Ischemia-reperfusion lung injury: contribution of ischemia, neutrophils, and hydrostatic pressure.
We used an isolated, blood-perfused rat lung model to evaluate the separate roles of ischemia and reperfusion time, the changes in pulmonary artery pressure (Ppa), and the circulating neutrophil number in mediating ischemia-reperfusion lung injury. Extravascular albumin accumulation was used to quantify changes in the permeability of the alveolar capillary membranes. In animals subjected to 30 and 45 min of ischemia without reperfusion, extravascular albumin accumulation was significantly higher than in controls subjected to continuous perfusion (P < 0.05). Albumin accumulation in animals subjected to 45 min of ischemia was greater compared with those undergoing 30 min of ischemia followed by 30 min of reperfusion (P < 0.05). In animals undergoing 45 min of ischemia followed by 30 min of reperfusion, a linear relationship was demonstrated between changes in Ppa and extravascular albumin accumulation. Reducing Ppa with a thromboxane antagonist (ICI-192605) and a smooth muscle relaxant (papaverine) produced, in both cases, a significant decrease in albumin extravasation (P < 0.05). No significant difference in extravascular albumin accumulation or change in Ppa was shown in neutrophil-depleted animals compared with nondepleted animals. We conclude that ischemia time contributes significantly to ischemia-reperfusion lung injury and that transient changes in Ppa after reperfusion exacerbate and injury in this model. This early injury demonstrated here was neutrophil dependent.
Lu
Y T
YT
Unit Critical Care, Royal Brompton National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom.
Hellewell
P G
PG
Evans
T W
TW
D000818:Animals; D002196:Capillaries / Q000502:physiology; D002199:Capillary Permeability; D006801:Humans; D006874:Hydrostatic Pressure; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology*; D011651:Pulmonary Artery / Q000502:physiology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D012709:Serum Albumin / Q000493:pharmacokinetics; D013997:Time Factors
D007457:Iodine Radioisotopes; D012709:Serum Albumin