Blood-contacting Surfaces Research Articles

Fabrication and Short-Term in Vivo Performance of a Natural Elastic Lamina-Polymeric Hybrid Vascular Graft.

Although significant advances have been made in the development of artificial vascular grafts, small-diameter grafts still suffer from excessive platelet activation, thrombus formation, smooth muscle cell intimal hyperplasia, and high occurrences of restenosis. Recent discoveries demonstrating the excellent blood-contacting properties of the natural elastic lamina have raised the possibility that an acellular elastic lamina could effectively serve as a patent blood-contacting surface in engineered vascular grafts. However, the elastic lamina alone lacks the requisite mechanical properties to function as a viable vascular graft. Here, we have screened a wide range of biodegradable and biostable medical-grade polymers for their ability to adhere to the outer surface of the elastic lamina and allow cellular repopulation following engraftment in the rat abdominal aorta. We demonstrate a novel method for the fabrication of elastic lamina-polymeric hybrid small-diameter vascular grafts and identify poly(ether urethane) (PEU 1074A) as ideal for this purpose. In vivo results demonstrate graft patency over 21 days, with low thrombus formation, mild inflammation, and the general absence of smooth muscle cell hyperplasia on the graft's luminal surface. The results provide a new direction for developing small-diameter vascular grafts that are mass-producible, shelf-stable, and universally compatible due to a lack of immune response and inhibit the in-graft restenosis response that is common to nonautologous materials.

Animal studies with the Carmat bioprosthetic total artificial heart.

The Carmat bioprosthetic total artificial heart (TAH) contains bioprosthetic blood-contacting surfaces, and is designed for orthotopic cardiac replacement. In preparation for clinical studies, we evaluated the TAH performance and its effects on end-organ function in an animal model. Twelve female Charolais calves, 2-3 months of age and weighing 102-122 kg, were implanted with the TAH through a mid-sternotomy to ensure an adequate anatomic fit. The intended support duration was 4-10 days. Haematological values, creatinine, bilirubin and lactate levels were measured and mean arterial and central venous pressure, central venous oxygen saturation and TAH parameters were monitored. The calves were placed in a cage immediately postoperatively, and extubated on postoperative day 1 in most cases. Average support duration was 3 days, with 4 of 12 calves supported for 4, 4, 8 and 10 days. The initial procedures were used to refine surgical techniques and postoperative care. Pump output ranged from 7.3 to 10 l/min. Haemodynamic parameters and blood analysis were within acceptable ranges. No device failures occurred. No anticoagulation was used in the postoperative phase. The calves were euthanized in case of discomfort compromising the animal well-being, such as respiratory dysfunction, severe blood loss and cerebral dysfunction. Device explant analysis showed no thrombus formation inside the blood cavities. Histological examination of kidneys showed isolated micro-infarction in 2/12 animals; brain histology revealed no thromboembolic depositions. The Carmat bioprosthetic TAH implanted in calves up to 10 days provided adequate blood flow to organs and tissues. Low levels of haemolysis and no visible evidence of thromboembolic depositions in major organs and device cavities, without the use of anticoagulation, may indicate early-phase haemocompatibility of the TAH.

Construction of d-α-tocopheryl polyethylene glycol succinate/PEO core-shell nanofibers on a blood-contacting surface to reduce the hemolysis of preserved erythrocytes.

The hemolysis of erythrocytes is a big obstacle to the development of new non-plasticizer polymer containers for erythrocyte preservation. To construct a long-term anti-hemolytic surface of a plasticizer-free polymer, we coaxially electrospin core-shell structured d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)/poly(ethylene oxide) nanofibers on the surface of a styrene-b-(ethylene-co-butylene)-b-styrene (SEBS) elastomer that is covered with grafted poly(ethylene glycol) (PEG) chains. Our strategy is based on the fact that the grafted layers of PEG reduce mechanical damage to red blood cells (RBCs) while the TPGS released from the nanofibers on a blood-contacting surface can act as an antioxidant to protect RBCs from oxidative damage. We demonstrate that TPGS/PEO core-shell structured nanofibers have been well prepared on the surface of PEG modified SEBS; the controlled release of TPGS in distilled water is obtained and the release can last for almost 4 days at 4 °C; during RBC preservation, TPGS acts as the antioxidant to decrease the membrane oxidation and hemolysis of RBCs. Our work paves a new way for the development of non-plasticizer polymers for RBC preservation, which may be helpful for the fabrication of long-term anti-hemolytic biomaterials in vivo.

