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Title: A study of factors determining the crossbridge kinetics, work and power of cardiac muscle analysed with sinusoidal oscillation and other techniques
Author: Varghese, Jamie J.
ISNI:       0000 0001 3542 8021
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2002
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Myocardium