| Summary: | This thesis describes an investigation into the pathophysiological mechanism responsible for inducing lung functional deficits in maedi. As a prelude to establishing the nature of the functional deficit in maedi, repeated measurements of static lung compliance (Cst), lung distensibility (<I>K</I>), effective alveolar volume (VA,eff) and transfer factor for carbon monoxide (TL,CO,'sb') were made in anaesthetised control sheep, seronegative for MVV, over a period of 5 months. This study furnished regression equations and prediction intervals for lung function indices in normal sheep using bodyweight as the independent variable. By comparison with predicted normal values sheep naturally infected with MVV had reduced lung volumes and gas diffusing capabilities and increased lung elastic recoil. A pathophysiological study was instigated to identify structural correlates of lung functional deficits. Preliminary investigation involved the quantitative morphometric characterisation of the normal sheep lung. Data from this study indicated that the ratio of fixed to physiological lung volume ranged from 0.49 to 0.59 and that this ratio was positively correlated with the time between euthanasia and inflation fixation of the lungs. Values for tissue volume fraction within the lung parenchyma (<I>V</I><SUB>vt</SUB>) ranged from 0.18 to 0.25 and values for alveolar surface density (<I>S</I><SUB>vt</SUB>) ranged from 592 to 716 cm<SUP>2</SUP>/cm<SUP>3</SUP>. Pathophysiological correlations in MVV-infected sheep indicated that lung volume and transfer factor measurements were more sensitive indices of pathology than measurements of Cst or <I>K</I>. Transfer factor was reduced even in sheep with minimal histopathology suggesting this index as a sensitive means of assessing this condition. The density of surface forces could not account for variation in <I>K</I> seen <I>in vivo</I>, however tissue factors such as the quantity and functional tone of contractile tissue in the parenchyma, airways or blood vessels may contribute. Given that parenchymal smooth muscle hyperplasia is a pathological feature of maedi, it was hypothesised that this tissue element is responsible for the observed reduction in <I>K</I>.
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