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© 2014 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation
Editor-in-Chief’s Review
Artificial Organs 2013: A Year in Review Paul S. Malchesky Artificial Organs Editorial Office, Painesville, OH, USA
Abstract: In this Editor’s Review, articles published in 2013 are organized by category and briefly summarized. We aim to provide a brief reflection of the currently available worldwide knowledge that is intended to advance and better human life while providing insight for continued application of technologies and methods of organ Replacement, Recovery, and Regeneration. As the official journal of The International Federation for Artificial Organs, The International Faculty for Artificial Organs, the International Society for Rotary Blood Pumps, the International Society for Pediatric Mechanical Cardiopulmonary Support, and the Vienna International Workshop on Functional Electrical Stimulation, Artificial Organs continues in the original mission of its founders “to foster communications in the field of artificial organs on an international level”. Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ Replacement, Recovery, and Regeneration from all over the world. We take this time also to express our gratitude to our authors
for offering their work to this journal. We offer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide so meaningful suggestions to the author’s work whether eventually accepted or rejected and especially to those whose native tongue is not English. Without these excellent and dedicated reviewers the quality expected from such a journal could not be possible. We also express our special thanks to our Publisher, Wiley Periodicals, for their expert attention and support in the production and marketing of Artificial Organs. We look forward to recording further advances in the coming years. Key Words: Apheresis—Biocompatibility—Bioengineering— Biomaterials—Blood substitutes—Blood pumps—Cardiac support—Cardiopulmonary—Dermal—Dialysis—Liver— Lung—Membrane oxygenation—Organ preservaion—Orthopedic—Neuromuscular—Pancreas—Pulmonary—Renal —Surgery—Tissue engineering—Transplantation—Valves —Vascular—Vision.
APHERESIS
T-cells and Th cells, whereas they had increased NK cells after a single DFPP session. Transiently decreased percentages of T-cells after the full DFPP course could enhance the effectiveness of plasmapheresis for MG patients. Martin Russ et al. (2) of Charité-University Medicine Berlin, Berlin, Germany, provided a review of convection-based apheresis in intensive care medicine to improve biocompatibility and performance of capillary membrane apheresis. Through stepwise investigations based on in vitro and animal experiments, they identified a stasis of blood flow followed by blood cell sedimentation and aggregation (“clogging”) as the main factor of hollow fiber blockage in hemo- and plasma filters. An etiological triad for the blockage of hollow fibers due to filter clogging and consecutive filter failure was formed. Jiann-Horng Yeh et al. (3) of the Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, studied the effects of double filtration plasmapheresis (DFPP)
Pei-Ju Chien et al. (1) of the Taipei Medical University, Taipei, Taiwan, investigated the effect of double-filtration plasmapheresis (DFPP) on the ratio of lymphocyte subsets in 26 patients treated with myasthenia gravis (MG). After a single session of DFPP treatment, the percentages of T-cells, T helper (Th) cells, and the Th/T suppressor ratio decreased significantly, whereas the percentage of natural killer (NK) cells increased significantly. After one course of DFPP treatment, the reduced clinical quantitative MG (QMG) score was correlated with the decrease of the percentage of T-cells. Fourteen thymectomized MG patients had decreased percentages of doi:10.1111/aor.12284 Received December 2013. Address correspondence and reprint requests to Dr. Paul S. Malchesky, Artificial Organs Editorial Office, 10 West Erie St. Suite 200, Painesville, OH 44077 USA. E-mail: [email protected]
Artificial Organs 2014, 38(3):239–267
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on nocturnal respiratory function in 18 myasthenia gravis (MG) patients. The respiratory monitoring was performed in the morning, afternoon, and at sleep. The mean MG score was markedly lower after DFPP treatment (5.7) than before treatment (7.9). Before DFPP, the minimum pulse oximetric saturation (SpO2) obtained during the night session was significantly lower than the levels obtained during the two daytime sessions as was the maximum transcutaneous carbon dioxide tension (PtcCO2). After DFPP treatment, the maximum and mean PtcCO2 levels were significantly higher in the morning than in the afternoon. Overall, the minimum SpO2 levels as well as mean and maximum PtcCO2 levels improved significantly during sleep after DFPP. ARTIFICIAL OXYGEN CARRIERS Akira T. Kawaguchi et al. (4) of the Tokai University School of Medicine, Isehara, Japan, reported on the use of liposome-encapsulated hemoglobin (LEH) for the amelioration of brain ischemia in 10 monkeys beyond the acute phase of brain ischemia and reperfusion. The monkeys underwent middle cerebral artery occlusion and received LEH (2 mL/kg, n = 5) or saline (2 mL/kg, n = 5) 5 min later, and reperfusion 3 h later. There was no difference in oxygen metabolism until 3 h after reperfusion, when the cerebral metabolic rate of oxygen (CMRO2) was significantly better preserved in the cortex, but not in basal ganglia, on Day 0 in LEH-treated monkeys. The extent of cortical infarction (saline 68% vs. LEH 38%) and CMRO2 (mild suppression: saline 34% vs. LEH 14%) remained significantly better preserved 8 days later, when the cerebral metabolic rate of glucose (CMRglc) showed a similar pattern of cortical protection (mild suppression: saline 49% vs. LEH 37%) in LEH-treated monkeys, together with regained body weight. Somatic weight control, morphological integrity, CMRO2, and CMRglc were better preserved immediately, as well as 8 days after occlusion and reperfusion of the middle cerebral artery in monkeys receiving LEH early after onset of ischemia.
