VISCOELASTIC NON-UNIFORM VENTILATION

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The proposed research addresses two aspects of basic respiratory physiology, nonuniform ventilation and tissue viscosity, and shows the relation between the two. Ventilation has recently been shown to be significantly different in regions that are separated by 1cm or less, apparently because of intrinsic nonuniformities in the mechanical properties of the parenchyma. In the prone dog, small-scale regional ventilation varies by approximately 20% from the mean, and this nonuniformity of ventilation contributes significantly to the width of the V/Q distribution. Tissue resistance has been shown to be the major component of pulmonary resistance in dogs at normal breathing frequencies, but the dissipative mechanisms that underlie tissue resistance for small tidal volumes have not been identified. The proposed research combines in vivo measurements of dynamic ventilation with engineering modeling and analysis. The experimental method is the tracking, by biplane fluoroscopy, of markers implanted in the parenchyma of dog lungs. This method is capable of measuring volume excursions of parenchymal units with volumes of the order of 1 cm3 with a time resolution of 30 ms. Preliminary data, obtained with the parenchymal marker technique, show that the ventilation of small regions within a lobe differ in phase and that the amplitude of regional ventilation is frequency dependent. These are indicators of viscoelastic mechanisms. Therefore, by means of modeling and analysis, these data not only provide direct information about nonuniform ventilation, they also provide a window into tissue viscoelasticity mechanisms. Regional ventilation will be measured for sinusoidal lung volume oscillations over a wide range of frequencies, and for vital capacity maneuvers with a wide range of expiratory flow rates. Models that summarize the statistical properties of regional ventilation and that relate regional ventilation to other measures of gas mixing and to tissue resistance will be developed. The data and modeling will be used to test hypotheses about dissipative mechanisms, namely that there are two mechanisms, surface tension equilibration with a broad range of longer time constants, and alveolar pressure relaxation with a shorter time constant. The initial focus of the research is on understanding normal physiology, but this also lays the groundwork for extension to the study of pathological conditions. Nonuniform ventilation is a hallmark of virtually all pulmonary diseases, including asthma and emphysema. After the study of normal lungs is complete, the methods will be applied to dogs that have been exposed to methacholine.