Date of Award

Fall 2005

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Mechanical Engineering - (Ph.D.)

Department

Mechanical Engineering

First Advisor

N. Aubry

Second Advisor

S. F. Vatner

Third Advisor

E. S. Geskin

Fourth Advisor

William Corson Hunter

Fifth Advisor

I. Joga Rao

Sixth Advisor

Pushpendra Singh

Abstract

It is well established that the aging heart exhibits left ventricular (LV) diastolic dysfunction and changes in mechanical properties, which have been attributed to alterations in the extracellular matrix (ECM). The investigators tested the hypothesis that the mechanical properties of cardiac myocytes significantly change with aging thereby contributing to the LV diastolic dysfunction. Cellular mechanical properties were determined by indenting cells with an atomic force microscope (AFM). The indentation results were interpreted by modeling the AFM probe as a blunted cone and determining an apparent elastic modulus (B) with classical infinitesimal strain theory (CIST). A commercially available finite element software package (ABAQUS) was used to further explore nano-indentation and the use of CIST to determine material properties. The cellular mechanical property changes, measured in young and old cardiac cells isolated from rats, showed a significant increase (p<0.05) in B with aging. Cellular protein changes were assessed by immunoblot (western) analyses in order to establish if material property changes also occurred with aging. The western results indicate significant (p<0.05) changes in cytoskeletal and mechanotransduction proteins with aging. These data support the concept that the mechanism mediating LV diastolic dysfunction in the aging hearts resides, in part, at the level of the myocyte. The effect of these aging induced cellular changes on global cardiac function will be further explored with instrumentation developed for implantation in an in vivo animal model.

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