Synergistic Deleterious Effect of Hypoxemia and Hypovolemia on Microcirculation in Intestinal Villi

Objective: To investigate the effect of hypoxemia, hemorrhagic shock, and the association of both of these on intestinal microcirculation (microcirculatory perfusion and leukocytes-endothelium interactions in postcapillary venules), as it can be encountered in hemorrhagic shock following trauma. Design: Prospective controlled experimental study. Setting: University research laboratory. Subjects: Forty-eight anesthetized and mechanically ventilated Balb/c mice. Intervention: Mice were randomly assigned to hypoxemia group in which we decreased inspired oxygen fraction during 60 minutes to reach a Pao(2) of 40 mm Hg, hemorrhagic shock group in which animals were exsanguinated to a mean arterial pressure level of 40 mm Hg during 30 minutes, hypoxemia-hemorrhagic shock group in which Pao(2) was decreased to 40 mm Hg during 60 minutes with exsanguination from the 30th to the 60th minute to a mean arterial pressure level of 40 mm Hg; or control group. Measurements and Main Results: Hypoxemia decreased RBCs velocity in intestinal villi but did not alter the fraction of perfused villi. Hypoxemia also triggered leukocytes adhesion to the venular endothelium. Hemorrhagic shock not only decreased RBCs velocity in villi but also slightly altered the fraction of perfused villi (94% 2% in hemorrhagic shock group vs 100% +/- 0% in control group, p < 0.005). Furthermore, hemorrhagic shock triggered leukocytes adhesion to the venular endothelium to the same extent as hypoxemia. When hypoxemia was associated to hemorrhagic shock, it decreased villous RBCs velocity in an additive manner and the fraction of perfused villi dropped in a synergistic manner (69% +/- 3% in hypoxemia-hemorrhagic shock group vs 94 +/- 2 in hemorrhagic shock group, p < 0.005). The association of hypoxemia and hemorrhagic shock did not further amplify leukocytes adhesion to intestinal venules compared with either hypoxemia or hemorrhagic shock alone. Conclusions: During hemorrhagic shock, the occurrence of hypoxemia considerably alters villous intestinal perfusion as it decreases the fraction of perfused villi in a synergistic manner, thereby increasing the risk of villous ischemia. The association of hypoxemia and hemorrhagic shock did not amplify leukocytes adhesion to the endothelium further than either hemorrhagic shock or hypoxemia alone did. As hypoxemia frequently occurs simultaneously with hemorrhagic shock in traumatic conditions, it can worsen gut ischemia leading to the exacerbation of multiple organ failure syndrome.