STRUCTURAL, MECHANICAL AND BIOLOGICAL ALTERATIONS TO THE LEFT VENTRICLE IN CHRONIC MITRAL REGURGITATION

Corporan, Daniella

Title:

STRUCTURAL, MECHANICAL AND BIOLOGICAL ALTERATIONS TO THE LEFT VENTRICLE IN CHRONIC MITRAL REGURGITATION

dc.contributor.advisor	Padala, Muralidhar
dc.contributor.author	Corporan, Daniella
dc.contributor.committeeMember	Margulies, Kenneth
dc.contributor.committeeMember	Quinn, Kyle
dc.contributor.committeeMember	Sun, Wei
dc.contributor.committeeMember	Oshinski, John
dc.contributor.department	Biomedical Engineering (Joint GT/Emory Department)
dc.date.accessioned	2022-01-14T16:03:29Z
dc.date.available	2022-01-14T16:03:29Z
dc.date.created	2020-12
dc.date.issued	2020-11-11
dc.date.submitted	December 2020
dc.date.updated	2022-01-14T16:03:30Z
dc.description.abstract	Heart failure (HF) is often the result of a direct stressor such as myocardial ischemia that injures the myocardium, or an indirect stressor such as valvular heart disease that alters the hemodynamic state in the heart and elevates wall stresses on the myocardium. In either state, the heart chambers undergo remodeling, which includes functional deterioration, structural rearrangement, and altered tissue mechanical properties. With direct stressors such as ischemia, these changes occur rapidly and over a shorter duration, whereas with indirect stressors, the remodeling is phasic with time periods of accelerated and decelerated remodeling. The timing of remodeling from the onset of the valvular lesion is vague, and whether there is a point-of-no-return beyond which removing the stressor by treating the valve lesion can be of benefit is unknown. In this thesis, I sought to investigate the chronic, left ventricular remodeling that occurs in response to mitral regurgitation, a common heart valve lesion. The challenging aspect of this lesion is that mitral regurgitation imposes a volume overload stressor on the left ventricle, which causes persistent left ventricular remodeling, without inducing symptoms of cardiac dysfunction in the patients for long periods of time. Thus, traditional markers to identify patients at risk and treat them appropriately are lacking. In this thesis, three aims were accomplished: (Aim 1) Developed an ultrasound guided, beating heart mitral valve puncture technique to induce mitral regurgitation in rats, and mapped left ventricular functional and geometric changes over 280 days of follow-up (equivalent to 20 human years). (Aim 2) Quantified the biomechanical changes in left ventricular tissue from these rats to test the hypothesis that changes in myocardial passive stiffness, parallel dysfunction, providing a potential marker to identify patients at risk. (Aim 3) Performed an unbiased transcriptomics analysis to investigate the signaling cascades involved in the left ventricular remodeling process, and identify potential biomarkers that reflect the myocardial changes. Altogether, the three aims accomplished in this thesis provide a rodent model that parallels the human patient with mitral regurgitation, and provides several new markers that can be useful in identifying patients for mitral valve intervention.
dc.description.degree	Ph.D.
dc.format.mimetype	application/pdf
dc.identifier.uri	http://hdl.handle.net/1853/65990
dc.language.iso	en_US
dc.publisher	Georgia Institute of Technology
dc.subject	Heart failure, heart valve disease, mitral valve, mitral regurgitation, cardiac remodeling, biomechanics
dc.title	STRUCTURAL, MECHANICAL AND BIOLOGICAL ALTERATIONS TO THE LEFT VENTRICLE IN CHRONIC MITRAL REGURGITATION
dc.type	Text
dc.type.genre	Dissertation
dspace.entity.type	Publication
local.contributor.advisor	Padala, Muralidhar
local.contributor.corporatename	Wallace H. Coulter Department of Biomedical Engineering
local.contributor.corporatename	College of Engineering
relation.isAdvisorOfPublication	e18f30b4-37b8-44a8-b87c-b641ab1b7b32
relation.isOrgUnitOfPublication	da59be3c-3d0a-41da-91b9-ebe2ecc83b66
relation.isOrgUnitOfPublication	7c022d60-21d5-497c-b552-95e489a06569
thesis.degree.level	Doctoral