Master of Science, The Ohio State University, 1970, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1971, Graduate School

Committee: Not Provided (Other) Subjects:

Doctor of Philosophy, The Ohio State University, 2024, Biomedical Sciences

Heart disease remains the leading cause of death in the United States with heart failure specifically accounting for 13.4% of all heart disease-related deaths. In 2019, Andersson et al., utilized a multi-omics approach to evaluate participant samples from the Framingham Heart Study and showed that ankyrin-R (AnkR; encoded by ANK1) is associated with diastolic function, left ventricular remodeling and heart failure with preserved ejection fraction. Ankyrins are a family of proteins that link integral membrane proteins with the actin/β-spectrin cytoskeleton. Ankyrins-B/G have been extensively studied and identified within the heart and their dysfunction is associated with cardiac structural and electrical phenotypes. Ankyrin-R, first identified in erythrocytes, has yet to be studied in the context of cardiac function, heart failure or arrhythmias. To study AnkR in the context of the heart we isolated tissues from adult wild-type mice as well as isolated myocytes and cardiac fibroblasts and performed immunoblot and qPCR analysis for ankyrin-R protein and Ank1 mRNA expression. Concurrently, we generated an Ank1-cKO mouse to genetically delete canonical AnkR in cardiomyocytes under the αMHC promoter. We found that isolated cardiomyocytes express only the small AnkR isoform while cardiac fibroblasts express the canonical large AnkR isoform at both the protein and mRNA level. Canonical AnkR is diffusely expressed in the fibroblast membrane, cytoplasm, cytoskeleton, and soluble nuclear fractions. Further, when AnkR is knocked out of cultured fibroblasts we observed a significant decrease in contractility. When we generated an Ank1-ifKO mouse model to selectively delete AnkR in activated fibroblasts, we observed no significant increase to fibrotic deposition after AngII/PE challenge. These results are the first to show canonical AnkR expression specifically within the cardiac fibroblasts and the loss of AnkR, coordinating with Golgi machinery, reduces the amount and changes (open full item for complete abstract)

Committee: Peter Mohler (Advisor); Sara Koenig (Advisor); Mona El Refaey (Committee Member); Thomas Hund (Committee Member); Sakima Smith (Committee Member) Subjects: Biomedical Research; Cellular Biology; Molecular Biology

Doctor of Philosophy, The Ohio State University, 2023, Biomedical Engineering

Cardiovascular disease is a leading cause of death and is growing in prevalence, afflicting almost 50% of American adults and contributing to about one fifth of yearly deaths in the United States alone. The increasing incidence is driven largely by the prevalence of chronic diseases like obesity, atrial fibrillation, and heart failure, each of which are associated with additional risk factors, including development of cardiac arrhythmias. Although previous studies have identified a range of molecular players involved in disease pathogenesis via structural remodeling, ion channel dysfunction, and acquired Ca2+-handling defects, many of the current therapies for treatment of chronic heart disease are limited by cost, accessibility, efficacy, and detrimental side-effects. Recent work has identified putative roles for the TWIK-related K+ channel 1 (TREK1) in modulating cardiac excitability and pacemaking in normal physiology and disease. Additionally, upregulation of late Na+ current by Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation of the cardiac voltage-gated Na+ channel (Nav1.5) has been implicated in atrial fibrillation. However, the involvement of each of these targets in arrhythmogenesis and cardiac remodeling resulting from chronic stress, such as in diet-induced obesity or heart failure, is largely understudied. In the present studies, it was hypothesized that chronic stress conditions promote dysfunction of Na+ and K+ channels to promote electroanatomical remodeling via a combination of disrupted Ca2+ homeostasis and non-canonical signaling pathways. To test this hypothesis, a combination of experimental techniques were employed, including genetic mouse models, bioimaging, molecular biology, metabolic testing, and diverse electrophysiological techniques. These studies demonstrate that inhibition of CaMKII-dependent upregulation of the Nav1.5 late Na+ current reduces atrial arrhythmia susceptibility, inhibits fibrotic remodeling, and impro (open full item for complete abstract)

Committee: Thomas Hund (Advisor); Przemyslaw Radwanski (Committee Member); Sakima Smith (Committee Member); Isabelle Deschenes (Committee Member) Subjects: Biomedical Engineering; Biomedical Research

