Effect of isoproterenol or exercise on pulmonary lymph flow and hemodynamics

Experiments were performed to determine whether different methods of increasing cardiac output would have similar effects on lung lymph flow, and to assess the contribution of the microvasculature (fluid-exchanging vessels) to the total calculated pulmonary vascular resistance. Yearling unanesthetized sheep with chronic vascular catheters and lung lymph fistulas underwent intravenous infusions of isoproterenol at 0.2 micrograms X kg-1. min-1 (n = 8) or were exercised on a treadmill (n = 16). Both isoproterenol and exercise increased cardiac output, lowered calculated total pulmonary and systemic vascular resistances, and had no effect on the calculated pulmonary microvascular pressure. Isoproterenol infusions did not affect lung lymph flow, whereas exercise increased lung lymph flow in proportion to the increase in cardiac output. We conclude that 1) the sheep has a different pulmonary hemodynamic response to exercise than dogs and man, 2) the microvasculature is recruited during exercise-induced but not isoproterenol-induced increases in cardiac output, and 3) the microvasculature represents only a small proportion of the total calculated pulmonary vascular resistance.     

Effect of flow pulsatility on modeling the hemodynamics in the total cavopulmonary connection

Total cavopulmonary connection is the result of a series of palliative surgical repairs performed on patients with single ventricle heart defects. The resulting anatomy has complex and unsteady hemodynamics characterized by flow mixing and flow separation. Although varying degrees of flow pulsatility have been observed in vivo, non-pulsatile (time-averaged) boundary conditions have traditionally been assumed in hemodynamic modeling, and only recently have pulsatile conditions been incorporated without completely characterizing their effect or importance. In this study, 3D numerical simulations with both pulsatile and non-pulsatile boundary conditions were performed for 24 patients with different anatomies and flow boundary conditions from Georgia Tech database. Flow structures, energy dissipation rates and pressure drops were compared under rest and simulated exercise conditions. It was found that flow pulsatility is the primary factor in determining the appropriate choice of boundary conditions, whereas the anatomic configuration and cardiac output had secondary effects. Results show that the hemodynamics can be strongly influenced by the presence of pulsatile flow. However, there was a minimum pulsatility threshold, identified by defining a weighted pulsatility index (wPI), above which the influence was significant. It was shown that when wPI<30%, the relative error in hemodynamic predictions using time-averaged boundary conditions was less than 10% compared to pulsatile simulations. In addition, when wPI<50, the relative error was less than 20%. A correlation was introduced to relate wPI to the relative error in predicting the flow metrics with non-pulsatile flow conditions.     

Effect of alterations in femoral artery flow on abdominal vessel hemodynamics in swine

In support of an in vivo investigation in swine of the influence of changes in fluid dynamic wall shear on arterial macromolecular permeability, a procedure has been developed to alter the flows in the porcine posterior arterial vasculature by opening and closing a reversible arteriovenous shunt placed on one of the femoral arteries. Laparoscopic techniques were used to place appropriately modified Transonic Systems ultrasonic flow probes on both external and circumflex iliac arteries, and on the terminal aorta. Flow measurements were made prior to shunt placement, and with the shunt open and closed, to measure the influence of altered external iliac artery flow on the distribution to the infrarenal abdominal vessels. Similar experiments were carried out to relate the flow rates in the external iliac arteries to those in the femoral arteries, which are more accessible. Based on the relationships among the measured flow rates, rules have been developed to estimate the major infrarenal flows in the pig, at baseline and with the shunt opened and closed, from only the flow rates measured at the two femoral arteries.     

The effects of variation in the arterial pulse waveform on perivascular flow

Cerebrospinal fluid (CSF) enters nervous tissues through perivascular spaces. Flow through these pathways is important for solute transport and to prevent fluid accumulation. Syringomyelia is commonly associated with subarachnoid space obstructions such as Chiari I malformation. However, the mechanism of development of these fluid-filled cavities is unclear. Studies have suggested that changes in the arterial and CSF pressures could alter normal perivascular flow. This study uses an idealised model of the perivascular space to investigate how variation in the arterial pulse influences fluid flow. The model used simulated subarachnoid pressures from healthy controls (N = 9), Chiari patients with (N = 7) and without (N = 8) syringomyelia. A parametric analysis was conducted to determine how features of the arterial pulse altered flow. The features of interest included: the timing and magnitude of the peak displacement, and the area under the curve in the phases of uptake and decline. A secondary aim was to determine if the previously observed differences between subject groups were sensitive to variation in the arterial pulse wave. The study demonstrated that the Chiari patients without a syrinx maintained a significantly higher level of perivascular inflow over a physiologically likely range of pulse wave shapes. The analysis also suggested that age-related changes in the arterial pulse (i.e. increased late systolic pulse amplitude and faster diastolic decay), could increase resistance to perivascular inflow affecting solute transport.     

Effect of body posture on spatial distribution of pulmonary blood flow

Single-photon emission-computed tomography (SPECT) on intact dogs and humans suggests that one aspect of regional blood flow in the lung (Qr) is independent of gravity, e.g., the gradient in Qr between the core and the periphery. To further evaluate these findings, six anesthetized healthy dogs (approximately 30 kg), two in the supine posture, two in the prone posture, and two suspended in the upright posture, breathing spontaneously, were injected (iv) at end expiration with 20 mCi99mTc-labeled albumin macroaggregates. The animals were killed, their chests were opened, their lungs were removed and dissected free of other tissue, and the blood was drained. The lungs were dried by blowing warm air (50 degrees C) while they were inflated to full capacity for about 18 h. The fully inflated and dry lungs were placed in the supine position and SPECT was performed to determine the three-dimensional distribution of activity. One hundred and twenty projections of the activity in the entire lungs were obtained at 3 degrees steps with a rotating gamma camera and stored in computer memory. Once SPECT was completed, either a coronal slice or a sagittal slice (1 cm thick) was cut and imaged directly by placing it against the gamma camera collimator for 6 min. The tomographic-reconstructed slices revealed that at isogravity, in all body postures, Qr in the central region of the lungs was up to 10 times that in the periphery. Furthermore, the central-peripheral gradient was discernible within the individual lobes. The direct images of slices also confirmed these findings. Although flow inequalities independent of gravity were present, the central region with the highest flow often was closer to the dependent regions of the lungs, suggesting that gravity had some influence on the final distribution. The results suggest that factors other than gravity also play an important role in the distribution of pulmonary blood flow. These factors may be related to the conductance of the vascular pathways that lead to different regions in the lungs.