Lung Injury after Supraceliac Aortic Cross-Clamping: No Benefit from Unfractionated Heparin in Rats.

Abstract

BACKGROUND: Supraceliac aortic cross-clamping can induce remote organ injury, particularly affecting the lungs through ischemia-reperfusion mechanisms. Pulmonary endothelial dysfunction plays a central role in acute lung injury, potentially involving degradation of the endothelial glycocalyx. Unfractionated heparin (UFH), routinely used during aortic surgery, is known for its anti-inflammatory, glycocalyx-protective properties and protective effects on lung parenchyma. This study aimed to evaluate the role of UFH in preventing remote lung injury following aortic cross-clamping. METHODS: Rats underwent 40 min of supraceliac aortic cross-clamping followed by 3 hr of reperfusion and were randomized to receive UFH or saline (n = 10/group). Plasma glycocalyx degradation products (Syndecan-1, Heparan Sulfate) and inflammatory cytokines were measured. Lung tissue was analyzed for cytokine expression, heparanase activity, and histological injury. Pulmonary endothelial glycocalyx was assessed by electron microscopy. Blood gas analysis evaluated systemic metabolic response. RESULTS: UFH did not significantly affect systemic cytokine levels (GM-CSF, IFN-gamma, IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, and TNF-a), glycocalyx degradation products, blood gas parameters, or histological lung injury scores. Lactate levels were higher in the UFH group (P < 0.05). Lung heparanase activity was significantly reduced with UFH (P < 0.001). Electron microscopy seemed to identify better-preserved and more regularly distributed pulmonary endothelial glycocalyx in the UFH group, with less intraluminal shedding compared to controls. CONCLUSION: Although UFH did not reduce lung injury or systemic inflammation after aortic cross-clamping, it was associated with lower pulmonary heparanase activity and seemed to improved preservation of the endothelial glycocalyx. These findings suggest a potential endothelial-protective effect of UFH that warrants further investigation.