Artificial organs最新文献

Background: A major reason for the failure of bioprosthetic heart valves is calcification. Various pretreatment methods are developed to reduce the calcification behavior. The effectiveness of these methods has so far been investigated in expensive and time-consuming large animal studies. To provide a cost-effective, animal- and possibly also time-saving method, we developed an accelerated dynamic in vitro calcification test method.

Methods: We validated this method using a comparative study of two differently pretreated groups of porcine heart valve bioprostheses. Each group contained N = 4 identical aortic bioprostheses. Calcification onsets, progression, and extent were detected by high-speed video (HSV) documentation and microscopy. Structural identification of the deposits was carried out by X-ray powder diffraction (XRD). Semi-destructive quantification of the calcifications was done by μ-CT as well as destructive chemical quantification via colorimetry and complexometry. The histomorphologic localization of the calcifications was examined by von Kossa staining.

Results: Structural analysis of the deposits indicated "biological apatite" for both test groups. Histological examination revealed localization of the calcifications in the spongiosa zone of the cusps. Quantification of the calcifications showed a distinctly stronger calcification tendency of the No-T6 compared to the anti-calcifying pretreated T6 bioprostheses.

Conclusions: We developed and validated a novel and unique test method for in vitro calcification assessment. The quantitative calcification tendencies of the two test groups are comparable with the results of an in vivo study in sheep. The structural findings are in line with published in vivo observations. The histomorphological localization appears as known for porcine prostheses.

Normothermic machine perfusion (NMP) of donor kidneys provides an opportunity not only for organ preservation but also for therapeutic intervention to reduce ischemia-reperfusion injury (IRI) and support tissue repair. Sevoflurane, a volatile anesthetic known to protect against IRI in other organ systems, has not previously been explored in the context of kidney NMP. This study aimed to establish a stable and reproducible porcine kidney NMP model incorporating sevoflurane delivery. Different administration techniques and oxygenator setups were evaluated to identify the most effective method of sevoflurane application. Administering sevoflurane directly as a liquid into the perfusate resulted in excessive gas formation and unstable drug concentrations. In contrast, using a vaporizer connected to an Inspire 8F M oxygenator allowed for stable and reproducible sevoflurane levels over a 90-min perfusion period, while maintaining sufficient oxygenation. This method proved to be a reliable approach for sevoflurane delivery in kidney NMP. However, oxygenators exposed to sevoflurane should not be reused due to the risk of membrane damage. These findings support the feasibility of using sevoflurane in kidney NMP and provide a platform for further investigation into its potential to improve renal graft outcomes.

Background: The influence of operating modes on pump-induced hemolysis in continuous-flow left ventricular assist devices (LVADs) can be assessed using computational fluid dynamics (CFD) simulations alongside power law models derived from shearing device experiments. However, this conventional method incurs high computational costs, limiting the exploration of diverse operating conditions and hindering online hemolysis prediction. This work presents a CFD-free and trial-based methodology for determining online-capable hemolysis models for continuous-flow LVADs.

Methods: The trial-based hemolysis model is based on a modified power law model, with parameters identified from LVAD hemolysis trials. The dynamic behavior is modeled using the Lagrangian approach. Specifically, this model was determined for the Sputnik1 LVAD and integrated with a lumped-parameter model of the LVAD-supported cardiovascular system. Subsequently, hemolysis was predicted across various operating modes and patient conditions.

Results: The RMSE and the R² of the modified power law fit were 18.4 [%·mL/h] and 0.69, respectively. The relative error introduced by the Lagrangian approach was below 0.7%. For the Sputnik1, hemolysis decreased with reduced speed. Additionally, lower systemic resistance and diminished left ventricular contractility were associated with lower hemolysis, whereas speed modulation increased hemolysis across most profiles.

Discussion: The proposed hemolysis model allows to assess various LVAD operating modes and patient conditions, assisting in the selection of low-hemolysis treatment strategies. For Sputnik1 patients, it is advisable to maintain low pump speed and systemic resistance, while speed modulation should be reserved for those with low hemolysis markers. Integrating this model with online flow sensing would enable online hemolysis prediction.