Doctor of Philosophy, The Ohio State University, 2023, Biomedical Engineering

Quantitative colocalization analysis is a standard method in the life sciences used for evaluating the global spatial proximity of labeled biomolecules captured by fluorescence microscopy images. It is typically performed by characterizing the pixel-wise signal overlap or intensity correlation between spectral channels. However, this approach is critically flawed due to its focus on individual pixels which limits assessment to a single spatial scale constrained by the pixel's size, thus making the analysis dependent on the achieved optical resolution and ignorant of the spatial information presented by non-overlapping signals. In this dissertation, I present an improved method for quantifying biomolecule spatial proximity using a novel application of point process analysis adapted for discrete image data, and subsequently utilize it to address two novel cardiac conundrums. The tool, called Spatial Pattern Analysis using Closest Events (SPACE), leverages the distances between signal-positive pixels to statistically characterize the spatial relationship between labeled biomolecules from fluorescence microscopy images. In chapter two, SPACE's underlying theory and its adaption for discrete image-based data is described. Additionally, I characterize its sensitivity to segmentation parameters, image resolution, and signal sample size, and demonstrate its advantages over standard colocalization methods. With this tool, I hope to provide microscopists an improved method to robustly characterize spatial relationships independent of imaging modality or achieved resolution. In chapter three, SPACE is used to elucidate a novel, microtubule-based system for the distributed synthesis of membrane proteins in cardiomyocytes. Canonically, these cells are thought to produce membrane proteins in the peri-nuclear rough endoplasmic reticulum, then leverage the secretory-protein-trafficking pathway to transport nascent proteins to their sites of membrane insertion. By labeling car (open full item for complete abstract)

Committee: Rengasayee Veeraraghavan (Advisor); Przemysław Radwański (Committee Member); Peter Craigmile (Committee Member); Seth Weinberg (Committee Member) Subjects: Biology; Biomedical Engineering; Biomedical Research; Biophysics; Biostatistics; Cellular Biology; Engineering; Scientific Imaging; Statistics

Master of Sciences, Case Western Reserve University, 2023, Clinical Research

Identifying patients with cardiac sarcoidosis (CS) at increased risk of sudden cardiac death (SCD) is challenging. To better understand this, we evaluated a retrospective cohort of 273 adults with CS. The primary endpoint was a composite of ventricular arrhythmia (VA) and cardiovascular mortality. At median follow-up of 7.9 years, the rate of the primary endpoint was 35%. On Cox proportional hazard analysis, younger age, history of VA, lower left ventricular ejection fraction (LVEF) and any presence of scar by cardiac magnetic resonance (CMR) and/or positron emission tomography (PET) were found to be independent risk factors for the primary endpoint and for VA, whereas lower LVEF was an independent risk factor for cardiovascular mortality. The optimal cutoff LVEF for the primary composite endpoint was 45% in the entire cohort and 42% in subjects without a history of VA. In conclusion, history of VA, scar by either CMR or PET and a mild reduction in LVEF are strong risk factors for SCD in CS.

Committee: Wael Jaber (Committee Chair); James Spilsbury (Advisor); Paul Cremer (Committee Member); Wilson Tang (Committee Member) Subjects: Health Care; Medicine; Scientific Imaging

Master of Science, The Ohio State University, 2022, Biomedical Engineering

Many cardiac diseases are characterized by an increased late sodium current, including heart failure, hypertrophic cardiomyopathy, and inherited long QT syndrome type 3 (LQT3). The late sodium current in LQT3 is caused by a gain-of- function mutation in the voltage-gated sodium channel Nav1.5. Despite a well- defined genetic cause of LQT3, treatment remains inconsistent due to incomplete penetrance of the mutation and variability of anti-arrhythmic efficacy. Here, we investigate the relationship between LQT3-associated mutation incomplete penetrance and variability in ion channel expression, simulating a population of 1,000 “individuals” using the O'Hara-Rudy model of the human ventricular myocyte. We first simulate healthy electrical activity (i.e., in the absence of a mutation), then in- corporate heterozygous expression for three LQT3-associated mutations (Y1795C, I1768V, and ∆KPQ), to directly compare the effects of each mutation on individuals across a diverse population. For all mutations, we find that susceptibility, defined either by the presence of an early afterdepolarization (EAD) or prolonged action potential duration (APD), primarily depends on the balance between the conductance of IKr and INa, for which individuals with a higher IKr-INa ratio are less susceptible. Further, we find distinct differences across the population, observing ii individuals susceptible to zero, one, two, or all three mutations. Individuals tend to be less susceptible with an appropriate balance of repolarizing currents, typically via increased IKs or IK1. Interestingly, the more critical repolarizing current is mutation-specific. We conclude that balance between key currents plays a significant role in mutant-specific presentation of the disease phenotype in LQT3.

