The Effects of Nitric Oxide on Air Embolism-Induced Acute Lung Injury

• Main Author: 李才宇
• Other Authors: 李敏輝
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/89157314833735111136

碩士 === 國防醫學院 === 航太醫學研究所 === 87 === 　　Air embolism, occurring in pilots during high-altitude tests, in divers undergoing decompression after hyperbaric exposure, and in a number of clinical situations, can lead to pulmonary hypertension, lung edema, and lung injury. Accumulating evidences suggest that nitric oxide (NO) plays a key role in the development of lung edema in various models of acute lung injury. Therefore, we conducted the present study to evaluate the role of endogenous NO in air emboli-induced acute lung injury. The in situ isolated rat lungs perfused with blood-HBSS buffer solution, a mixture of 10 ml rat blood and 10 ml Hank's balanced salt solution (HBSS), were applied to quantify the effects of NO precursor (L-arginine) and NO synthase inhibitor (L-NAME) on acute lung injury induced by air emboli which was produced by infusion of air into pulmonary artery. Lung weight gain (LGW) and pulmonary artery pressure (PAP) were continuously monitored, and pulmonary filtration coefficient (Kfc) as an index of microvascular injury was measured by elevation of venous pressure and time zero extrapolation of the slope of the weight gain curve. In the end of experiment, lung lavage was also collected to analyze the protein concentration (LPC). 　　Infusion of air with the rate of 0.25 ml/min for 1 minute into the pulmonary artery resulted in pulmonary hypertension and lung injury. PAP increased steeply and reached its maximum when air infusion stop and then fell progressively with P5 (the reducing ratio of pulmonary artery pressure at time 5 minute) as 0.39□0.02. The maximal increase of pulmonary artery pressure (△PAP) was 31.9□0.8 mmHg. Air embolism caused the increase of LWG, LPC, and Kfc with the values of 1.39□0.08 g, 135.6□47.3 mg/dl, 0.8549□0.1135 g/min/cmH2O/100g, respectively (P<0.05). Histological findings of the lung tissue demonstrated pulmonary congestion, alveolar septum edema, and inflammatory cell infiltration. Pretreatment with L-arginine (15 mg/kg) completely abolished the development of lung injury with LWG=0□0.1 g, LPC=41.2□7.7 mg/dl, and Kfc=0.3425□0.0058 g/min/cmH2O/100g (P<0.05). The pathology showed no sign of lung edema and inflammatory cell infiltration. Although L-arginine could not attenuate the pulmonary hypertension with △PAP=31.0□0.5 mmHg (P>0.05). However, it speeded up the reduction of pulmonary hypertension with P5=0.49□0.01 (P<0.05). In contrast to the effects of L-arginine, pretreatment with L-NAME (15 mg/kg) worsened the LWG, LPC and P5 with the values of 3.17□0.15 g, 431.0□128.9 mg/dl, and 0.22□0.01, respectively (P<0.05). More sever lung edema was also observed in pathological examination. 　　In conclusion, our findings suggest that endogenous NO plays a key role in the development of lung edema and pulmonary hypertension induced by air-emboli. NO precursor, L-arginine, can prevent the lung from air emboli-induced lung injury.