A study of factors determining the crossbridge kinetics, work and power of cardiac muscle analysed with sinusoidal oscillation and other techniques

Varghese, Jamie J. (2002) A study of factors determining the crossbridge kinetics, work and power of cardiac muscle analysed with sinusoidal oscillation and other techniques. PhD thesis, University of Glasgow.

Abstract

The pumping action of the heart is the driving force of the cardiovascular system that supplies all the organs and tissue with blood. The mechanical basis behind generation of sufficient pressure for the task lies in the ability of the cardiac cell to shorten. Shortening of the cardiac cells is accomplished by the interaction of two sets of proteins divided up into thick and thin filaments. Together these protein filaments form the backbone of the contractile protein matrix. The interaction between the myosin, of the thick filament, and actin, of the thin filament, also known as crossbridge cycling, is the basic process that can generate the force that is needed for the myocytes to shorten against a certain load. Regulation of the kinetics of crossbridge cycling is therefore a crucial element in myocardial contraction. This thesis focuses on studying how changes in muscle pH and [Pi], as well as variations in certain muscle protein isoforms, affect crossbridge kinetics. These studies were done using sinusoidal oscillation and other methods on rat and mouse cardiac muscle. Ischaemia of cardiac muscle is seen in a high percentage of heart failure cases. It is known that during acute ischaemic episodes, the intracellular pH within the cardiac muscle can drop as low as 6.2 and the intracellular [Pi] rises from a value of 1-3 mM to 20 mM or more. (In the present work, the intracellular space of the cardiac cells was brought under direct control by chemically skinning the rat myocardial muscle preparations to destroy the membranes.) The experiments in this thesis examined the effects on force and the frequency-dependence of dynamic stiffness over a range of pH and [Pi] when rapid, small length changes are imposed on the rat cardiac muscle trabeculae using a sinusoidal oscillation method. A primary finding of this study was that, at maximal Ca2+ activation, stiffness (at all frequencies) reduced progressively as pH was lowered, in agreement with previous studies. (Abstract shortened by ProQuest.).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Physiology.
• Colleges/Schools: College of Medical Veterinary and Life Sciences
• Supervisor's Name: Miller, Dr. D.J.
• Date of Award: 2002
• Depositing User: Enlighten Team
• Unique ID: glathesis:2002-71409
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 10 May 2019 10:49
• Last Modified: 27 May 2021 10:10
• URI: https://theses.gla.ac.uk/id/eprint/71409