Ovine Leukocyte Microparticles Generated by the CentriMag Ventricular Assist Device In Vitro

Ventricular assist devices (VADs) are a life‐saving form of mechanical circulatory support in heart failure patients. However, VADs have not yet reached their full potential due to the associated side effects (thrombosis, bleeding, infection) related to the activation and damage of blood cells and proteins caused by mechanical stress and foreign materials. Studies of the effects of VADs on leukocytes are limited, yet leukocyte activation and damage including microparticle generation can influence both thrombosis and infection rates. Therefore, the aim was to develop a multicolor flow cytometry assessment of leukocyte microparticles (LMPs) using ovine blood and the CentriMag VAD as a model for shear stress. Ovine blood was pumped for 6 h in the CentriMag and regular samples analyzed for hemolysis, complete blood counts and LMP by flow cytometry during three different pump operating conditions (low flow, standard, high speed). The high speed condition caused significant increases in plasma‐free hemoglobin; decreases in total leukocytes, granulocytes, monocytes, and platelets; increases in CD45⁺ LMPs as well as two novel LMP populations: CD11b^bright/HLA‐DR^? and CD11b^dull/HLA‐DR⁺, both of which were CD14^?/CD21^?. CD11b^bright/HLA‐DR^? LMPs appeared to respond to an increase in shear magnitude whereas the CD11b^dull/HLA‐DR⁺ LMPs significantly increased in all pumping conditions. We propose that these two populations are released from granulocytes and T cells, respectively, but further research is needed to better characterize these two populations.     

Blood Trauma Testing of CentriMag and RotaFlow Centrifugal Flow Devices: A Pilot Study

Mechanical circulatory assist devices that provide temporary support in heart failure patients are needed to enable recovery or provide a bridge to decision. Minimizing risk of blood damage (i.e., hemolysis) with these devices is critical, especially if the length of support needs to be extended. Hematologic responses of the RotaFlow (Maquet) and CentriMag (Thoratec) temporary support devices were characterized in an in vitro feasibility study. Paired static mock flow loops primed with fresh bovine blood (700 mL, hematocrit [Hct] = 25 ± 3%, heparin titrated for activated clotting time >300 s) pooled from a single‐source donor were used to test hematologic responses to RotaFlow (n = 2) and CentriMag (n = 2) simultaneously. Pump differential pressures, temperature, and flow were maintained at 250 ± 10 mm Hg, 25 ± 2°C, and 4.2 ± 0.25 L/min, respectively. Blood samples (3 mL) were collected at 0, 60, 120, 180, 240, 300, and 360 min after starting pumps in accordance with recommended Food and Drug Administration and American Society for Testing and Materials guidelines. The CentriMag operated at a higher average pump speed (3425 rpm) than the RotaFlow (3000 rpm) while maintaining similar constant flow rates (4.2 L/min). Hematologic indicators of blood trauma (hemoglobin, Hct, platelet count, plasma free hemoglobin, and white blood cell) for all measured time points as well as normalized and modified indices of hemolysis were similar (RotaFlow: normalized index of hemolysis [NIH] = 0.021 ± 0.003 g/100 L, modified index of hemolysis [MIH] = 3.28 ± 0.52 mg/mg compared to CentriMag: NIH = 0.041 ± 0.010 g/100 L, MIH = 6.08 ± 1.45 mg/mg). In this feasibility study, the blood trauma performance of the RotaFlow was similar or better than the CentriMag device under clinically equivalent, worst‐case test conditions. The RotaFlow device may be a more cost‐effective alternative to the CentriMag.     

The Evaluation of Leukocytes in Response to the In Vitro Testing of Ventricular Assist Devices

