Lung transplant reperfusion injury involves pulmonary macrophages and circulating leukocytes in a biphasic response.

OBJECTIVE Both donor pulmonary macrophages and recipient circulating leukocytes may be involved in reperfusion injury after lung transplantation. By using the macrophage inhibitor gadolinium chloride and leukocyte filters, we attempted to identify the roles of these two populations of cells in lung transplant reperfusion injury. METHODS With our isolated, ventilated, blood-perfused rabbit lung model, all groups underwent lung harvest followed by 18-hour cold storage and 2-hour blood reperfusion. Measurements of pulmonary artery pressure, lung compliance, and arterial oxygenation were obtained. Group I (n = 8) served as a control. Group II (n = 8) received gadolinium chloride at 14 mg/kg 24 hours before lung harvest. Group III (n = 8) received leukocyte-depleted blood reperfusion by means of a leukocyte filter. RESULTS The gadolinium chloride group had significantly improved arterial oxygenation and pulmonary artery pressure measurements compared with control subjects and an improved arterial oxygenation compared with the filter group after 30 minutes of reperfusion. After 120 minutes of reperfusion, however, the filter group had significantly improved arterial oxygenation and pulmonary artery pressure measurements compared with the control group and an improved arterial oxygenation compared with the gadolinium chloride group. CONCLUSIONS Lung transplant reperfusion injury occurs in two phases. The early phase is mediated by donor pulmonary macrophages and is followed by a late injury induced by recipient circulating leukocytes.

[1]  S. Hussain,et al.  Contribution of macrophages to pulmonary nitric oxide production in septic shock. , 1998, American journal of respiratory and critical care medicine.

[2]  Gerhard E.H. Kuhnlea,et al.  Microhemodynamics and leukocyte sequestration after pulmonary ischemia and reperfusion in rabbits. , 1998 .

[3]  J. Cooper,et al.  Carbohydrate selectin inhibitor CY-1503 reduces neutrophil migration and reperfusion injury in canine pulmonary allografts. , 1997, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[4]  S. Bolling,et al.  Mediators of ischemia-reperfusion injury of rat lung. , 1997, The American journal of pathology.

[5]  R. Novick,et al.  Lung preservation: the importance of endothelial and alveolar type II cell integrity. , 1996, The Annals of thoracic surgery.

[6]  J. Brain,et al.  Gadolinium induces macrophage apoptosis , 1996, Journal of leukocyte biology.

[7]  D. Laskin,et al.  Inhibition of macrophages with gadolinium chloride abrogates ozone-induced pulmonary injury and inflammatory mediator production. , 1995, American journal of respiratory cell and molecular biology.

[8]  S. Bolling,et al.  Pattern of injury and the role of neutrophils in reperfusion injury of rat lung. , 1995, The Journal of surgical research.

[9]  M. Oz,et al.  The nitric oxide/cyclic GMP pathway in organ transplantation: critical role in successful lung preservation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Scott,et al.  Evolving strategies in lung transplantation for emphysema. , 1994, The Annals of thoracic surgery.

[11]  W. Baumgartner,et al.  Successful twenty-four-hour lung preservation with donor core cooling and leukocyte depletion in an orthotopic double lung transplantation model. , 1992, The Journal of thoracic and cardiovascular surgery.

[12]  M. Pasque,et al.  Management of dysfunction in the transplanted lung: experience with 7 clinical cases. Washington University Lung Transplant Group. , 1992, The Annals of thoracic surgery.

[13]  B. Griffith,et al.  Increased perioperative lung preservation injury with lung procurement by Euro-Collins solution flush. , 1991, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[14]  C. Valeri,et al.  Pathophysiology of ischaemia reperfusion injury: Central role of the neutrophil , 1991, The British journal of surgery.

[15]  R. Bolman,et al.  Heart-lung and lung transplantation: perioperative pulmonary dysfunction. , 1991, Transplantation proceedings.

[16]  B. Griffith,et al.  Primary graft failure following pulmonary transplantation. , 1990, Transplantation.

[17]  W. Baumgartner,et al.  Twenty-four hour lung preservation by hypothermia and leukocyte depletion. , 1985, The Journal of heart transplantation.

[18]  W. Baumgartner,et al.  Neutrophil modulation results in improved pulmonary function after 12 and 24 hours of preservation. , 1995, The Annals of thoracic surgery.

[19]  B. Griffith,et al.  Analysis of time-dependent risks for infection, rejection, and death after pulmonary transplantation. , 1995, The Journal of thoracic and cardiovascular surgery.

[20]  S. Bolling,et al.  Neutrophils are not necessary for ischemia-reperfusion lung injury. , 1992, The Annals of thoracic surgery.

[21]  B. Griffith,et al.  Donor cerebral emboli as a cause of acute graft dysfunction in lung transplantation. , 1992, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[22]  S. Bolling,et al.  Neutrophils are not necessary for induction of ischemia-reperfusion lung injury. , 1990, Journal of applied physiology.