Cardiac Rhythm Laboratory

A fatal cardiovascular event such as sudden cardiac death (SCD) kills hundreds of thousands of people each year. In SCD, the heart stops to beat abruptly because of chaotic electrical activity and leaves the patient with a time window of only a few minutes to get therapy before it becomes fatal. It is because such a large portion of the population is affected and the urgency at which they need to be treated that the researchers in our lab are motivated to study cardiac rhythms.

Dr. Patwardhan's Greeting

Rhythm dynamics and arrhythmias are two of the main areas that are extensively studied in our lab. Other past and present research in the Cardiac Rhythm Laboratory includes, but is not limited to, exploration of the role of cardiorespiratory dynamic interaction and neural regulatory mechanisms that disturb stability of circulation, signal analysis of various neonatal biological rhythms, determination of the function of autonomic control of the short-term blood pressure regulation in diabetic patients with and without neuropathy, mathematical modelling of the heart, 3D reconstruction of heart geometry and production of micro-scale photon actuated cardiac scaffolding.

The dynamics of cardiovascular function are studied by integrated systems level investigation of cardiac function and dysfunction. These experiments are conducted to provide better understanding of the regulatory mechanisms in cardiovascular control and to develop tools for diagnosis of dysfunction. For the systems level studies, we investigate the dynamics of control systems that maintain circulatory stability. Tools such as linear and non-linear systems and signal analysis are used in these investigations.

Dr. Patwardhan's Greeting

Focus is also directed towards developing therapies to remedy malignant arrhythmias. These therapies arise from cellular level investigation of cardiac electrophysiology. Our focus is on determining the mechanisms that lead to a disturbance of the rhythmic electrical activity of the heart to degenerate into lethal ventricular arrhythmia that leads to sudden cardiac death. We are particularly interested in exploring fundamental cellular level mechanisms that will ultimately lead to development of better predictors of adverse electrophysiological events and in development of better medical devices such as defibrillators and pacemakers. In these studies, mathematical modeling and experiments are conducted to study dynamic changes in electrical function of heart from events that occur at cellular level to those that are observed in the ECG.

The Cardiac Rhythm Laboratory is well equipped to allow researchers to perform clinically relevant investigations with some of the most modern tools available.

Anuj Agarwal

Hometown: Indore, India

Degree Program: Ph.D.

Year: 4th Year

Anuj's Project

My research is focused on studying the mechanisms that lead to a disturbance of the rhythmic electrical activity of the heart to degenerate into lethal ventricular arrhythmia followed by sudden cardiac death.

The facilities in our lab enable us to record electrical activity from the surface of a heart either using microelectrode recordings to record from a piece of the tissue of the heart or by optical mapping via fluorescent dyes to record from the entire surface of the heart. We then do signal analysis using advanced time-frequency distribution methods to study the spatio-temporal organization of the electrical activity within the heart to elucidate the mechanisms of ventricular arrhythmia. All this research is implicitly focused towards development of better medical devices such as defibrillators and pacemakers.

Linyuan Jing

Hometown: Qingdao, China

Degree Program: Ph.D.

Year: 2nd Year

Linyuan's Project

My research is in the area of electrical stability of the heart. Through observing electrical activities using microelectrode recording in cardiac tissue preps or optical mapping of the entire heart, explore the mechanisms related to restitution hypothesis with the existence memory that induce arrhythmias such as conduction block, re-entrant activity or fibrillation.

One of the projects done so far is testing the effect of L-type calcium current in the hysteresis, i.e. memory in restitution by comparing the differences of the hysteresis loops under different levels of L-type calcium current. It turned out that calcium reduced memory consistently in tissue experiments and in computer simulation, suggesting that calcium plays an important role in affecting the memory and thus, the electrical stability of the heart. A paper has been published in Pacing and Clinical Electrophysiology based on the study.

