In Vitro Investigation of Platelet Dysfunction Induced by Osmotic Pressure Variations.

BACKGROUND: Severe variations in osmotic pressure are significant contributors to critical patient morbidity and mortality and might also affect platelet volume. We aimed to investigate possible osmotic-induced changes in mean platelet volume (MPV) and their possible effects on platelet aggregation activity (PLAG). METHODS: We induced experimental variations of serum osmolality in blood samples from healthy volunteers (heparinized whole blood, WB) and isolated platelets (Platelet Rich Plasma, PRP) by adding isotonic, hypertonic, and hypotonic solutions of saline/water (pH = 7.2-7.4). PLAG was tested in WB samples with Impedance Aggregometry (IA) and in PRP samples with Light Transmission Aggregometry (LTA) using three agonists Adenosine Diphosphate (ADP, 10 µΜ), Thrombin Receptor Activating Peptide (TRAP-6, 10 µΜ) and Arachidonic Acid (AA, 500 µΜ). Osmolality was either calculated using a formula or measured directly. RESULTS: We found almost identical osmolalities in WB and PRP preparations. Osmotic stress did not produce significant changes in MPV. In IA testing the hypotonic challenge of WB preparations produced significant reductions at 50 % (p = 0.056) (95 % CI: 11.2-2.4, in Ohms) of ADP and at 31 % (p = 0.017) (95 % CI: 13.4-8.6, in Ohms) of TRAP-6 -induced PLAG respectively. In PRP we did not observe any variations in PLAG with LTA. CONCLUSIONS: We conclude that in vitro hypotonic stress of WB samples has an inhibitory effect on the PAR-1 (TRAP-6 induced) pathway and on the P2Y12 (ADP induced) pathway and reflects a distinct in vivo effect of hypo-osmotic stress on WB human platelet preparations.

Standardized Comparison of Selected Physiological Controllers for Rotary Blood Pumps: In Vitro Study.

Various physiological controllers for left ventricular assist devices (LVADs) have been developed to prevent flow conditions that may lead to left ventricular (LV) suction and overload. In the current study, we selected and implemented six of the most promising physiological controllers presented in literature. We tuned the controllers for the same objectives by using the loop-shaping method from control theory. The in vitro experiments were derived from literature and included different preload, afterload, and contractility variations. All experiments were repeated with an increased or decreased contractility from the baseline pathological circulation and with simulated sensor drift. The controller performances were compared with an LVAD operated at constant speed (CS) and a physiological circulation. During preload variations, all controllers resulted in a pump flow change that resembled the cardiac output response of the physiological circulation. For afterload variations, the response varied among the controllers, whereas some of them presented a high sensitivity to contractility or sensor drift, leading to LV suction and overload. In such cases, the need for recalibration of the controllers or the sensor is indicated. Preload-based physiological controllers showed their clinical significance by outperforming the CS operation and promise many benefits for the LVAD therapy. However, their clinical implementation in the near future for long-term use is highly dependent on the sensor technology and its reliability.

Control of the Fluid Viscosity in a Mock Circulation.

A mock circulation allows the in vitro investigation, development, and testing of ventricular assist devices. An aqueous-glycerol solution is commonly used to mimic the viscosity of blood. Due to evaporation and temperature changes, the viscosity of the solution drifts from its initial value and therefore, deviates substantially from the targeted viscosity of blood. Additionally, the solution needs to be exchanged to account for changing viscosities when mimicking different hematocrits. This article presents a method to control the viscosity in a mock circulation. This method makes use of the relationship between temperature and viscosity of aqueous-glycerol solutions and employs the automatic control of the viscosity of the fluid. To that end, an existing mock circulation was extended with an industrial viscometer, temperature probes, and a heating nozzle band. The results obtained with different fluid viscosities show that a viscosity controller is vital for repeatable experimental conditions on mock circulations. With a mixture ratio of 49 mass percent of aqueous-glycerol solution, the controller can mimic a viscosity range corresponding to a hematocrit between 29 and 42% in a temperature range of 30-42°C. The control response has no overshoot and the settling time is 8.4 min for a viscosity step of 0.3 cP, equivalent to a hematocrit step of 3.6%. Two rotary blood pumps that are in clinical use are tested at different viscosities. At a flow rate of 5 L/min, both show a deviation of roughly 15 and 10% in motor current for high rotor speeds. The influence of different viscosities on the measured head pressure is negligible. Viscosity control for a mock circulation thus plays an important role for assessing the required motor current of ventricular assist devices. For the investigation of the power consumption of rotary blood pumps and the development of flow estimators where the motor current is a model input, an integrated viscosity controller is a valuable contribution to an accurate testing environment.