Infection is a clinically relevant adverse event in patients with ventricular assist device (VAD) support. The risk of infection could be linked to a reduced immune response resulting from damage to leukocytes during VAD support. The purpose of this study was to develop an understanding of leukocyte responses during the in vitro testing of VADs by analyzing the changes to their morphology and biochemistry. The VentrAssist implantable rotary blood pump (IRBP) and RotaFlow centrifugal pump (CP) were tested in vitro under constant hemodynamic conditions. Automated hematology analysis of samples collected regularly over 25‐h tests was undertaken. A new flow cytometric assay was employed to measure biochemical alteration, necrosis (7‐AAD) and morphological alteration (CD45 expression) of the circulating leukocytes during the pumping process. The results of hematology analysis show the total leukocyte number and subset counts decreased over the period of in vitro tests dependent on different blood pumps. The percentage of leukocytes damaged during 6‐h tests was 40.8 ± 5.7% for the VentrAssist IRBP, 17.6 ± 5.4% for the RotaFlow CP, and 2.7 ± 1.8% for the static control (all n = 5). Flow cytometric monitoring of CD45 expression and forward/side scatter characteristics revealed leukocytes that were fragmented into smaller pieces (microparticles). Scanning electron microscopy and imaging flow cytometry were used to confirm this. Device developers could use these robust cellular assays to gain a better understanding of leukocyte‐specific VAD performance.     

Influence of a Rotational Speed Modulation System Used With an Implantable Continuous‐Flow Left Ventricular Assist Device on von Willebrand Factor Dynamics

We have developed a rotational speed (RS) modulation system for a continuous‐flow left ventricular assist device (EVAHEART) that can change RS in synchronization with a patient's electrocardiogram. Although EVAHEART is considered not to cause significant acquired von Willebrand syndrome, there remains a concern that the repeated acceleration and deceleration of the impeller may degrade von Willebrand factor (vWF) multimers. Accordingly, we evaluated the influence of our RS modulation system on vWF dynamics. A simple mock circulation was used. The circulation was filled with whole bovine blood (650 mL), and the temperature was maintained at 37 ± 1°C. EVAHEART was operated using the electrocardiogram‐synchronized RS modulation system with an RS variance of 500 rpm and a pulse frequency of 60 bpm (EVA‐RSM; n = 4). The pumps were operated at a mean flow rate of 5.0 ± 0.2 L/min against a mean pressure head of 100 ± 3 mm Hg. The continuous‐flow mode of EVAHEART (EVA‐C; n = 4) and ROTAFLOW (ROTA; n = 4) was used as controls. Whole blood samples were collected at baseline and every 60 min for 6 h. Complete blood counts (CBCs), normalized indexes of hemolysis (NIH), vWF antigen (vWF:Ag), vWF ristocetin cofactor (vWF:Rco), the ratio of vWF:Rco to vWF:Ag (Rco/Ag), and high molecular weight multimers (HMWM) of vWF were evaluated. There were no significant changes in CBCs throughout the 6‐h test period in any group. NIH levels of EVA‐RSM, EVA‐C, and ROTA were 0.0035 ± 0.0018, 0.0031 ± 0.0007, and 0.0022 ± 0.0011 g/100 L, respectively. Levels of vWF:Ag, vWF:Rco, and Rco/Ag did not change significantly during the test. Immunoblotting analysis of vWF multimers showed slight degradation of HMWM in all groups, but there were no significant differences between groups in the ratios of HMWM to low molecular weight multimers, calculated by densitometry. This study suggests that our RS modulation system used with EVAHEART does not have marked adverse influences on vWF dynamics. The low NIH and the absence of significant decreases in CBCs indicate that EVAHEART is hemocompatible, regardless of whether it is operated with the RS modulation system.     

Evaluation of centrifugal blood pumps in term of hemodynamic performance using simulated neonatal and pediatric ECMO circuits

