Tissue hypoxanthine reflects gut vulnerability in porcine endotoxin shock

Objective: To study differences in organ sensitivity during progressive end otoxin shock tissue levels of hypoxanthine, used as an indicator of adenosi ne triphosphate depletion and cellular energy failure, were monitored simul taneously in several organs by in vivo microdialysis. Design: Prospective, controlled animal study. Setting: University research laboratory. Subjects: Seventeen landrace pigs. Measurements and Main Results: Tissue levels of hypoxanthine, assessed by i n vivo microdialysis, were monitored (in the ileum, liver, lung, skeletal m uscle, subcutaneous fat, and arterial blood) simultaneously in addition to central hemodynamics during endotoxin shock in ten pigs. Seven sham animals not receiving endotoxin served as controls. Marked changes were seen in ce ntral hemodynamic parameters in response to endotoxemia. Very prominent inc reases were seen in the ileum and liver, followed by the lung, whereas only limited changes were observed in subcutaneous fat. These results indicate a differentiated development of cellular energy failure in response to endo toxemia in different organs. By considering the high amounts of xanthine ox idase seen in the gut, the increases in hypoxanthine may provide an importa nt substrate for reactive oxygen species formation in this organ. The limit ed changes seen in subcutaneous fat suggest that this tissue may provide li mited sensitivity when monitoring the septic patient. Conclusions: These findings support the concept of specific vulnerability o f the gut during endotoxemia.