diameter to erythrocytes, were visualized across a transparent SGB at various gap heights. A reduction in the force across the bearing for human blood, compared with fluids of comparable viscosity, was found. The corresponding images clearly show both cells and spheres being excluded from the gap by entering the grooves. This furthers our understanding of how blood responds to different flows but could also lead to improvements in the future design of medical devices. Qijin Lu et al. (6) of the US Food and Drug Administration, Silver Spring, MD, USA, investigated the sensitivity of platelet responses to shear stress stimulation of human and bovine blood using multiple platelet activation markers. The exposure to shear stresses above 20 Pa caused significant changes in all three of the platelet markers (platelet counts, platelet surface P-selectin expression, and serotonin release into blood plasma) for human blood, and the changes were usually greater with anticoagulant citrate dextrose, solution A than with heparin. In contrast, for bovine blood, the markers did not change with shear stress stimulation except for plasma serotonin in heparin anticoagulated blood. The differences observed between human and bovine platelet responses suggest that the value of using bovine blood for in vitro platelet testing to evaluate devices may be limited. Vance G. Nielsen et al. (7) of the University of Arizona College of Medicine, Tucson, AZ, USA, reviewed the commonly known causes of deviceassociated thrombophilia and introduced recent literature concerning the effect of carbon monoxide on coagulation, and presented new patient data linking endogenously produced carbon monoxide with device-associated thrombosis. A new paradigm involving the interaction of red blood cell lysisinduced up-regulation of hemoxygenase-1, increased endogenous carbon monoxide, hyperfibrinogenemia, and contact protein/microparticle-induced thrombin generation was presented. BIOENGINEERING
BIOCOMPATIBILITY Laura J. Leslie et al. (5) of Aston University, Birmingham, UK, evaluated cell exclusion in couette flow by evaluations through flow visualization and mechanical forces in order to minimize hemolysis by initiating cell exclusion through the use of a spiralgroove bearing (SGB) that will provide escape routes by which the cells may separate themselves from the plasma and the high stresses in the gap. Stained erythrocytes, along with silver spheres of similar Artif Organs, Vol. 38, No. 3, 2014
Yangsheng Chen et al. (8) of the University of Louisville, Louisville, KY, USA, evaluated test models of flow-induced hemolysis in blood flow through hypodermic needles. Three computational fluid dynamic (CFD)-integrated blood damage models were applied to flow-induced hemolysis in 16-G needles and compared with experimental results. A modified needle with chamfered entrance increased hemolysis, while a rounded entrance decreased it, compared with the standard needle with
2013 YEAR IN REVIEW a sharp entrance. A strain-based cell membrane failure model and two empirical power-law blood damage models were used to predict hemolysis on each streamline. Results showed that only the strainbased blood damage model correctly predicted increased hemolysis in the beveled needle and decreased hemolysis in the rounded needle, while the power-law models predicted the opposite trends. Paula Ruiz et al. (9) of Queen Mary University of London, London, UK, presented a new design of a bioreactors or “mock” simulator of cardiovascular loops (SCVLs). The SCVL described included models for all four chambers of the heart, and the systemic and pulmonary circulation loops. Four cases were simulated: healthy, congestive heart failure, left ventricular diastolic dysfunction conditions, and left ventricular dysfunction with the addition of a mechanical circulatory support (MCS) device. The addition of an MCS device resulted in a significant reduction in mean blood pressure and re-establishment of cardiac output. The results show the capability of the SCVL to replicate various physiological and pathological conditions with and without MCS. Gianluca De Santis et al. (10) of Ghent University, Ghent, Belgium, analyzed the shape and flow changes of a patient-specific carotid artery after carotid artery stenting (CAS) performed using an open-cell (stent-O) or a closed-cell (stent-C) stent design. After CAS, the minimum cross-sectional area of the internal carotid artery (ICA) (external carotid artery [ECA]) changed by +54% (−12%) with stent-O and +78% (−17%) with stent-C; the resistance to flow of the ICA (ECA) changed by −21% (+13%) with stent-O and -26% (+18%) with stent-C. The computer simulations of stenting in a patient’s carotid artery reveal a trade-off between crosssectional size and flow resistance of the ICA (enlarged and circularized) and the ECA (narrowed and ovalized). Such a trade-off, together with malapposition, atherogenic risk, and thrombogenic risk, is stent-design dependent. BIOMATERIALS Hidemi Hattori et al. (11) of the National Defense Medical College, Tokorozawa, Japan, reported on the development of an emergency hemostatic kit for severe hemorrhage based on photocrosslinkable chitosan (Az-CH-LA). To improve the UV irradiation apparatus, they produced a portable, batterypowered UV irradiation apparatus. When the hemostatic kit using the UV irradiation apparatus was examined using a rat model of severe hemorrhage, the survival rate increased up to 73%.
