Effect of VNS on Gastric Motor Functions

VNS 对胃运动功能的影响

• 批准号: 10610561
• 负责人: MICHAEL L. CAMILLERI
• 金额: $ 7.58万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-23 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10610561
• 关键词: Address; Adult; Adverse effects; Anatomy; Autonomic nervous system disorders; Cardiovascular Diseases; Cervical; Chronic; Clinic; Clinical; Clinical Research; Data; Disease; Dyspepsia; Electric Stimulation; Emergency department visit; Epilepsy; FDA approved; Face; Fasting; Fatty acid glycerol esters; Female; Foundations; Frequencies; Future; Gastric Emptying; Gastrointestinal Diseases; Gastroparesis; Generations; Goals; Heart; Heart failure; High Prevalence; Image; Immune System Diseases; Implant; Incidence; Inflammation; Ingestion; Insulin-Dependent Diabetes Mellitus; Left; Measurement; Measures; Mediating; Mental Depression; Metabolic Diseases; Methods; Metoclopramide; Minnesota; Motor; Movement; Movement Disorders; Muscle; Neurons; Nitrogen; Non-Insulin-Dependent Diabetes Mellitus; Normal Range; Obesity; Operative Surgical Procedures; Organ; Outpatients; Patients; Peripheral; Persons; Pharmaceutical Preparations; Physiologic pulse; Play; Population; Prevalence; Protocols documentation; Radiolabeled; Reporting; Research; Review Literature; Risk; Role; Sensory; Solid; Stomach; Symptoms; Tardive Dyskinesia; Testing; Time; Universities; Vagus nerve structure; Width; Work; cholinergic; cohort; comorbidity; effective therapy; egg; gastrointestinal symptom; hospitalization rates; innovation; insight; intravenous injection; meetings; mortality; motor disorder; nerve supply; novel; open label; post stroke; response; single photon emission computed tomography; sleep pattern; stroke recovery; systematic review; vagus nerve stimulation

ANCILLARY PROJECT 2 Abstract: Effect of VNS on Gastric Motor Functions The prevalence of gastroparesis (i.e., inability for the stomach to empty itself normally) ranges from 13.8 to 267.7 per 100,000 adults; in addition, 2.5% are hospitalized each year, with 0.3% mortality. There is no consistently effective treatment for this condition: the only FDA-approved medication, metoclopramide, can only be used for <12 weeks because of risk of the debilitating movement disorder tardive dyskinesia. To gather key data as a foundation for new gastroparesis treatment, we propose to evaluate the effect of left vagus nerve stimulation (VNS) on gastric emptying and accommodation functions in patients undergoing treatment for depression or epilepsy. Whereas the effects of VNS on other functions such as sleep patterns or heart period responses reflecting cardiovagal innervation have been reported, the effects of such treatment on gastric functions are unknown. It is clear, however, that the vagus nerve provides the extrinsic input to cholinergic intrinsic neurons that stimulate gastric muscle contractility and to the nitrogen-intrinsic neurons that mediate gastric accommodation. Our hypothesis is that cervical VNS increases gastric accommodation and accelerates gastric emptying. Our specific aim is to compare simultaneous assessment of gastric emptying and gastric accommodation in response to the same caloric meal before and three months after activation of left cervical VNS. The functions of the stomach will be measured using validated methods conducted simultaneously using SPECT camera imaging and a radiolabeled meal, with a first measurement of gastric volume during fasting after intravenous injection of pertechnetate and a second measurement of postprandial gastric volume accommodation and gastric emptying following the ingestion of a 320 kilocalorie, 30% fat egg meal. These innovative studies will document the effect of VNS as the foundation for a potential novel treatment for correcting disorders of gastric motor function.

辅助方案2摘要：迷走神经对胃运动功能的影响 胃轻瘫(即胃无法正常排空)的患病率从每100,000人中有13.8%到267.7人不等；此外，每年有2.5%的人住院，死亡率为0.3%。对于这种情况没有一贯有效的治疗方法：FDA批准的唯一药物甲氧氯普胺只能用于 &lt；12周，因为有患衰弱运动障碍的风险，迟发性运动障碍。为了收集关键数据作为新的胃瘫治疗的基础，我们建议评估左侧迷走神经刺激(VNS)对抑郁症或癫痫治疗患者胃排空和调节功能的影响。虽然VNS对其他功能的影响已有报道，如反映心脏迷走神经支配的睡眠模式或心动周期反应，但此类治疗对胃功能的影响尚不清楚。然而，很明显，迷走神经为刺激胃肌肉收缩的胆碱能内源性神经元和调节胃适应的内源性氮神经元提供外源性输入。我们的假设是，颈性迷走神经增加了胃的适应能力，加速了胃的排空。我们的具体目的是比较左颈VNS激活前和激活后三个月对相同热量餐的胃排空和胃适应的同步评估。胃的功能将通过同时使用SPECT相机成像和放射性标记餐的验证方法进行测量，第一次测量静脉注射高铁酸盐后禁食期间的胃容量，第二次测量餐后胃容量调节和胃排空在摄入320千卡、30%脂肪蛋粉后。这些创新的研究将证明VNS的效果，为潜在的纠正胃运动功能障碍的新疗法奠定基础。