A Supraceliac Aortic Cross Clamping Model to Explore Remote Lung Injury and the Endothelial Glycocalyx.

BACKGROUND

We hypothesized that supraceliac aortic cross clamping could induce lung injury mediated by an inflammatory ischemia-reperfusion (IR) trigger. We aimed to characterize glycocalyx (GCX), a component of endothelial membrane, participating to remote lung injury.

METHODS

Rats underwent supraceliac aortic cross clamping for 40 min and were sacrificed at 0, 3, 6, and 24 hr of reperfusion (n = 10/group). Each group was compared to sham (n = 6/group). GCX products (syndecan-1 [Sdc-1] and heparan sulfate [HS]), tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) were measured in plasma (enzyme-linked immunosorbent assay[ELISA]). Lungs were harvested for measurements of TNF-α, IL-1β (polymerase chain reaction) and Sdc-1 (western blotting [WB]). Histologic lung injury scoring and pulmonary gravimetry were analyzed in a blinded manner.

RESULTS

Plasmatic Sdc-1, HS, TNF-α, and IL-1β reached peak levels at 3 hr. Levels were significantly higher in clamping groups than sham at 6 hr for Sdc-1, at 0 and 3 hr for HS, at 3 and 6 hr for TNF-α, and at 3 hr for IL-1β. Lung TNF-α and Interleukin-1β reached peak levels at 6 hr. Levels were significantly higher than sham at 6 and 24 hr for TNF-α and at 6 hr for IL-1β. Lung Sdc-1 was lowest at 3 hr. Sdc-1 was not significantly different compared to sham at the different reperfusion times. At 3 hr, it was 0.27 ± 0.03 vs. 0.33 ± 0.02 (sham) (P = 0.09). Histopathologic scores at 6 and 24 hr were higher in clamping groups than sham. At 6 and 24 hr, it was higher for hemorrhage, polynuclear neutrophil (PNN) infiltration and intravascular leukocytes. Pulmonary edema was higher by gravimetry at 0 and 6 hr.

CONCLUSIONS

Supra celiac aortic clamping causes early lung injury in relation with a systemic inflammatory response associated with altered GCX structure.