Evaluation of cardiovascular parameters of a selenium-based antihypertensive using pulsed Doppler ultrasound.

The pharmacology of selenium is of much interest because selenium deficiency has been linked to cardiovascular diseases, cancer, and arthritis, and selenoenzymes are critical cellular antioxidants. We have previously reported that phenyl-2-aminoethylselenide (PAESe) and its derivatives represent a novel class of selenium-based antihypertensive agents that exhibit unique biochemical and pharmacologic properties. We now report on experiments designed to probe the hemodynamic mechanism of action of these compounds in spontaneously hypertensive rats (SHR). A noninvasive pulsed Doppler ultrasound probe was used to measure peak blood flow velocity in the aortic arch from the right second intercostal space. PAESe was found to increase peak aortic blood flow velocity (+44%), heart rate (+16%), and blood flow acceleration (+105%), while decreasing left ventricular ejection time (LVET) (-37%) concomitant with a decrease in mean arterial pressure (-54%). These results were compared with the known vasodilator hydralazine, which had similar effects on mean arterial pressure (MAP) and peak velocity but caused an increase in LVET (+42%) and a decrease in heart rate (-18%). Taken together, our results suggest that PAESe decreases blood pressure via a decrease in peripheral resistance, which overcomes the initial increase in heart rate and acceleration to give a net decrease in MAP.

In vivo flow dynamics of the total cavopulmonary connection from three-dimensional multislice magnetic resonance imaging.

BACKGROUND: The total cavopulmonary connection (TCPC) design continues to be refined on the basis of flow analysis at the connection site. These refinements are of importance for myocardial energy conservation in the univentricular supported circulation. In vivo magnetic resonance phase contrast imaging provides semiquantitative flow visualization information. The purpose of this study was to understand the in vivo TCPC flow characteristics obtained by magnetic resonance phase contrast imaging and compare the results with our previous in vitro TCPC flow experiments in an effort to further refine TCPC surgical design. METHODS: Twelve patients with TCPC underwent sedated three-dimensional, multislice magnetic resonance phase contrast imaging. Seven patients had intraatrial lateral tunnel TCPC and 5 had extracardiac TCPC. RESULTS: In all patients in both groups a disordered flow pattern was observed in the inferior caval portion of the TCPC. Flow at the TCPC site appeared to be determined by connection geometry, being streamlined at the superior vena cava-pulmonary junction when the superior vena cava was offset and flared toward the left pulmonary artery. Without caval offset, intense swirling and dominance of superior vena caval flow was observed. In TCPC with bilateral superior vena cavae, the flow patterns observed included secondary vortices, a central stagnation point, and influx of the superior vena cava flow into the inferior caval conduit. A comparative analysis of in vivo flow and our previous in vitro flow data from glass model prototypes of TCPC demonstrated significant similarities in flow disturbances. Three-dimensional magnetic resonance phase contrast imaging in multiple coronal planes enabled a comprehensive semiquantitative flow analysis. The data are presented in traditional instantaneous images and in animated format for interactive display of the flow dynamics. CONCLUSIONS: Flow in the inferior caval portion of the TCPC is disordered, and the TCPC geometry determines flow characteristics.

Importance of accurate geometry in the study of the total cavopulmonary connection: computational simulations and in vitro experiments.

Previous in vitro studies have shown that total cavopulmonary connection (TCPC) models incorporating offset between the vena cavae are energetically more efficient than those without offsets. In this study, the impact of reducing simplifying assumptions, thereby producing more physiologic models, was investigated by computational fluid dynamics (CFD) and particle flow visualization experiments. Two models were constructed based on angiography measurements. The first model retained planar arrangement of all vessels involved in the TCPC but incorporated physiologic vessel diameters. The second model consisted of constant-diameter vessels with non-planar vascular features. CFD and in vitro experiments were used to study flow patterns and energy losses within each model. Energy losses were determined using three methods: theoretical control volume, simplified control volume, and velocity gradient based dissipation. Results were compared to a simplified model control. Energy loss in the model with physiologically more accurate vessel diameters was 150% greater than the simplified model. The model with nonplanar features produced an asymmetric flow field with energy losses approximately 10% higher than simplified model losses. With the velocity gradient based dissipation technique, the map of energy dissipation was plotted revealing that most of the energy was dissipated near the pulmonary artery walls.

Fluid mechanic assessment of the total cavopulmonary connection using magnetic resonance phase velocity mapping and digital particle image velocimetry.