Another project is to explore the existence of heterogeneous memory in restitution in different types of cardiac myocytes of the heart. The results showed significant differences between endocardial and epicardial tissues in both ventricles. As memory has been hypothesized to increase stability, thus, our results suggest that in the endocardium a decrease in stability predicted by increased slope may be offset by an increase in memory. Memory may provide an explanation for the inconsistent experimental observations of alternans with the stability predicted by heterogeneous restitution. A manuscript based on the results of this study has been accepted for publication by Journal of Electrocardiology.

Following the observations of the study on heterogeneous memory, I am further pursuing the effect of hysteresis in restitution on stability of activation in the entire heart using optical mapping. Transient changes of electrical conduction on the heart surface when a disturbance of cycle length is induced are going to be used as an index of stability to test the differences before and after manipulation of restitution characteristics. In addition to these experiments, a new mathematical model related to restitution characteristics, which becomes a non-linear relationship after memory is introduced, is being developed in order to find the role of memory in stability of activation. The expectation is that such basic research will lead to better understanding of the mechanisms that affect the electrical stability and further build a theory that is able to make predictions on the occurrence of arrhythmias, and therefore, prevent sudden cardiac death.

Sonam Chourasia

Hometown: Indore, India

Degree Program: M.S.

Year: 2nd Year

Sonam's Project

Sudden cardiac arrest (SCA) is a leading cause of death in the United States and the recent statistics show that it accounts for 325,000 deaths every year. A major cause of death due to sudden cardiac arrest is ventricular fibrillation (VF). Beat to beat changes in cardiac cell excitability and refractoriness such as variation in repolarization phase also known as action potential duration (APD) and depolarization phase known as action potential amplitude (APA) is often correlated with and is thought to cause electrical instability, an important precursor to VF. The variation in APD and APA for successive beats is termed as alternans. Several studies have shown that alternans of APD play an important role in prediction of ventricular fibrillation. Although alternans of APD are widely investigated, there are only few studies on APA alternans. Further, the relationship between the two alternans is also largely unknown. The purpose of our study, therefore, is to examine the relationship between the APD and APA alternans and to determine the potential mechanisms of causing these alternans.

Siqi Wang

Hometown: Foshan, China

Degree Program: Ph.D.

Year: 2nd Year

Siqi's Project

The area I am investigating is the function of autonomic control of the short-term blood pressure regulation in diabetic patients with or without neuropathy which is a serious complication of diabetes. We measure ECG, noninvasive continuous blood pressure, bio-impedance of thorax, abdomen, upper leg and lower leg, skin perfusion of palm and forearm, respiration activity and hormone levels in blood. These measures were taken on health control subjects and diabetic patients with or without neuropathy during supine rest and 70-degree head up tilt. Heart rate and systolic blood pressure variability and baroreflex sensitivity were analyzed by using the tools of spectral power, baroreflex sequences and coherence. The goals of the study was to investigate the effect of diabetes on control of the heart, peripheral vascular function and the baroreflex, and to test noninvasive indices of sympathetic and parasympathetic activities and baroreflex function for their capability to identify diabetic neuropathy.

Hunter Gerlach

Hometown: Louisville, KY

Degree Program: Ph.D.

Year: 1st Year

Hunter's Project

Malignant cardiac arrhythmias require advanced therapies in order to be remedied. Even when function is returned to its normal level, the damage sustained to the heart could have been significant enough to cause permanent damage. I am working on a new technology that will likely allow for electrical activity in the heart to be completely restored. This micro-scale electrical scaffolding will hopefully allow patients that have impaired function to one day regain full use of cardiac function in one capacity or another. I am using CAD/FEM development tools such as SolidWorks® and SolidWorks Simulation®.

I am also working on collaborative projects with investigators in the Univeristy of Kentucky Medical Center and the Department of Physiology. One of these projects is looking into the relationship between the sympathetic nervous system and cardiac function in humans. The research that is done with the investigator from the Department of Physiology will be analyzing telemetric data from rats in hopes of better understanding the role of the circadian rhythm and arrhythmias.