The objective of this translational study was to evaluate the FDA-approved PediMag, CentriMag, and RotaFlow centrifugal blood pumps in terms of hemodynamic performance using simulated neonatal and pediatric extracorporeal membrane oxygenation (ECMO) circuits with different sizes of arterial and venous cannulae. Cost of disposable pump heads was another important variable for this particular study. The experimental circuit was composed of one of the centrifugal pump heads, a polymethylpentene membrane oxygenator, neonatal and pediatric arterial/venous cannulae, and 1/4-inch ID tubing. Circuits were primed with lactated Ringer’s solution and packed human red blood cells (hematocrit 35%). Trials were conducted at 36°C using the three pump heads and different cannulae (arterial/venous cannulae: 8 Fr/18 Fr, 10 Fr/20 Fr, and 12 Fr/22 Fr) at various flow rates (200–2400 mL/min, 200 mL/min increments) and rotational speeds. Pseudo patient pressure was 60 mm Hg. Real-time pressure and flow data were recorded for analysis. The RotaFlow pump had a higher pressure head and flow range compared with the PediMag and CentriMag pumps at the same rotational speed and identical experimental settings (P < 0.001). The PediMag pump had lower flow output than others (P < 0.001). Small-caliber arterial cannulae and higher flow rates predictably created higher circuit pressures and pressure drops. There was no significant difference in hemodynamic energy delivered to the pseudo patient with each of the three pumps. The arterial cannula had the highest pressure drop and hemodynamic energy loss in the circuit when compared to the oxygenator and arterial tubing. The RotaFlow centrifugal pump had a significantly better hemodynamic performance when compared to the PediMag and CentriMag blood pumps at identical experimental conditions in simulated neonatal and pediatric ECMO settings. In addition, the cost of the RotaFlow pump head ($400) is 20 to 30-fold less than the other centrifugal pumps [CentriMag ($12 000) or PediMag ($8000)] that were evaluated in this translational study.     

Modification of a Pivot Bearing System on a Compact Centrifugal Pump

Abstract: The pivot bearing centrifugal blood pump was developed as a long-term centrifugal ventricular assist device (VAD) as well as a cardiopulmonary bypass pump. This pivot bearing supported centrifugal pump with an eccentric port (C1E) incorporates a seal-less design with a blood stagnation-free structure. This pump can provide flows of 12 L/min against 650 mm Hg total pressure head at 3,600 rpm, and in a CPB condition 5 L/min against 350 mm Hg total pressure head at 2,600 rpm. Very recently, the pivot bearing system was modified to obtain a stable and smooth spinning movement. The material of the female pivot was changed from ceramic to polyethylene. Three kinds of bearings were tested simultaneously with bovine blood in two types of in vitro circuits to determine the blood damage from the bearings. Pressure differences across the pump (total head pressure, A/¹) of 140 mm Hg (n = 12) and 330 mm Hg (n = 12) were examined. The normalized index of hemolysis (NIH) was slightly higher in a ball bearing (BB) pump than in a polyethylene bearing (PB) pump and statistically higher than the BioMedicus Pump (BP-80) on ΔP of 140 mm Hg. When the ΔP was at 330 mm Hg, a comparison between the three types of pumps revealed no difference in NIH. In addition, the primary vane of the impeller was redesigned to obtain an atraumatic structure. In the second study (n = 14), there was no difference in the NIH between BP-80 and the current model when the A/⁵ was 300 mm Hg (0.019 ± 0.002 vs. 0.027 ± 0.006, p = 0.3) and/or when the A/¹ was 100 mm Hg (0.0008 ± 0.0001 vs. 0.0014 ± 0.0002, p = 0.07). The modified pivot bearing had an improved spinning condition and no change in hemolysis. A proper selection of pivot bearing materials is important to develop an atraumatic centrifugal pump. The modification of the bearing system and redesign of the vane enabled a compact centrifugal pump to become a reality.     

Preclinical Models for Translational Investigations of Left Ventricular Assist Device‐Associated von Willebrand Factor Degradation

Evidence suggests a major role for von Willebrand factor (vWF) in left ventricular assist device (LVAD)‐associated bleeding. However, the mechanisms of vWF degradation during LVAD support are not well understood. We developed: (i) a simple and inexpensive vortexer model; and (ii) a translational LVAD mock circulatory loop to perform preclinical investigations of LVAD‐associated vWF degradation. Whole blood was obtained from LVAD patients (n = 8) and normal humans (n = 15). Experimental groups included: (i) blood from continuous‐flow LVAD patients (baseline vs. post‐LVAD, n = 8); (ii) blood from normal humans (baseline vs. 4 h in vitro laboratory vortexer, ～ 2400 rpm, shear stress ～175 dyne/cm², n = 8); and (iii) blood from normal humans (baseline vs. 12 h HeartMate II mock circulatory loop, 10 000 rpm, n = 7). vWF multimers and degradation fragments were characterized with electrophoresis and immunoblotting. Blood from LVAD patients, blood exposed to in vitro supraphysiologic shear stress, and blood circulated through an LVAD mock circulatory loop demonstrated a similar profile of decreased large vWF multimers and increased vWF degradation fragments. A laboratory vortexer and an LVAD mock circulatory loop reproduced the pathologic degradation of vWF that occurs during LVAD support. Both models are appropriate for preclinical studies of LVAD‐associated vWF degradation.     

