R01HL159203

Mechanism of Glucose-Dependent Insulinotropic Polypeptide (GIP) on Splanchnic Venous Capacitance in Postural Tachycardia Syndrome - 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.

Vanderbilt University Medical Center

TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Nashville, Tennessee 37203 United States

Single Zip Code

Research Project Grant (Parent R01 Clinical Trial Required) (PA-20-183)

Amendment Since initial award the total obligations have increased 312% from $806,487 to $3,322,582.