Mechanism of Glucose-dependent insulinotropic polypeptide (GIP) on Splanchnic Venous Capacitance in Postural Tachycardia Syndrome

项目总结 体位性心动过速综合征(POTS)影响着美国约300万成年人。这些病人有一种 由于慢性晕厥前症状和站立时出现的心动过速，生活质量较差。我们的 研究表明，富含碳水化合物的膳食显著加剧了锅中的晕厥前症状， 然而，解释这一临床观察的潜在机制仍不清楚。 因此，我们小组进行了一项初步研究，以评估POTS过度的病理生理学 摄取葡萄糖后的直立性心动过速；我们观察了血液动力学和神经激素的变化 POTS患者和健康人在75GR口服葡萄糖挑战后长达2小时(餐后)发生 控制。与禁食条件相比，摄入葡萄糖加重了盆腔直立性心动过速。 患者，与健康人相比，这与直立性卒中体积的更显著减少有关 控制。关于POTS患者直立每搏量不成比例的减少，这可能， 部分原因是内脏循环中有大量的血液积聚。内脏循环是 人体内最大的血容量储存库，可储存总血容量的25%。一站起来， 有明显的血块，主要发生在内脏静脉。最后，我们的研究还 结果显示，摄取75-GR葡萄糖后30分钟，POTS患者的分泌物选择性增加 葡萄糖依赖型促胰岛素多肽(GIP)激素与健康对照组比较。这 激素在内脏循环中具有血管扩张特性。重要的是，GIP分泌的增加 在锅中摄入葡萄糖后，直立每搏量的下降与时间相关。 因此，这些发现指出GIP在增生性心脏病的病理生理学中的潜在贡献。 POTS患者餐后立位性心动过速和突触前症状。因此，总的目标是 这项建议是为了研究直立性心动过速恶化的潜在机制和 因摄取葡萄糖而出现的突触前症状。具体地说，我们将评估贡献 GIP对大鼠口服葡萄糖后及直立状态下内脏静脉电容变化的影响 盆腔炎患者。

Project summary Postural Tachycardia Syndrome (POTS) affects ~3 million adults in the United States. These patients have a poor quality of life due to chronic presyncopal symptoms and tachycardia that occur upon standing. Our research has shown that meals rich in carbohydrates significantly exacerbate presyncopal symptoms in POTS, however, the underlying mechanism that explains this clinical observation remains unknown. Accordingly, our group conducted a preliminary study to evaluate the pathophysiology of POTS’ excessive orthostatic tachycardia after glucose intake; we surveyed the hemodynamic and neurohormonal changes that occurred after a 75-gr oral glucose challenge for up to 2-hrs (postprandial period) in POTS patients and healthy controls. Compared with fasting conditions, the ingestion of glucose worsened upright tachycardia in POTS patients, which was associated with a more robust reduction in upright stroke volume compared with healthy controls. With regards to the disproportionate decrease in upright stroke volume in POTS patients, this could, in part, be explained by a significant blood pooling in the splanchnic circulation. The splanchnic circulation is the largest blood volume reservoir of the human body, storing ~25% of the total blood volume. Upon standing, there is a significant blood pooling, which occurs mostly in the splanchnic veins. Finally, our study has also shown that 30-min after the ingestion of 75-gr of glucose, POTS patients had a selectively increased secretion of the glucose-dependent insulinotropic polypeptide (GIP) hormone compared with healthy controls. This hormone has vasodilatory properties in the splanchnic circulation. Importantly, the increase in GIP secretion was time-dependently associated with a fall in upright stroke volume after glucose intake in POTS. Consequently, these findings point to the potential contribution of GIP in the pathophysiology of the increased postprandial orthostatic tachycardia and presyncopal symptoms in POTS patients. As such, the overall goal of this proposal is to investigate the mechanisms underlying the exacerbation of orthostatic tachycardia and POTS presyncopal symptoms in response to glucose ingestion. Specifically, we will evaluate the contribution of GIP on the changes in the splanchnic venous capacitance after oral glucose and during upright posture in POTS patients.