Background: Heart valve diseases remain a leading cause of death in industrialized nations. Polycarbonate urethane (PCU) is a promising material for heart valve prostheses due to its biocompatibility and low calcification tendency. However, the impact of processing methods on calcification remains unclear.

Methods: PCU patches were fabricated via hot pressing or solution casting. Both groups (n = 3 each), along with bovine pericardium patches as positive controls (n = 3), were incubated for 10 weeks in a custom in vitro calcification fluid. Calcification, cytocompatibility, and material properties were assessed using light and electron microscopy, infrared spectroscopy, and gel permeation chromatography (GPC).

Results: Calcification was observed in hot-pressed PCU and control patches but not in solution-cast PCU. Both PCU types showed comparable cytocompatibility. Spectroscopy and GPC revealed chemical and structural changes in hot-pressed PCU, likely promoting calcification.

Conclusion: Hot pressing alters the chemical structure of PCU and increases its calcification propensity without affecting cytocompatibility. These findings highlight the importance of process control and in vitro screening during heart valve material development.

Background: Normothermic machine perfusion (NMP) could serve as a platform to assess deceased-donor kidney viability before transplantation, yet it remains unclear which parameters indicate renal viability. As vascular integrity is important for adequate renal function after transplantation, this study aimed to investigate the influence of warm ischemic injury on vascular smooth muscle cell (VSMC) responsiveness to vasoactive drugs during NMP.

Methods: Fourteen porcine kidneys (n = 7 per group) were exposed to either 30 or 60 min of warm ischemia (WI), followed by 3.5 h of cold machine perfusion. After cold perfusion, kidneys underwent 4 h of NMP (37°C). During NMP, vasoactive drugs were sequentially infused into the renal artery at 30-min intervals, starting with epoprostenol (10 μg), followed by dopamine (1 mg), sodium nitroprusside (2 mg), acetylcholine (1 mg), norepinephrine (10 μg), and finally verapamil (2.5 mg).

Results: Renal blood flow during NMP changed significantly in both groups after administration of dopamine, acetylcholine, norepinephrine, and verapamil, but not following epoprostenol and sodium nitroprusside infusion. In kidneys subjected to 30 min of WI, the response to dopamine and norepinephrine was more pronounced, and oxygen consumption and blood pH were higher compared to kidneys that sustained 60 min of WI.

Conclusion: This study indicates that prolonged WI damage diminishes the contractility of VSMCs through the α-adrenergic receptors. Our findings suggest that the renal vascular responses to dopamine and norepinephrine, as well as decreased oxygen consumption and blood pH, could serve as objective indicators to quantify warm ischemic injury during renal NMP.

Background: Individuals with incomplete spinal cord injury (iSCI) often face challenges initiating reactive steps, leading to an increased risk of falls. Reactive balance training (RBT) can improve balance control; however, it is difficult to participate in RBT without the ability to initiate a reactive step independently. Functional electrical stimulation (FES) has been used to facilitate participation in RBT. FES applied to the common fibular nerve (CFN) following iSCI initiates a flexor withdrawal response, promoting rapid hip and knee flexion and ankle dorsiflexion, potentially aiding the execution of reactive stepping responses. This cross-sectional study aimed to evaluate the orthotic (i.e., immediate) effect of FES on reactive stepping parameters in participants with chronic, motor iSCI.

Methods: Sixteen individuals with chronic motor iSCI completed the Lean-and-Release test, which elicits reactive stepping through a simulated forward fall. Participants completed 10-20 trials, with FES applied in half at random. The behavioral response (i.e., single-step, two-step, ≥ 3-step, or fall) of each trial was recorded. Temporal parameters (i.e., foot-off time, swing time, and stepping time) and spatial parameters (i.e., length, height, and width) of the first reactive step were also recorded.

