Platelet adhesion to polyurethane urea under pulsatile flow conditions.

Platelet adhesion to a polyurethane urea surface is a precursor to thrombus formation within blood-contacting cardiovascular devices, and platelets have been found to adhere strongly to polyurethane surfaces below a shear rate of approximately 500 s(-1). The aim of the current work is to determine the properties of platelet adhesion to the polyurethane urea surface as a function of time-varying shear exposure. A rotating disk system was used to study the influence of steady and pulsatile flow conditions (e.g., cardiac inflow and sawtooth waveforms) for platelet adhesion to the biomaterial surface. All experiments were conducted with the same root mean square angular rotation velocity (29.63 rad/s) and waveform period. The disk was rotated in platelet-rich bovine plasma for 2 h, with adhesion quantified by confocal microscopy measurements of immunofluorescently labeled bovine platelets. Platelet adhesion under pulsating flow was found to decay exponentially with increasing shear rate. Adhesion levels were found to depend upon peak platelet flux and shear rate, regardless of rotational waveform. In combination with flow measurements, these results may be useful for predicting regions susceptible to thrombus formation within ventricular assist devices.

The Use of Fluid Mechanics to Predict Regions of Microscopic Thrombus Formation in Pulsatile VADs.

We compare the velocity and shear obtained from particle image velocimetry (PIV) and computational fluid dynamics (CFD) in a pulsatile ventricular assist device (VAD) to further test our thrombus predictive methodology using microscopy data from an explanted VAD. To mimic physiological conditions in vitro, a mock circulatory loop is used with a blood analog that matched blood's viscoelastic behavior at 40% hematocrit. Under normal physiologic pressures and for a heart rate of 75 bpm, PIV data is acquired and wall shear maps are produced. The resolution of the PIV shear rate calculations are tested using the CFD and found to be in the same range. A bovine study, using a model of the 50 cc Penn State V-2 VAD, for 30 days at a constant beat rate of 75 beats per minute (bpm) provides the microscopic data whereby after the 30 days, the device is explanted and the sac surface analyzed using scanning electron microscopy (SEM) and, after immunofluorescent labeling for platelets and fibrin, confocal microscopy. Areas are examined based on PIV measurements and CFD, with special attention to low shear regions where platelet and fibrin deposition are most likely to occur. Data collected within the outlet port in a direction normal to the front wall of the VAD shows that some regions experience wall shear rates less than 500 s-1, which increases the likelihood of platelet and fibrin deposition. Despite only one animal study, correlations between PIV, CFD, and in vivo data show promise. Deposition probability is quantified by the thrombus susceptibility potential, a calculation to correlate low shear and time of shear with deposition.

A thrombus susceptibility comparison of two pulsatile Penn State 50 cc left ventricular assist device designs.

Left ventricular assist devices (LVADs) have proven successful as bridge to transplant devices for patients awaiting donor organs. While survival rates continue to increase, destination therapy remains hindered by thrombus formation within the device. Research has shown that thrombosis is correlated to the fluid dynamics within the device and may be a result of sustained shear rates below 500 s(-1) on the polyurethane blood sac used in the Penn State pulsatile LVAD. Particle image velocimetry is used to compare flow within two 50 cc LVAD designs to assess fluid patterns and quantify wall shear rates in regions known from in vivo studies to be susceptible to thrombus formation. The two designs differ in their front face geometry. The V-1 model has an outward-facing "dome" whereas the face of the V-2 model is flat. A thrombus susceptibility metric, which uses measured wall shear rates and exposure times, was applied to objectively compare pump designs over the entire cardiac cycle. For each design, there are regions where wall shear rates remained below 500 s(-1) for the entire cardiac cycle resulting in high thrombus susceptibility potential. Results of this study indicate that the V-2 device had an overall lower propensity for thrombus formation in the current region of interest.

A fluid dynamics study in a 50 cc pulsatile ventricular assist device: influence of heart rate variability.

Although left ventricular assist devices (LVADs) have had success in supporting severe heart failure patients, thrombus formation within these devices still limits their long term use. Research has shown that thrombosis in the Penn State pulsatile LVAD, on a polyurethane blood sac, is largely a function of the underlying fluid mechanics and may be correlated to wall shear rates below 500 s(-1). Given the large range of heart rate and systolic durations employed, in vivo it is useful to study the fluid mechanics of pulsatile LVADs under these conditions. Particle image velocimetry (PIV) was used to capture planar flow in the pump body of a Penn State 50 cubic centimeters (cc) LVAD for heart rates of 75-150 bpm and respective systolic durations of 38-50%. Shear rates were calculated along the lower device wall with attention given to the uncertainty of the shear rate measurement as a function of pixel magnification. Spatial and temporal shear rate changes associated with data collection frequency were also investigated. The accuracy of the shear rate calculation improved by approximately 40% as the resolution increased from 35 to 12 µm/pixel. In addition, data collection in 10 ms, rather than 50 ms, intervals was found to be preferable. Increasing heart rate and systolic duration showed little change in wall shear rate patterns, with wall shear rate magnitude scaling by approximately the kinematic viscosity divided by the square of the average inlet velocity, which is essentially half the friction coefficient. Changes in in vivo operating conditions strongly influence wall shear rates within our device, and likely play a significant role in thrombus deposition. Refinement of PIV techniques at higher magnifications can be useful in moving towards better prediction of thrombosis in LVADs.