Year of Publication

2018

Degree Name

Master of Science in Biomedical Engineering

Document Type

Master's Thesis

College

Engineering

Department

Biomedical Engineering

First Advisor

Dr. Abhijit Patwardhan

Abstract

Cardiovascular complications associated with elevated levels of glucose in the blood (Hyperglycemia, HG) is a growing health concern. HG is known to be associated with a variety of cardiovascular morbidities including higher incidence of electrical disturbances. Although effects of chronic HG have been widely investigated, electrophysiological effects of acute hyperglycemia are relatively less known. Further, hyperglycemic effects on adrenergic response is not widely investigated. We used excised ventricular tissues from mice to record trans-membrane potentials during a variety of pacing protocols to investigate cellular/tissue level electrophysiological effects of acute hyperglycemia and adrenergic stimulation (1µM Isoproterenol, a β-adrenergic agonist). A custom program was used to compute action potential durations (APD), maximal rates of depolarization (dv/dtmax), and action potential amplitudes (APA) from the recorded trans-membrane potentials. From these computed measures, electrical restitution and alternans threshold were quantified. Restitution was quantified using the Standard Protocol (SP; basic cycle length BCL= 200ms), Dynamic Protocol (DP; 200-40ms or until blockade) and a novel diastolic interval (DI) control protocol with Sinusoidal Changes in DI. Results from 6 mice show that acute hyperglycemia causes prolongation of the APD. Effects of adrenergic stimulation during acute hyperglycemia were partially blunted compared with non-hyperglycemic state, i.e. hyperglycemia minimized the decrease in APD that was produced by adrenergic stimulation. Similar, but less consistent (across animals) effects were seen in other electrophysiological parameters such as alternans threshold. These results show that acute hyperglycemia may itself alter cellular level electrophysiology of myocytes and importantly, modify adrenergic response. These results suggest that in addition to long term re-modeling that occurs in diabetes, acute changes in glucose levels also affect electrical function and further may contribute to systemically observed changes in diabetes by blunting adrenergic response. Therefore, further investigation into the electrophysiological effects of acute changes in glucose levels are warranted.

Digital Object Identifier (DOI)

https://doi.org/10.13023/ETD.2018.051

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