Results: The proportion of single-step (p = 0.31), two-step (p = 0.19), ≥ 3-step (p = 0.44) and fall (p = 0.42) behavioral responses did not differ between FES and No-FES conditions. Additionally, the temporal (foot-off time (p = 0.43), swing time (p = 0.80), and step time (p = 0.95)) and spatial parameters (length (p = 0.73), height (p = 0.70), and width (p = 0.54)) of the first reactive step did not differ between conditions.

Conclusions: FES had no orthotic effect on reactive stepping parameters in individuals with chronic motor iSCI.

Purpose: Significant advances have been made in the design and manufacture of artificial blood pumps. However, blood compatibility issues such as hemolysis, thrombosis, and inflammation during the clinical use of artificial blood pumps have reduced their reliability. Among these issues, hemolysis problems can lead to acute kidney injury, hyperkalemia, and in severe cases, even serious threats to life. To address hemolysis problems, blood transfusion, reduction of blood pump speed, and medication to promote erythropoiesis are generally used. This study explores the hemolysis problem from the perspective of the essence of problem solving, that is, the design of the blood pump structure.

Methods: A new centrifugal pump UJN-1 was designed based on empirical design theory and the velocity coefficient method of traditional centrifugal pumps. We used the commercial software Fluent to compare the data obtained from our simulation of FDA benchmark blood pumps with the results of other researchers to validate the accuracy of our simulation method. Based on the CFD numerical simulation method, we evaluated the hemolytic performance of three centrifugal pumps: Revolution, PuraLev 200SU, and UJN-1. The hydraulic performance of the designed UJN-1 blood pump was experimentally verified.

Results: The UJN-1 could provide a blood flow rate of 4-6 L/min and a blood pressure of 120 mmHg at 2500 rpm. The CFD numerical simulation and experimental results of the designed artificial blood pump UJN-1 were compared and verified, and the results showed that the error was small. The hemolysis results of the Revolution pump, 200SU pump, and UJN-1 pump were 3.35 × 10^-4%, 2.20 × 10^-4%, and 1.49 × 10^-4%, respectively. In a comparison of hemolysis among the three pumps, the UJN-1 pump had the lowest level of hemolysis.

Conclusion: This low hemolysis artificial blood pump design is important for long-term clinical use and high reliability of medical devices.

Background: Prolonged duration of polymyxin B hemoperfusion (PMX-HP) for septic shock is not widely investigated.

Methods: We used BEAT-SHOCK, a prospective registry including 309 adult patients with septic shock requiring high-dose norepinephrine (≥ 0.2 μg/kg/min). Our post hoc analysis included 82 patients that underwent PMX-HP, dichotomized into either the ultra-long PMX-HP group (first session duration ≥ 12 h; n = 53) or the non-ultra-long PMX-HP group (< 12 h; n = 29). The primary outcomes were changes in vasopressor/inotrope dosage, represented by vasoactive-inotropic score (VIS), and sequential organ failure assessment (SOFA) score from baseline to day 3.

Results: The median durations of the first PMX-HP session in the ultra-long and non-ultra-long PMX-HP groups were 1290 and 358 min, respectively. Their median baseline VIS was 38.3 (IQR 26.0-49.5) in the ultra-long group, 38.1 (IQR 30.9-55.6) in the non-ultra-long PMX-HP group. The median baseline SOFA score was 11 (IQR 9-13) in both groups. The changes in these scores from baseline to day 3 did not differ between them (adjusted difference -3.8 [95% confidence interval -9.0 to 11.3] for VIS and -0.0 [95% confidence interval -1.5 to 1.5] for SOFA score). The 90-day mortality rate was 24.7% in the ultra-long PMX-HP group and 21.1% in the non-ultra-long PMX-HP group (adjusted hazard ratio 1.35; 95% confidence interval 0.49-3.69).

Conclusions: Ultra-prolonged PMX-HP for ≥ 12 h was not associated with a greater reduction in vasopressor/inotrope dosage or improvement in organ dysfunction on day 3 than PMX-HP < 12 h in our patients with septic shock without endotoxin monitoring.

Trial registration: UMIN Clinical Trial Registry on 1 November 2019 (registration no. UMIN000038302).