Committee: Seth Weinberg (Advisor); Rengasayee Veeraraghavan (Committee Member) Subjects: Biology; Biomedical Engineering; Biomedical Research; Biophysics; Physiology

PhD, University of Cincinnati, 2022, Medicine: Systems Biology and Physiology

Ventricular tachyarrhythmias resulting in sudden cardiac death (SCD) continue to claim over 350,000 lives per year in the United States. Though several modes of treatment exist, these are palliative and do not address the root pathology of the disease. Treatment is further complicated by adverse side effects which increase mortality and decrease patient quality of life. Recent clinical trials have explored vagus nerve stimulation (VNS) as a potential therapy for patients with heart failure, though findings are mixed. VNS has yet to be explored in the context of SCD in the clinical setting. VNS has been shown to augment antioxidant capacity and may confer protection from ROS-induced cardiac remodeling, preventing SCD. However, VNS is known to decrease cardiac contractility and heart rate while prolonging ventricular repolarization, all of which could exacerbate symptoms of heart failure, increasing patient susceptibility to SCD. To better discern whether VNS is a potential candidate for patients with heart failure or SCD, insight into the molecular mechanisms of both VNS and SCD is essential. The results of this dissertation suggest that vagal signaling is cardioprotective. Using a unique guinea pig model of SCD, it was observed that animals dying from SCD experienced tachyarrhythmias resulting from prolonged and disperse ventricular repolarization, both of which are hallmarks of SCD. Further, animals that did not reach premature endpoints in the SCD group were observed to have undergone cardiac remodeling, resulting in prolonged and heterogeneous cardiac conduction. Reactive oxygen species (ROS) have been shown to play a critical role in the mechanism of SCD, leading to widespread damage, electrical instability, and cardiac electromechanical dysfunction. Using a ROS scavenger, we were able to abolish arrhythmia in ex vivo failing hearts. Importantly, studies have found that vagal stimulation confers anti-oxidant activity, suggesting a potential means of alle (open full item for complete abstract)

Committee: Roger Worrell Ph.D. (Committee Member); Karthickeyan Chella Krishnan Ph.D. (Committee Member); Margaret Powers-Fletcher Ph.D. (Committee Member); Sarah Pixley Ph.D. (Committee Member); Onur Kanisicak PhD (Committee Member) Subjects: Physiological Psychology

Doctor of Philosophy, The Ohio State University, 2022, Molecular, Cellular and Developmental Biology

Arrhythmias account for approximately 250,000 deaths in the U.S annually, with nearly half being associated with heart disease. Arrhythmogenic disorders are broken down into a variety of subcategories, with the vast majority being primarily caused by either activity changes or variants in ion channels/exchangers. Arrhythmogenic cardiomyopathy (ACM) is a unique form of heart disease that is primarily hereditary, where variants in genes encoding structural proteins are the most frequent cause of disease formation. Variants within desmosomal genes are one of the leading predisposing factors to ACM, primarily characterized by fibro-fatty infiltration in the ventricular myocardium with an increased propensity for ventricular arrhythmias. This frequently results in sudden cardiac death, even prior to the detection of any cardiac structural abnormalities. Previous work on a familial ACM variant in desmoplakin (DSP) (p.R451G) identified a post-translational degradation of DSP that stemmed from increased sensitivity to the protease calpain, a pattern identified in additional pathogenic variants. Despite these findings, incomplete penetrance within most familial ACM cases complicates understanding of the associated molecular pathways, as well as determining the external factors that contribute to disease development. While the generation of murine models have significantly contributed to the understanding of disease progression, most utilized knock-out or transgenic techniques, limiting the potential translational impact. Our group has developed one of the first mouse models of ACM derived from a human variant by introducing the murine equivalent of the R451G variant into endogenous desmoplakin (DspR451G/+). Mice homozygous for this variant displayed embryonic lethality. While DspR451G/+ mice were viable with reduced expression of DSP, no presentable arrhythmogenic phenotype was identified at baseline. Following acute stress through catecholaminergic challenge, DspR451G/+ mic (open full item for complete abstract)

Committee: Peter Mohler (Advisor); Maegen Borzok (Committee Member); Federica Accornero (Committee Member); Thomas Hund (Committee Member); Brandon Biesiadecki (Committee Member) Subjects: Cellular Biology; Physiology