Computational modeling of the Food and Drug Administration’s benchmark centrifugal blood pump

In order to simulate hemodynamics within centrifugal blood pumps and to predict pump hemolysis, CFD simulations must be thoroughly validated against experimental data. They must also account for and accurately model the specific working fluid in the pump, whether that is a blood-analog solution to match an experimental PIV study or animal blood in a hemolysis experiment. Therefore, the Food and Drug Administration (FDA) benchmark centrifugal blood pump and its database of experimental PIV and hemolysis data were used to thoroughly validate CFD simulations of the same blood pump. A Newtonian blood model was first used to compare to the PIV data with a blood analog fluid while hemolysis data were compared using a power-law hemolysis model fit to porcine blood data. A viscoelastic blood model was then incorporated into the CFD solver to investigate the importance of modeling blood’s viscoelasticity in centrifugal pumps. The established computational framework, including a dynamic rotating mesh, animal blood-specific fluid properties and hemolysis modeling, and a k-ω SST turbulence model, was shown to more accurately predict pump pressure heads, velocity fields, and hemolysis compared to previously published CFD studies of the FDA centrifugal pump. The CFD simulations were able to match the FDA pressure and hemolysis data for multiple pump operating conditions, with the CFD results being within the standard deviations of the experimental results. While CFD radial velocity profiles between the impeller blades also compared well to the PIV velocity results, more work is still needed to address the large variability among both experimental and computational predictions of velocity in the diffuser outlet jet. Small differences were observed between the Newtonian and viscoelastic blood models in pressure head and hemolysis at the higher flow rate cases (FDA Conditions 4 and 5) but were more significant at lower flow rate and pump impeller speeds (FDA Condition 1). These results suggest that the importance of accounting for blood’s viscoelasticity may be dependent on the specific blood pump operating conditions. This detailed computational framework with improved modeling techniques and an extensive validation procedure will be used in future CFD studies of centrifugal blood pumps to aid in device design and predictions of their biological responses.     

An estimation method of hemolysis within an axial flow blood pump by computational fluid dynamics analysis

Evaluation of hemolysis within a blood pump on a computer is useful for developing rotary blood pumps. The flow fields in the axial flow blood pump were analyzed using computational fluid dynamics (CFD). A blood damage index was calculated based on the changes in shear stress with time along 937 streamlines. Hemolysis of the pumps was measured using bovine blood. A good correlation between the computed and measured hemolysis results was observed. CFD analysis is useful for estimating hemolysis of rotary blood pumps on a computer.     

Computational and experimental evaluation of the fluid dynamics and hemocompatibility of the CentriMag blood pump

The CentriMag centrifugal blood pump is a newly developed ventricular assist device based on magnetically levitated bearingless rotor technology. A combined computational and experimental study was conducted to characterize the hemodynamic and hemocompatibility performances of this novel blood pump. Both the three-dimensional flow features of the CentriMag blood pump and its hemolytic characteristics were analyzed using computational fluid dynamics (CFD)-based modeling. The hydraulic pump performance and hemolysis level were quantified experimentally. The CFD simulation demonstrated a clean and streamlined flow field in the main components of the CentriMag blood pump. The predicted results by hemolysis model indicated no significant high shear stress regions in the pump. A comparison of CFD predictions and experimental results showed good agreements. The relatively large gap passages (1.5 mm) between the outer rotor walls and the lower housing cavity walls provide a very good surface washing through a secondary flow path while the shear stresses in the secondary flow paths are reduced, resulting in a low rate of hemolysis ([Normalized Index of Hemolysis] NIH = 0.0029 +/- 0.006) without a decrease of the pump's hydrodynamic performance (pressure head: 352 mm Hg at a flow rate of 5.0 L/min and a rotational speed of 4,000 rpm).     

