Robert J. Roselli

Alterations in pulmonary artery flow patterns and shear stress determined with three-dimensional phase-contrast magnetic resonance imaging in fontan patients

OBJECTIVE This study compares in vivo pulmonary blood flow patterns and shear stresses in patients with either the direct atrium-pulmonary artery connection or the bicaval tunnel connection of the Fontan procedure to those in normal volunteers. Comparisons were made with the use of three-dimensional phase contrast magnetic resonance imaging. METHODS Three-dimensional velocities, flows, and pulmonary artery cross-sectional areas were measured in both pulmonary arteries of each subject. Axial, circumferential, and radial shear stresses were calculated with the use of velocities and estimates of viscosity. RESULTS The axial velocities were not significantly different between subject groups. However, the flows and cross-sectional areas were higher in the normal group than in the two patient groups in both pulmonary arteries. The group with the bicaval connection had circular swirling in the cross section of both pulmonary arteries, causing higher shear stresses than in the controls. The disorder caused by the connection of the atrium to the pulmonary artery caused an increase in some shear stresses over the controls, but not higher than those found in the group having a bicaval tunnel. CONCLUSIONS We found that pulmonary flow was equally reduced compared with normal flow in both patient groups. This reduction in flow can be attributed in part to the reduced size of the pulmonary arteries in both patient groups without change in axial velocity. We also found higher shear stress acting on the wall of the vessels in the patients having a bicaval tunnel, which may alter endothelial function and affect the longevity of the repair.

Measurement of thermal effects on the optical properties of prostate tissue at wavelengths of 1,064 and 633 nm

The extent of thermal injury during laser prostatectomy is dependent on the light distribution in laser‐irradiated tissue. As tissue is irradiated, the optical properties change as a function of temperature due to an alteration of molecular and cellular structure. The purpose of the present study was to determine how the exposure of both fresh and previously frozen canine prostate tissue to elevated temperatures affects the optical properties.

Normal three-dimensional pulmonary artery flow determined by phase contrast magnetic resonance imaging

AbstractIn this study, an application was developed to measure three-dimensional blood flow in the main, right, and left pulmonary arteries of seven healthy volunteers using phase contrast magnetic resonance imaging (MRI). Presently, no other noninvasive technique is capable of providing this information. Flow, mean velocity, kinetic energy, and cross-sectional area were measured at multiple phases of the cardiac cycle and were consistent with previously reported values measured with one-dimensional velocity encoded MRI and Doppler echocardiography. Additionally, axial, circumferential, and radial shear stresses near the wall of the vessel at multiple phases of the cardiac cycle were estimated using the in-plane velocities. All three shear stresses were relatively constant along the vessel wall and throughout the cardiac cycle (∼ 7 dyn/cm2). This three-dimensional characterization of normal pulmonary blood flow provides a base line to which effects of altered pulmonary artery flow patterns in disease can be compared. [Morgan, V. L., T. P. Graham, Jr., and C. H. Lorenz. Circulation Suppl. 94:I–417 (abstract), 1996].

An effective-diffusivity model of pulmonary capillary exchange: General theory, limiting cases, and sensitivity analysis

Abstract A family of possible models of capillary-tissue exchange useful for interpreting multiple-tracer data from the pulmonary circulation was derived from the convective-diffusion equation. The models are simplifications of a uniform-transit-time model with two serial diffusion layers outside of the capillary. Modifications of this four-parameter model were derived, and the importance of simplifying assumptions were compared using moment analysis and transform-domain equivalence. A permeability-diffusion model was derived by assuming that the layer nearer the capillary contributed a constant resistance to tracer movement. Using sensitivity analysis, we found that the three parameters of this permeability-diffusion model could not be determined independently, and that further model simplification was highly desirable. Two distinct paths of further simplification were explored.The Sangren-Sheppard model was considered as one path. An alternative path of simplification led to a new model of tracer behavior which we have called an effective-diffusivity model. Moment matching was used to determine the relationships among these models. Sensitivity analysis of the Sangren-Sheppard and effective-diffusivity models showed that the parameters of both of these models were more easily identified. However, the sensitivity analysis also showed that these two models had quite different sensitivities to their respective volume parameters. The Sangren-Sheppard model prediction was affected at all times by a change in the extravascular volume parameter, while the effective-diffusivity model prediction was affected only at the longest times. We concluded that the effective-diffusivity model may be a better alternative to the Sangren-Sheppard model under some conditions. The parameters of the effective-diffusivity model provide a more reliable index of the physiology of capillary-tissue exchange as small molecules as measured by the multiple tracer method in the pulmonary circulation.

Exchange of macromolecules in the pulmonary microcirculation.