Doctor of Philosophy, Case Western Reserve University, 2021, Biomedical Engineering

Atrial fibrillation (AF) is a cardiac arrhythmia that originates in the left atrium (LA). Radiofrequency ablation (RFA) is one of the primary treatments of AF, of which the outcome greatly relies on good quality lesions, i.e., transmural lesions. However, current indirect RFA monitoring information, i.e., contact force, impedance, and temperature, has not been able to eliminate non-transmural lesions, which contributes to the high AF recurrence. Although many techniques have been investigated to provide real-time lesion quality monitoring to improve procedure outcomes, no technique has met the clinical requirements yet. Polarization-sensitive optical coherence tomography (PSOCT) is a non-invasive high-resolution imaging technique that can be implemented as a miniature endoscope to provide real-time tissue birefringence contrast in addition to structural images to evaluate the thermal damage caused by RFA. Our previous work has demonstrated that PSOCT can identify RFA lesions after lesion creation. In this work, we focus on developing the technology to enable real-time RFA lesion quality monitoring in a LA RFA procedure. First, an integrated PSOCT-RFA catheter was prototyped by modifying a commercial RFA catheter to including a forward-viewing PSOCT probe. The integrated catheter was proved able to provide real-time catheter-tissue orientation and lesion quality monitoring with benchtop experiments. Then, the guidance function of the integrated PSOCT-RFA catheter was demonstrated in the right atrium of a living swine with percutaneous access under the guidance of single-plane fluoroscopy. Results show that the integrated PSOCT-RFA catheter could provide real-time information to guide perpendicular catheter-tissue orientation, monitor lesion transmurality, and detect over-treatment. Finally, a customized integrated PSOCT-RFA catheter was prototyped to enable the LA RFA procedure in a living swine. In addition, we developed an algorithm for lesion transmurality qua (open full item for complete abstract)

Committee: Andrew Rollins (Advisor); Xin Yu (Committee Chair); Laurita Kenneth (Committee Member); Snyder Christopher (Committee Member) Subjects: Biomedical Engineering; Health Care; Medical Imaging

Master of Arts, Miami University, 2021, Psychology

Adaptive emotion regulation (ER) holds a critical role in promoting mental and physical health; thus, understanding the psychological and physiological processes that contribute to ER is important. Both perceived ER, and heart rate variability (HRV), a purported psychophysiological index of ER capacity, have been shown to relate to psychopathology and well-being. Further, meta-analytic work suggests that greater HRV is associated with more adaptive ER. However, little research has examined the longitudinal relation between HRV and perceived ER. Thus, the current study tested whether 1) increases in HRV preceded and predicted improvements in perceived ER, and 2) improvements in perceived ER preceded and predicted increases in HRV. It was hypothesized that a significant bidirectional relation would be found between HRV and perceived ER across time. Participants (N = 129) consisted of mothers assessed annually for three years. Results revealed that Respiratory Sinus Arrhythmia (RSA, an index of HRV) and perceived ER were not cross-sectionally associated at any timepoint, nor did RSA or perceived ER precede and predict the other longitudinally. The present study suggests the relation between HRV and perceived ER may be less robust than previously understood. Alternatively, methodological limitations or unidentified moderators (e.g., external stressors) may have attenuated findings.

Committee: Elise Clerkin PhD (Committee Chair); Joshua Magee PhD (Committee Member); Elizabeth Kiel PhD (Committee Member) Subjects: Psychology

PhD, University of Cincinnati, 2020, Medicine: Molecular, Cellular and Biochemical Pharmacology

