Higher centre and autonomic control of cardiorespiratory function
This thesis is concerned with the role of 'central command' in cardiorespiratory control during exercise and the peripheral autonomic modulation of cardiac excitability. Chapter One reviews the background to the work in the thesis. The cardiorespiratory and autonomic changes occurring during exercise and the ways in which they are brought about are discussed. This is followed by a review of some pathological changes in autonomic activity and the ways in which they might be arrhythmogenic. Chapter Two details the experimental techniques used in the thesis and discusses their theoretical background. Chapter Three studies the cardiorespiratory responses to imagination of exercise under hypnosis. This results in hyperventilation, hypocapnia and an increase in heart rate. In contrast, no cardiorespiratory changes are seen when the same protocol is repeated in the awake state. The response to imagined exercise under hypnosis is not affected by maintaining isocapnia. A powerful drive to breathe arising from higher centres, that is independent of peripheral muscular feedback, is elicited when 'exercise' is imagined under hypnosis. Chapter Four investigates the neural correlates of imagined exercise under hypnosis using positron emission tomography to see if they are the same as those classically implicated in 'central command' during exercise. Activation of 'motor' areas occurs, including the supplementary motor area, primary motor cortex for breathing, premotor area, thalamus, basal ganglia and cerebellum. The insular cortex, right dorsolateral prefrontal cortex and posterior parietal cortices are also activated. These activations are similar to those previously reported during actual exercise, but occur in the absence of peripheral feedback that accompanies actual exercise and may therefore reflect 'central command'. Chapter Five studies the responses to altered perception of work rate during actual exercise using hypnotic suggestions. If exercising hypnotised subjects are told that the work rate has increased (when it hasn't), they hyperventilate, become hypocapnic and heart rate increases, suggesting a partial uncoupling of 'central command' from peripheral feedback. Chapter Six investigates the cardiovascular effects of electrical stimulation of the thalamus and midbrain in awake man to determine the role of subcortical areas in cardiovascular control. High-frequency stimulation of the thalamus, subthalamic nucleus and substantia nigra results in increases in heart rate and blood pressure, whereas stimulation of the globus pallidus has no effect. In patients with implanted stimulating electrodes, chronic high-frequency electrical stimulation does not affect baroreflex sensitivity, heart rate variability or blood pressure variability. Chapter Seven characterises the cardiac electrophysiological consequences of sympathetic imbalance using multi-electrode array mapping techniques in the pig heart in vivo. A novel potential arrythmogenic mechanism of noradrenaline is also investigated in two in vitro preparations. Chapter Eight presents a brief summary of the findings in the thesis and discusses future research directions.