Detection of Neuropathic Pain in End-Stage Cancer Patients: Diagnostic Accuracy of Two Questionnaires.

INTRODUCTION: Neuropathic pain is a frequent consequence of cancer pain. Quite often, in the end stage, it is difficult to discern its presence and delineate its characteristics in the context of painful cancer complications. The aim of this study was to compare the diagnostic accuracy of the Douleur Neuropathique en 4 Questions (DN4) and painDETECT questionnaires, which were translated to the patient's native language, for the diagnosis of peripheral neuropathic pain in oncology patients. METHODS: End-stage cancer patients who presented to the outpatient pain clinic were prospectively followed. At presentation, all patients completed the DN4 and painDETECT questionnaires, which had been translated to their native language, and the output was compared to the pain specialist's diagnosis of the neuropathic or non-neuropathic nature of the pain, which was considered as the gold standard. The diagnostic accuracy of both questionnaires was tested with receiver operating characteristic curves plotted from the data collected. RESULTS: Ninety patients (48.5% of 185 in total) presented with severe pain. Seventy-six had neuropathic pain (41.1%) and 109 had non-neuropathic pain. Of those with neuropathic pain, most had a mixed pain (bone or visceral in addition to neuropathic pain). The DN4 questionnaire had a sensitivity of 71.1% and a specificity of 88.7% in detecting neuropathic pain, with a cutoff value of ≥ 4, while the painDETECT questionnaire had a sensitivity of 26.3% and a specificity of 100%, with a cutoff value of ≥ 19. CONCLUSION: At standard cutoff values, the DN4 and painDETECT questionnaires, despite having been translated to the patient's native language, failed to adequately discriminate between neuropathic and non-neuropathic pain in our end-stage cancer patients.

A Soft Total Artificial Heart-First Concept Evaluation on a Hybrid Mock Circulation.

The technology of 3D-printing has allowed the production of entirely soft pumps with complex chamber geometries. We used this technique to develop a completely soft pneumatically driven total artificial heart from silicone elastomers and evaluated its performance on a hybrid mock circulation. The goal of this study is to present an innovative concept of a soft total artificial heart (sTAH). Using the form of a human heart, we designed a sTAH, which consists of only two ventricles and produced it using a 3D-printing, lost-wax casting technique. The diastolic properties of the sTAH were defined and the performance of the sTAH was evaluated on a hybrid mock circulation under various physiological conditions. The sTAH achieved a blood flow of 2.2 L/min against a systemic vascular resistance of 1.11 mm Hg s/mL (afterload), when operated at 80 bpm. At the same time, the mean pulmonary venous pressure (preload) was fixed at 10 mm Hg. Furthermore, an aortic pulse pressure of 35 mm Hg was measured, with a mean aortic pressure of 48 mm Hg. The sTAH generated physiologically shaped signals of blood flow and pressures by mimicking the movement of a real heart. The preliminary results of this study show a promising potential of the soft pumps in heart replacements. Further work, focused on increasing blood flow and in turn aortic pressure is required.

Centhaquin Effects in a Swine Model of Ventricular Fibrillation: Centhaquin and Cardiac Arrest.

BACKGROUND: Centhaquin citrate is a novel agent being developed for use in the treatment of haemorrhagic shock. The aim of our study was to assess whether the administration of centhaquin would improve initial resuscitation success, 24-hour survival, and neurologic outcome compared with adrenaline alone in a porcine model of ventricular fibrillation. METHODS: Ventricular fibrillation was induced in 20 healthy Landrace/Large White piglets. The animals were randomised to receive placebo plus adrenaline 0.02mg/kg (n=10, Group C) and adrenaline 0.02mg/kg plus centhaquin 0.015mg/kg (n=10, Group S). All animals were resuscitated according to the 2010 European Resuscitation Council guidelines. Haemodynamic variables were measured before arrest, during arrest and resuscitation, and during the first two hours after return of spontaneous circulation (ROSC). Survival and a neurologic alertness score were measured at 24hours after ROSC. RESULTS: A significant difference was observed in ROSC rate between the two groups, as 10 animals (100%) from Group S and 4 animals (40%) from Group C achieved ROSC (p=0.011). Systolic, diastolic, and mean aortic pressure and coronary perfusion pressure were significantly higher in Group S at the end of the second cycle of CPR. In our study, all subjects with ROSC survived for 24hours, while we observed no statistically significant differences in neurologic examination (Group C 100±0, Group S 96±12.64; p=0.527). CONCLUSION: The addition of centhaquin to adrenaline improved ROSC rates in a swine model of VF cardiac arrest.