Abstract 19810: A Significant Decrease in Early Confirmed Left Ventricular Assist Device Pump Thrombosis: Recent Observations from a Large Multi-Institutional Experience

Introduction: Recent reports have documented an abrupt increase in 3-month confirmed HeartMate II left ventricular assist device (LVAD) thrombosis beginning in 2011 without a plateau observed to date. Because very little data exist from multi-institutional efforts, we report our experience. Methods: From January 2004 to December 2013, 516 pt underwent HeartMate II LVAD implant at three institutions (University of Michigan (n=254), Mayo Clinic Rochester (n=205), and Vanderbilt Heart and Vascular Institute (n=57)). Median age at implant was 60 yr (range, 18-82) and 428 (83%) were male. Confirmed pump thrombosis at 3 months was defined as thrombus found in the blood-contacting surfaces of the pump at the time of urgent transplant, device exchange or autopsy. Pt without at least 3 months of follow-up were excluded. Results: Confirmed pump thrombosis occurred in 9 pt within 3 months post implant. The incidence was greatest in the year 2012 (5.3%). Following this peak, the incidence of 3-month confirmed pump thrombosis decreased significantly to 2.9% (Figure). Significant differences in preoperative characteristics between patients with pump thrombosis and without thrombosis included female sex (36% vs. 16%, p=0.01), bridge to transplant (77% vs. 54%, p=0.03), atrial fibrillation (55% vs. 32%, p=0.04), and preop platelet count (231,000 vs. 172,000, p<0.001). Follow-up was available in all for a total of 857 patient years of support. At a median follow-up of 1.2 years (max., 9.8 years), a similar proportion of patients were alive (73% vs. 74%, p=0.9). Conclusions: We report a recent decrease in early, confirmed HeartMate II LVAD thrombosis to historically observed levels, which is disparate to recent reports. While we identified several differences in clinical characteristics between patient groups, the issue of pump thrombosis is complex and multifactorial. Most importantly, our findings demonstrate the need for more granular analyses from collaborative efforts.

Binary release of ascorbic acid and lecithin from core–shell nanofibers on blood-contacting surface for reducing long-term hemolysis of erythrocyte

There is an urgent need to develop blood-contacting biomaterials with long-term anti-hemolytic capability. To obtain such biomaterials, we coaxially electrospin [ascorbic acid (AA) and lecithin]/poly (ethylene oxide) (PEO) core–shell nanofibers onto the surface of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS) that has been grafted with poly (ethylene glycol) (PEG) chains. Our strategy is based on that the grafted layers of PEG render the surface hydrophilic to reduce the mechanical injure to red blood cells (RBCs) while the AA and lecithin released from nanofibers on blood-contacting surface can actively interact with RBCs to decrease the oxidative damage to RBCs. We demonstrate that (AA and lecithin)/PEO core–shell structured nanofibers have been fabricated on the PEG grafted surface. The binary release of AA and lecithin in the distilled water is in a controlled manner and lasts for almost 5 days; during RBCs preservation, AA acts as an antioxidant and lecithin as a lipid supplier to the membrane of erythrocytes, resulting in low mechanical fragility and hemolysis of RBCs, as well as high deformability of stored RBCs. Our work thus makes a new approach to fabricate blood-contacting biomaterials with the capability of long-term anti-hemolysis.

The use of thermal analysis in assessing the effect of bound water content and substrate rigidity on prevention of platelet adhesion

Implant surface-induced initiation of blood coagulation leading to thrombus formation is a major problem. It is an important challenge in biomedical research to enhance thromboresistance of polymer coatings of blood-contacting implants and devices by the reduction of platelet adhesion to their surfaces. Currently, the molecular mechanisms responsible for interfacial processes related to regulation of protein adsorption and platelet adhesion in antithrombotic coatings are not yet clearly understood. We studied the role of water binding energy in chitosan molecules using differential scanning calorimetry and thermogravimetric analysis and the role of chitosan coating rigidity using dynamic mechanical thermal analysis in the prevention of platelet adhesion. It was found that the presence of loosely bound water in chitosan coatings increases platelet adhesion. The high molecular weight (HMW) chitosan coating that contains only tightly bound water prevents platelet adhesion. The high molecular weight (HMW) chitosan coating is more rigid and has higher platelet adhesion compared with more soft LMW chitosan coatings. The degree of hydration of thromboresistant coatings is significant parameter that must be taken into account in the design of blood-contacting surfaces.

