Intestinal Motility During Hypoxia and Reoxygenation in Vitro

Ischemia-reperfusion injury leads to profoundfunctional and structural alterations of thegastrointestinal tract. We developed an in vitro modelof reperfusion injury to study the changes in intestinal motility during hypoxia followed byreoxygenation. We recorded the spontaneous motoractivity of intestinal rings from the proximal mousejejunum, using force displacement transducers. Inaddition to the rhythmic contractions, we studied thecontractile response to transmural stimulation ofintrinsic nerves. During hypoxia, the frequency of thespontaneous contractions and the resting tensiondecreased. While 29% of the tissues still responded toneural stimulation after 15 min of hypoxia, electricalfield stimulation did not evoke any response after 60min of hypoxia. Reoxygenation resulted in a transient increase in the baseline tension and an initialnormalization of the spontaneous rhythmic contractions,which subsequently became irregular. The percentage oftissues that recovered their ability to respond to electrical field stimulation 10 min afterreoxygenation decreased from 100% after 15 min ofhypoxia to 47% after 60 min of hypoxia. Theadministration of the antioxidant glutathione preventedthe functional abnormalities seen 10 min after reoxygenation.The pharmacological inhibition of Cu,Zn superoxidedismutase exacerbated the functional reoxygenationdamage. Conversely, the overexpression of thisradical-scavenging enzyme in transgenic mice increased thelikelihood of functional recovery. Reoxygenation in acalciumfree solution also prevented prolonged functionaldamage of the muscle rings. We conclude thathypoxia-reoxygenation significantly alters intestinal motility. Thegeneration of reactive oxygen species and disruptions inthe calcium homeostasis play an important role in thepathogenesis of reoxygenation damage. Interventions that alter the intracellular redox state oraffect the secondary changes in the intracellularcalcium concentration can prevent or blunt the effectsof reoxygenation injury on intestinalmotility.