When does the lung die?K _fc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung

Abstract

Lungs harvested from cadaveric circulation-arrested donors may increase the donor pool for lung transplantation. To determine the degree and time course of ischemia-reperfusion injury, we evaluated the effect of O2 ventilation on capillary permeability [capillary filtration coefficient (Kfc)], cell viability, and total adenine nucleotide (TAN) levels in in situ circulation-arrested rat lungs. Kfc increased with increasing postmortem ischemic time (r = 0.88). Lungs ventilated with O2 1 h postmortem had similar Kfc and wet-to-dry ratios as controls. Nonventilated lungs had threefold (P < 0.05) and sevenfold (P < 0.0001) increases in Kfc at 30 and 60 min postmortem compared with controls. Cell viability decreased in all groups except for 30-min postmortem O2-ventilated lungs. TAN levels decreased with increasing ischemic time, particularly in nonventilated lungs. Loss of adenine nucleotides correlated with increasing Kfc values (r = 0.76). This study indicates that lungs retrieved 1 h postmortem may have normal Kfc with preharvest O2 ventilation. The relationship between Kfc and TAN suggests that vascular permeability may be related to lung TAN levels.

Inflammatory Response to Pulmonary Ischemia–Reperfusion Injury

“…10 Moreover, maintaining alveolar ventilation with oxygen in warm ischemic (PA occluded) lungs attenuated the increase in pulmonary permeability and pulmonary edema, thus suggesting that direct oxygenation from alveolar ventilation may play an important role in preventing pulmonary ischemia. 33 Ventilating the lungs with oxygen during ischemic lung preservation in transplantation can also protect the lungs from injury by maintaining the aerobic metabolism, preserving pulmonary surfactant and epithelial transport intergrity. 34 Maintaining BA perfusion (without PA perfusion or lung ventilation) in the ischemic lung can also attenuate the increase in pulmonary vascular permeability and it may also limit pulmonary edema after reperfusion.…”

“…33,40 Prolonging pulmonary ischemia was also associated with higher MHC class II molecules expression by lung tissue, 32 a higher expression of human leukocyte antigen (HLA)-DR-b, 41 lower adenine nucleotide (TAN) levels, 33 and lower lung superoxide dismutase levels. 41 In addition, in the rodent IR model, significantly higher percentages of pulmonary cell necrosis were observed following increasing cold (4°C) ischemic times of beyond 12 h. 42 Furthermore, the percentage of necrotic cells was inversely correlated with the post-transplant graft function.…”

Fullerene derivatives protect against oxidative stress in RAW 264.7 cells and ischemia-reperfused lungs

“…LUNG TRANSPLANTATION has become an accepted and effective treatment for a variety of end-stage pulmonary diseases (10). Despite optimal lung preservation techniques, the lung remains extremely vulnerable to ischemia-reperfusion (IR) injury (6).…”

Nitroglycerin Reperfusion Reduces Ischemia-Reperfusion Injury in Non-Heart-Beating Donor Lungs

“…3,62 This correlation between Kfc and TAN confirms the importance of maintaining high-energy phosphate levels for cell function and integrity. NTG reperfusion had only modest effects on TAN levels, although NTG-reperfusion of O 2 -ventilated lungs retrieved 120 and 180 minutes post-mortem resulted in small but significant increases in TAN levels.…”