Computational Modelling of Cardiorespiratory Autoregulation to Investigate the Interactions between Respiratory Sinus Arrhythmia, Exercise, and Heart Failure

: (Alternative Format Thesis)

Abstract

Recent trials of a novel neuronal pacemaker suggested that the reinstatement of respiratory sinus arrhythmia (RSA), which is heart rate variability by respiration, could enhance cardiac function in heart failure; however, the improvement mechanisms of RSA on cardiac function are still disputed. In this thesis, a novel lumped parameter model of the cardiorespiratory and metabolic systems with autonomic control was developed to study the detailed physiological effects of RSA on cardiac function and the potential mechanisms by which it improves cardiac function in pathophysiology.

For healthy physiology, cardiac function was simulated by disentangling a sensory neural signal from the lungs, responsive to lung inflation, under rest and aerobic exercise. Subsequently, the improvement in cardiac function was also measured while maintaining the identical mean heart rate, therefore isolating the effect of RSA without the confounding effect of a raised heart rate. It was shown that cardiorespiratory coupling enhanced cardiac performance at low exercise intensity, while cardiac function was mainly improved by increasing mean heart rate at high exercise intensity.

The model was then fitted to clinical heart failure data taken from the literature to investigate the benefits of the reinstatement of RSA for this condition. The magnitude of RSA was modulated by controlling vagal activity. The vagal nervous system slows heart rate, and in a healthy heart, its activity increases during expiration and decreases during inspiration, thus producing RSA. The performance of RSA-modulated pacing by vagal enhancement was compared with atrioventricular delay (AVD) optimisation in monotonic heart rate. The AVD optimisation recovers a preferable pattern of contraction timings of heart chambers to improve cardiac function. The comparison showed that RSA modulation achieved equivalent, or significantly greater, improvements in cardiac function, including stroke volume and ejection fraction, with reduced cardiac work and O₂ consumption ratio in the heart.

Despite such benefits, an inefficient increase in RSA magnitude could drop true cardiac output delivered to the organ level. To compensate for the reduction, the hybrid method of RSA and AVD approaches was tested, using that AVD optimisation increased true cardiac output. As a result, the combined approach effectively compensated for a reduction in true cardiac output at low exercise and achieved better cardiac performance with more efficient energy consumption and O₂ exchange over monotonic pacing with optimal AVD.

These findings support a potential clinical application of an RSA pacemaker as a therapeutic treatment for heart failure patients. The hybrid method was equally effective or greater than the RSA-only pacing in cardiac function improvements, with at least a one-third reduction in energy consumption in the heart than the AVD method. To validate this pacing strategy, further experimental or clinical studies will be required.

Date of Award	24 Jun 2026
Original language	English
Awarding Institution	University of Bath
Supervisor	Andrew Cookson (Supervisor), Katharine Fraser (Supervisor) & Alain Nogaret (Supervisor)