Device‐induced platelet dysfunction in mechanically assisted circulation increases the risks of thrombosis and bleeding

Thrombotic and bleeding complications are the major obstacles for expanding mechanical circulatory support (MCS) beyond the current use. While providing the needed hemodynamic support, those devices can induce damage to blood, particularly to platelets. In this study, we investigated device‐induced alteration of three major platelet surface receptors, von Willebrand factor (VWF) and associated hemostatic functions relevant to thrombosis and bleeding. Fresh human whole blood was circulated in an extracorporeal circuit with a clinical rotary blood pump (CentriMag, Abbott, Chicago, IL, USA) under the clinically relevant operating condition for 4 hours. Blood samples were examined every hour for glycoprotein (GP) IIb/IIIa activation and receptor loss of GPVI and GPIbα on the platelet surface with flow cytometry. Soluble P‐selectin in hourly collected blood samples was measured by enzyme linked immunosorbent assay to characterize platelet activation. Adhesion of device‐injured platelets to fibrinogen, collagen, and VWF was quantified with fluorescent microscopy. Device‐induced damage to VWF was characterized with western blotting. The CentriMag blood pump induced progressive platelet activation with blood circulating time. Particularly, GPIIb/IIIa activation increased from 1.1% (Base) to 11% (4 hours) and soluble P‐selectin concentration increased from 14.1 ng/mL (Base) to 26.5 ng/mL (4 hours). Those device‐activated platelets exhibited increased adhesion capacity to fibrinogen. Concurrently, the CentriMag blood pump caused progressive platelet receptor loss (GPVI and GPIbα) with blood circulating time. Specifically, MFI of the GPVI and GPIbα receptors decreased by 17.2% and 16.1% for the 4‐hours sample compared to the baseline samples, respectively. The device‐injured platelets exhibited reduced adhesion capacities to collagen and VWF. The high molecular weight multimers (HMWM) of VWF in the blood disappeared within the first hour of the circulation. Thereafter the multimeric patterns of VWF were stable. The change in the VWF multimeric pattern was different from the progressive structural and functional changes of platelets with the circulation time. This study suggested that the CentriMag blood pump could induce two opposite effects on platelets and associated hemostatic functions under a clinically relevant operating condition. The device‐altered hemostatic function may contribute to thrombosis and bleeding simultaneously as occurring in patients supported by a rotary blood pump. Device‐induced damage of platelets may be an important cause for bleeding in patients supported with rotary blood pump MCS systems relative to device‐induced loss of HMWM‐VWF.     

Comparative Hemolysis Study of Clinically Available Centrifugal Pumps

Abstract
Centrifugal pumps have become important devices for cardiopulmonary bypass and circulatory assistance. Five types of centrifugal pumps are clinically available in Japan. To evaluate the blood trauma caused by centrifugal pumps, a comparative hemolysis study was performed under identical conditions. In vitro hemolysis test circuits were constructed to operate the BioMedicus BP-80 (Medtronic, BioMedicus), Sams Delphin (Sarns/3M Healthcare), Isoflow (St. Jude Medical [SJM]), HPM-15 (Nikkiso), and Capiox CX-SP45 (Terumo). The hemolysis test loop consisted of two 1.5 m lengths of polyvinyl chloride tubing with a 3/8 -inch internal diameter, a reservoir with a sampling port, and a pump head. All pumps were set to flow at 6 L/min against the total pressure head of 120 mm Hg. Experiments were conducted simultaneously for 6 h at room temperature (21^oC) with fresh bovine blood. Blood samples for plasma-free hemoglobin testing were taken, and the change in temperature at the pump outlet port was measured during the experiment. The mean pump rotational speeds were 1,570, 1,374, 1,438, 1,944, and 1,296 rpm, and the normalized indexes of hemolysis were 0.00070, 0.00745, 0.00096, 0.00066, 0.00090 g/100 L for the BP-80, Sarns, SJM, Nikkiso, and Terumo pumps, respectively. The change in temperature at the pump outlet port was the least for the Nikkiso pump (1.8^oC) and the most with the SJM pump (3.8^oC). This study showed that there is no relationship between the pump rotational speed (rpm) and the normalized index of hemolysis in 5 types of centrifugal pumps. The pump design and number of impellers could be more notable factors in blood damage.     

