scholarly journals Ghost Cells for Mechanical Circulatory Support In Vitro Testing: A Novel Large Volume Production

2020 ◽  
Vol 15 (4) ◽  
pp. 1900239
Author(s):  
Malte Schöps ◽  
Johanna C. Clauser ◽  
Matthias F. Menne ◽  
Dennis Faßbänder ◽  
Thomas Schmitz‐Rode ◽  
...  
2020 ◽  
Vol 43 (11) ◽  
pp. 710-718
Author(s):  
Nicholas Roberts ◽  
Uma Chandrasekaran ◽  
Soumen Das ◽  
Zhongwei Qi ◽  
Scott Corbett

Introduction: Short-term mechanical circulatory support devices provide temporary hemodynamic support in heart failure and are increasingly used to enable recovery or as a bridge to decision. Blood damage with mechanical circulatory support devices is influenced by many factors, including the magnitude and duration of shear stress and obstruction to blood flow. This study aimed to evaluate the effects of the Impella CP® heart pump positioning on hemolysis using in vitro hemolysis testing and computational fluid dynamics modeling. Methods: The in vitro hemolysis testing was conducted per the recommended Food and Drug Administration and American Society for Testing and Materials guidelines. The bench hemolysis testing and computational fluid dynamics simulation analysis were performed for both normal operating (outlet unobstructed) and outlet-obstructed condition of Impella CP (mimicking outlet on the aortic valve due to improper positioning). Results: The modified index of hemolysis was 2.78 ± 0.69 at normal operating conditions compared to 18.7 ± 7.8 when the Impella CP outlet was obstructed ( p = 0.002). Computational fluid dynamics modeling showed about three times increase in exposure time to regions of high shear stress when the Impella CP outlet was obstructed compared to unobstructed condition, thus supporting the experimental observations. Conclusion: Based on these results, it is recommended to ensure proper placement of Impella CP via regular monitoring using echocardiographic guidance or other methods to minimize the risk of hemolysis associated with an obstructed outflow.


2013 ◽  
Vol 37 (6) ◽  
pp. 549-560 ◽  
Author(s):  
Paula Ruiz ◽  
Mohammad Amin Rezaienia ◽  
Akbar Rahideh ◽  
Thomas R. Keeble ◽  
Martin T. Rothman ◽  
...  

2010 ◽  
Vol 4 (3) ◽  
Author(s):  
Dennis R. Trumble ◽  
Marshall Norris ◽  
Alan Melvin

Harnessing skeletal muscle for circulatory support would improve on current blood pump technologies by eliminating infection-prone drivelines and cumbersome transcutaneous energy transmission systems. Toward that end, we have built and tested an implantable muscle energy converter (MEC) designed to transmit the contractile energy of the latissimus dorsi muscle in hydraulic form. The MEC weighs less than 300 g and comprises a metallic bellows formed from AM350 stainless steel actuated by a rotary cam (440C) attached to a titanium rocker arm (Ti–6Al–4V). The rocker arm is fixed to the humeral insertion of the muscle via a looped artificial tendon developed specifically for this purpose. The device housing (Ti–6Al–4V) is anchored to the ribcage using a perforated mounting ring and a wire suture. Lessons learned through seven previous design iterations have produced an eighth-generation pump with excellent durability, energy transfer efficiency, anatomic fit, and tissue interface characteristics. This report describes recent improvements in MEC design and summarizes results from in silico and in vitro testing. Long-term implant studies will be needed to confirm these findings prior to clinical testing.


2015 ◽  
Vol 39 (6) ◽  
pp. 502-513 ◽  
Author(s):  
Mohammad Amin Rezaienia ◽  
Akbar Rahideh ◽  
Borhan Alhosseini Hamedani ◽  
Dawid Emanuel Maximilian Bosak ◽  
Silviya Zustiak ◽  
...  

2021 ◽  
Author(s):  
Moritz K. Brockhaus ◽  
Mehdi J. Behbahani ◽  
Farina Muris ◽  
Sebastian V. Jansen ◽  
Thomas Schmitz‐Rode ◽  
...  

Author(s):  
Yana Roka-Moiia ◽  
Samuel Miller-Gutierrez ◽  
Daniel E. Palomares ◽  
Joseph E. Italiano ◽  
Jawaad Sheriff ◽  
...  

