Hamvas A, Palazzo R, Kaiser L, Cooper J, Shuman T, Velazquez M, Freeman B, Schuster D P
Department of Pediatrics, Washington University Medical School, St. Louis, Missouri 63110.
J Appl Physiol (1985). 1992 Feb;72(2):621-8. doi: 10.1152/jappl.1992.72.2.621.
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.
在一项相关研究中，我们发现，一侧肺脏进行2小时的温热性局部缺血后再灌注，会导致双侧组织损伤，这表现为血管外密度（EVD）增加以及通透性升高，通透性通过放射性标记转铁蛋白的肺毛细血管逃逸率（PTCER）来衡量。EVD和PTCER测量值通过正电子发射断层扫描（PET）的定量成像技术获得。在本研究中，我们通过组织学方法评估了EVD的这种增加情况，并将EVD和PTCER与血浆中作为氧自由基（OFR）形成标志物的氧化还原巯基（RSH）测量值进行关联。组织学检查显示，缺血侧在再灌注后出现水肿、白细胞浸润和出血，但仅在再灌注后出现，而非缺血侧仅观察到中性粒细胞浸润。组织学评分与EVD（r = 0.81）和PTCER（r = 0.75）相关，但即使在没有中性粒细胞浸润的情况下，通透性有时也会异常。在肺缺血期间（即再灌注前），缺血肺的血浆RSH浓度显著降低（P < 0.05），再灌注时恢复至基线水平。RSH氧化程度与通过PET或组织学测量的损伤严重程度不相关。因此，肺缺血 - 再灌注损伤的特征是炎症、出血、水肿和OFR形成。损伤发生在再灌注后，而非仅在缺血后。此外，对侧非缺血肺的损伤提示存在一种不依赖中性粒细胞的循环损伤介质。
