Ascorbic acid reduces the endotoxin‐induced lung injury in awake sheep

Abstract

Our aim was to investigate whether ascorbic acid can reduce reactive oxygen metabolite‐mediated acute lung injury. The effects of intravenous administration of Escherichia coli endotoxin were studied, with and without ascorbic acid infusion, on haemodynamics, lung lymph flow, cardio‐respiratory and neutrophil function in chronically instrumented sheep. Paired experiments were performed on eight sheep in which they received either endotoxin alone (0·5 μg kg^‐1 b.w.) (ET group) or in combination with an ascorbic acid infusion (1 g kg^‐1 b.w. bolus injection followed by 0·2 g kg^‐1 h^‐1 continuous infusion) (ET + ASC group) in random order. Four of the animals also received ascorbic acid alone (ASC group). As a result, for the ET + ASC group a general and mostly significant improvement (P < 0·05) in the early hypertensive phase (0·60 min, P values) and in the late permeability phase (2–4 h, *P values) of cardiorespiratory function (mean artery pressure: P/*P= 0·283/0·049; mean pulmonary artery pressure: P/*P= 0·0.0001; mean pulmonary artery wedge pressure: P/*P= 0·02/0·001; right ventricular stroke work index: P/*P= 0·02/0·0001; cardiac index: P/*P= 0·797/0·755; arterial oxygen saturation: P/*P= 0·0059/0·01; arterial‐venous difference of oxygen tension: P/*P= 0·011/0·0005), oxygen consumption: P/*P=0·013/0·035, lung lymph flow: P/*P=0·562/0·012, lymph/plasma protein ratio: P/*P= 0·304/0·008 and protein clearance: P/*P= 0·56/0·05 was observed in comparison with the ET group. The decrease of the neutrophil chemiluminescence response of the ET + ASC group in the late phase: P/*P= 0·419/0·026 was most likely due to ascorbic acid, whereas β‐N‐acetylglucosaminidase secretion was identical for both groups. In conclusion, we suggest that reactive oxygen metabolite scavenging by ascorbic acid is responsible for the improvement of endotoxin‐induced acute lung injury.