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dc.contributor.authorGreer-Short, Amara D.en_US
dc.date.accessioned2016-04-30T08:00:20Z
dc.date.available2016-04-30T08:00:20Z
dc.date.issued2016-04-29en_US
dc.identifier.othervt_gsexam:7215en_US
dc.identifier.urihttp://hdl.handle.net/10919/70880
dc.description.abstractThe temporal nature of ectopic activity is important to elucidating the mechanisms that can lead to arrhythmogenesis. However, challenges remain in distinguishing between ectopic and non-ectopic beats. A new methodology was developed and validated to distinguish between beat types. Rapid pacing was used to induce both ectopic and non-ectopic beats. Using an electrocardiogram, the post-pacing recovery beat cycle length (RCL) and QRS were normalized to pre-paced R-R and QRS intervals and analyzed using a K-means clustering algorithm. Control hearts only produced beats with RCL ratios that increased with rapid pacing, suggestive of non-ectopic activity. Hypercalcemia and digoxin both produced significantly earlier beats with wider QRS durations, suggestive of ectopic activity. Increasing pacing further shortened RCL during digoxin + hypothermia, a mechanistic identifier of ectopic activity. When tested against a previously validated analysis, our algorithm performed well. Therefore, this electrocardiogram based algorithm distinguishes between ectopic and non-ectopic beats. In a prospective study, tetrodotoxin increased RCL ratio without changing the QRS duration of excited beats, suggesting neuronal sodium channels play an important role in ectopic beat timing. The next goal was to create a consistent model of ectopic activity. Both sympathetic and parasympathetic stimulation independently potentiate arrhythmogenesis, and we investigated the effects of independent and simultaneous stimulation on the temporal nature of arrhythmogenesis. Isoproterenol (ISO), a sympathetic agonist, transiently produced ectopic activity and increased heart rate. Acetylcholine (ACh), a parasympathetic agonist, did not significantly produce ectopic activity but did slow heart rate. ACh added after ISO also transiently produced ectopic activity, while heart rate remained slowed. Importantly, ISO following ACh persistently increased ectopic activity and heart rate. Therefore, ISO following ACh is an ideal model for creating sustained ectopic activity. Mature animals exhibited sustained arrhythmogenesis while young animals did not. When ACh was removed and then followed by ISO, ectopic activity and heart rate transiently increased, similar to ISO alone. This suggests that maintained ACh perfusion can sustain ISO sensitivity, in contrast to ISO perfusion alone. The data in this dissertation provide an insight into the mechanisms that affect the ectopic beat timing and arrhythmia propensity.en_US
dc.format.mediumETDen_US
dc.publisherVirginia Techen_US
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectectopicen_US
dc.subjectarrhythmogenesisen_US
dc.subjectelectrophysiologyen_US
dc.subjecttetrodotoxinen_US
dc.subjectacetylcholineen_US
dc.subjectisoproterenolen_US
dc.titleThe Temporal Nature of Ectopic Activity in Guinea Pig Ventricular Myocardiumen_US
dc.typeDissertationen_US
dc.contributor.departmentBiomedical Engineeringen_US
dc.description.degreePh. D.en_US
thesis.degree.namePh. D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineBiomedical Engineeringen_US
dc.contributor.committeechairPoelzing, Stevenen_US
dc.contributor.committeememberGabler, Hampton C.en_US
dc.contributor.committeememberHuckle, William Ruperten_US
dc.contributor.committeememberAlmahameed, Soufianen_US
dc.contributor.committeememberGourdie, Roberten_US


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