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Marina de Oliveira Cardoso Macêdo et al. (12) of the Federal University of Rio Grande do Norte, Natal, Brazil, reported on the inhibition of microbial growth on chitosan membranes by gas plasma treatment. The membranes were treated with oxygen, methane, or argon plasma for different time periods (15, 30, 45, or 60 min). For inhibition of microbial growth with oxygen plasma, the time needed was 60 min. For the methane plasma, samples were successfully treated after 30, 45, and 60 min. For argon plasma, all treatment periods were effective. CARDIAC SUPPORT: ANATOMICAL CONSIDERATIONS Ho Chul Kim et al. (13) of Eulji University, Seongnam, Korea, evaluated computerized indices for the quantitative evaluation of depression and asymmetry in patients with chest wall deformities. Six reference chest wall boundary curves were obtained from 60 computed tomography (CT) images of a normal chest. An active contour modelbased image processing technique was used to extract boundary curves from images of patients with real chest wall deformities. The required parameters were extracted from the boundary curves and the targeted indices were calculated. The performance of the proposed indices was evaluated using 33 synthetic images and 60 real chest CT images of patients with chest wall deformities. The proposed indices can be automatically calculated from the original CT images and showed sufficient performance for all types of chest wall deformities. Shaun D. Gregory et al. (14) of Queensland University of Technology, Brisbane, Australia, evaluated anatomical fitting of the total artificial heart (TAH) in sheep for in vivo evaluation of a rotary device. Following excision of the native ventricles, a prototype TAH was inserted within the chest cavity of six sheep. Adjustable rods representing inlet and outlet conduits were oriented toward the center of each atrial chamber and the great vessels. A threedimensional, computer-aided design-operated anatomic fitting tool was then developed, based on the results of this study, and used to determine the inflow and outflow conduit orientation of the TAH. The center-to-center distance and outeredge-to-outer-edge distance between the atria were identified as the most critical geometries for successful TAH connection. This geometric constraint restricts the maximum separation allowable between left and right inlet ports of a TAH to ensure successful alignment within the available atrial circumference. Artif Organs, Vol. 38, No. 3, 2014
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CARDIAC SUPPORT AND BLOOD PUMPS Felix Fleissner et al. (15) of Hannover Medical School, Hannover, Germany, evaluated whether a reduction of driveline infections achieved through doubled driveline tunneling in left ventricular assist device (VAD) implantation technique may lower the incidence of infections. The technique involves tunneling of the driveline into the fascia of the musculus rectus abdominis, resulting in a longer, intrafascial run. Forty patients in group 1 where compared retrospectively to 41 patients in group 2 (new technique). One year after implantation, the infection rate was markedly reduced by the new implantation method; however, there was no significant improvement in overall mortality. Yves Durandy (16) of the Institut Hospitalier Jacques Cartier, Massy, France, discussed the characteristics of a non-occlusive pressure-regulated blood roller pump (Rhône-Poulenc 06 developed in the 1970s) for extracorporeal life support (ECLS). The specific design of the chamber allows the pump to generate a pulsatile flow and to act as a bubble trap. This old-fashioned pump is perfectly adapted for any kind of short- or long-term bypass. Priti G. Albal et al. (17) of Carnegie Mellon University, Pittsburgh, PA, USA, investigated fenestration designs for controlled venous flow shunting in failing Fontans with systemic venous hypertension. Novel plus-shaped and S-shaped fenestration designs with leaflets were introduced as alternatives to the traditional circular fenestration. For the plusshaped fenestration, the flow rate was found to increase nonlinearly with increased driving systemic venous pressures at high physiological-pressure drops which did not cause the leaflets to fully open, and linearly for low driving pressures. These results indicate that leaflets of the plus-shaped fenestration design activated passively after a critical systemic venous pressure threshold. This feature is ideal for minimizing undesirable excessive venous shunting. Shigang Wang et al. (18) of Penn State Hershey Children’s Hospital, Hershey, PA, USA, reported on a novel pulsatile rotary flow pump that has been used in clinical extracorporeal life support (ECLS) in Europe (Medos Deltastream DP3 diagonal pump), in a simulated pediatric ECLS system. All trials were conducted at flow rates ranging from 200 to 800 mL/ min at a blood temperature of 35°C using human blood (hematocrit 40%). The results showed that the pump can generate effective pulsatile flow without backflow, provide higher flow rates and pressures than nonpulsatile flow, and then create surplus Artif Organs, Vol. 38, No. 3, 2014
hemodynamic energy and more total hemodynamic energy than nonpulsatile flow. Prahlad G. Menon et al. (19) of Carnegie Mellon University, Pittsburgh, PA, USA, evaluated two viable routes for Fontan conduit connection in patients with apicocaval juxtaposition (ACJ) using computational fluid dynamics. Internal energy loss evaluations showed that the percentage of energy loss contribution was found to be greater in the case of a curved extracardiac conduit connection traveling behind the ventricular apex, connecting the inferior vena cava to the left pulmonary artery, than the straighter lateral tunnel conduit installed through the ventricular apex, 44% versus 6%. In contrast, net energy loss across the anastomosis was significantly lower with extracardiac total cavopulmonary connection in comparison with lateral tunnel, highlighting that a curved Fontan conduit is favorable provided that it is traded off for a superior cavopulmonary connection efficiency. Therefore, a relatively longer and curved Fontan conduit has been demonstrated to be a suitable connection option independent of anatomical situations. Bin Gao et al. (20) of the Beijing University of Technology, Beijing, China, investigated in simulated studies the hemodynamic effect of “constant speed” mode, “co-pulse” mode, and “counter-pulse” mode in the intra-aorta pump on the cardiovascular system. Results demonstrated that both the “copulse” mode and “counter-pulse” mode can achieve better unloading performance than the “constant speed” mode and that the “co-pulse” mode is beneficial for improving coronary flow and its pulsatility ratio is the maximum of the three modes. The “counter-pulse” mode was deemed beneficial for the perfusion of vital organs. Diyar Saeed et al. (21) of the Ruhr-University of Bochum, Bad Oeynhausen, Germany, evaluated the safety and performance of the Arrow CorAide left ventricular assist system (LVAS) as bridge to transplantation or recovery as well as destination therapy in patients with New York Heart Association (NYHA) class IV heart failure. Twenty-one patients were implanted in a prospective, multicenter, nonrandomized trial. Seventeen patients survived to >180 days or to transplantation. Nine patients died on device, two were converted to other devices, and 10 were transplanted. Three patient deaths were attributed to delamination of the pump’s internal surface polymer coating. No embolic or driveline infection event was recorded. Elimination of the polymer coating and replacement with an amorphous carbon coating has resolved this in preclinical testing, prior to initiation of further clinical testing of this device.
