Pulmonary nitric oxide metabolism following infrarenal aortic cross-clamp-induced ischaemia-reperfusion injury

Objectives: to investigate endogenous pulmonary nitric oxide metabolism fol lowing infrarenal aortic cross-clamp-induced ischaemia-reperfusion injury. Methods: groups of male Wistar rats (n=6) curve subjected to 60 minutes of infrarenal aortic cross-clamping under general anaesthesia. Rats were culle d after 0, 60 and 120 minutes' reperfusion, following release of the aortic clamp. A sham-operated control group was also studied. Acute lung injury ( ALI) was quantified by measuring the protein concentration in lung bronchoa lveolar lavage (BAL) fluid. Pulmonary myeloperoxidase activity (MPO) was me asured as an index of neutrophil infiltration and degranulation in the lung . Plasma tumour-necrosis factor-alpha (TNF-alpha) was measured as an index of the pro-inflammatory cytokine response and pulmonary nitric oxide syntha se (NOS) activity was determined by measuring conversion of H-3 L-arginine to H-3 L-citrulline in tissue homogenates. Results: these data show significant ALI with increased pulmonary microvasc ular permeability and MPO activity in animals subject to 60 minutes' ischae mia and 60 minutes or 120 minutes of reperfusion compared to control animal s (P<0.01). Plasma TNF-alpha levels were significantly increased following 60 minutes of ischaemia compared to controls (p<0.01) and remained signific antly increased in animals subject to reperfusion (P<0.01). Pulmonary NOS a ctivity was significantly increased in animals subject to reperfusion (p<0. 01). Conclusions: the reperfusion phase of infrarenal aortic cross-clamping prov okes a significant increase in pulmonary NOS metabolism. The increase in pl asma TNF-alpha and MPO activity suggests that this response may be secondar y to inducible NOS expression. Manipulation of this response may benefit pa tients at risk of acute injury following infrarenal aortic reconstruction.