BACKGROUND: There is evidence that lung ischemia reperfusion injury is a result of the activation of components of the inflammatory cascade. However, the role of neutrophils in lung reperfusion injury continues to be a source of controversy. METHODS: Using an isolated, whole blood-perfused, ventilated rabbit lung model, we sought to characterize the pattern of reperfusion injury and investigate the contribution of neutrophils to this injury. Donor rabbits underwent lung harvest after pulmonary arterial prostaglandin E1 injection and Euro-Collins preservation solution flush. Group I lungs (n = 8) were immediately reperfused without ischemic storage. Group II lungs (n = 8) were stored for 18 h at 4 degrees C before reperfusion. Group III lungs (n = 10) underwent 18 h of ischemic storage and were reperfused with whole blood that was first passed through a leukocyte-depleting filter. All lungs were reperfused for 2 h. RESULTS: Arterial oxygenation in group III progressively improved, and was significantly higher than that of group II after 2 h of reperfusion (272.58+/-58.97 vs 53.58+/-5.34 mm Hg, p = 0.01). Both pulmonary artery pressure and pulmonary vascular resistance were significantly reduced in group III when compared with group II (27.85+/-1.45 vs 44.15+/-4.77 mm Hg, p = 0.002; and 30,867+/-2,323 vs 52,775+/-6,386 dynes x sec x cm(-5), p = 0.003, respectively). Microvascular permeability in group III lungs was reduced to 73.98+/-6.15 compared with 117.16+/-12.78 ng Evans blue dye/g tissue in group II (p = 0.005). Group III myeloperoxidase activity was 56.92+/-6.31 deltaOD/g/min compared with 102.84+/-10.41 delta0d/g/min in group II (p = 0.002). CONCLUSIONS: Leukocyte depletion of the blood reperfusate protects against microvascular permeability and significantly improves pulmonary graft function. The neutrophil plays a major role in amplifying lung injury later during reperfusion, and this lung ischemia reperfusion injury may be reversed through the interruption of the inflammatory cascade and the interference with neutrophil infiltration.
BACKGROUND: There is evidence that lung ischemia reperfusion injury is a result of the activation of components of the inflammatory cascade. However, the role of neutrophils in lung reperfusion injury continues to be a source of controversy. METHODS: Using an isolated, whole blood-perfused, ventilated rabbit lung model, we sought to characterize the pattern of reperfusion injury and investigate the contribution of neutrophils to this injury. Donorrabbits underwent lung harvest after pulmonary arterial prostaglandin E1 injection and Euro-Collins preservation solution flush. Group I lungs (n = 8) were immediately reperfused without ischemic storage. Group II lungs (n = 8) were stored for 18 h at 4 degrees C before reperfusion. Group III lungs (n = 10) underwent 18 h of ischemic storage and were reperfused with whole blood that was first passed through a leukocyte-depleting filter. All lungs were reperfused for 2 h. RESULTS: Arterial oxygenation in group III progressively improved, and was significantly higher than that of group II after 2 h of reperfusion (272.58+/-58.97 vs 53.58+/-5.34 mm Hg, p = 0.01). Both pulmonary artery pressure and pulmonary vascular resistance were significantly reduced in group III when compared with group II (27.85+/-1.45 vs 44.15+/-4.77 mm Hg, p = 0.002; and 30,867+/-2,323 vs 52,775+/-6,386 dynes x sec x cm(-5), p = 0.003, respectively). Microvascular permeability in group III lungs was reduced to 73.98+/-6.15 compared with 117.16+/-12.78 ng Evans blue dye/g tissue in group II (p = 0.005). Group III myeloperoxidase activity was 56.92+/-6.31 deltaOD/g/min compared with 102.84+/-10.41 delta0d/g/min in group II (p = 0.002). CONCLUSIONS: Leukocyte depletion of the blood reperfusate protects against microvascular permeability and significantly improves pulmonary graft function. The neutrophil plays a major role in amplifying lung injury later during reperfusion, and this lung ischemia reperfusion injury may be reversed through the interruption of the inflammatory cascade and the interference with neutrophil infiltration.
Authors: Daniel P Mulloy; Ashish K Sharma; Lucas G Fernandez; Yunge Zhao; Christine L Lau; Irving L Kron; Victor E Laubach Journal: Ann Thorac Surg Date: 2013-03-28 Impact factor: 4.330
Authors: Mary E Huerter; Ashish K Sharma; Yunge Zhao; Eric J Charles; Irving L Kron; Victor E Laubach Journal: Ann Thorac Surg Date: 2016-04-22 Impact factor: 4.330
Authors: Beñat Mallavia; Fengchun Liu; Emma Lefrançais; Simon J Cleary; Nicholas Kwaan; Jennifer J Tian; Mélia Magnen; David M Sayah; Allison Soong; Joy Chen; Rajan Saggar; Michael Y Shino; David J Ross; Ariss Derhovanessian; Joseph P Lynch; Abbas Ardehali; S Sam Weigt; John A Belperio; Steven R Hays; Jeffrey A Golden; Lorriana E Leard; Rupal J Shah; Mary Ellen Kleinhenz; Aida Venado; Jasleen Kukreja; Jonathan P Singer; Mark R Looney Journal: Am J Respir Cell Mol Biol Date: 2020-03 Impact factor: 6.914
Authors: Matthew L Stone; Ashish K Sharma; Yunge Zhao; Eric J Charles; Mary E Huerter; William F Johnston; Irving L Kron; Kevin R Lynch; Victor E Laubach Journal: Am J Physiol Lung Cell Mol Physiol Date: 2015-04-24 Impact factor: 5.464
Authors: David M Sayah; Beñat Mallavia; Fengchun Liu; Guadalupe Ortiz-Muñoz; Axelle Caudrillier; Ariss DerHovanessian; David J Ross; Joseph P Lynch; Rajan Saggar; Abbas Ardehali; Lorraine B Ware; Jason D Christie; John A Belperio; Mark R Looney Journal: Am J Respir Crit Care Med Date: 2015-02-15 Impact factor: 21.405