2013 YEAR IN REVIEW Takashi Yamane et al. (22) of the National Institute of Advanced Industrial Science and Technology, Kobe, Japan, investigated the enhancement of hemocompatibility of the MERA monopivot centrifugal pump for up to 4 weeks’ use. Flow visualization studies have shown sufficient pivot wash, and as stagnation at the sharp corner of the pivot support was suggested these sharp corners were removed. The index of hemolysis of the pump operating at more than 200 mm Hg was lower than that of a commercial pump. In 4-week animal tests, improvement of thrombus formation was seen in the female pivot through modification of female pivot geometry. An additional 4-week durability test revealed that the rate of the axial pivot wear was as small as 1.1 μm/day. Kavitha Muthiah et al. (23) of St. Vincent’s Hospital, Sydney, Australia, reported on the risk factors and nonsurgical management and outcomes of five patients implanted with continuous flow centrifugal left ventricular assist devices who displayed clinical, hemodynamic, and laboratory features of intrapump thrombosis. When clinically significant pump thrombosis occurs, it can usually be treated with intravenous therapy. Libera Fresiello et al. (24) of the National Council for Research, Rome, Italy, evaluated the effects of intra-aortic balloon pump (IABP) timing on baroreflex activities in a closed-loop cardiovascular hybrid model, a baroreflex computational model that was connected to a hydraulic model with a 40-cm balloon. The IABP was operated at different inflation trigger timings (−0.14 to 0.31 s) and inflation durations (0.05–0.45 s), with time of the dicrotic notch being taken as t = 0. Balloon early inflation (0.09 s before the dicrotic notch) with inflation duration of 0.25 s generated a maximum net increment of afferent pathway activity of 10%, thus leading to a decrement of efferent sympathetic activity by 15.3% compared with baseline values. These times resulted in a reduction in peripheral resistance and heart rate by 4% and 4.3% compared with baseline value. Jiafeng Zhang et al. (25) of the University of Maryland School of Medicine, Baltimore, MD, USA, made a comparison and experimental validation of computational fluid dynamic (CFD) numerical models for the CentriMag centrifugal ventricular assist device. The laminar and five turbulence models (Spalart-Allmaras, k-ε [k-epsilon], k-ω [k-omega], SST [Menter’s Shear Stress Transport], and Reynolds Stress) were implemented. In parallel, a transparent replica of the pump was constructed and selected views of the flow fields were measured with digital particle image velocimetry (DPIV). All the selected CFD models predicted the flow pattern
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fairly well except the area of the outlet. Quantitatively, the laminar model results were the most deviated from the experimental data. The k-ε renormalization group theory models and Reynolds Stress model are the most accurate. Amy Throckmorton et al. (26) of Virginia Commonwealth University, Richmond, VA, USA, reported on dual-pump support in the inferior and superior vena cavae of a patient-specific Fontan physiology. The performance of the dual-support scenario was compared to conditions of mechanical support in the inferior vena cava only and to a nonsupported cavopulmonary circuit. The blood pumps positively augment the hydraulic energy in the total cavopulmonary connection circuit as a function of flow rate and rotational speed. Concurrent, mechanical assistance of the inferior vena cava and superior vena cava in Fontan patients has the potential to be beneficial. Antonio Loforte et al. (27) of S. Camillo Hospital, Rome, Italy, compared the early planned institution of temporary right ventricular assist device (RVAD) support in left ventricular assist device (LVAD) recipients with permanent biventricular assist device (BVAD) or total artificial heart (TAH) support. Forty-six patients underwent LVAD placement combined with temporary RVAD support (group A) and in 31 patients a permanent BVAD or TAH implantation (group B) was performed. Thirty patients in group A were weaned from temporary RVAD support and three underwent permanent RVAD placement. A total of 26 patients were discharged home in group A versus 17 in group B. Three patients received heart transplantation in group A and six in group B. In group A, 1-year survival was 45.6% (n = 21) versus 45.1% (n = 14) in group B. The strategy of planned temporary RVAD support in LVAD recipients showed encouraging results when compared with those of a similar permanent BVAD/ TAH population. Jerson R. Martina et al. (28) of the University Medical Center Utrecht, Utrecht, The Netherlands, evaluated the simulation of changes in myocardial tissue properties during left ventricular assistance with a rotary blood pump. The simulations showed that indices of ventricular geometry, left ventricular shortening fraction, and ejection fraction had the same response to variations in myofiber contractility and myocardial tissue stiffness. Pulse pressure and arterial dP/dtmax increased when myofiber contractility increased, whereas increasing myocardial tissue stiffness decreased these measures. Simultaneous monitoring of hemodynamic parameters and ventricular geometry indirectly reflects the status of the myocardial tissue. Artif Organs, Vol. 38, No. 3, 2014
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Nobusuke Kato et al. (29) of Tokai University School of Medicine, Isehara, Kanagawa, Japan, reported on static cardiomyoplasty with a synthetic elastic net to suppress ventricular dilatation and dysfunction after myocardial infarction in a chronic rat study. Left ventricle (LV) pressure-volume relationships (PVR) were successively analyzed before, after intravenous volume load, and 10 min after occlusion of the left anterior descending artery. Rats were then randomized into groups receiving synthetic net wrapping around the heart (NET+, n = 8) and only partially behind the left ventricle (LV) (NET–, n = 9), and they underwent the same PVR studies 6 weeks later. There was no difference in Day 0; increases in LV end-diastolic and end-systolic volumes were significantly attenuated in NET+ rats 6 weeks later. Static cardiomyoplasty using a synthetic elastic net significantly attenuated LV dilatation and dysfunction without restriction late after myocardial infarction. Yoshio Iwashima et al. (30) of the National Cerebral and Cardiovascular Center, Suita City, Osaka, Japan, reported on the clinical implication of pump replacement because of thrombus formation. The study included 87 patients who underwent implantation of a Nipro (Toyobo) pulsatile extracorporeal left ventricular assist system (LVAS) intended as a bridge to transplantation and were alive more than 3 months after implantation. Pump replacement was performed for significant thrombus formation that became visible. At 3 months after LVAS implantation, 41 patients had undergone pump replacement because of pump thrombus. Baseline body surface area
© 2014 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation
Editor-in-Chief’s Review
Artificial Organs 2013: A Year in Review Paul S. Malchesky Artificial Organs Editorial Office, Painesville, OH, USA
Abstract: In this Editor’s Review, articles published in 2013 are organized by category and briefly summarized. We aim to provide a brief reflection of the currently available worldwide knowledge that is intended to advance and better human life while providing insight for continued application of technologies and methods of organ Replacement, Recovery, and Regeneration. As the official journal of The International Federation for Artificial Organs, The International Faculty for Artificial Organs, the International Society for Rotary Blood Pumps, the International Society for Pediatric Mechanical Cardiopulmonary Support, and the Vienna International Workshop on Functional Electrical Stimulation, Artificial Organs continues in the original mission of its founders “to foster communications in the field of artificial organs on an international level”. Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ Replacement, Recovery, and Regeneration from all over the world. We take this time also to express our gratitude to our authors
for offering their work to this journal. We offer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide so meaningful suggestions to the author’s work whether eventually accepted or rejected and especially to those whose native tongue is not English. Without these excellent and dedicated reviewers the quality expected from such a journal could not be possible. We also express our special thanks to our Publisher, Wiley Periodicals, for their expert attention and support in the production and marketing of Artificial Organs. We look forward to recording further advances in the coming years. Key Words: Apheresis—Biocompatibility—Bioengineering— Biomaterials—Blood substitutes—Blood pumps—Cardiac support—Cardiopulmonary—Dermal—Dialysis—Liver— Lung—Membrane oxygenation—Organ preservaion—Orthopedic—Neuromuscular—Pancreas—Pulmonary—Renal —Surgery—Tissue engineering—Transplantation—Valves —Vascular—Vision.
