The Role of Oxygen Delivery in Mediating Voluntary Excitation-Contraction Coupling: An Oxygen Conforming Response of Muscle Contraction Force

Abstract

As we exercise long and/or hard enough, exercise related metabolites impair the ability of muscle excitation to cause muscle contraction – reflecting an impairment of excitation-contraction coupling. Like metabolite mediated impairment, a decrease in oxygen delivery can also impair excitation-contraction coupling. During electrically stimulated exercise (i.e., maintained muscle excitation), when muscle oxygen delivery decreases, muscle contraction force decreases to protect the metabolic environment (i.e., muscle metabolites). What’s interesting about this phenomenon, and what distinguishes it from metabolite mediated impairment of excitation-contraction coupling, is that when normal oxygen delivery is restored, muscle contraction force per excitation is rapidly reversed back to normal levels. Because muscle contraction force conforms to oxygen delivery, we have termed this phenomenon the oxygen conforming response. To date this oxygen conforming response has only been demonstrated under electrically stimulated exercise designs where key characteristics of voluntary muscle recruitment are violated. Therefore, the general purpose of this dissertation was to assess whether the key characteristics of this oxygen conforming response exist during voluntary exercise in humans. In thesis study 1, we developed a model enabling forearm muscle excitation targeted exercise and then we used brachial artery compression to reversibly reduce forearm blood flow by ~50%. By doing so, we demonstrated that muscle contraction force rapidly follows changes in oxygen delivery at or above 75% critical force exercise intensities – demonstrating the existence and exercise intensity dependence of the oxygen conforming response. Next, thesis study 2 used a remote skeletal metaboreflex to reversibly increase forearm blood flow. By doing so we demonstrated that an increase in oxygen delivery above ‘normal’ can reversibly improve excitation-contraction coupling. Finally, thesis study 3 used arm position to alter forearm perfusion pressure during maximal effort exercise. By doing so we demonstrated that oxygen conforming can (a) modify the progressive decline of muscle contraction force and (b) rapidly shift the stabilized muscle contraction critical force. Combined, these key findings highlight the underappreciated cellular disturbance independent role oxygen delivery can play in modifying excitation-contraction coupling. Critically, this dissertation has only begun to shed light on this oxygen conforming phenomenon that – like skeletal muscle fatigue – deserves continued attention.