FIGURE 1 illustrates several concepts upon which the current understanding of macromolecular exchange in the lung microcirculation is based. Fluid and solutes normally filter into the interstitial space from capillaries running in alveolar walls. The filtered fluid then migrates through the interstitial space to the terminal lymphatics ending around small airways, and fluid and solutes are drained away by lymphatics reentering the venous system. The walls of lung capillaries are porous, that is, they leak substantial amounts of macromolecules (proteins] as well as fluid even under normal circumstances. In contrast, the alveolar-epithelial barrier is “tight.” Under normal conditions, very small amounts of fluid and solutes cross that barrier. If the concepts contained in FIGURE 1 are essentially correct, then transvascular movement of fluid and solutes can be studied by measuring lung lymph flow and solute composition. We and others have used this approach in chronically instrumented, unanesthetized sheep.’-‘ The preparation we have used is diagramed in FIGURE 2. Through a series of thoracotomies, we placed catheters in the main pulmonary artery, the left atrium, the thoracic aorta, and the right atrium and cannulated the main efferent duct from the caudal mediastinal lymph node, which receives approximately two-thirds of the lung lymph in sheep. The tail of that node is resected from the inferior margin of the pulmonary ligaments caudal to the diaphragm to eliminate nonpulmonary lymph. Animals instrumented in this way are allowed to recover from surgery, and then experiments are done without anesthesia. This paper will summarize data relating to the movement of macromolecules from plasma to lung lymph in chronically instrumented, unanesthetized sheep under normal conditions, under conditions of elevated pulmonary vascular hydrostatic pressures, and under conditions of increased lung vascular permeability. The central thesis emerging from these studies is that the movement of macromolecules from plasma to Iung lymph occurs as though transport were through a semipermeable membrane by passive mechanisms. Measurement of lung lymph solute concentrations permits estimation of some properties of the filtering barrier and the development of theoretical models of transvascular transport that may have predictive value.

The effects of red cell and tissue exchange on the evaluation of capillary permeability from multiple indicator data.

The two phase (vascular-extravascular) Sangren-Sheppard (SS) model is often used to estimate capillary permeability-surface area product (PS) from multiple indicator data. Our objective was to identify conditions where erroneous estimates of capillary PS or extravascular volume (VE) result from the application of this model to data obtained from non-homogeneous capillary units. We used a 4-phase capillary-tissue model (plasma, erythrocytes, interstitial fluid and extravascular cellular fluid) to simulate data collected from a heterogeneous capillary unit. A moment-matching technique was used to compute the parameters of the simpler SS model which would adequately describe the 4 phase tracer concentration-time (c(t)) curve. Deviations of computed values of VE and PS from the PS and extravascular volume specified in the 4-phase model were determined as functions of dimensionless red cell permeability αRC, hematocrit value, plasma-to-red cell velocity ratio, dimensionless extravascular cellular volume and permeability, capillary permeability αcap, and the fraction of indicator orginally deposited in the plasma at the capillary inlet. Our results indicate that application of the SS model to simulated low capillary permeability data produces underestimates in both VE and PS. Equations are presented which correct for this effect so long as the SS and 4-phase model c(t) curves are similar. Application of the whole blood-tissue SS model in situations where red cells are only slightly permeable or use of the plasma-tissue SS model when red cells admit tracer can lead to significant errors in VE and PS estimates. When αcap is relatively large neither SS model yields an accurate estimate of PS in the intermediate αRC range (i.e., near unity). Less than 10% error will result, regardless of αRC, if the blood-tissue SS model is used (αcap ≤ .30, Hct≤.50) and the tracer is equilibrated with a blood sample before injection.

Models of lung transvascular fluid and protein transport

Transport theory has been applied to lymph flow (QL), protein lymph to plasma concentration ratios (L/P), and permeability surface area for urea (PSu) in unanesthetized sheep. Three models of the plasma-interstitial barrier have been used: a single pathway fiber matrix model, a continuous cylindrical-pore model with log normal distribution of filtration coefficients, and a cylindrical two-pore model. The fiber matrix model was unable to match mesured PSu, QL, and L/P. The continuous-pore model was capable of describing the data, but the fitted median pore size was inconsistent with a continuum theory. The two-pore model described steadystate data and was used in additional model applications. We explored the 90% confidence limits for the fitted structural parameters of the two-pore theory. We found that many sets of model parameters were capable of fitting the available experimental data. We therefore sought combinations of parameters that might characterize the microvascular barrier under baseline and altered permeability situations. One combination that looks promising is the ratio of large-pore to small-pore radius raised to the sixth power and multiplied by the large-pore frequency. This value remains relatively constant following elevations in microvascular pressure, saline infusions, and plasma infusions but increases dramatically after endotoxin infusion.

Comparison between pore model predictions and sheep lung fluid and protein transport

The multiple pore model of T. R. Harris and R. J. Roselli (1981, J. Appl. Physiol: Respir. Environ. Exercise Physiol. 50, 1-14), was used to simulate lung lymph flow and protein transport at various levels of microvascular pressure. Response of the three-pore structure determined in that study was found to be in excellent agreement with the experimental sheep lung lymph measurements of R. E. Parker, R. J. Roselli, T. R. Harris, and K. L. Brigham (1981, Circ. Res. 49, 1164-1172). Optimal one- and two-pore model structures were also determined and their responses compared with the experimental data. The two-pore model behavior was found to be very similar to that of the three-pore model but a homoporous model which reproduced the experimental findings could not be found. All simulations required interstitial fluid pressure to increase as microvascular pressure was elevated. True filtration-independent conditions could only be simulated when lung vascular pressures were raised to physiologically unrealistic values.

A model of fluid, erythrocyte, and solute transport in the lung

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.

Mass Transfer Fundamentals

When we speak of mass transfer, we are generally referring to the movement of one or more molecular species relative to the others. Before we can describe this relative movement, we need to understand the most common ways of quantifying the presence of each species. Consider the closed system with volume V shown in Fig. 12.1 which contains three different molecular species A, B, and C, represented by three different colors.