APHERESIS
T-cells and Th cells, whereas they had increased NK cells after a single DFPP session. Transiently decreased percentages of T-cells after the full DFPP course could enhance the effectiveness of plasmapheresis for MG patients. Martin Russ et al. (2) of Charité-University Medicine Berlin, Berlin, Germany, provided a review of convection-based apheresis in intensive care medicine to improve biocompatibility and performance of capillary membrane apheresis. Through stepwise investigations based on in vitro and animal experiments, they identified a stasis of blood flow followed by blood cell sedimentation and aggregation (“clogging”) as the main factor of hollow fiber blockage in hemo- and plasma filters. An etiological triad for the blockage of hollow fibers due to filter clogging and consecutive filter failure was formed. Jiann-Horng Yeh et al. (3) of the Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, studied the effects of double filtration plasmapheresis (DFPP)
Pei-Ju Chien et al. (1) of the Taipei Medical University, Taipei, Taiwan, investigated the effect of double-filtration plasmapheresis (DFPP) on the ratio of lymphocyte subsets in 26 patients treated with myasthenia gravis (MG). After a single session of DFPP treatment, the percentages of T-cells, T helper (Th) cells, and the Th/T suppressor ratio decreased significantly, whereas the percentage of natural killer (NK) cells increased significantly. After one course of DFPP treatment, the reduced clinical quantitative MG (QMG) score was correlated with the decrease of the percentage of T-cells. Fourteen thymectomized MG patients had decreased percentages of doi:10.1111/aor.12284 Received December 2013. Address correspondence and reprint requests to Dr. Paul S. Malchesky, Artificial Organs Editorial Office, 10 West Erie St. Suite 200, Painesville, OH 44077 USA. E-mail: [email protected]
Artificial Organs 2014, 38(3):239–267
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P.S. MALCHESKY
on nocturnal respiratory function in 18 myasthenia gravis (MG) patients. The respiratory monitoring was performed in the morning, afternoon, and at sleep. The mean MG score was markedly lower after DFPP treatment (5.7) than before treatment (7.9). Before DFPP, the minimum pulse oximetric saturation (SpO2) obtained during the night session was significantly lower than the levels obtained during the two daytime sessions as was the maximum transcutaneous carbon dioxide tension (PtcCO2). After DFPP treatment, the maximum and mean PtcCO2 levels were significantly higher in the morning than in the afternoon. Overall, the minimum SpO2 levels as well as mean and maximum PtcCO2 levels improved significantly during sleep after DFPP. ARTIFICIAL OXYGEN CARRIERS Akira T. Kawaguchi et al. (4) of the Tokai University School of Medicine, Isehara, Japan, reported on the use of liposome-encapsulated hemoglobin (LEH) for the amelioration of brain ischemia in 10 monkeys beyond the acute phase of brain ischemia and reperfusion. The monkeys underwent middle cerebral artery occlusion and received LEH (2 mL/kg, n = 5) or saline (2 mL/kg, n = 5) 5 min later, and reperfusion 3 h later. There was no difference in oxygen metabolism until 3 h after reperfusion, when the cerebral metabolic rate of oxygen (CMRO2) was significantly better preserved in the cortex, but not in basal ganglia, on Day 0 in LEH-treated monkeys. The extent of cortical infarction (saline 68% vs. LEH 38%) and CMRO2 (mild suppression: saline 34% vs. LEH 14%) remained significantly better preserved 8 days later, when the cerebral metabolic rate of glucose (CMRglc) showed a similar pattern of cortical protection (mild suppression: saline 49% vs. LEH 37%) in LEH-treated monkeys, together with regained body weight. Somatic weight control, morphological integrity, CMRO2, and CMRglc were better preserved immediately, as well as 8 days after occlusion and reperfusion of the middle cerebral artery in monkeys receiving LEH early after onset of ischemia.
