Applied Physiology Thesis Defense

Henry Chionuma

School of Biological Sciences

Advisor:

Dr. Flavio Fenton

Georgia Institute of Technology

School of Physics

Open to the Community

The dispersion of action potential duration and intracellular calcium as a function of period of stimulation in explanted human hearts using optical mapping

May 14th, 2026

1:00pm

Howey Physics Building (837 State Street NW), Room C204

Committee Members:

Dr. Edward Balog, School of Biological Sciences; Georgia Institute of Technology

Dr. Elizabeth Cherry, School of Physics; Georgia Institute of Technology

Dr. Mindy Millard-Stafford, School of Biological Sciences; Georgia Institute of Technology

Dr. T. Richard Nichols, School of Biological Sciences [Professor Emeritus]; Georgia Institute of Technology

Background: Cardiovascular disease represents the leading cause of death globally, killing an estimated 17.9 million individuals each year. One of the most serious types of cardiovascular disease is cardiac arrhythmia, or ‘abnormal’ beating of the heart. Cardiac electrical wave disruption is the causative factor behind several of the most severe forms of cardiac arrhythmia, including fibrillation and tachycardia. Treatments for these arrhythmias are generally not optimal, owing in part to the fact that the mechanism of these arrhythmias are not well understood. Alternans, defined as periodic beat-to-beat oscillation in cardiac electrical activity and contraction strength, is as an important initiating event for tachyarrhythmias. Alternans can be detected electrocardiographically as T-wave alternans, a condition associated with a high mortality rates when not treated. At the cellular level, alternans can present as alternating long-short patterns of action potential duration (APD) and/or in alternating peak values of intracellular calcium ([Ca]i) concentration. Alternans in space dynamically increases dispersion of repolarization across the heart, which leads to large variations in refractory periods and conduction blocks which induce wave break and fibrillation.

Objectives: The proposed research will address the mechanisms of initiation of electrical arrhythmias driven by dynamically induced heterogeneities of refractoriness produced by alternans. Overall, the proposed project aims to increase the understanding of the mechanisms of human fibrillation, which could lead to the development of improved pharmacological or electrical interventions. Moreover, utilization of detailed optical-mapping data from human heart subjects has the potential to provide further insight into how experimental results in other mammalian hearts can be applied to understand human heart mechanisms. Similarly, insight from the proposed research can help to improve computational modeling of arrhythmias in human hearts through improved calibration and validation.

Specific aims: 1: Perform the first detailed spatiotemporal quantification of APD and [Ca]i dispersion in explanted human hearts across many physiological periods of stimulation. 2: Compare APD and [Ca]i dispersion between human and non-human hearts. 3: Quantify the effects of temperature on dispersion of APD and [Ca]i.

Research design and methods: Simultaneous optical mapping of voltage and calcium will be used. Human hearts will be obtained through an existing collaboration with the Emory University Hospital transplant program and non-human hearts will be obtained from other terminal studies. Hearts will be stimulated using established protocols where rates are increased to induce alternans followed by either initiation of fibrillation or conduction block. Computational models of human heart cells and tissue will be used for comparison with experiments.