Endotoxin after gut ischemia/reperfusion causes irreversible lung injury.
We have recently reported that 45 min of gut ischemia causes moderate 125I-albumin lung leak at 6 hr of reperfusion which was reversed at 18 hr. Our purpose was to determine the effect of a second insult, low dose endotoxin (LPS, 2.5 mg/kg), given 6 hr after gut ischemia/reperfusion (I/R) on this lung injury as assessed by 125I-albumin leak, neutrophil influx (myeloperoxidase assay, MPO), histopathology, and mortality. Rats were randomized to either sham laparotomy (LAP) or 45 min of superior mesenteric artery occlusion and 6 hr later were treated with LPS or saline. At 18 hr reperfusion the lungs were harvested, assayed for 125I-albumin leak and MPO, and microscopically examined by an unbiased observer after routine H&E staining. We observed that LPS increased lung neutrophil levels both with or without gut I/R. However, only the combined insult (I/R + LPS) increased 125I-albumin leak at 18 hr of reperfusion. Lung histology confirmed that the sequential combination of I/R + LPS caused marked interstitial edema and neutrophil sequestration accompanied by alveolar edema, hemorrhage, and fibrinous exudate, while I/R or LAP + LPS did not. The mortality rate of I/R + LPS was 39% which was significantly higher than LAP alone (0%), gut I/R alone (0%), or LAP + LPS (4%). In conclusion, a delayed exposure to low dose endotoxin converts moderate gut I/R-induced lung dysfunction into advanced organ failure.
Koike
K
K
Department of Surgery, Denver General Hospital, Colorado 80204.
Moore
F A
FA
Moore
E E
EE
Poggetti
R S
RS
Tuder
R M
RM
Banerjee
A
A
D000418:Albumins / Q000378:metabolism; D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D007422:Intestines / Q000098:blood supply*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008171:Lung Diseases / Q000209:etiology*; D008297:Male; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000150:complications*; D012128:Respiratory Distress Syndrome / Q000209:etiology
D000418:Albumins; D008070:Lipopolysaccharides; D009195:Peroxidase