diameter to erythrocytes, were visualized across a transparent SGB at various gap heights. A reduction in the force across the bearing for human blood, compared with fluids of comparable viscosity, was found. The corresponding images clearly show both cells and spheres being excluded from the gap by entering the grooves. This furthers our understanding of how blood responds to different flows but could also lead to improvements in the future design of medical devices. Qijin Lu et al. (6) of the US Food and Drug Administration, Silver Spring, MD, USA, investigated the sensitivity of platelet responses to shear stress stimulation of human and bovine blood using multiple platelet activation markers. The exposure to shear stresses above 20 Pa caused significant changes in all three of the platelet markers (platelet counts, platelet surface P-selectin expression, and serotonin release into blood plasma) for human blood, and the changes were usually greater with anticoagulant citrate dextrose, solution A than with heparin. In contrast, for bovine blood, the markers did not change with shear stress stimulation except for plasma serotonin in heparin anticoagulated blood. The differences observed between human and bovine platelet responses suggest that the value of using bovine blood for in vitro platelet testing to evaluate devices may be limited. Vance G. Nielsen et al. (7) of the University of Arizona College of Medicine, Tucson, AZ, USA, reviewed the commonly known causes of deviceassociated thrombophilia and introduced recent literature concerning the effect of carbon monoxide on coagulation, and presented new patient data linking endogenously produced carbon monoxide with device-associated thrombosis. A new paradigm involving the interaction of red blood cell lysisinduced up-regulation of hemoxygenase-1, increased endogenous carbon monoxide, hyperfibrinogenemia, and contact protein/microparticle-induced thrombin generation was presented. BIOENGINEERING
BIOCOMPATIBILITY Laura J. Leslie et al. (5) of Aston University, Birmingham, UK, evaluated cell exclusion in couette flow by evaluations through flow visualization and mechanical forces in order to minimize hemolysis by initiating cell exclusion through the use of a spiralgroove bearing (SGB) that will provide escape routes by which the cells may separate themselves from the plasma and the high stresses in the gap. Stained erythrocytes, along with silver spheres of similar Artif Organs, Vol. 38, No. 3, 2014
Yangsheng Chen et al. (8) of the University of Louisville, Louisville, KY, USA, evaluated test models of flow-induced hemolysis in blood flow through hypodermic needles. Three computational fluid dynamic (CFD)-integrated blood damage models were applied to flow-induced hemolysis in 16-G needles and compared with experimental results. A modified needle with chamfered entrance increased hemolysis, while a rounded entrance decreased it, compared with the standard needle with
2013 YEAR IN REVIEW a sharp entrance. A strain-based cell membrane failure model and two empirical power-law blood damage models were used to predict hemolysis on each streamline. Results showed that only the strainbased blood damage model correctly predicted increased hemolysis in the beveled needle and decreased hemolysis in the rounded needle, while the power-law models predicted the opposite trends. Paula Ruiz et al. (9) of Queen Mary University of London, London, UK, presented a new design of a bioreactors or “mock” simulator of cardiovascular loops (SCVLs). The SCVL described included models for all four chambers of the heart, and the systemic and pulmonary circulation loops. Four cases were simulated: healthy, congestive heart failure, left ventricular diastolic dysfunction conditions, and left ventricular dysfunction with the addition of a mechanical circulatory support (MCS) device. The addition of an MCS device resulted in a significant reduction in mean blood pressure and re-establishment of cardiac output. The results show the capability of the SCVL to replicate various physiological and pathological conditions with and without MCS. Gianluca De Santis et al. (10) of Ghent University, Ghent, Belgium, analyzed the shape and flow changes of a patient-specific carotid artery after carotid artery stenting (CAS) performed using an open-cell (stent-O) or a closed-cell (stent-C) stent design. After CAS, the minimum cross-sectional area of the internal carotid artery (ICA) (external carotid artery [ECA]) changed by +54% (−12%) with stent-O and +78% (−17%) with stent-C; the resistance to flow of the ICA (ECA) changed by −21% (+13%) with stent-O and -26% (+18%) with stent-C. The computer simulations of stenting in a patient’s carotid artery reveal a trade-off between crosssectional size and flow resistance of the ICA (enlarged and circularized) and the ECA (narrowed and ovalized). Such a trade-off, together with malapposition, atherogenic risk, and thrombogenic risk, is stent-design dependent. BIOMATERIALS Hidemi Hattori et al. (11) of the National Defense Medical College, Tokorozawa, Japan, reported on the development of an emergency hemostatic kit for severe hemorrhage based on photocrosslinkable chitosan (Az-CH-LA). To improve the UV irradiation apparatus, they produced a portable, batterypowered UV irradiation apparatus. When the hemostatic kit using the UV irradiation apparatus was examined using a rat model of severe hemorrhage, the survival rate increased up to 73%.