New Method of Evaluating Sublethal Damage to Erythrocytes by Blood Pumps

Abstract We recently proposed a new concept, the total destruction time of erythrocytes, to indicate sublethal damage to erythrocytes by blood pumps. In this article, results of additional experiments concerning this new concept are reported. Five paired in vitro hemolysis tests with bovine blood were conducted using a cone-type centrifugal pump (Group A) and an impeller-type pump (Group B). A total pressure head of 100 mm Hg was applied. The factors evaluated were the normalized index of hemolysis and the total destruction time, or the pumping duration, required to raise the level of the plasma-free hemoglobin to 50% of the total hemoglobin. The morphologic change of the erythrocytes also was analyzed. The percentage of crenated cells was calculated from blood smear specimens 1 min after starting the pumps and 2 h before the total destruction time of Group A in each experiment. Although there was no statistical difference in the normalized index of hemolysis between the two groups, the total destruction time of Group A erythrocytes was significantly shorter than that of Group B (18.9 ± 4.5 h and 33.7 ± 9.9 h in Group A and group B, respectively; p < 2). The rate of crenated erythrocytes was higher in Group A than in Group B at a point 2 h before the total destruction time of Group A. The total destruction time values seem to define a good method for establishing sublethal traumatic damage to erythrocytes in blood pumps.     

Hemocompatibility of Axial Versus Centrifugal Pump Technology in Mechanical Circulatory Support Devices

The hemocompatible properties of rotary blood pumps commonly used in mechanical circulatory support (MCS) are widely unknown regarding specific biocompatibility profiles of different pump technologies. Therefore, we analyzed the hemocompatibility indicating markers of an axial flow and a magnetically levitated centrifugal device within an in vitro mock loop. The HeartMate II (HM II; n = 3) device and a CentriMag (CM; n = 3) adult pump were investigated in a human whole blood mock loop for 360 min using the MCS devices as a driving component. Blood samples were analyzed by enzyme‐linked immunosorbent assay for markers of coagulation, complement system, and inflammatory response. There was a time‐dependent activation of the coagulation (thrombin–antithrombin complexes [TAT]), complement (SC5b‐9), and inflammation system (polymorphonuclear [PMN] elastase) in both groups. The mean value of TAT (CM: 4.0 μg/L vs. 29.4 μg/L, P < 0.001; HM II: 4.5 μg/L vs. 232.2 μg/L, P < 0.05) and PMN elastase (CM: 53.4 ng/mL vs. 253.8 ng/mL, P < 0.05; HM II: 28.0 ng/mL vs. 738.8 ng/mL, P < 0.001) significantly increased from baseline until the end of the experiments (360 min). After 360 min, TAT and PMN values were significantly higher in the HM II group compared with the values in the CM adult group. The values of SC5b‐9 increased from baseline to 360 min in the CM group (CM: 141.8 ng/mL vs. 967.9 ng/mL, P < 0.05) and the HM II group. However, the increase within the HM II group (97.3 vs. 2462.0, P = 0.06) and the comparison of the 360‐min values between CM group and HM II group did not reach significance (P = 0.18). The activation of complement, coagulation, and inflammation system showed a time‐dependent manner in both devices. The centrifugal CM device showed significantly lower activation of coagulation and inflammation than that of the HM II axial flow pump. Both HM II and CM have demonstrated an acceptable hemocompatibility profile in patients. However, there is a great opportunity to gain a clinical benefit by developing techniques to lower the blood surface interaction within both pump technologies and a magnetically levitated centrifugal pump design might be superior.     

Timely use of a CentriMag heart assist device improves survival in postcardiotomy cardiogenic shock

