Authors:Á. Adamicza, J. Kaszaki, M. Boros and Zoltán Hantos
During intestinal ischaemia-reperfusion, endotoxin can be translocated. Pretreatment with sublethal doses of endotoxin develops tolerance to ischaemia-reperfusion in different organs; however, the tolerance to intestinal ischaemia-reperfusion in the lung has rarely been investigated. Our aim was to study the role of endotoxin pretreatment in the mechanical responses and inflammatory activation induced by intestinal ischaemia-reperfusion in the lung. Wistar rats were preconditioned with a sublethal dose of endotoxin on day −3 or −1. On day 0, anesthetized, paralyzed and mechanically ventilated rats were subjected to a 60-min occlusion of the superior mesenteric artery and a subsequent 240-min reperfusion. The low-frequency forced oscillation technique was employed to characterize the separate mechanical responses of the airways and respiratory tissues. Intestinal ischaemia-reperfusion caused a significant decrease in airway resistance and increases in tissue resistance and elastance, nitric oxide synthase and myeloperoxidase activities. Pretreatment with endotoxin modified both the pulmonary mechanical responses and the inflammatory markers in the lung during intestinal ischaemia-reperfusion. We conclude that endotoxin or the endotoxin-induced processes (and humoral mediators) have significant roles in the pathomechanism of the remote pulmonary effect of intestinal ischaemia-reperfusion.
Because of similar pathophysiologic changes, oleic acid (OA)-induced pulmonary edema has been well established as an experimental model of certain types of ARDS. Data in the literature indicate changes mostly in global pulmonary mechanical parameters (lung resistance and compliance) during permeability-type edema. Therefore, we designed this study (1) to separate the OA-induced mechanical responses into airway and parenchymal components, and (2) to examine the relationship between the mechanical parameters and the degree of edema. Anaesthetized, paralyzed, mechanically ventilated rats were given iv. OA in doses of 0 (C n=9), 0.05 (OA0.05 n=8), 0.1 (OA0.1 n=10) and 0.3 (OA0.3 n=5) ml/kg. Respiratory system impedance was measured with a wave-tube low-frequency forced oscillation technique, and a model fitting was used to estimate airway (Raw) and lung tissue parameters (G, parenchymal damping; H, elastance). Pulmonary edema was quantified by gravimetric analysis (WW/DW, wet-to-dry weight ratio). In the OAL0.05 group, transient, but significant increase in Raw, only slight increase in H, and no response in G was observed. Different responses were obtained in OA0.1: significant Raw, G, and H values in survivors; rapid and significantly higher responses in all three parameters in non-survivors. Extremely large parameter values were measured in OA0.3. We found that OA caused dose-related increases in WW, DW and WW/DW. Highly significant correlations were found between the degree of edema and G or H, but not Raw. This study demonstrates that low dose of OA had only transient lung mechanical effects; however, it resulted in mild edema. The higher dose elicited significant airway and tissue changes (smaller responses in survivors than in non-survivors), and severe edema. The strong correlation between lung tissue parameters and the degree of edema suggests that the OA-induced acute lung injury is manifested primarily in the alterations in parenchymal mechanics.