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Marina de Oliveira Cardoso Macêdo et al. (12) of the Federal University of Rio Grande do Norte, Natal, Brazil, reported on the inhibition of microbial growth on chitosan membranes by gas plasma treatment. The membranes were treated with oxygen, methane, or argon plasma for different time periods (15, 30, 45, or 60 min). For inhibition of microbial growth with oxygen plasma, the time needed was 60 min. For the methane plasma, samples were successfully treated after 30, 45, and 60 min. For argon plasma, all treatment periods were effective. CARDIAC SUPPORT: ANATOMICAL CONSIDERATIONS Ho Chul Kim et al. (13) of Eulji University, Seongnam, Korea, evaluated computerized indices for the quantitative evaluation of depression and asymmetry in patients with chest wall deformities. Six reference chest wall boundary curves were obtained from 60 computed tomography (CT) images of a normal chest. An active contour modelbased image processing technique was used to extract boundary curves from images of patients with real chest wall deformities. The required parameters were extracted from the boundary curves and the targeted indices were calculated. The performance of the proposed indices was evaluated using 33 synthetic images and 60 real chest CT images of patients with chest wall deformities. The proposed indices can be automatically calculated from the original CT images and showed sufficient performance for all types of chest wall deformities. Shaun D. Gregory et al. (14) of Queensland University of Technology, Brisbane, Australia, evaluated anatomical fitting of the total artificial heart (TAH) in sheep for in vivo evaluation of a rotary device. Following excision of the native ventricles, a prototype TAH was inserted within the chest cavity of six sheep. Adjustable rods representing inlet and outlet conduits were oriented toward the center of each atrial chamber and the great vessels. A threedimensional, computer-aided design-operated anatomic fitting tool was then developed, based on the results of this study, and used to determine the inflow and outflow conduit orientation of the TAH. The center-to-center distance and outeredge-to-outer-edge distance between the atria were identified as the most critical geometries for successful TAH connection. This geometric constraint restricts the maximum separation allowable between left and right inlet ports of a TAH to ensure successful alignment within the available atrial circumference. Artif Organs, Vol. 38, No. 3, 2014
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CARDIAC SUPPORT AND BLOOD PUMPS Felix Fleissner et al. (15) of Hannover Medical School, Hannover, Germany, evaluated whether a reduction of driveline infections achieved through doubled driveline tunneling in left ventricular assist device (VAD) implantation technique may lower the incidence of infections. The technique involves tunneling of the driveline into the fascia of the musculus rectus abdominis, resulting in a longer, intrafascial run. Forty patients in group 1 where compared retrospectively to 41 patients in group 2 (new technique). One year after implantation, the infection rate was markedly reduced by the new implantation method; however, there was no significant improvement in overall mortality. Yves Durandy (16) of the Institut Hospitalier Jacques Cartier, Massy, France, discussed the characteristics of a non-occlusive pressure-regulated blood roller pump (Rhône-Poulenc 06 developed in the 1970s) for extracorporeal life support (ECLS). The specific design of the chamber allows the pump to generate a pulsatile flow and to act as a bubble trap. This old-fashioned pump is perfectly adapted for any kind of short- or long-term bypass. Priti G. Albal et al. (17) of Carnegie Mellon University, Pittsburgh, PA, USA, investigated fenestration designs for controlled venous flow shunting in failing Fontans with systemic venous hypertension. Novel plus-shaped and S-shaped fenestration designs with leaflets were introduced as alternatives to the traditional circular fenestration. For the plusshaped fenestration, the flow rate was found to increase nonlinearly with increased driving systemic venous pressures at high physiological-pressure drops which did not cause the leaflets to fully open, and linearly for low driving pressures. These results indicate that leaflets of the plus-shaped fenestration design activated passively after a critical systemic venous pressure threshold. This feature is ideal for minimizing undesirable excessive venous shunting. Shigang Wang et al. (18) of Penn State Hershey Children’s Hospital, Hershey, PA, USA, reported on a novel pulsatile rotary flow pump that has been used in clinical extracorporeal life support (ECLS) in Europe (Medos Deltastream DP3 diagonal pump), in a simulated pediatric ECLS system. All trials were conducted at flow rates ranging from 200 to 800 mL/ min at a blood temperature of 35°C using human blood (hematocrit 40%). The results showed that the pump can generate effective pulsatile flow without backflow, provide higher flow rates and pressures than nonpulsatile flow, and then create surplus Artif Organs, Vol. 38, No. 3, 2014
hemodynamic energy and more total hemodynamic energy than nonpulsatile flow. Prahlad G. Menon et al. (19) of Carnegie Mellon University, Pittsburgh, PA, USA, evaluated two viable routes for Fontan conduit connection in patients with apicocaval juxtaposition (ACJ) using computational fluid dynamics. Internal energy loss evaluations showed that the percentage of energy loss contribution was found to be greater in the case of a curved extracardiac conduit connection traveling behind the ventricular apex, connecting the inferior vena cava to the left pulmonary artery, than the straighter lateral tunnel conduit installed through the ventricular apex, 44% versus 6%. In contrast, net energy loss across the anastomosis was significantly lower with extracardiac total cavopulmonary connection in comparison with lateral tunnel, highlighting that a curved Fontan conduit is favorable provided that it is traded off for a superior cavopulmonary connection efficiency. Therefore, a relatively longer and curved Fontan conduit has been demonstrated to be a suitable connection option independent of anatomical situations. Bin Gao et al. (20) of the Beijing University of Technology, Beijing, China, investigated in simulated studies the hemodynamic effect of “constant speed” mode, “co-pulse” mode, and “counter-pulse” mode in the intra-aorta pump on the cardiovascular system. Results demonstrated that both the “copulse” mode and “counter-pulse” mode can achieve better unloading performance than the “constant speed” mode and that the “co-pulse” mode is beneficial for improving coronary flow and its pulsatility ratio is the maximum of the three modes. The “counter-pulse” mode was deemed beneficial for the perfusion of vital organs. Diyar Saeed et al. (21) of the Ruhr-University of Bochum, Bad Oeynhausen, Germany, evaluated the safety and performance of the Arrow CorAide left ventricular assist system (LVAS) as bridge to transplantation or recovery as well as destination therapy in patients with New York Heart Association (NYHA) class IV heart failure. Twenty-one patients were implanted in a prospective, multicenter, nonrandomized trial. Seventeen patients survived to >180 days or to transplantation. Nine patients died on device, two were converted to other devices, and 10 were transplanted. Three patient deaths were attributed to delamination of the pump’s internal surface polymer coating. No embolic or driveline infection event was recorded. Elimination of the polymer coating and replacement with an amorphous carbon coating has resolved this in preclinical testing, prior to initiation of further clinical testing of this device.
