The research conducted in our laboratory has a focus on determining mechanisms of arrhythmic activity in the heart and stability of circulation. Ongoing studies investigate cardiovascular-brain interactions during rhythmic auditory sensory stimulation, approaches to improve specificity of use of T wave alternans to predict risk of adverse cardiac events, and how glucose alters cardiac electrical function in terms of electrical restitution. We use mathematical modeling, and signal analytic and control systems approaches in addition to empirical data towards meeting these goals. We conduct studies using human subjects to study cardio-respiratory and cardiovascular autonomic- brain interaction in stability and control of circulation and for cardiovascular morbidity, and use animals and mathematical models to study cardiac electrophysiology at cellular, tissue and organ level. We also use clinical grade ECGs to test the predictions made by using mathematical models and experimental data obtained from animal studies. The tools that are routinely used in the laboratory include developing and implementing signal and image processing algorithms, computerized control of devices and instruments, high speed fluorescence imaging, and design and fabrication of associated hardware. Our laboratory has developed signal and image analyses programs which are routinely used by other laboratories for processing of ECGs from telemetry units, detection and quantification of hypoxic events in neonates, real time pacing control, and automatic enumeration of parasite loads for investigation of infectious diseases.

 Current Projects

Auditory Entrainment of Respiration and RR Intervals:

Dibyajyoti Biswal (PhD student) is working on this project which is the part of a larger project. In this project, she recruits subjects who listen to songs using circumaural headphones. The songs which are selected by her are based on slow and fast rhythms. Subjects also listen to a song selected by them which ‘moves’ them. Then, she phases randomizes that song in order to minimize the cognitive part.  She records the subjects’ ECG, Respiration and Blood pressure signals during the study. From these data, she computes respiratory and heart rates, and heart rate and respiratory spectra and cross spectra. The goal is to understand modification of autonomic tone when auditory sensory stimulation is present, and to find entrainment of respiration and RR intervals.

Cerebro-cardiac and cerebro-respiratory interactions during rhythmic auditory sensory stimulation:

Mohammad Javad Mollakazemi investigates the cerebro-cardiac and cerebro-respiratory interactions that are manifest as low frequency oscillations in the electrical activity of the brain and those that are synchronous with the rhythms in the heart and respiratory cycles while subjects listen to music. For studying the effects of cognition and memory recall, he uses different types of auditory stimuli such as subjects’ favorite song and those that have a similar sensory structure but are unlikely to evoke a cognitive response. He analyzes rhythms in the electro encephalograms (EEGs) and co-variability between the EEGs and cardiac and respiratory rhythms. The goal of this study is to better understand how auditory stimuli can affect cardiovascular function

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Adrenergic Stimulation in Acute Hyperglycemia: Effects on Cellular and Tissue Level Murine Cardiac Electrophysiology:

Sridevi Thyagarajan investigates cardiovascular complications associated with elevated levels of glucose in the blood (Hyperglycemia, HG) which 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. She uses 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 is 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 are quantified. Restitution is 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.

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Exploration of the Possible Link Between Depolarization and Repolarization Alternans:

Sahar Alaei is exploring a possible link between depolarization and repolarization alternans in the ECG signal. T-Wave Alternan (TWA) in the ECG signal has been widely investigated as a potential predictor of ventricular arrhythmia. However, large clinical trials show that TWA has a poor positive predictive value in opposition to a strong negative predictive value. Therefore, exploration of approaches to improve positive predictive value of TWA is likely to be valuable. Studies by several investigators suggest that concordant versus discordant alternans subgrouping may affect arrhythmic potential. Also, previous studies from our laboratory indicate that alternans of the R wave height may contain information that would be related to concordant or discordant alternans. In consideration of these studies, her overall objective in this project is to explore the use of R Wave Amplitude Alternan (RWAA) as a complement to the TWA in order to improve positive predictive value of arrhythmia risk.