Tumor necrosis factor-alpha (TNF-alpha) activates sodium channels in Type II alveolar epithelial cells, an important mechanism for the reported fluid resorption capacity of the cytokine. Both TNF-alpha receptor-dependent and -independent effects were proposed for this activity in vitro, the latter mechanism mediated by the lectin-like domain of the molecule. In this study, the relative contribution of the receptor-dependent versus receptor-independent activities was investigated in an in situ mouse lung model and an ex vivo rat lung model. Fluid resorption due to murine TNF-alpha (mTNF-alpha) was functional in mice that were genetically deficient in both types of mTNF-alpha receptor, establishing the importance of mTNF-alpha receptor-independent effects in this species. In addition, we assessed the capacity of an mTNF-alpha-derived peptide (mLtip), which activates sodium transport by a receptor-independent mechanism, to reduce lung water content in an isolated, ventilated, autologous blood-perfused rat lung model. The results show that in this model, mLtip, in contrast to mTNF-alpha, produced a progressive recovery of dynamic lung compliance and airway resistance after alveolar flooding. There was also a significant reduction in lung water. These results indicate that the receptor-independent lectin-like domain of mTNF-alpha has a potential physiological role in the resolution of alveolar edema in rats and mice.

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Objective: Lung injury is a severe complication of acute pancreatitis that increases the mortality rate of the disease. The pathophysiology of acute pancreatitis has been studied in several experimental models, but the kinetics of pulmonary complications in relation to the pancreatic disease is not completely understood. We then studied the severity of acute pancreatitis-associated lung injury over 18 h in rats that had taurocholic acid injection in the pancreatic duct and determined whether blood collected from rats with pancreatitis is toxic enough to induce injury in normal lungs. Design and setting: Prospective, randomized, and controlled animal study in an animal research laboratory in a university hospital. Interventions: We isolated lungs from rats with acute pancreatitis 2, 6, and 18 h after taurocholic acid injection in the biliopancreatic duct and perfused them with blood collected from the same rats. Additionally, blood collected from rats with acute pancreatitis (time-points: 2 and 6 h) was perfused in normal lungs. Measurements and results: Taurocholic acid injection induced a severe pancreatic injury that started as early as 2 h after the injection and persisted without recovery over the 18-h study period. In contrast, the pulmonary injury was transient, appearing at the 6-h time point with recovery by the end of the study. Pulmonary injury was moderate and evidenced mostly during lung reperfusion. Interestingly, blood collected at the 2-h time point in pancreatic rats induced pulmonary injury in normal lungs while blood collected at the 6-h time-point was not toxic. Conclusions: While pancreatic injury persists over the full experimental period, pulmonary injury is transient in our experimental model. The recovery of lung injury by 18 h might be explained by a decrease in the overall toxicity of pancreatic blood over time.

The BIOSTEMI trial will determine whether ultrathin-strut BP-SES are superior to thin-strut DP-EES with respect to TLF in patients with STEMI undergoing PPCI.