Abstract Background: Postcardiotomy cardiogenic shock (PCS) is often fatal despite inotropic and circulatory support. We compared our experience with the CentriMag left ventricular assist device (LVAD) for patients with PCS at two time periods: in the operating room (OR) after unsuccessful weaning from cardiopulmonary bypass (CPB) and after transfer to the intensive care unit (ICU). Methods: We reviewed 22 patients’ records (13 men, nine women; age, 65 ± 12 years) who underwent open heart surgery (January 2004 to September 2009) and required LVAD support for PCS despite maximal inotropic and intra‐aortic balloon pump (IABP) support. In ten patients who could not be weaned from CPB despite high‐dose inotropic therapy (≥ 3 agents) and IABP support, the CentriMag was implanted in the OR (immediate group). The other 12 patients were weaned from CPB with high‐dose inotropic therapy and IABP but became increasingly unstable or had a cardiac arrest in the ICU, and the CentriMag was implanted for circulatory support (delayed group). Results: Preoperatively, the average ejection fraction was 40%± 12%, the creatinine level was 1.6 ± 0.6 mg/dL, and the European Systematic Coronary Risk Evaluation was 13.1 ± 4.6. The duration of CentriMag support was 5 ± 3 days. The immediate group had significantly better survival (7/10 vs. 2/12, p = 0.027), higher cardiac index (2.4 ± 0.3 L/min/m² vs. 1.7 ± 0.3 L/min/m², p = 0.001), and lower pulmonary capillary wedge pressure (20 ± 6 mmHg vs. 29 ± 8 mmHg, p = 0.024) than the ICU group. No perioperative complications related to device implantation occurred. Conclusion: In patients with PCS, timely placement of a CentriMag LVAD may increase the chance of eventual recovery. (J Card Surg 2011;26:548‐552)     

Hemolysis in Different Centrifugal Pumps

Abstract: Different types of centrifugal pumps cause different amounts of hemolysis based on shear stress and blood exposure time. However, the hemolytic characteristics of centrifugal pumps in each clinical condition are not always clear. We compared the hemolytic characteristics of one cone-type centrifugal pump (Medtronic Bio-Medicus BP-80) and 2 impeller-type centrifugal pumps (Nikkiso HMS-12 and Terumo Capiox) under experimental conditions simulating their use in cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), and percutaneous cardiopulmonary support (PCPS) as well as their use as left ventricular assist devices (LVADs). The normalized indexes of hemolysis (NIHs; grams free plasma hemoglobin per 100 L blood pumped) during use as LVADs were not significantly different among the 3 pumps. The BP-80 pump produced almost 3–fold more hemolysis than the HMS-12 and Capiox pumps during CPB, 3– to 4–fold more hemolysis during ECMO, and 5.5–fold more hemolysis during PCPS. The 2 impeller-type centrifugal pumps will therefore cause less hemolysis under high flow, high pressure difference (as in CPB) and low flow, high pressure difference (as in ECMO and PCPS) conditions than the cone-type pump.     

Evaluation of Platelet Damage in Two Different Centrifugal Pumps Based on Measurements of α-Granule Packing Proteins

Abstract Mechanical trauma caused by centrifugal pumps is usually evaluated in terms of hemolysis. However, platelet damage caused by centrifugal pumps has not been studied well. We evaluated platelet damage in 2 different centrifugal pumps, the Medtronic BioMedicus BP-80 and the Terumo Capiox, in vitro and compared the results in terms of hemolysis. To evaluate platelet damage, the rate of increase (RI) for β -thromboglobulin (β-TG) and platelet factor-4 (PF-4) were measured by enzyme immunoassay. RI was defined as follows: RI for β-TG is Δβ-TG/ΔN and RI for PF-4 is Δ PF-4/ΔN where Δβ-TG is the increase in β-TG, ΔPF-4 is the increase in PF-4, and ΔN is the increase of the passing number, which is defined in the following equation: N = Q_r / V ( t , time; V , priming volume; Q , flow rate). Each pump was tested in a mock circuit for 3 h under a flow rate of 5 L/min and a pressure head of 100 mm Hg using fresh human heparinized blood (n = 5). For comparison, the normalized index of hemolysis (NIH) values were calculated for both pumps. The NIH values did not indicate a significant difference between the Capiox and the BP-80 pumps (Capiox vs. BP-80, 0.0021 ± 0.0004 vs. 0.0034 ± 0.0007, NS). However, the RI values for β-TG and PF-4 in the Capiox were significantly lower than in the BP-80 (β-TG, 0.198 ± 0.047 vs. 0.376 ± 0.049; PF-4, 0.080 ± 0.014 vs. 0.268 ± 0.043, p < 0.05). In conclusion, although there was no significant difference between the 2 pumps in terms of hemolysis, the Capiox centrifugal pump induced less platelet damage than the BP-80. The results suggest that measurements of RI for β-TG and PF-4 are more sensitive parameters than NIH values for evaluating blood cell damage.     