Durable modification of segmented polyurethane for elastic blood-contacting devices by graft-type 2-methacryloyloxyethyl phosphorylcholine copolymer

We propose a novel application of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers for enhancing the performance of modified segmented polyurethane (SPU) surfaces for the development of a small-diameter vascular prosthesis. The SPU membranes were modified by random-type, block-type, and graft-type MPC polymers that were prepared using a double-solution casting procedure on stainless steel substrates. Among these MPC polymers, the graft-type poly(MPC-graft-2-ethylhexyl methacrylate [EHMA]), which is composed of a poly(MPC) segment as the main chain and poly(EHMA) segments as side chains, indicated a higher stability on the SPU membrane after being peeled off from the stainless steel substrate, as well as after immersion in an aqueous medium. This stability was caused by the intermiscibility in the domain of the poly(EHMA) segments and the soft segments of the SPU membrane. Each SPU/MPC polymer membrane exhibited a dramatic suppression of protein adsorption from human plasma and endothelium cell adhesion. Based on these results, the performance of SPU/poly(MPC-graft-EHMA) tubings 2 mm in diameter as vascular prostheses was investigated. Even after blood was passed through the tubings for 2 min, the graft-type MPC polymers effectively protected the blood-contacting surfaces from thrombus formation. In summary, SPU modified by graft-type MPC polymers has the potential for practical application in the form of a non-endothelium, small-diameter vascular prosthesis.

Controlled lecithin release from a hierarchical architecture on blood-contacting surface to reduce hemolysis of stored red blood cells.

Hemolysis of red blood cells (RBCs) caused by implant devices in vivo and nonpolyvinyl chloride containers for RBC preservation in vitro has recently gained much attention. To develop blood-contacting biomaterials with long-term antihemolysis capability, we present a facile method to construct a hydrophilic, 3D hierarchical architecture on the surface of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS) with poly(ethylene oxide) (PEO)/lecithin nano/microfibers. The strategy is based on electrospinning of PEO/lecithin fibers onto the surface of poly [poly(ethylene glycol) methyl ether methacrylate] [P(PEGMEMA)]-modified SEBS, which renders SEBS suitable for RBC storage in vitro. We demonstrate that the constructed 3D architecture is composed of hydrophilic micro- and nanofibers, which transforms to hydrogel networks immediately in blood; the controlled release of lecithin is achieved by gradual dissolution of PEO/lecithin hydrogels, and the interaction of lecithin with RBCs maintains the membrane flexibility and normal RBC shape. Thus, the blood-contacting surface reduces both mechanical and oxidative damage to RBC membranes, resulting in low hemolysis of preserved RBCs. This work not only paves new way to fabricate high hemocompatible biomaterials for RBC storage in vitro, but provides basic principles to design and develop antihemolysis biomaterials for implantation in vivo.

Hemocompatibility and film stability improvement of crosslinkable MPC copolymer coated polypropylene hollow fiber membrane

Hollow fiber membranes (HFMs) based artificial lungs require a large blood-contacting membrane surface area to provide adequate gas exchange. However, such a large surface presents significant challenges to hemocompatibility. For improving the hemocompatibility, amphiphilic and cell outer membrane mimetic 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers containing 3-(Trimethoxysilyl)propyl methacrylate (TSMA) and/or n-butyl methacrylate (BMA) units, poly(MPC-co-BMA-co-TSMA) (PMBT) and poly(MPC-co-BMA) (PMB) were coated on a commercial polypropylene (PP) HFM. Dynamic contact angle, ATR-FTIR and XPS results showed that both the PMB and PMBT phospholipid polymer coatings are stable in water, but only the crosslinked PMBT coating can resist the dissolution by ethanol or SDS aqueous solution. Protein adsorption, platelet adhesion and whole blood contact experiments showed significant improvement in hemocompatibility after being coated with the PMBT. Moreover, oxygenation experiments indicated that the blood compatible coating could resist blood permeance and did not hinder the gas exchange. Overall these findings revealed improved hemocompatibility which can be realized through crosslinkable phospholipid polymer coating, enabling more stable and more biocompatible HFMs respiratory assist devices.

