C C Horn1,2,3,4, L Zirpel5, M G Sciullo1, D M Rosenberg6. 1. Biobehavioral Oncology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. 2. Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 3. Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 4. Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA. 5. Neuromodulation Global Research, Medtronic, Minneapolis, MN, USA. 6. Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
Abstract
BACKGROUND: Gastric electrical stimulation (GES) is implicated as a potential therapy for difficult-to-treat nausea and vomiting; however, there is a lack of insight into the mechanisms responsible for these effects. This study tested the relationship between acute GES and emesis in musk shrews, an established emetic model system. METHODS: Urethane-anesthetized shrews were used to record emetic responses (monitoring intra-tracheal pressure and esophageal contractions), respiration rate, heart rate variability, blood pressure, and gastrointestinal electromyograms. We investigated the effects of acute GES pulse duration (0.3, 1, 5, and 10 ms), current amplitude (0.5, 1, and 2 mA), pulse frequency (8, 15, 30, and 60 Hz), and electrode placement (antrum, body, and fundus) on emesis induced by gastric stretch, using a balloon. KEY RESULTS: There were four outcomes: (i) GES did not modify the effects of gastric stretch-induced emesis; (ii) GES produced emesis, depending on the stimulation parameters, but was less effective than gastric stretch; (iii) other physiological changes were closely associated with emesis and could be related to a sub-threshold activation of the emetic system, including suppression of breathing and rise in blood pressure; and (iv) a control experiment showed that 8-OH-DPAT, a reported 5-HT1A receptor agonist that acts centrally as an antiemetic, blocked gastric stretch-induced emesis. CONCLUSIONS AND INFERENCES: These results do not support an antiemetic effect of acute GES on gastric distension-induced emesis within the range of conditions tested, but further evaluation should focus on a broader range of emetic stimuli and GES stimulation parameters.
BACKGROUND: Gastric electrical stimulation (GES) is implicated as a potential therapy for difficult-to-treat nausea and vomiting; however, there is a lack of insight into the mechanisms responsible for these effects. This study tested the relationship between acute GES and emesis in musk shrews, an established emetic model system. METHODS:Urethane-anesthetized shrews were used to record emetic responses (monitoring intra-tracheal pressure and esophageal contractions), respiration rate, heart rate variability, blood pressure, and gastrointestinal electromyograms. We investigated the effects of acute GES pulse duration (0.3, 1, 5, and 10 ms), current amplitude (0.5, 1, and 2 mA), pulse frequency (8, 15, 30, and 60 Hz), and electrode placement (antrum, body, and fundus) on emesis induced by gastric stretch, using a balloon. KEY RESULTS: There were four outcomes: (i) GES did not modify the effects of gastric stretch-induced emesis; (ii) GES produced emesis, depending on the stimulation parameters, but was less effective than gastric stretch; (iii) other physiological changes were closely associated with emesis and could be related to a sub-threshold activation of the emetic system, including suppression of breathing and rise in blood pressure; and (iv) a control experiment showed that 8-OH-DPAT, a reported 5-HT1A receptor agonist that acts centrally as an antiemetic, blocked gastric stretch-induced emesis. CONCLUSIONS AND INFERENCES: These results do not support an antiemetic effect of acute GES on gastric distension-induced emesis within the range of conditions tested, but further evaluation should focus on a broader range of emetic stimuli and GES stimulation parameters.
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