The total cavopulmonary connection (TCPC) is currently the most promising modification of the Fontan surgical repair for single ventricle congenital heart disease. The TCPC involves a surgical connection of the superior and inferior vena cavae directly to the left and right pulmonary arteries, bypassing the right heart. In the univentricular system, the ventricle experiences a workload which may be reduced by optimizing the cavae-to-pulmonary anastomosis. The hypothesis of this study was that the energetic efficiency of the connection is a consequence of the fluid dynamics which develop as a function of connection geometry. Magnetic resonance phase velocity mapping (MRPVM) and digital particle image velocimetry (DPIV) were used to evaluate the flow patterns in vitro in three prototype glass models of the TCPC: flared zero offset, flared 14 mm offset, and straight 21 mm offset. The flow field velocity along the symmetry plane of each model was chosen to elucidate the fluid mechanics of the connection as a function of the connection geometry and pulmonary artery flow split. The steady flow experiments were conducted at a physiologic cardiac output (4 L/min) over three left/right pulmonary flow splits (70/30, 50/50, and 30/70) while keeping the superior/inferior vena cavae flow ratio constant at 40/60. MRPVM, a noninvasive clinical technique for measuring flow field velocities, was compared to DPIV, an established in vitro fluid mechanic technique. A comparison between the results from both techniques showed agreement of large scale flow features, despite some discrepancies in the detailed flow fields. The absence of caval offset in the flared zero offset model resulted in significant caval flow collision at the connection site. In contrast, offsetting the cavae reduced the flow interaction and caused a vortex-like low velocity region between the caval inlets as well as flow disturbance in the pulmonary artery with the least total flow. A positive correlation was also found between the direct caval flow collision and increased power losses. MRPVM was able to elucidate these important fluid flow features, which may be important in future modifications in TCPC surgical designs. Using MRPVM, two- and three-directional velocity fields in the TCPC could be quantified. Because of this, MRPVM has the potential to provide accurate velocity information clinically and, thus, to become the in vivo tool for TCPC patient physiological/functional assessment.

Valve orifice area alone is an insufficient index of aortic stenosis severity: effects of the proximal and distal geometry on transaortic energy loss.

BACKGROUND AND AIMS OF THE STUDY: Standard measures of hemodynamic severity of aortic valve stenosis vary widely among patients with and without clinical symptoms. Our hypothesis is that valve orifice area alone is not the sole determinant of adverse clinical outcome. Stenotic orifice area ratio is ratio of the cross-sectional stenotic orifice area to the down-stream, ascending aorta cross-sectional area. Determination of workload together with aortic valve orifice area ratio might improve risk stratification among asymptomatic patients with critical aortic stenosis. Accordingly, application of both parameters together might be useful in guiding management decisions in this condition. METHODS: In this study the dependency of transaortic fluid mechanical energy transfer (one component of left ventricular workload) on aortic valve orifice area is shown using modeling and experimental techniques. RESULTS: For a stroke volume of 62 ml at a heart rate of 60 beats/min, the piston work (analogous to left ventricular work) increased by 17% as the stenotic orifice area ratio decreased from 0.60 to 0.25, by 35% as the ratio fell from 0.25 to 0.20, and by 73% as the ratio fell from 0.20 to 0.10. CONCLUSIONS: As predicted by the fundamental fluid mechanical theory, simulated left ventricular work and energy loss in aortic stenosis are influenced not only by the effective stenotic valve orifice area, but also by the geometry of the inflow and outflow conduits, proximal and distal to the valve. These findings might explain clinically observed discrepancies between valve orifice area and the onset of the classical symptoms of severe aortic stenosis that reflect the left ventricular workload. Consideration of the left ventricular work in addition to the effective valve orifice area should enhance clinical evaluation, prognostication and risk stratification among patients with severe aortic stenosis.

Toward designing the optimal total cavopulmonary connection: an in vitro study.