Surface modification of implanted cardiovascular metal stents: From antithrombosis and antirestenosis to endothelialization

Driven by the complications occurring with bare metal stents and drug-eluting stents, concerns have been raised over strategies for long-term safety, with respect to preventing or inhibiting stent thrombosis, restenosis, and in-stent restenosis in particularly. Surface modification is very important in constructing a buffer layer at the interface of the organic and inorganic materials and in ultimately obtaining long-term biocompatibility. In this review, we summarize the developments in surface modification of implanted cardiovascular metal stents. This review focuses on the modification of metal stents via coating drugs or biomolecules to enhance antithrombosis, antirestenosis, and/or endothelialization. In addition, we indicate the probable future work involving the modification of the metallic blood-contacting surfaces of stents and other cardiovascular devices that are under development.

Derivation of human peripheral blood derived endothelial progenitor cells and the role of osteopontin surface modification and eNOS transfection

Endothelial coverage of blood-contacting biomaterial surfaces has been difficult to achieve. A readily available autologous source of endothelium combined with an appropriate attachment substrate would improve the chances of developing functional surfaces. Here we describe methods to derive high quantities of human endothelial progenitor cells (EPCs) from peripheral blood monocytes (PBMCs) obtained by leukapheresis. These cells are morphologically and phenotypically similar to human umbilical vein endothelial cells (HUVECs); however, their expression of the key vascular factor – endothelial nitric oxide synthase (eNOS) – is markedly lower than that observed in HUVECs. We demonstrate that eNOS levels can be restored with plasmid-based transfection. To promote EPC adherence we examined substrate enhancement with a matricellular protein associated with vascular repair, osteopontin (OPN). We observed dose- and time-dependent responses of OPN in EPC adhesion, spreading, and haptotactic migration of EPCs in Boyden chamber assays. In addition, the combination of the OPN coating and enhanced eNOS expression in EPCs maximally enhanced cell adhesion (39.6 ± 1.7 and 49.4 ± 2.4 cells/field for 0 and 1 nM OPN) and spreading (84.7 ± 3.5% and 92.1 ± 3.9% for 0 nM and 1 nM OPN). These data highlight the direct effects of OPN on peripheral blood derived EPCs, suggesting that OPN works by mediating progenitor cell adhesion during vascular injury. The combination of autologous EPCs and OPN coatings could be a promising method of developing functional endothelialized surfaces.

Biochemical and spatial control of human pluripotent stem cell mesoderm formation

Purpose: This study aims to develop the surface architecture enabling selective in-situ capturing of endothelial progenitor cells (EPCs) and subsequent rapid endothelialization on blood-contacting surfaces under arterial flow. First, based on ex vivo cellular potentials on various surface-bound candidate ligands, the best-suited pair of cell receptor exclusively expressed on endothelial lineage cells and surface-bound ligand is defined. Second, prolonged activation of intracellular signaling transduction pathways of EPCs adhered on surface-bound ligand is examined. Lastly, in-situ capture of EPCs and endothelialization in a porcein model is verified. Methods: Methods included (1) covalent bonding of molecules [vascular endothelial growth factor (VEGF) and two VEGF receptor antibodies and Tie-1 and -2 antibodies] on vinyl alcoholcopolymer; (2) culture of human mononuclear cells(MCs) on these proteinbound substrates and histocytochemical analyses; and (3) implantation of stent in coronaries. Results: Proteins were covalently bound to the copolymer surface via activation of hydroxyl group. Among molecules examined, only VEGF exhibited high adhesion and proliferation characteristics and a quite high differentiation potential of MCs with culture time. Day-order continuous activation of intracellular signaling transduction pathways (phosphorylation of VEGF receptor, FAK, ERK and Akt) was observed for ECs adhered on VEGF-bound substrate. Implantation study using VEGF-bound stents showed that cells expressing VEGF receptor adhered on stent surface followed by endothelialization was observed within several days. Conclusions: This study concludes that surface-bound VEGF enables selective capture of EPCs and complete endothelialization in vivo, and simple surface architecture promise to exert non-thrombogenic potential to cardiovascular devices.

