Interventional Effect Of Whole Lung Lavage On Lung Injury Induced By Depleted Uranium Aspiration

Depleted uranium (DU) is a by-product of the uranium isotope enrichment process, which has chemical and radiological toxicity. Because of the high density, self-sharpening capability and low cost, DU as military raw material had been selected by weapon developers. Now, more than twenty countries and regions have equipped DU weapons and introduced them into battlefields, such as Gulf war, Balkan war and Iraq War. On impact, DU in projectiles was dispersed as particles which contaminate air, water, plants and soils. Many combatants and civilians in the wars suffered from the illnesses caused by DU exposures. Therefore, many countries pay more attentions to the protection of DU injuries. There is a general agreement that inhalation of DU particles is probably the most significant route of exposure. DU particles deposit in alveolar surface through airway and induce acute or chronic lung injury,so that reducing the time and concentration of DU exposure is the fundamental way to remedy lung tissue lesion. However, a desirable agent to clear DU has not been discovered until now,a new method need to be developed. In this experiment, a canine model of subacute lung injury had been setup, which induced by depleted uranium instillation through bronchoscopes, and then whole lung lavage (WLL) had been operated in this model, in order to observe the therapeutic role of WLL to DU induced lung injury. The experiment is divided into two sections:Part1: Establishment of a canine model of subacute lung injury induced by DU instillation.Objective To establish a canine model of subacute lung injury induced by depleted uranium inhalation.Method Twenty-six healthy canines were randomized into three group: control group (CG, n=6), low-dose group (LG, n=10), high-dose group (HG, n=10). In low dosage group (CG), 2mg/kg DU, and in high dosage group (HG), 20mg/kg DU were injected through tracheal intubation. In control group, 0.2ml/kg of normal saline was intratracheally given. The survival time of each group was observed in 30days, and chest CT scan was performed in survival animals. They were sacrificed for pathological examination of lung tissues on the 30th days post of them intratracheal introduction of various agents.Result During the observation period, no dog died in CG, 1 dog died on the 22nd and 9 of them survived longer than 30 days. All the animals in HG group died within 30days with a mean survival time of 11.2±8.9 days . In comparison with HG, significant difference on survival time was found between LG and CG(P<0.05), while no significant difference was found between the latter two groups . Pathologically, changes were noted in lung tissue of LG, such as escape of inflammatory cells into alveoli, hemorrhage and hyaline membrane formation in alveolar space, dilation and congestion of alveolar capillaries, and infiltration of inflammatory cells in interstitial tissue. CT scanning revealed patchy and effusion and solid consolidation in left lung.Conclusion The canine model of sub-acute lung injury induced by a dose of 2mg/kg depleted uranium introduced through tracheal intubation is suitable for the study of subacute toxicity induced by depleted uranium.Part2: Whole lung lavage attenuates DU instillation-induced lung injury in canines Objective The canine models were treated by whole lung lavage at different time, observe the effect of early whole lung lavage group and late early whole lung lavage group, finally detect a optimal time to cure subacute lung injury induced by depleted uranium inhalation. Method To use the low-dose group canine as the laboratory animals, the canines of subacute lung injury were randomized into three group: control group (CG, n=15), early whole lung lavage group (EG, n=15) and late whole lung lavage group (LG, n=15). The canines in EG and LG were treated with whole lung lavage in 3,14 days respectively, then retrieved the bronchoalveolar lavage fluid (BALF1) of each group and evaluated the DU contents in BALF1. Observed chest CT of survived animals after 30 days, then three groups were carried out bronchoalveolar lavage, detected the TNF-α, IL-6 concentration in BAFL2 of each group. The survival time of animals were observed after 60 days, the survival animals were sacrificed for DU contents, TNF-α, IL-6 examination of lung tissues.Result Significant difference on survival time was found between CG and EG, while no significant difference between CG and LG. The DU contents in BALF1 in EG were apparently higher than that in LG (P<0.05). After 30 days, semi-quantitative analysis was performed in the CT images of the lung and show that: in comparison with CG, DU induced lung injury was markedly attenuated in EG (P<0.05), but wasn't attenuated in LG . The concentration of TNF-α, IL-6 of BALF2 in EG was apparently lower than that in CG (P<0.05), but there were no statistical differences between EG and LG (P>0.05). The DU contents of lung tissue, the concentration of TNF-α, IL-6 in supernatant of lung homogenate in EG were apparently lower than those in CG (P<0.05), but there was no statistical differences between CG and LG (P>0.05).Conclusion Both of early and late whole lung lavage may wash out depleted uranium particles from lung ,but early whole lung lavage can extend the survival time notably, attenuate CT scanning changes and lung inflammation.