Objective: Mechanical circulatory support has emerged as lifesaving therapy for patients with advanced heart failure. However, mechanical circulatory support remains limited by a paradoxical coagulopathy accompanied by both thrombosis and bleeding. While mechanisms of mechanical circulatory support thrombosis are increasingly defined, mechanical circulatory support-related bleeding, as related to shear-mediated alteration of platelet function, remains poorly understood. We tested the hypothesis that platelet exposure to elevated shear stress, while a defined prothrombotic activator of platelets, coordinately induces downregulation of key platelet adhesion receptors GPIb (glycocalicin)-IX-V, α IIb β 3 , and P-selectin, thus decreasing platelet functional responsiveness to physiological stimuli. Approach and Results: Human gel-filtered platelets were exposed to continuous or pulsatile shear stress in vitro. Surface expression of platelet receptors and platelet-derived microparticle generation were quantified by flow cytometry. Shedding of receptor soluble forms were assessed via ELISA, and platelet aggregation was measured by optical aggregometry. We demonstrate that platelet exposure to elevated shear stress led to a downregulation of GPIb and α IIb β 3 receptors on platelets with a progressive increase in the generation of platelet-derived microparticles expressing elevated levels of α IIb β 3 and GPIb on their surface. No shear-mediated shedding of GPIb and β 3 subunit soluble fragments was detected. Soluble P-selectin was extensively shed from platelets, while surface expression of P-selectin on platelets and microparticles was not significantly altered by shear. Shear-mediated downregulation of GPIb, α IIb β 3 , and P-selectin on platelets was associated with an evident decrease of platelet aggregatory response induced by ADP and TRAP 6 (thrombin receptor activating peptide 6). Conclusions: Our data clearly indicate that accumulation of shear stress, consistent with supraphysiologic conditions characterizing device-supported circulation (1) induces adequate platelet degranulation, yet (2) causes downregulation of primary platelet adhesion receptors via ejection of receptor-enriched platelet-derived microparticles, thus mechanistically limiting platelet activation and the aggregatory response.


2014 ◽  
pp. n/a-n/a
Author(s):  
Mohammad Amin Rezaienia ◽  
Akbar Rahideh ◽  
Martin Terry Rothman ◽  
Scott A. Sell ◽  
Kyle Mitchell ◽  
...  

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S.J Deconinck ◽  
C Nix ◽  
E Bennek-Schopping ◽  
A Rauch ◽  
E Roose ◽  
...  

Abstract Introduction Bleeding is the most frequent adverse event in patients with continuous flow mechanical circulatory support (CF-MCS) and has been linked to the occurrence of acquired von Willebrand syndrome (aVWS). MCS devices cause an increased shear-induced proteolysis of von Willebrand factor (VWF) by ADAMTS13, leading to aVWS. Hence, specifically blocking ADAMTS13 might be an efficient way to rescue the loss of HMW VWF multimers in CF-MCS patients. Purpose To investigate if blocking ADAMTS13, using an in-house developed inhibitory anti-ADAMTS13 monoclonal antibody (mAb), prevents the loss of high molecular weight (HMW) VWF multimers in in vitro CF-MCS systems and to determine the efficacy of this therapy in a CF-MCS calf model. Methods Human blood was perfused through in vitro CF-MCS systems (Heartmate II and Impella CP, axial flow heart pumps) in the presence of the inhibitory or control mAb (20 μg/mL). Bovine blood was perfused through an in vitro Impella 5.5 system with the inhibitory mAb (20 μg/mL) or PBS. Next, Impella 5.5 pumps were implanted in calves. One dose of the inhibitory mAb (600 μg/kg) or PBS was injected eight days after Impella implantation. Plasma samples were analysed for VWF multimers, VWF antigen (VWF:Ag) and VWF collagen binding activity (VWF:CB). Results A time-dependent decrease in HMW VWF multimers was observed in both in vitro CF-MCS systems in the presence of the control mAb, leading to a 70% reduction of HMW VWF multimers, 180 minutes (min) after blood perfusion (p=0.01 for HM II and p=0.0003 for Impella). This was also reflected by a severely decreased VWF:CB/VWF:Ag ratio (0.59±0.11 and 0.52±0.10 at 180 min versus 1.00±0.06 and 1.07±0.09 before perfusion, for the HM II (p=0.03) and Impella (p=0.001) respectively). Interestingly, blocking ADAMTS13 using the inhibitory mAb prevented the loss of HMW VWF multimers in both systems (p=0.50 for the HM II and p=0.06 for the Impella, 180 min after the start of perfusion). The preservation of HMW VWF multimers was also reflected by normal VWF:CB/VWF:Ag ratios (0.92±0.16 and 0.97±0.11 at 180 min versus 0.93±0.09 and 1.19±0.12 before perfusion for the HM II (p=0.75) and Impella (p=0.06) respectively). Blocking bovine ADAMTS13 using the inhibitory mAb could prevent the loss of HMW VWF multimers in the in vitro Impella 5.5 system, showing that the calf is a good preclinical animal model to study the in vivo effect of this novel therapy. Impella implantation in the calves led to a decrease in HMW VWF multimers (Figure 1A and B). Hence, this animal model represents the VWF laboratory features of MCS-induced aVWS. Moreover, the loss of HMW VWF multimers after pump implantation could be rescued after injection of the inhibitory mAb (Figure 1A and B). Conclusion Blocking ADAMTS13 rescues MCS-induced VWF proteolysis in calves. Hence, inhibiting ADAMTS13 function could become a promising therapeutic strategy to rescue aVWS-induced bleeding in MCS patients. Figure 1. Impella calf model Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Fund for Scientific Research Flanders


2008 ◽  
Vol 7 ◽  
pp. 173-173
Author(s):  
A GKOUZIOUTA ◽  
E LEONTIADIS ◽  
S ADAMOPOULOS ◽  
A MANGINAS ◽  
G KARAVOLIAS ◽  
...  

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