Democratic representation and apportionment: public and private good markets.
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Biomedical subjects
Publications and source records attributed to T R Harris.
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Pulmonary edema is a debilitating effect of acute respiratory distress syndrome. The ability to measure it noninvasively with high sensitivity and in three dimensions could be useful in not only detection but also in assessment and guidance of treatment. To this end, a three-dimensional MRI pulse sequence to measure the formation of edema was developed and tested. Another sequence was tested to measure blood flow in distal pulmonary arteries. Pulmonary edema was induced in nine dogs via venous injections of oleic acid. Edema was verified by wet-to-dry weight ratio (5.30 +/- .38) and extra-vascular lung water at baseline (2.03 +/- 1.12 ml/g dry lung weight) versus postinjury (3.00 +/- 1.45 ml/g) (P < .005). The signal-to-noise ratio within the lungs increased from 5.47 +/- 1.00 at baseline to 7.51 +/- 1.96 (P < .005), and the time course of edema formation was resolved. Results from MR phase-contrast blood flow measurements were variable. The authors conclude that the three-dimensional scan provides a sensitive relative quantification of pulmonary edema formation without the use of contrast agents or ionizing radiation.
Sulfhemoglobinated erythrocytes (SHb-RBC's) were examined for utility as an optical multiple indicator dilution tracer in lung studies. A device was developed to measure this tracer optically in flowing blood. Arterial blood was sampled from cannulated, anesthetized dogs and pumped through the device that measured the optical density (OD) of blood at 620 nm. This system was calibrated for increasing SHb-RBC concentrations using an unsteady-state indicator dilution procedure. Areas under optical density (delta OD) profiles were well correlated with injected SHb-RBC volumes using linear regression (r2 > 0.9). This linearity was independent of blood oxygenation, hematocrit, or pH. In vivo lung indicator dilution studies in the intact dog were performed and compared to radioisotope indicator studies using 51Cr labeled erythrocytes. Coefficient of variation (CV) between the two curves was 0.065 under baseline conditions, 0.085 for studies performed during hypoxia, and 0.073 after pH was lowered. We conclude that this device linearly measured SHb-RBC content in whole blood and that SHb-RBC is as accurate a lung indicator dilution tracer as 51Cr-erythrocytes.
The confident identification of parameters is important in the practical application of physiological models. However, the task of parameter identification is often complicated by interactions among parameters and by the fact that the sensitivity of the model to changes in a given parameter is generally a function of all the other parameters. Here we illustrate a graphical approach to parameter identification that allows the modeler to visualize the behavior of the model, the sensitivity functions, and certain functions characteristic of parameter interdependence. The visual display can be generated over any desired portion of parameter space. The technique is applied to a simple, four-parameter, myocardial pump model of the coronary circulation. The results indicate that over specified ranges of parameters, it is possible to distinguish among the four parameters of the model: the ratio of proximal-to-distal resistance, alpha; the overall resistance of the vascular bed, R; the compliance of the vascular bed, C; and a parameter, kappa, relating tissue pressure to left ventricular pressure. It was found that in order to identify all parameters uniquely, it was necessary to regress upon both coronary inflow and outflow.
A mathematical model of fluid, solute, and red cell transport in the lung has been developed that includes the effects of simultaneous changes in lung vascular and interstitial volumes. The model provides separate arterial, microvascular, and venous pulmonary regions and a systemic vascular region in addition to a pulmonary interstitial compartment. Pressure, volume, hematocrit, flow, and concentration of up to 12 solutes and tracers can be computed in each compartment. Computer code is written in the C programming language, with Microsoft Excel serving as a user interface. Implementation is currently on PC-486 microcomputer systems, but the core program can easily be moved to other computer systems. The user can select different models for the blood-interstitial barrier (e.g., multiple pore, nonlinear Patlak equation), osmotic pressure-concentration relationships (e.g., Nitta, Navar-Navar), solute reflection coefficients interstitial macromolecule exclusion, or lymph barrier characteristics. Each model parameter or a combination of parameters can be altered with time in a predetermined fashion. The model is particularly useful in interpreting lung experimental data where simultaneous changes occur in vascular and extravascular compartments. Several applications are presented and discussed, including interpretation of optical filtration experiments, venous occlusion experiments, external detection of macromolecular exchange, and blood-lymph studies that use exogenous tracers. A number of limitations of the model are identified and improvements are proposed. A major strength of the model is that it is specifically designed to incorporate newly discovered relationships as the field of lung physiology expands.
In order to successfully use a model for parameter identification, it must be carefully analyzed. Current analysis methods, however, are ad hoc and provide only partial information. We extended these methods through the application of stacked dimensions, a scientific visualization method. The end result of our extensions are multi-dimensional parametric model-images. These images depict a model as a function of all its parameters in a single graphic. We applied parametric model-images to model verification (behavioral analysis), sensitivity analysis, and identifiability analysis. We applied our methodology to the evaluation of pulmonary vascular capillary-transport models. Results have shown that the visualization-based method provides a more complete view of a model's behavior and its other characteristics. Furthermore, our method has also proven to be more computationally efficient than the traditional approaches.