Abstract
This thesis outlines the candidate's contribution to the study of Respiratory
Physiology in two main areas
1. The effect of lung morphometry on lung function and
2. Reflex control of pattern of breathing.
The work that makes up this thesis is laid out in largely chronological order
describing the evolution of the investigations.
The effect of bronchial tree structure on function was investigated using a number
of new techniques developed by the author. These include a method of modelling
the bronchial tree to previously unobtained detail in the form of a hollow cast.
This enabled gas transit times to airways of 2-3 mm diameter to be measured and
the contribution made by architecture, tissue compliance and the gradient of
pleural pressure to the distribution of ventilation to be apportioned. This was the
first time transit times to individual airways had been measured. Using these
techniques the effect of bronchial tree structure on the phenomenon of separation
of gas mixtures into their components during breathing, and the effect of the
beating heart on the mixing of gases during breathing was quantified.
The author's contributions to the investigation of neural control of breathing
follow. A fortuitous observation that SO₂ blocks pulmonary stretch receptors
(PSR) in rabbits, which took place while developing an animal model of
bronchitis, lead to the observation of a non PSR mechanism determining
inspiratory time (ti). Investigation of the action of rapidly adapting pulmonary
receptors (RAR) using SO₂ confirmed their role in provoking sighs or augmented
breaths and demonstrated that they terminated expiratory duration (tn) with a
constant latency. A consistent effect of RARs on inspiration proved elusive until
it was discovered that after provoking an augmented breath ft is refractory to the
direct effects of RAR activity for about 2 minutes. This observation lead to the
development of a theoretical model of control of ft via a central linking. This
explained our observation of a non-PSR effect restricting ft after SO₂ block.
Further investigations confirmed a role for RAR in control of breathing in
conscious dogs. The action of RAR in initiating inspiration was demonstrated
using PSR block. The same technique was used to elucidate the role played by
PSR in shifts in functional residual capacity during changes in posture. An
interesting observation made at this time is that although cough is primarily
associated with RAR activity it can not be triggered from the lungs. The results
of experiments demonstrating a similar role for RAR in conscious animals are
presented.
The influence of high frequency ventilation, on pulmonary receptors, the reflexes
they produce and on the non-Newtonian properties of bronchial mucus is
described.
The way in which different species control their very different frequencies of
breathing is included and the way pulmonary receptor activity is changed in some
models of lung disease. The effects of modern anaesthetics on receptor activity
and the effect of acupuncture as a respiratory stimulant are reported.
The results of some investigations of human movement and tremor are presented.
The candidates contributions to books and books published are described.