Computational fluid dynamics analysis of an intra-cardiac axial flow pump

A low rate of hemolysis is an important factor for the development of a rotary blood pump. It is, however, difficult to identify the areas where hemolysis occurs. Computational fluid dynamics (CFD) analysis enables the engineer to predict hemolysis on a computer. In this study, fluid dynamics throughout intracardiac axial flow pumps with different designs were analyzed three-dimensionally using CFD software. The computed pressure-flow characteristics of the pump were in good agreement with the measurements. The Reynolds shear stress was computed along particle trace lines. Hemolysis was estimated on the basis of shear stress (tau) and its exposure time (Deltat): dHb/Hb = 3.62 x 10(-7)(tau)(i)(2.416) x Delta(t)(i)(0.785). Particle damage increased with time along the particle trace lines. Hemolysis of each of the pumps was measured in vitro. The computed hemolysis values were in good agreement with the experimental results. CFD is a useful tool for developing a rotary blood pump.     

Paradoxical Effect of Nonphysiological Shear Stress on Platelets and von Willebrand Factor

Blood can become hypercoagulable by shear‐induced platelet activation and generation of microparticles. It has been reported that nonphysiological shear stress (NPSS) could induce shedding of platelet receptor glycoprotein (GP) Ibα, which may result in an opposite effect to hemostasis. The aim of this study was to investigate the influence of the NPSS on platelets and von Willebrand factor (vWF). Human blood was exposed to two levels of NPSS (25 Pa, 125 Pa) with an exposure time of 0.5 s, generated by using a novel blood‐shearing device. Platelet activation (P‐selectin expression, GPIIb/IIIa activation and generation of microparticles) and shedding of three platelet receptors (GPIbα, GPVI, GPIIb/IIIa) in sheared blood were quantified using flow cytometry. Aggregation capacity of sheared blood induced by ristocetin and collagen was evaluated using an aggregometer. Shear‐induced vWF damage was characterized with Western blotting. Consistent with the published data, the NPSS caused significantly more platelets to become activated with increasing NPSS level. Meanwhile, the NPSS induced the shedding of platelet receptors. The loss of the platelet receptors increased with increasing NPSS level. The aggregation capacity of sheared blood induced by ristocetin and collagen decreased. There was a loss of high molecular weight multimers (HMWMs) of vWF in sheared blood. These results suggest that the NPSS induced a paradoxical effect. More activated platelets increase the risk of thrombosis, while the reduction in platelet receptors and the loss of HMWM‐vWF increased the propensity of bleeding. The finding might provide a new perspective to understand thrombosis and acquired bleeding disorder in patients supported with blood contacting medical devices.     

In Vivo Assessment of a New Method of Pulsatile Perfusion Based on a Centrifugal Pump

The aim of this study was to assess platelet dysfunction and damage to organs after extracorporeal circulation using a pump based on a new method that adds a pulsatile flow to the continuous flow provided by a centrifugal pump. The continuous component of the total flow (2–3 L/min) is created by a Bio‐Pump centrifugal pump, while the pulsatile component is created by the pulsating of an inner membrane pneumatically controlled by an intra‐aortic counterpulsation balloon console (systolic volume of 37.5 mL in an asynchronous way with a frequency of 60 bpm). Six pigs were subjected to a partial cardiopulmonary bypass lasting 180 min and were sacrificed 60 min after extracorporeal circulation was suspended. The hematological study included the measurement of hematocrit, hemoglobin, leukocytes, and platelet function. The new pump did not significantly alter either platelet count or platelet function. In contrast, hematocrit and hemoglobin were significantly reduced during extracorporeal circulation (approximately 5% P = 0.011, and 2 g/dL P = 0.01, respectively). The leukocyte count during extracorporeal circulation showed a tendency to decrease, but this was not significant. In general, the short‐term use of the new pump (4 h) did not cause any serious morphological damage to the heart, lung, kidney, or liver. The results suggest that the hemodynamic performance of the new pump is similar to a conventional centrifugal pump and could therefore be appropriate for use in extracorporeal circulation.