Effect Of Gastric Electrical Stimulation On Drug-Induced Emesis In Dogs And The Possible Central Mechanism

Part 1 Drug-Induced Gastric Dysrhythmia and Emesis in DogsAims: The aims of this study were to investigate the effects of Cisplatin (DDP) andApomorphine (APO) on gastric myoelectrical activity in dogs.Methods: Seven female dogs chronically implanted with four pairs of electrodes ongastric serosa were used in a two-session study.Intravenous infusion of DDP (1.5 mg / kg)was given for 1h in DDP session.APO (0.1 mg/kg) was injected subcutaneously in APOsession.Gastric slow waves and emesis as well as behaviors suggestive of nausea wererecorded in each session.Results: 1.DDP and APO induced emesis and behaviors suggestive of nausea.(1) TheEmesis frequency was 5.5±1.2 in DDP session.The symptoms were slight in the period ofinfusion and before vomiting, and the symptoms scores were 1.86±0.26 and 7.43±1.39.Allthe dogs presented more frequent nausea-like responses such as licking tongue, belchingand chasma, and multiple vomiting.The behavioral score in the vomiting period was20.3±0.9, which was higher than that in other periods (each P < 0.01).(2) In the APOsession, the vomiting frequency was 5.29±0.87.All the dogs presented more frequentnausea-like responses within 15min after APO infusion, and the symptoms score in thisperiod was 12±0.95 (P < 0.001 vs.baseline).Within 30 - 45 min after APO infusion, thesymptoms score decreased to 2.00±0.62 (P=0.085 vs.baseline).2.DDP and APO inducedgastric dysrhythmia.(1) In DDP session, the percentage of normal slow waves decreasedsignificantly during the 2.5 h before vomiting ((77.7±5.6) %, P=0.01 ) and the period ofvomiting ((69.8±4.5) %, P < 0.001) compared with baseline.In addition, the dominantpower of gastric slow wave decreased from (1.5±2.1) dB in baseline to (-3.3±0.7) dB in the period of vomiting (P=0.038).(2) It also induced bradygastria and tachygastria in thefirst 15min after APO infusion (P=0.015 and P=0.011 vs.baseline).The normal slowwave was (53.07±6.72) % (P=0.001 vs.baseline).Conclusion: Cisplatin and Apomorphine induced emesis and nausea-like responses,which caused gastric dysrhythmia. Part 2 Effect of Gastric Electrical Stimulationon Drug-Induced EmesisObjective The aims of this study were to investigate the effects of Cisplatin (DDP)and Apomorphine (APO) on gastric myoelectrical activity and the roles of GES in treatingdrug-induced emesis in dogs.Methods Seven female dogs chronically implanted with four pairs of electrodes ongastric serosa were used in a two -session study.1.APO (0.1 mg/kg) was injectedsubcutaneously in APO-control session and APO + GES session.4 kinds of GES wereapplied on the proximal pair of gastric electrodes from drugs infusion in APO-GESsessions.Select the best parameter according to the result and apply it to the DDP-GESsession.2.Intravenous infusion of DDP (1.5 mg/kg) was given for 1h in DDP -controlsession and DDP + GES session.It lasted 6 h in GES session and 1 h in APO + GESsession.Gastric slow waves and animal behaviors were recorded in each session.Results 1.Cisplatin and Apomorphine induced emesis and behaviors suggestive ofnausea, and gastric dysrhythmia.(1) The total number of emesis was 5.5±1.2 in DDP-control session, and thc total symptom score was 31.83±2.75.The gastric slow waveshowed both bradygastria and tachygastria during the period of emesis (P=0.031 and P=0.02 vs.baseline).The percentage of normal slow wave was 69.61±5.81% during thisperiod (P=0.003 vs.baseline).(2) In the APO -control session, the total number of emesiswas 5.29±0.87 and the symptom score was 20.57±1.81.It also induced bradygastria andtachygastria in the first 15 min after APO infusion (P=0.015 and 0.011 vs.baseline).Thenormal slow wave was (53.07±6.72) % (P=0.001 vs.baseline).2.GES reduced emesisand the animal behavioral score suggestive of nausea compared with control sessions.(1)Among these 4 parameters, GES4 can reduced the vomiting time significantly.The totalsymptoms score in APO + GES4 session decreased (15.86±1.82, P=0.033 vs.controlsession).GES4 can also decrease the vomiting time in this session (3.71±0.61, P=0.025vs.control session).(2) The total symptom score in DDP + GES session decreased to 24.5±1.45 (P=0.028 vs.control session), and the vomiting times was 3.67±0.8(P=0.028vs.control session).However, GES had no effects on gastric dysrhythmia.Conclusion APO and DDP induced emesis and gastric dysrhythmia.GES with trainsof short pulses relieves drug -induced emetic responses but has no effects on dysrhythmia. Part 3 Functional Magnetic Resonance Imaging on GastricElectrical Stimulation in DogsObjective To investigate the effect of gastric electrical stimulation (GES) withdifferent parameters on the neuronal activity in central nervous system, and find thepossible mechanism of GES.Methods Five female dogs chronically implanted with four pairs of electrodes ongastric serosa were used in a three - part study.Each dog was anesthetized and given 3kinds of GES (trains of short pulse, shout pulse and long pulse) for 15min after baseline (5min) respectively.The location of cerebral activation induced by GES was investigated byfMRI.Result fMRI showed that GES with trains of short pulse induced BOLD - signalincreased in brainstem, frontal lobe, occipital lobe, and limbic brain areas, including theamygdale and hippocampus, which were considered to be correlated with chemoreceptortrigger zone and visceral sensation.GES with short pulse induced signal increased inbrainstem, occipital lobe, frontal lobe and cerebellum, but GES with long pulse only causedneuron activity in brainstem, frontal lobe and occipital lobe.Conclusion Each of these GES caused BOLD - signal increased in brainstem, whichindicate that the brainstem may be the same original pathway in the effect of GES oncentral nervous system.GES with short pulse and trains of short pulse also caused neuronalactivity in the areas correlated with visceral sensation.However, GES with long pulse hadno effect on the visceral sensation correlated areas.