Despite the prevailing use of the continuous flow left ventricular assist devices (cf-LVADs), acquired von Willebrand syndrome (AvWS) associated with cf-LVADs still remains a major complication. As AvWS is known to be dependent on shear stress ( ) and exposure time (t exp ), this study examined the degradation of high molecular weight multimers (HMWM) of von Willebrand factor (vWF) in terms of τ and t exp . Two custom apparatus, i.e., capillary-tubing-type degrader (CTD) and Taylor-Couettetype degrader (TCD) were developed for short-term (0.033 sec ≤ t exp ≤ 1.05 s) and long-term (10 s ≤ t exp ≤ 10 min) shear exposures of vWF, respectively. Flow conditions indexed by Reynolds number (Re) for CTD were 14 ≤ Re ≤ 288 with corresponding laminar stress level of 52 ≤ CTD ≤ 1042 dyne/ cm 2 . Flow conditions for TCD were 100 ≤ Re ≤ 2500 with corresponding rotor speed of 180 ≤ ω o ≤ 4000 RPM and laminar stress level of 50 ≤ TCD ≤ 1114 dyne/cm 2 . Due to transitional and turbulent flows in TCD at Re > 1117, total stress (i.e., total = laminar + turbulent) was also calculated using a computational fluid dynamics (CFD) solver, Converge CFD. Inhibition of ADAMTS13 with different concentrations of EDTA (5 mM and 10 mM) was also performed to investigate the mechanism of cleavage in terms of mechanical and enzymatic aspects. Degradation of HMWM with CTD was negligible at all given testing conditions. Although no degradation of HMWM was observed with TCD at Re < 1117 ( total = 1012 dyne/cm 2 ), an increase in degradation of HMWM was observed beyond Re of 1117 for all given exposure times. At Re ~ 2500 ( total = 3070 dyne/ cm 2 ) with t exp = 60 s, a severe degradation of HMWM (90.7 ± 3.8%, abnormal) was observed, and almost complete degradation of HMWM (96.1 ± 1.9%, abnormal) was observed with t exp = 600 s. The inhibition studies with 5 mM EDTA at Re ~ 2500 showed that loss of HMWM was negligible (<10%, normal) for all given exposure times except for t exp = 10 min (39.5 ± 22.3%, borderline-abnormal).
The Penn State Infant Ventricular Assist Device is a 12-14 ml stroke volume pneumatically actuated pump, with custom Björk-Shiley monostrut valves, developed under the National Heart, Lung, and Blood Institute (NHLBI) Pediatric Circulatory Support program. In this report we describe the 7 most recent chronic animal studies of the Infant VAD in the juvenile ovine model, with a mean body weight of 23.5 +/- 4.1 kg. The goal of 4-6 weeks survival was achieved in 5 of 7 studies, with support duration ranging from 5 to 41 days; mean 26.1 days. Anticoagulation was accomplished using unfractionated heparin, and study animals were divided into 2 protocol groups: the first based on a target activated partial thromboplastin time of 1.5 to 2 times normal, and a second group using a target thromboelastography R-time of 2 times normal. The second group required significantly less heparin, which was verified by barely detectable heparin activity (anti-Xa). In both groups, there was no evidence of thromboembolism except in one animal with a chronic infection and fever. Device thrombi were minimal, and were further reduced by introduction of the custom valve. These results are consistent with results of adult VAD testing in animals, and are encouraging given the extremely low levels of anticoagulation in the second group.
Reynolds shear stress (RSS) has served as a metric for the effect of turbulence on hemolysis. Forstrom (1969) and Sallam and Hwang (1984) determined the RSS threshold for hemolysis to be 50,000 and 4,000 dyne/cm, respectively, using a turbulent jet. Despite the order of magnitude discrepancy, the threshold by Sallam and Hwang has been frequently cited for hemolytic potential in blood pumps. We recreated a Sallam apparatus (SA) to resolve this discrepancy and provide additional data to be used in developing a more accurate hemolysis model. Hemolysis was measured over a large range of Reynolds numbers (Re) (Re = 1,000-80,000). Washed bovine red blood cells (RBCs) were injected into the free jet of phosphate buffered saline, and hemolysis was quantified using a percent hemolysis, Hp = h (100 - hematocrit [HCT])/Hb, where h (mg/dl) is free hemoglobin and Hb (mg/dl) is total hemoglobin. Reynolds shear stress was calculated using two-dimensional laser Doppler velocimetry. Reynolds shear stress of ≥30,000 dyne/cm corresponding to Re of ≥60,000 appeared to cause hemolysis (p < 0.05). This RSS is an order of magnitude greater than the RSS threshold that Sallam and Hwang suggested, and it is similar to Forstrom's RSS threshold. This study resolved a long-standing uncertainty regarding the critical values of RSS for hemolysis and may provide a foundation for a more accurate hemolysis model.
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