In situ capture technology of endothelial progenitor cells

Purpose: This study aims to develop the surface architecture enabling selective in-situ capturing of endothelial progenitor cells (EPCs) and subsequent rapid endothelialization on blood-contacting surfaces under arterial flow. First, based on ex vivo cellular potentials on various surface-bound candidate ligands, the best-suited pair of cell receptor exclusively expressed on endothelial lineage cells and surface-bound ligand is defined. Second, prolonged activation of intracellular signaling transduction pathways of EPCs adhered on surface-bound ligand is examined. Lastly, in-situ capture of EPCs and endothelialization in a porcein model is verified. Methods: Methods included (1) covalent bonding of molecules [vascular endothelial growth factor (VEGF) and two VEGF receptor antibodies and Tie-1 and -2 antibodies] on vinyl alcoholcopolymer; (2) culture of human mononuclear cells(MCs) on these proteinbound substrates and histocytochemical analyses; and (3) implantation of stent in coronaries. Results: Proteins were covalently bound to the copolymer surface via activation of hydroxyl group. Among molecules examined, only VEGF exhibited high adhesion and proliferation characteristics and a quite high differentiation potential of MCs with culture time. Day-order continuous activation of intracellular signaling transduction pathways (phosphorylation of VEGF receptor, FAK, ERK and Akt) was observed for ECs adhered on VEGF-bound substrate. Implantation study using VEGF-bound stents showed that cells expressing VEGF receptor adhered on stent surface followed by endothelialization was observed within several days. Conclusions: This study concludes that surface-bound VEGF enables selective capture of EPCs and complete endothelialization in vivo, and simple surface architecture promise to exert non-thrombogenic potential to cardiovascular devices.

Surface projections of titanium substrates increase antithrombotic endothelial function in response to shear stress

Despite the therapeutic benefits of both mechanical circulatory assist devices and nitinol stents with titanium (Ti) outer surfaces, problems remain with thrombosis at the blood-contacting surface. Covering these surfaces with a layer of endothelium would mimic the native lining of the cardiovascular system, potentially decreasing thrombotic complications. Since surface topography is known to affect the phenotype of a seeded cell layer and since stents and ventricular assist devices exhibit surface protrusions, we tested the hypothesis that endothelial cells (ECs) have altered function on Ti surfaces with protrusions of 1.25, 3, and 5 μm height, compared with smooth Ti surfaces. ECs and nuclei were more aligned and ECs were more elongated on all patterned surfaces. Cell area was reduced on the 3 and 5 μm features. Expression of eNOS and COX2 was not altered by patterned surfaces, but expression of KLF-2 was higher on 1.25 and 5 μm features. Nitric oxide production following exposure to flow was higher on the 5 μm features. These results show that some antithrombogenic functions of ECs are significantly enhanced for ECs cultured on surface protrusions, and no functions are diminished, informing the future design of implant surfaces for endothelialization.

