Effect of VNS on Gastric Motor Functions

辅助项目2摘要：迷走神经刺激对胃运动功能的影响 胃轻瘫的患病率（即，胃不能正常排空）的比例为每10万成人13.8至267.7人;此外，每年有2.5%的人住院，死亡率为0.3%。对于这种情况没有持续有效的治疗方法：FDA批准的唯一药物甲氧氯普胺只能用于 <12周，因为存在使人衰弱的运动障碍迟发性运动障碍的风险。为了收集关键数据作为新的胃轻瘫治疗的基础，我们建议评估左迷走神经刺激（VNS）对接受抑郁症或癫痫治疗的患者胃排空和调节功能的影响。尽管已经报道了VNS对其他功能的影响，如睡眠模式或反映心迷走神经支配的心脏周期反应，但这种治疗对胃功能的影响尚不清楚。然而，很明显，迷走神经向刺激胃肌肉收缩的胆碱能内源性神经元和介导胃调节的氮内源性神经元提供外源性输入。我们的假设是，颈部VNS增加胃的适应性和加速胃排空。我们的具体目的是比较在激活左颈VNS之前和之后三个月对相同热量膳食的胃排空和胃适应性的同时评估。将使用经验证的方法测量胃的功能，同时使用SPECT相机成像和放射性标记的膳食，在静脉注射高锝酸盐后空腹期间首次测量胃容量，在摄入320千卡、30%脂肪的鸡蛋餐后第二次测量餐后胃容量调节和胃排空。这些创新的研究将记录VNS的作用，作为纠正胃运动功能障碍的潜在新治疗的基础。

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.