Acute lung injury and acute respiratory distress syndrome: experimental and clinical investigations

Chen, Hsing I

In 1990s, my associates and I were interested in the study of chest disorders. We developed an isolated perfused rat's lung in situ preparation ( Figure 3 ). Previous method involved removing the isolated lungs from the body and placing the organ on a force-displacement transducer to record the changes in lung weight and these procedures were rather complicated and unstable. Our in situ preparation does not require removing the lungs. Instead, the isolated lungs were left in situ. The whole rat was placed in a scale platform to measure the change in body weight (BW). Since the lungs are completely isolated from the body, the changes in BW reflect the lung weight (LW) changes. The preparation can be accomplished in 15 min. We used a digital-analogue converter to transfer the weight change from the scale platform to a recorder. The LW thus could be continuously monitored during the experiment. In this model, we can obtain the lung weight gain, LW/BW ratio, the changes in pulmonary arterial, capillary and venous pressures, the microvascular permeability (capillary filtration coefficient, K fc ), protein concentration in bronchoalveolar lavage (PCBAL), dye leakage, and exhaled nitric oxide (NO). The concentration of nitrate/nitrite, methyl guanidine (an index for hydroxyl radical), proinflammatory cytokines [tumor necrosis factor α (TNF α ) and interleukin-1 β (IL-1 β )] and other factors in the lung perfusate can also be detected. Early animal experimentations investigated the pathogenesis, modulators and mediators involved in the ALI induced by phorphol, air embolism, platelets, hypoxia, ischemia/reperfusion, endotoxin [lipopolysaccharide (LPS)]. The major finding is that cyclooxygenase products of arachidonic acid, thromboxane A 2 in particular is involved in the ALI and pulmonary hypertension caused by phorbol, platelets and air embolism. [27, 28] Furthermore, we found that L-arginine and inhaled NO enhanced the lung injury caused by air embolism, while blockade of NO synthase (NOS) with N ω -nitro-L-arginine methyl ester (L-NAME) attenuated the ALI. [28] The result suggests that NO is also involved.