title: Inflammation and oxygen free radical formation during pulmonary ischemia-reperfusion injury.
abstract: In a companion study, we showed that 2 h of warm unilateral lung ischemia followed by reperfusion resulted in bilateral tissue injury, indicated by increases in extravascular density (EVD) and permeability, measured as the pulmonary transcapillary escape rate (PTCER) for radiolabeled transferrin. EVD and PTCER measurements were obtained with the quantitative imaging technique of positron emission tomography (PET). In the current study, we evaluated this increase in EVD histologically and correlated EVD and PTCER with measurements of oxidant-reactive sulfhydryls (RSH) in plasma as a marker of oxygen free radical (OFR) formation. Histologically edema, leukocyte infiltration, and hemorrhage were all present on the ischemic side, but only after reperfusion, whereas only neutrophil infiltration was observed on the nonischemic side. Histology scores correlated with EVD (r = 0.81) and PTCER (r = 0.75), but permeability was abnormal at times even in the absence of neutrophil infiltration. Plasma RSH concentration from the ischemic lung decreased significantly (P less than 0.05) during pulmonary ischemia (i.e., before reperfusion) and returned to baseline on reperfusion. The degree of RSH oxidation did not correlate with the severity of injury as measured by PET or histology. Thus pulmonary ischemia-reperfusion injury is characterized by inflammation, hemorrhage, edema, and OFR formation. Injury occurred after reperfusion, not after ischemia alone. In addition, injury to the contralateral nonischemic lung suggests a neutrophil-independent circulating mediator of injury.
authors.affiliation: Department of Pediatrics, Washington University Medical School, St. Louis, Missouri 63110.
authors.forename: A
authors.initials: A
authors.lastname: Hamvas
authors.forename: R
authors.initials: R
authors.lastname: Palazzo
authors.forename: L
authors.initials: L
authors.lastname: Kaiser
authors.forename: J
authors.initials: J
authors.lastname: Cooper
authors.forename: T
authors.initials: T
authors.lastname: Shuman
authors.forename: M
authors.initials: M
authors.lastname: Velazquez
authors.forename: B
authors.initials: B
authors.lastname: Freeman
authors.forename: D P
authors.initials: DP
authors.lastname: Schuster
mesh_terms: D000818:Animals; D004285:Dogs; D005609:Free Radicals; D007249:Inflammation / Q000209:etiology*; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D055370:Lung Injury; D010100:Oxygen / Q000378:metabolism*; D011654:Pulmonary Edema / Q000209:etiology; D015427:Reperfusion Injury / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000097:blood; D014055:Tomography, Emission-Computed
chemical_list: D005609:Free Radicals; D013438:Sulfhydryl Compounds; D010100:Oxygen