BACKGROUND: Understanding the total cavopulmonary connection (TCPC) hemodynamics may lead to improved surgical procedures which result in a more efficient modified circulation. Reduced energy loss will translate to less work for the single ventricle and although univentricular physiology is complex, this improvement could contribute to improved postoperative outcomes. Therefore to conserve energy, one surgical goal is optimization of the TCPC geometry. In line with this goal, this study investigated whether addition of caval curvature or flaring at the connection conserves energy. METHODS: TCPC models were made varying the curvature of the caval inlet or by flaring the anastomosis. Steady flow pressure measurements were made to calculate the power loss attributed to each connection design over a range of pulmonary flow splits (70:30 to 30:70). Particle flow visualization was performed for each design and was qualitatively compared to the power losses. RESULTS: Results indicate that curving the cavae toward one pulmonary artery is advantageous only when the flow rate from that cavae matches the flow to the pulmonary artery. Under other pulmonary flow split conditions, the losses in the curved models are significant. In contrast, fully flaring the anastomosis reduced losses over the range of pulmonary flow splits. Power losses were 56% greater for the curving as compared to flaring. Fully flaring without caval offset reduced losses 45% when compared to previous models without flaring. If flaring on all sides was implemented with caval offset, power losses reduced 68% compared to the same nonflared model. CONCLUSIONS: The results indicate that preferentially curving the cavae is only optimal under specific pulmonary flow conditions and may not be efficient in all clinical cases. Flaring of the anastomosis has great potential to conserve energy and should be considered in future TCPC procedures.

The hemodynamic effects of mechanical prosthetic valve type and orientation on fluid mechanical energy loss and pressure drop in in vitro models of ventricular hypertrophy.

BACKGROUND AND AIMS OF THE STUDY: When choosing a prosthetic replacement for a natural heart valve, one objective should be to minimize the workload placed on the heart. This workload can be raised by fluid mechanical energy losses imposed by the valve. For a patient with left ventricular hypertrophy, certain aortic valve types and orientations could be hemodynamically superior to others. METHODS: This study used a control volume analysis to investigate the effects of prosthetic mechanical aortic valve type and orientation on fluid mechanical energy losses in four in vitro models of the left ventricular outflow/aortic inflow tract in various degrees of hypertrophy. Flow visualization studies were performed to qualitatively validate this analysis. The two most commonly used mechanical valve designs were studied: the St. Jude Medical (SJM) bileaflet valve and the Medtronic Hall (MH) tilting disk valve. Experiments were performed in pulsatile flow at a constant heart rate of 60 beats per min for five valve type/orientation combinations. The stroke volume was varied between 40 and 120 ml in five increments for each model and valve/orientation studied. RESULTS: Valve type and orientation was found to have a significant effect on energy losses in these models (p < 0.05). Valve/orientation combinations with leaflets or disks approximately parallel to the proximal flow direction created lower energy losses than others. The MH valve in the 180 degrees orientation caused significantly less energy losses and pressure drops (orifice and recovered) than any of the SJM valve/orientations studied (p < 0.05). The SJM and MH valves in the 0 degree orientation were responsible for significantly more energy loss than other valve/orientations studied (p < 0.05). An aortic inflow tract model with severe (45 degrees) curvature created significantly more energy loss (p < 0.05) than those with less curvature (15 and 30 degrees). However, the insertion of an obstruction simulating a hypertrophic tissue outgrowth caused much more energy loss than increasing the severity of outflow tract curvature from 15 to 45 degrees. Both orifice pressure drop and recovered pressure drop had excellent linear correlations with energy losses found in these models. CONCLUSIONS: These results imply that: (i) prosthetic valve type and orientation should be considered when replacing the aortic valve of a hypertropic patient; (ii) removal of obstructions within the aortic inflow tract will decrease ventricular workload; and (iii) the Doppler-estimated pressure gradients commonly use by cardiologists to assess the performance of a prosthetic valve, correlate very well with left ventricular energy loss and work load.

Hemodynamics of the Fontan connection: an in-vitro study.

The Fontan operation is one in which the right heart is bypassed leaving the left ventricle to drive the blood through both the capillaries and the lungs, making it important to design an operation which is hemodynamically efficient. The object here was to relate the pressure in Fontan connections to its geometry with the aim of increasing the hemodynamically efficiency. From CT or magnetic resonance images, glass models were made of realistic atrio-pulmonary (AP) and cavo-pulmonary (CP) connections in which the right atrium and/or ventricle are bypassed. The glass models were connected to a steady flow loop and flow visualization, pressure and 3 component LDA measurements made. In the AP model the large atrium and curvature of the conduit created swirling patterns, the magnitude of which was similar to the axial velocity. This led to an inefficient flow and a subsequent large pressure loss (780 Pa). In contrast, the CP connection with a small intra-atrial chamber had reduced swirling and a significantly smaller pressure loss (400 Pa at 8 l.min) and was therefore a more efficient connection. There were, however, still pressure losses and it was found that these occurred where there was a large bending of the flow, such as from the superior vena cava to the MPA and from the MPA to the right pulmonary artery.