Sub-Acute Animal Implantation of a Novel Bioprosthethic Artificial Heart

Purpose The Carmat total artificial heart (TAH) is a recently developed electro-hydraulically driven biventricular system. It is designed as an alternative to heart transplant and placed in orthotopic position. The TAH has bioprosthetic blood-contacting surfaces and provides 3-9 l/min pulsatile flow in response to preload changes detected by the device. The purpose of this pre-clinical study was to monitor device performance and physiologic response during 48 hours functioning in an animal model. Methods and Materials Five female calves of the Charolais race, 2-4 months old, weighing 100-110kg, were selected. The TAH was implanted via mid-sternotomy and powered by an external console through a percutaneous driveline. Animals were maintained under anesthesia during the study. The procedure was managed by a team of veterinarians, cardiac surgeons and clinical anesthesiologists/intensivists. Hemodynamic measurements, diuresis and blood samples to assess venous oxygen saturation and serum lactate were taken before implantation and during device functioning. Results Baseline cardiac output of the native heart was 13.0±2.2 l/min. The TAH maintained a pulsatile flow between 7 and 9 l/min in all animals. The mean arterial pressure was 119±8 mmHg at baseline, 75±4 mmHg at 24 and 82±10 mmHg at 48 hours, with pulse pressure (systolic-diastolic) 42±9 mmHg at baseline 36±11 mmHg at 24 hours and 41±12 mmHg at 48 hours. Serum lactate decreased from 9.8±4.5 mmol/l post-CPB to 1.6±0.2 mmol/l at 24 hours and 1.2±0.6 mmol/l at 48 hours. Venous oxygen saturation at baseline was 73±18%, and remained stable at 78±7.5% at 24 hours and 83±0% at 48 hours. Diuresis averaged 321±172 ml/hour. It was decided to stop the procedures at 3.5 and 16 hours for technical reasons and at 36, 49 and 51 hours per protocol. Conclusions The implantation technique for the Carmat TAH is similar to heart transplantation. In a Charolais calf model under anesthetized conditions, the TAH is capable to produce pulsatile flow up to 9 l/min and restore tissue perfusion.

Fibronectin coating of oxygenator membranes enhances endothelial cell attachment

BackgroundExtracorporeal membrane oxygenation (ECMO) can replace the lungs’ gas exchange capacity in refractory lung failure. However, its limited hemocompatibility, the activation of the coagulation and complement system as well as plasma leakage and protein deposition hamper mid- to long-term use and have constrained the development of an implantable lung assist device. In a tissue engineering approach, lining the blood contact surfaces of the ECMO device with endothelial cells might overcome these limitations. As a first step towards this aim, we hypothesized that coating the oxygenator’s gas exchange membrane with proteins might positively influence the attachment and proliferation of arterial endothelial cells.MethodsSheets of polypropylene (PP), polyoxymethylpentene (TPX) and polydimethylsiloxane (PDMS), typical material used for oxygenator gas exchange membranes, were coated with collagen, fibrinogen, gelatin or fibronectin. Tissue culture treated well plates served as controls. Endothelial cell attachment and proliferation were analyzed for a period of 4 days by microscopic examination and computer assisted cell counting.ResultsEndothelial cell seeding efficiency is within range of tissue culture treated controls for fibronectin treated surfaces only. Uncoated membranes as well as all other coatings lead to lower cell attachment. A confluent endothelial cell layer develops on fibronectin coated PDMS and the control surface only.ConclusionsFibronectin increases endothelial cells’ seeding efficiency on different oxygenator membrane material. PDMS coated with fibronectin shows sustained cell attachment for a period of four days in static culture conditions.

Nanowell-trapped charged ligand-bearing nanoparticle surfaces: a novel method of enhancing flow-resistant cell adhesion.

Assuring cell adhesion to an underlying biomaterial surface is vital in implant device design and tissue engineering, particularly under circumstances where cells are subjected to potential detachment from overriding fluid flow. Cell-substrate adhesion is a highly regulated process involving the interplay of mechanical properties, surface topographic features, electrostatic charge, and biochemical mechanisms. At the nanoscale level, the physical properties of the underlying substrate are of particular importance in cell adhesion. Conventionally, natural, pro-adhesive, and often thrombogenic, protein biomaterials are frequently utilized to facilitate adhesion. In the present study, nanofabrication techniques are utilized to enhance the biological functionality of a synthetic polymer surface, polymethymethacrylate, with respect to cell adhesion. Specifically we examine the effect on cell adhesion of combining: 1. optimized surface texturing, 2. electrostatic charge and 3. cell adhesive ligands, uniquely assembled on the substrata surface, as an ensemble of nanoparticles trapped in nanowells. Our results reveal that the ensemble strategy leads to enhanced, more than simply additive, endothelial cell adhesion under both static and flow conditions. This strategy may be of particular utility for enhancing flow-resistant endothelialization of blood-contacting surfaces of cardiovascular devices subjected to flow-mediated shear.