Cardiac Myosin Binding Protein-C (cMyBP-C) is highly phosphorylated under basal conditions. However, its phosphorylation level is decreased in patients with heart failure. The necessity of cMyBP-C phosphorylation for proper contractile function is established, but the physiological and pathological consequences of decreased cMyBP-C phosphorylation in the heart are not clear. Herein, we report that cMyBP-C dephosphorylation is sufficient to reduce contractile parameters and calcium kinetics associated with a prolonged decay time of the calcium transient and increased diastolic calcium levels. This finding is based on the use of intact adult cardiomyocytes from mouse models expressing phospho-ablated (AAA) and phospho-mimetic (DDD) cMyBP-C, as well as controls. Isoproterenol stimulation reversed the depressive contractile and Ca-kinetic parameters. In addition, caffeine-induced calcium release indicated no difference between AAA/DDD and controls in sarcoplasmic-reticulum calcium content. On the other hand, sodium-calcium exchanger function and phosphorylation levels of calcium handling proteins were significantly decreased in AAA hearts compared to controls. Stress conditions resulted in increases in both spontaneous after-contractions in AAA cardiomyocytes and the incidence of arrhythmias in vivo, compared to controls. Treatment with omecamtiv mecarbil, a positive cardiac inotropic drug, rescued contractile deficit in AAA cardiomyocytes, but not calcium handling abnormalities. Taken together, these findings indicate a cascade effect whereby dephosphorylation of cMyBP-C causes contractile defects, which then lead to calcium cycling abnormalities, finally resulting in after-contractions and increased incidence of cardiac arrhythmias under stress conditions. As an essential lynchpin in this cascade of pathophysiological events, the present study has elucidated the link between impairment in sarcomere contractility and abnormal Ca2+ cycling, thus presenting (open full item for complete abstract)

Committee: Sakthivel Sadayappan Ph.D. (Committee Chair); Terry Kirley Ph.D. (Committee Member); Evangelia Kranias Ph.D. (Committee Member); John Lorenz Ph.D. (Committee Member); Douglas Millay Ph.D. (Committee Member) Subjects: Animal Sciences; Biology

Doctor of Philosophy, The Ohio State University, 2020, Biomedical Sciences

Atrial fibrillation (AF), a fast and chaotic atrial rhythm, is the most prevalent sustained arrhythmia and is of particular concern in healthcare. Treatment of AF itself has proven difficult since the underlying mechanism is still debated. One proposed mechanism of AF maintenance is localized micro-anatomic reentries within the 3D atrial wall, called reentrant AF drivers. Targeted ablation of these AF drivers can significantly improve AF treatment success. However, identification and treatment of AF drivers in clinical settings remains hindered by the limitations of standard surface-only electrode mapping. The work described herein, represents a truly translational effort to leverage the strengths of integrated high-resolution 3D functional and structural mapping to uncover the mechanisms of AF to improve treatment; from novel in-vivo imaging studies of a clinically-relevant large animal model, to validating and improving clinical tools in the ex-vivo intact human heart, to directly applying ex-vivo findings of AF drivers to treatment of patients with persistent AF. We first validate that cardiac electrophysiology and AF mechanisms seen by near-infrared optical mapping ex-vivo accurately recapitulate in-vivo phenomena. We accomplish this by mapping the same canine atria, for the first time, with near-infrared optical mapping and multi-electrode mapping both in-vivo and ex-vivo. We then sought to validate and improve AF driver identification by clinical multi-electrode mapping. We found multi-electrode mapping had a high sensitivity to reentrant AF driver locations, but may not accurately depict the reentrant pattern of the driver and was prone to false-positive detections. However, analysis of intramural fibrotic tissue in driver regions by contrast-enhanced MRI could distinguish false from true positive drivers. We next tested the hypothesis that transiently modulating atrial refractoriness can organize unstable conduction and unmask hidden reentrant AF drivers fo (open full item for complete abstract)

Committee: Vadim Fedorov PhD (Advisor); Brandon Biesiadecki PhD (Committee Member); Jill Rafael-Fortney PhD (Committee Member); Sandor Gyorke PhD (Committee Member); Orlando Simonetti PhD (Committee Member) Subjects: Biomedical Research; Medicine; Physiology

Master of Science, The Ohio State University, 2019, Genetic Counseling

Background: Sudden arrhythmia death syndrome (SADS) conditions, including ion channelopathies and cardiomyopathies, are genetic conditions that cause sudden cardiac death (SCD). Genetic testing in SADS conditions is imperative as there is a significant amount of phenotypic variability in these conditions. Current management options, including medications and implantable cardioverter defibrillators (ICDs), do not effectively treat all SADS conditions and may even have significant negative psychosocial implications. Genetic treatment technologies, such as gene therapy and gene editing, may be utilized in the future as a treatment option in the care of individuals with SADS conditions. No studies have been done to assess the SADS community's familiarity with and likelihood to utilize genetic treatment technologies as a treatment option. Methods: Members of the SADS Foundation email directory with a personal or family history of a SADS condition were available to participate in a cross-sectional online survey. The survey focused on the familiarity of and likelihood to utilize ICDs, gene therapy, medications, and gene editing. To explore the factors that influence the likelihood of utilizing the various treatment options, state and trait anxiety, genetic knowledge, and perceived risks were measured. Results: A total of 109 completed surveys were obtained from individuals with a personal diagnosis of a SADS condition and individuals with a family member with a SADS condition. A majority of participants reported being familiar with ICDs (n=102, 93.6%) and medications (n=97, 89%), but unfamiliar with gene therapy (n=81, 74.3%) and gene editing (n=89, 81.7%) as a treatment option for SADS conditions. A majority of individuals reported being likely to utilize ICDs (n=86, 78.9%), medications (n=99, 90.8%), and gene editing (n=65, 59.6%), while fewer were likely to utilize gene therapy (n=55, 50.5%). Participants who were unfamiliar with gene therapy were unlike (open full item for complete abstract)