2013 YEAR IN REVIEW Takashi Yamane et al. (22) of the National Institute of Advanced Industrial Science and Technology, Kobe, Japan, investigated the enhancement of hemocompatibility of the MERA monopivot centrifugal pump for up to 4 weeks’ use. Flow visualization studies have shown sufficient pivot wash, and as stagnation at the sharp corner of the pivot support was suggested these sharp corners were removed. The index of hemolysis of the pump operating at more than 200 mm Hg was lower than that of a commercial pump. In 4-week animal tests, improvement of thrombus formation was seen in the female pivot through modification of female pivot geometry. An additional 4-week durability test revealed that the rate of the axial pivot wear was as small as 1.1 μm/day. Kavitha Muthiah et al. (23) of St. Vincent’s Hospital, Sydney, Australia, reported on the risk factors and nonsurgical management and outcomes of five patients implanted with continuous flow centrifugal left ventricular assist devices who displayed clinical, hemodynamic, and laboratory features of intrapump thrombosis. When clinically significant pump thrombosis occurs, it can usually be treated with intravenous therapy. Libera Fresiello et al. (24) of the National Council for Research, Rome, Italy, evaluated the effects of intra-aortic balloon pump (IABP) timing on baroreflex activities in a closed-loop cardiovascular hybrid model, a baroreflex computational model that was connected to a hydraulic model with a 40-cm balloon. The IABP was operated at different inflation trigger timings (−0.14 to 0.31 s) and inflation durations (0.05–0.45 s), with time of the dicrotic notch being taken as t = 0. Balloon early inflation (0.09 s before the dicrotic notch) with inflation duration of 0.25 s generated a maximum net increment of afferent pathway activity of 10%, thus leading to a decrement of efferent sympathetic activity by 15.3% compared with baseline values. These times resulted in a reduction in peripheral resistance and heart rate by 4% and 4.3% compared with baseline value. Jiafeng Zhang et al. (25) of the University of Maryland School of Medicine, Baltimore, MD, USA, made a comparison and experimental validation of computational fluid dynamic (CFD) numerical models for the CentriMag centrifugal ventricular assist device. The laminar and five turbulence models (Spalart-Allmaras, k-ε [k-epsilon], k-ω [k-omega], SST [Menter’s Shear Stress Transport], and Reynolds Stress) were implemented. In parallel, a transparent replica of the pump was constructed and selected views of the flow fields were measured with digital particle image velocimetry (DPIV). All the selected CFD models predicted the flow pattern
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fairly well except the area of the outlet. Quantitatively, the laminar model results were the most deviated from the experimental data. The k-ε renormalization group theory models and Reynolds Stress model are the most accurate. Amy Throckmorton et al. (26) of Virginia Commonwealth University, Richmond, VA, USA, reported on dual-pump support in the inferior and superior vena cavae of a patient-specific Fontan physiology. The performance of the dual-support scenario was compared to conditions of mechanical support in the inferior vena cava only and to a nonsupported cavopulmonary circuit. The blood pumps positively augment the hydraulic energy in the total cavopulmonary connection circuit as a function of flow rate and rotational speed. Concurrent, mechanical assistance of the inferior vena cava and superior vena cava in Fontan patients has the potential to be beneficial. Antonio Loforte et al. (27) of S. Camillo Hospital, Rome, Italy, compared the early planned institution of temporary right ventricular assist device (RVAD) support in left ventricular assist device (LVAD) recipients with permanent biventricular assist device (BVAD) or total artificial heart (TAH) support. Forty-six patients underwent LVAD placement combined with temporary RVAD support (group A) and in 31 patients a permanent BVAD or TAH implantation (group B) was performed. Thirty patients in group A were weaned from temporary RVAD support and three underwent permanent RVAD placement. A total of 26 patients were discharged home in group A versus 17 in group B. Three patients received heart transplantation in group A and six in group B. In group A, 1-year survival was 45.6% (n = 21) versus 45.1% (n = 14) in group B. The strategy of planned temporary RVAD support in LVAD recipients showed encouraging results when compared with those of a similar permanent BVAD/ TAH population. Jerson R. Martina et al. (28) of the University Medical Center Utrecht, Utrecht, The Netherlands, evaluated the simulation of changes in myocardial tissue properties during left ventricular assistance with a rotary blood pump. The simulations showed that indices of ventricular geometry, left ventricular shortening fraction, and ejection fraction had the same response to variations in myofiber contractility and myocardial tissue stiffness. Pulse pressure and arterial dP/dtmax increased when myofiber contractility increased, whereas increasing myocardial tissue stiffness decreased these measures. Simultaneous monitoring of hemodynamic parameters and ventricular geometry indirectly reflects the status of the myocardial tissue. Artif Organs, Vol. 38, No. 3, 2014
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Nobusuke Kato et al. (29) of Tokai University School of Medicine, Isehara, Kanagawa, Japan, reported on static cardiomyoplasty with a synthetic elastic net to suppress ventricular dilatation and dysfunction after myocardial infarction in a chronic rat study. Left ventricle (LV) pressure-volume relationships (PVR) were successively analyzed before, after intravenous volume load, and 10 min after occlusion of the left anterior descending artery. Rats were then randomized into groups receiving synthetic net wrapping around the heart (NET+, n = 8) and only partially behind the left ventricle (LV) (NET–, n = 9), and they underwent the same PVR studies 6 weeks later. There was no difference in Day 0; increases in LV end-diastolic and end-systolic volumes were significantly attenuated in NET+ rats 6 weeks later. Static cardiomyoplasty using a synthetic elastic net significantly attenuated LV dilatation and dysfunction without restriction late after myocardial infarction. Yoshio Iwashima et al. (30) of the National Cerebral and Cardiovascular Center, Suita City, Osaka, Japan, reported on the clinical implication of pump replacement because of thrombus formation. The study included 87 patients who underwent implantation of a Nipro (Toyobo) pulsatile extracorporeal left ventricular assist system (LVAS) intended as a bridge to transplantation and were alive more than 3 months after implantation. Pump replacement was performed for significant thrombus formation that became visible. At 3 months after LVAS implantation, 41 patients had undergone pump replacement because of pump thrombus. Baseline body surface area