A Physiological Controller for Turbodynamic Ventricular Assist Devices Based on Left Ventricular Systolic Pressure.

The current article presents a novel physiological feedback controller for turbodynamic ventricular assist devices (tVADs). This controller is based on the recording of the left ventricular (LV) pressure measured at the inlet cannula of a tVAD thus requiring only one pressure sensor. The LV systolic pressure (SP) is proposed as an indicator to determine the varying perfusion requirements. The algorithm to extract the SP from the pump inlet pressure signal used for the controller to adjust the speed of the tVAD shows robust behavior. Its performance was evaluated on a hybrid mock circulation. The experiments with changing perfusion requirements were compared with a physiological circulation and a pathological one assisted with a tVAD operated at constant speed. A sensitivity analysis of the controller parameters was conducted to identify their limits and their influence on a circulation. The performance of the proposed SP controller was evaluated for various values of LV contractility, as well as for a simulated pressure sensor drift. The response of a pathological circulation assisted by a tVAD controlled by the introduced SP controller matched the physiological circulation well, while over- and underpumping events were eliminated. The controller presented a robust performance during experiments with simulated pressure sensor drift.

The impact of right ventricular hemodynamics on the performance of a left ventricular assist device in a numerical simulation model.

OBJECTIVES: Left ventricular assist devices (LVADs) have been established as alternative to heart transplantation for patients with end-stage heart failure refractory to medical therapy. Right heart failure (RHF) after LVAD implantation is associated with inferior outcome. Its preoperative anticipation may influence the selection between a pure left ventricular and a biventricular device type and, thus, improve outcomes. Reliable algorithms to predict RHF are missing. METHODS: A numerical model was used for simulation of a cardiovascular circulation. The LVAD was placed as parallel circuit between left ventricle and aorta. In contrast to other studies, the dynamic hydraulic behavior of a pulsatile LVAD was replaced by that of a continuous LVAD. A variety of hemodynamic states was tested mimicking different right heart conditions. Adjustable parameters included heart rate (HR), pulmonary vascular resistance (PVR), tricuspid regurgitation (TR), right ventricular contractility (RVC) and pump speed. Outcome parameters comprised central venous pressure (CVP), mean pulmonary artery pressure (mPAP), cardiac output (CO) and occurrence of suction. RESULTS: Alteration of HR, PVR, TR, RVC and pump speed resulted in diverse effects on CO, CVP and mPAP, resulting in improvement, impairment or no change of the circulation, depending on the degree of alteration. CONCLUSIONS: The numerical simulation model allows prediction of circulatory changes and LVAD behaviour following variation of hemodynamic parameters. Such a prediction may be of particular advantage to anticipate RHF after LVAD implantation. It may help preoperatively to choose the appropriate strategy of only left ventricular or both left and right ventricular support.

The Effect of Cell Salvage on Bleeding and Transfusion Needs in Cardiac Surgery.