Committee: Jamie Jackson (Advisor); Sara Fitzgerald-Butt (Committee Member); Elizabeth Jordan (Committee Member) Subjects: Genetics; Health Care

Master of Science, The Ohio State University, 2018, Biomedical Engineering

The mechanisms underlying CaMKII-induced arrhythmias in ischemia/reperfusion (I/R) are not fully understood. My thesis research tested the hypothesis that CaMKII increases late Na+ current (INa,L) via phosphorylation of Nav1.5 at Ser571 during I/R, thereby increasing arrhythmia susceptibility. Action potential duration (APD) and arrhythmic events were measured by optical mapping in isolated, Langendorff-perfused mouse hearts during global ischemia and reperfusion. To provide mechanistic information on the role of CaMKII-dependent phosphorylation of Nav1.5 in arrhythmia, Scn5a knockin mice expressing Nav1.5 with constitutive phosphorylation [Nav1.5-Ser571Glut (S571E)] or ablation [Nav1.5-Ser571Ala (S571A)] of the CaMKII site at Ser571 were used. Wildtype (WT) hearts showed a significant increase in the levels of phosphorylated CaMKII and Nav1.5 at Ser 571 [(p-Nav1.5(S571)] following 15 minutes of ischemia (just before onset of reperfusion). Optical mapping studies revealed a significant prolongation of APD, increased recovery time, and increased arrhythmia susceptibility during I/R in S571E and WT mice compared to S571A mice. Pretreatment of hearts with Na+ channel blocker mexiletine (10 uM) increased recovery of APD and reduced arrhythmia susceptibility in WT mice during I/R. We conclude that CaMKII-dependent phosphorylation of Nav1.5 is a crucial driver for increased INa,L, arrhythmia susceptibility during I/R. Selective targeting of this CaMKII-dependent pathway may have therapeutic potential for reducing arrhythmias in the setting of I/R.

Committee: Tom Hund Dr. (Advisor); Sakima Smith Dr. (Committee Member) Subjects: Biomedical Engineering

Master of Sciences, Case Western Reserve University, 2018, Clinical Research

Periodic limb movements during sleep (PLMS) are associated with sympathetic nervous system activation and may be associated with nonsustained ventricular tachycardia (NSVT). PLMS and NSVT temporal associations were assessed via a bidirectional case-crossover design of 41 participants with polysomnography-identified NSVT events during sleep. Sleep time was divided into ~30-minute segments. For each NSVT event (n=96), a preceding 30-second hazard period and three 30-second control periods were selected within the same 30-minute segment and evaluated for PLMS, respiratory events, minimum saturation, and arousals. Conditional logistic regression determined odds ratios and 95% confidence intervals; covariates included arousals, minimum saturation, and respiratory events. PLMS were not significantly associated with NSVT (OR=1.5, 95%CI 0.7-3.3). PLMS with arousal were associated with NSVT (OR=3.5, 95%CI 1.4-8.8). Arousals were associated with NSVT in unadjusted analyses (OR=2.1, 95%CI 1.2-3.8), but not after exclusion of PLMS-related arousals (OR=1.6, 95%CI 0.8-12.5). PLMS-related arousals may be physiologically important ventricular arrhythmia triggers.

Committee: Reena Mehra (Committee Chair); Kingman Strohl (Committee Member); Kristie Ross (Committee Member) Subjects: Health Sciences

Doctor of Philosophy, The Ohio State University, 1979, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1977, Graduate School

Committee: Not Provided (Other) Subjects: Engineering

Doctor of Philosophy, The Ohio State University, 1975, Graduate School

Committee: Not Provided (Other) Subjects: Health Sciences

Doctor of Philosophy, The Ohio State University, 1974, Graduate School

Committee: Not Provided (Other) Subjects: Health Sciences