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinase Inhibition Decreases Ischemia-Reperfusion Injury After Lung Transplantation

Soccal

Gasche

Miniati

et al. 2004

American Journal of Transplantation

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Increased microvascular permeability and extravasation of inflammatory cells are key events of lung ischemia-reperfusion (IR) injury. The purpose of this study was to investigate the role of matrix metalloproteinases (MMP) in IR-induced alveolar capillary membrane disruption after experimental lung transplantation. We used a rat model of lung orthotopic transplantation (n = = 86) with a prolonged cold ischemic phase. MMP2 and MMP9 were elevated 4 h after the onset of ischemia and further increased during reperfusion. Compared to sham values, the alveolarcapillary membrane permeability increased by 105% and 82.6% after 4 h of ischemia and 2 h or 24 h of reperfusion, respectively. A 4-and 5-fold increase of the infiltration of ischemic tissue by neutrophils was also observed after 2 h and 24 h of reperfusion. The PO 2 /FIO 2 ratio dropped significantly from 244 to 76.6 after 2 h of reperfusion and from 296.4 to 127.6 after 24 h of reperfusion. A nonselective inhibitor of MMP, administered to the rats and added to the preservation solution, reduced significantly the alveolar-capillary leakage, the transmigration of neutrophils and improved gas exchanges in animals submitted to 4 h of ischemia combined with 2 h or 24 h of reperfusion. We conclude that inhibition of MMP attenuates IR injury after experimental lung transplantation.

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Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinase Inhibition Decreases Ischemia-Reperfusion Injury After Lung Transplantation

Soccal

Gasche

Miniati

et al. 2004

American Journal of Transplantation

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“…In one study, it was suggested that severe ischemia-reperfusion injury increases the risk of chronic rejection and long-term mortality (9); however, others have found no such relationship (3). Furthermore, survivors of severe acute lung injury from a variety of other causes have increased mortality and impaired quality of life extending far beyond the initial hospitalization (10)(11)(12).…”

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confidence: 99%

The Effect of Primary Graft Dysfunction on Survival after Lung Transplantation

Christie

Kotloff²,

Ahya³

et al. 2005

Am J Respir Crit Care Med

302

212

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Rationale: Primary graft dysfunction is a severe acute lung injury syndrome after lung transplantation. Long-term outcomes of subjects with primary graft dysfunction have not been studied. Objectives: We sought to test the relationship of primary graft dysfunction with both short-and long-term mortality using a large registry. Methods: We used data collected on 5,262 patients in the United Network for Organ Sharing/International Society of Heart and Lung Transplantation registry between 1994 and 2000. We assessed outcomes in all subjects; to assess potential bias from the effects of early mortality, we also evaluated subjects who survived at least 1 year, using Cox proportional hazards models with time-varying covariates. Main Results: The overall incidence of primary graft dysfunction was 10.2% (95% confidence intervals [CI], 9.2, 10.9). The incidence did not vary by year over the period of observation (p ϭ 0.22). All-cause mortality at 30 days was 42.1% for primary graft dysfunction versus 6.1% in patients without graft dysfunction (relative risk ϭ 6.95; 95% CI, 5.98, 8.08; p Ͻ 0.001); among subjects who died by 30 days, 43.6% had primary graft dysfunction. Among patients surviving at least 1 year, those who had primary graft dysfunction had significantly worse survival over ensuing years (hazard ratio, 1.35; 95% CI, 1.07, 1.70; p ϭ 0.011). Adjustment for clinical variables including bronchiolitis obliterans syndrome did not change this relationship. Conclusion: Primary graft dysfunction contributes to nearly half of the short-term mortality after lung transplantation. Survivors of primary graft dysfunction have increased risk of death extending beyond the first post-transplant year.Keywords: acute lung injury; lung transplantation; outcomes; primary graft dysfunction; reperfusion injury Primary graft dysfunction (PGD), also known as primary graft failure, is a form of lung allograft ischemia-reperfusion injury (1, 2). Occurring in the first hours to days after transplantation, the clinical course and pathophysiology of the most severe forms are most similar to the acute respiratory distress syndrome (1,3,4). With an incidence reported between 10 and 25%, and a high mortality (5), PGD represents the leading cause of early death after transplantation (1, 2, 5-8).However, the long-term outcomes of PGD have not been (Received in original form September 20, 2004; accepted in final form March 3, 2005) Supported by grants NHLBI K23 HL04243 and the Craig and Elaine Dobbin Pulmonary Research Fund.Correspondence and requests for reprints should be addressed to

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“…Airway virus infection, ischemiaperfusion injury, human leukocyte antigen mismatching, and lymphocyte-epithelial interactions also are implicated. 4,19,20,[22][23][24] Unlike acute rejection, which reverses with increased immunosuppression, chronic OB/BOS responds poorly.…”

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confidence: 99%

Transcript Signatures of Lymphocytic Bronchitis in Lung Allograft Biopsy Specimens

Golden

Dolganov³

et al. 2005

The Journal of Heart and Lung Transplantation

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Ischemia-reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndrome

Cited by 240 publications

References 26 publications

Matrix Metalloproteinase Inhibition Decreases Ischemia-Reperfusion Injury After Lung Transplantation

Matrix Metalloproteinase Inhibition Decreases Ischemia-Reperfusion Injury After Lung Transplantation

The Effect of Primary Graft Dysfunction on Survival after Lung Transplantation

Transcript Signatures of Lymphocytic Bronchitis in Lung Allograft Biopsy Specimens

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