Gastroparesis is a common disease defined as the delayed emptying of the stomach. It is present in at least 20% of about 150 million patients with diabetes worldwide and in more than 20% of patients with functional dyspepsia that affects about 10-25% of the general population. Gastroparesis is a refractory disease with a lack of therapeutic options. While gastroparesis results from gastric motility disorders, the correlation between gastric motility (emptying of the stomach) and symptoms is poor. Recent clinical and laboratory research data in the PI's laboratory and some other investigators' laboratories have indicated that gastric electrical stimulation (GES) with short pulses (in the order of mu s) improves symptoms of nausea and vomiting, whereas gastric electrical stimulation with long pulses (in the order of ms) improves gastric motility. We, therefore, propose a novel method of GES: dual pulse GES. It uses a stimulus composed of a short pulse (or pulses) followed with a long pulse. It is hypothesized that GES with such a stimulus improves both gastric emptying (via long pulses) and symptoms of gastroparesis (via short pulses). The objective of this particular project is to study the feasibility of the proposed dual pulse method. The specific aims are to study: a) the effects of the proposed GES on fundic tone and vagal activity; b) the effects of the proposed method on gastric electrical dysrhythmia and symptoms; and c) the possible mechanisms involved with the improvement of gastric motility and symptoms with the proposed GES. Experiments will be performed in laboratory animals to study the efficacy and mechanisms of the proposed method. The optimization of the stimulation parameters will be performed in a series of experimental sessions aiming at its maximum effects on gastric motility and vagal tone assessed by an established method of spectral analysis of heart rate variability. The effect of the proposed method on gastric tone and compliance will be studied using the computerized barostat system. Symptoms associated with nausea and vomiting will be induced using vasopressin and the efficacy of the proposed method for the treatment of these symptoms will be investigated. The mechanistic hypotheses will be tested by investigating the cause-and-effect relationship and by the blockage of the hypothesized pathway. Once the efficacy of the proposed method is proven, an implantable stimulator will be developed and its long-term efficacy for the treatment of gastroparesis will be evaluated in a Phase II project.
Thesaurus Terms: electrostimulus, gastrointestinal motility /pressure, gastrointestinal sign /symptom, gastrointestinal stimulator, paralysis, stomach, technology /technique development emesis, gastric mucosa, heart rate, nausea, nitric oxide, vagotomy, vagus nerve, vasopressin dog, electrocardiography, electrode
