Date of Award
1995
Embargo Period
8-1-2024
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Physiology
College
College of Graduate Studies
First Advisor
Francis G. Spinale
Abstract
Chronic pacing supraventricular tachycardia (SVT) in animals causes a dilated cardiomyopathy (DCM) similar to the clinical spectrum of congestive heart failure observed in humans. However, cellular mechanisms for the changes in left ventricular (LV) geometry with SVT-DCM remain unclear. Accordingly, LV and myocyte structure and function were examined in 7 pigs with chronic SVT (pace 240 bpm, 3 wks) and in 7 control pigs. Left ventricular end-diastolic dimension increased (5.3±0.2* vs 3.8±0.2 cm), and LV fractional shortening (14±1* vs 34±1%) and wall thickness decreased (0.49±0.01* vs 0.72+0.03 cm) with SVT (*p<0.05 compared to control). Left ventricular isolated myocyte function using computer assisted video-microscopy revealed decreased percent shortening (2.6±0.1* vs 4.9±0.1 %), velocity of shortening (31 ±1* vs 58±1 µm/s), and velocity of relengthening (32±0.8* vs 63±1.6 µm/s) with SVT. A potential mechanism for these changes in LV and myocyte function and geometry was studied by examining myocyte protein extractability, as well as isolated myocyte cytoarchitecture. The findings of this study show that with SVT, the percent extractable protein per myocyte increased by over 160% compared to controls. This increase in extractable protein is correlated to changes in LV geometry (r2 = 0.39, p = 0.016), and is also negatively correlated to myocyte contractile function (r2 = 0.318, p = 0.036). Electrophoretic analysis of myocyte extractable protein revealed an increase in protein in the 114 and 58 kD ranges, as well as in a very high molecular weight protein. Immunofluorescent staining of SVT cardiomyopathic myocytes revealed an altered pattern of cytoskeletal staining for a-tubulin and a thickened weave of β-tubulin. These results suggest that alterations· in myocyte protein extractability and cytoarchitecture may be related to the depressed contractile performance in this form of cardiomyopathic disease.
Recommended Citation
Arnim-Barker, Alice E., "Alterations in Myocyte Protein Extractability and Composition Accompany the Development of Supraventricular Tachycardia Induced Dilated Cardiomyopathy" (1995). MUSC Theses and Dissertations. 42.
https://medica-musc.researchcommons.org/theses/42
Rights
All rights reserved. Copyright is held by the author.