Survey of blood pump diaphragm damage in the NIPRO-ventricular assist device

We surveyed the incidence of blood pump diaphragm damage (rupture or crack) in the NIPRO-ventricular assist device (VAD). In the cases in which rupture or suspected blood pump crack was detected, we disassembled the pumps to visually check the condition of the diaphragm after replacement or use. Of 366 blood pumps surveyed, diaphragm damage was observed in 2.7%. The duration of use of the blood pumps with diaphragm damage was significantly longer than that of pumps without damage. The incidence of diaphragm damage increased with longer duration of use. On the basis of these findings, blood pump diaphragm damage in the NIPRO-VAD may be associated with duration of use. However, some blood pumps were used for prolonged periods without diaphragm damage. All blood pumps with damage had a crack in the diaphragm on the air chamber side near the diaphragm-housing (D-H) junction. Cracks were not found in any specific part of the diaphragm. In blood pumps with diaphragm rupture, the crack had a through-hole reaching the blood-contacting surface. Although we were unable to identify the causes of the cracks, it is suggested that when a crack appears in the diaphragm it will gradually expand and eventually lead to rupture. If a crack is detected in a blood pump, we advocate replacing the pump before it grows. When the NIPRO-VAD is used, it is necessary to keep in mind that blood pump diaphragm damage may occur.

How the Dream of an “Artificial Heart” Was Realized in Japan

How the Dream of an “Artificial Heart” Was Realized in Japan

In vitro haemocompatibility of a novel bioprosthetic total artificial heart

The CARMAT total artificial heart (TAH) is an implantable, electro-hydraulically driven, pulsatile flow device with four bioprosthetic valves. Its blood-pumping surfaces consist of processed bioprosthetic pericardial tissue and expanded polytetrafluorethylene (ePTFE), potentially allowing for the reduction of anti-coagulation. This pre-clinical study assessed the in vitro haemocompatibility of these surfaces. Coupons of pericardial tissue and ePTFE were placed in closed tubular circuits filled with 12.5 ml of fresh human blood exposed to the pulsatile flow at 120 ml/min for 4 h (37°C). Silicone- and heparin-coated polyvinyl chloride (PVC) tubes served as positive and negative controls, respectively. Fresh blood from six donors was used to fill four sets of 12 circuits. Blood samples were taken at baseline and from each circuit after 4 h. Coupons of materials were examined with scanning electron microscopy. The platelet count was 202 ± 45 10(9) l(-1) at baseline. Four hours after circulation, the platelet counts were 161 ± 30 10(9) l(-1) (compared with baseline, P = 0.0207) for pericardial tissue, 162 ± 35 10(9) l(-1) (P = 0.0305) for ePTFE and 136 ± 42 10(9) l(-1) for positive controls (P = 0.0021). Baseline plasma fibrinogen was 2.9 ± 0.5 mg/dl compared with 3.0 ± 0.5 mg/dl for pericardial tissue and 3.1 ± 0.7 mg/dl for ePTFE, indicating no marked fibrinogen consumption. Thromboxane B2 levels for positive controls were 33.3 ± 8.7 ng/ml compared with 16.2 ± 11.5 ng/ml for pericardial tissue (P = 0.0015) and 15.2 ± 4.7 ng/ml for ePTFE (P < 0.0001). Platelet adhesion was 2.87 ± 1.01 10(9) cm(-2) for positive controls compared with 1.06 ± 0.73 10(9) cm(-2) for pericardial tissue (P < 0.0001) and 0.79 ± 0.75 10(9) cm(-2) for ePTFE (P < 0.0001). Thrombin-antithrombin III complex levels were 3.8 ± 0.5 μg/ml for positive controls compared with 1.9 ± 0.9 for pericardial tissue (P < 0.0001) and 2.1 ± 1.0 for ePTFE (P < 0.0001). With an electro-microscopic examination at ×600, only small depositions of platelets, erythrocytes and fibrin were noticed on the pericardial tissue samples and ePTFE samples. Silicone surfaces showed marked areas of thrombi, and PVC tubings a thin protein layer. Haemocompatibility of the TAH blood-contacting surfaces was confirmed by in vitro studies showing a limited consumption of fibrin, limited thromboxane B2 release and platelet adhesion, and minor blood cell depositions on the surfaces. These results will be validated in clinical studies, with the aim of reducing anti-coagulation when using the CARMAT TAH.