Intestinal motility during hypoxia and reoxygenation in vitro.

Ischemia-reperfusion injury leads to profound functional and structural alterations of the gastrointestinal tract. We developed an in vitro model of reperfusion injury to study the changes in intestinal motility during hypoxia followed by reoxygenation. We recorded the spontaneous motor activity of intestinal rings from the proximal mouse jejunum, using force displacement transducers. In addition to the rhythmic contractions, we studied the contractile response to transmural stimulation of intrinsic nerves. During hypoxia, the frequency of the spontaneous contractions and the resting tension decreased. While 29% of the tissues still responded to neural stimulation after 15 min of hypoxia, electrical field stimulation did not evoke any response after 60 min of hypoxia. Reoxygenation resulted in a transient increase in the baseline tension and an initial normalization of the spontaneous rhythmic contractions, which subsequently became irregular. The percentage of tissues that recovered their ability to respond to electrical field stimulation 10 min after reoxygenation decreased from 100% after 15 min of hypoxia to 47% after 60 min of hypoxia. The administration of the antioxidant glutathione prevented the functional abnormalities seen 10 min after reoxygenation. The pharmacological inhibition of Cu,Zn superoxide dismutase exacerbated the functional reoxygenation damage. Conversely, the overexpression of this radical-scavenging enzyme in transgenic mice increased the likelihood of functional recovery. Reoxygenation in a calcium-free solution also prevented prolonged functional damage of the muscle rings. We conclude that hypoxia-reoxygenation significantly alters intestinal motility. The generation of reactive oxygen species and disruptions in the calcium homeostasis play an important role in the pathogenesis of reoxygenation damage. Interventions that alter the intracellular redox state or affect the secondary changes in the intracellular calcium concentration can prevent or blunt the effects of reoxygenation injury on intestinal motility.