LAUSR

To the Editor: P eng et al. showed that, after severe hemorrhagic shock, intestinal intraluminal treatment with tranexamic acid (TXA) reduced intestinal and pulmonary injury associated with a decreased shedding of syndecan-1. Interestingly, the authors found that hemorrhagic shock increased the protein level and activity of A Disintegrin and Metalloproteinase-17 (ADAM-17). Following TXA treatment, protein levels and activity of ADAM-17 were both decreased along with reduced plasma levels of TNF-α and syndecan-1. ADAM-17 is an important protease that regulates many physiological and pathophysiological processes such as inflammation and coagulation and thus warrants special attention in studies related to hemorrhagic shock-induced organ injury. Therefore, we were particularly fascinated by the findings from Peng et al. that the severity of pulmonary and intestinal injury following hemorrhagic shock is correlated with ADAM17, which might be a potential therapeutic target. On the basis of the results and conclusions presented, we have several comments for the authors. Ischemiaor proteolysis-induced organ injury? Following severe (prolonged) hypovolemic shock, lowoxygen and energy supply leads to ATP depletion and mitochondrial dysfunction, the key mechanisms for cell deterioration and apoptosis as well as subsequent organ injury. However, on the basis of the current study, enhanced proteolysis appears to be a fundamental mechanism, because TXA treatment (decreasing ADAM17) alone with no resuscitation significantly decreased organ injury. This raises a question whether TXA treatment or inhibition of ADAM-17 also improves cellular energy homeostasis and tissue oxygenation. In fact, there is evidence that inhibition of ADAM-17 leads to an increased metabolic rate because of elevated mitochondrial uncoupling protein, but such manipulation could be a fatal process after hemorrhagic shock because of a lower ATP production but a higher oxygen and energy expenditure. Notably, a recently study by Altshuler et al. addressed this question by showing that, following hemorrhagic shock, treatment with TXA alone failed to decrease