Introduction: Cell salvaging is well established in the blood management of cardiac patients, but there remain some concerns about its effects on perioperative bleeding and transfusion variables. This randomized controlled study investigated the potential effects of the centrifuged end-product on bleeding, transfusion rates, and other transfusion-related variables in adult cardiac surgery patients submitted to extracorporeal circulation. Materials and Methods: Patients were randomly chosen to receive (cell-salvage group, 99 patients) or not to receive (control group, 110 patients) the centrifuged product of a cell salvage apparatus. Bleeding and transfusion rates according to the universal definition of perioperative bleeding (UDPB) classification, postoperative hemoglobin, coagulation, and oxygenation indices were recorded and compared between the groups. Results: Both groups had almost identical bleeding and transfusion rates (median value: 2 units of red blood cells (RBC) and no units of fresh frozen plasma (FFP) and platelets (PLT) for both groups, p > 0.05). Patients in the cell-salvage group presented slightly higher hemoglobin concentrations (10.6 ± 1.1 vs. 10.1 ± 1.7 g/dL, p < 0.05, respectively) and a tendency towards better oxygenation indices (PaO2/FiO2: 241 ± 94 vs. 207 ± 84, p=0.013) in the postoperative period albeit with a tendency for prolongation of prothrombin time (INR: 1.31 ± 0.18 vs. 1.26 ± 0.12, p=0.008). Conclusion: Within the study's constraints, the perioperative use of the cell salvage concentrate does not seem to affect bleeding or transfusion variables, although it could probably ameliorate postoperative oxygenation in adult cardiac surgery patients. A tendency to promote coagulation disturbances was detected.

Antiemetic prophylaxis in thyroid surgery: a randomized, double-blind comparison of three 5-HT3 agents.

PURPOSE: The aim of this double-blind randomized study was to compare the antiemetic efficacy of three 5-hydroxytryptamine type 3 antagonists in terms of the incidence and intensity of postoperative nausea and vomiting (PONV) in a homogenous group of female patients undergoing thyroidectomy. METHODS: The study cohort consisted of 203 American Society of Anesthesiologists PS I-II female patients randomized into four groups to receive at induction of anesthesia an intravenous (IV) bolus of 5 ml solution of one of the following: normal saline (placebo), granisetron 3 mg, ondansetron 4 mg, or tropisetron 5 mg. Nausea and vomiting were evaluated at five time points: during the first hour in the postanesthesia care unit (PACU) and 6, 12, 18, and 24 h postoperatively. Nausea intensity was measured using a visual analogue scale score (0-10). RESULTS: Patients in the placebo group displayed a high incidence of nausea in the PACU and at 6, 12, and 18 h postoperatively (44, 60, 50, and 34%, respectively) and of vomiting (26, 42, 30 and 10%). The administration of granisetron reduced significantly the incidence of nausea at 6, 12, and 18 h (26, 18, and 2%, respectively) and vomiting at 6 and 12 h (10 and 6%, respectively). Ondansetron reduced significantly the incidence of nausea and vomiting only at 6 h postoperatively (28 and 12%, respectively). The administration of tropisetron did not affect the incidence of PONV compared to placebo. CONCLUSION: Among the female patients of this study undergoing thyroid surgery, granisetron 3 mg provided the best prophylaxis from PONV. Ondansetron 4 mg was equally effective, but its action lasted only 6 h, whereas tropisetron 5 mg was found ineffective.

Cardiac Output Estimation: Online Implementation for Left Ventricular Assist Device Support.

OBJECTIVE: We present a novel pipeline that consists of various algorithms for the estimation of the cardiac output (CO) during ventricular assist devices (VADs) support using a single pump inlet pressure (PIP) sensor as well as pump intrinsic signals. METHODS: A machine learning (ML) model was constructed for the prediction of the aortic valve opening status. When a closed aortic valve is detected, the estimated CO equals the estimated pump flow. Otherwise, the estimated CO equals the sum of the estimated pump flow and the aortic valve flow, estimated via a Kalman-filter approach. Both the pathophysiological conditions and the pump speed of an in-vitro test bench were adjusted in various combinations to evaluate the performance of the pipeline, as well as the individual estimators. RESULTS: The ML model yielded a Matthews correlation coefficient of 0.771, a sensitivity of 0.913 and a specificity of 0.871. An overall CO root mean square error (RMSE) of 0.69 L/min was achieved. Replacing the pump flow and aortic pressure estimators with sensors would decrease the RMSE below 0.5 L/min. CONCLUSION: The performance of the proposed pipeline is considered the state of the art for VADs with an integrated PIP sensor. The effect of the individual estimators on the overall performance of the pipeline was thoroughly investigated and their limitations were identified for future research. SIGNIFICANCE: The clinical application of the proposed solution could provide the clinicians with essential information about the interaction between the patient's heart and the VAD to further improve the VAD therapy.

A Versatile Hybrid Mock Circulation for Hydraulic Investigations of Active and Passive Cardiovascular Implants.

During the development process of active or passive cardiovascular implants, such as ventricular assist devices or vascular grafts, extensive in-vitro testing is required. The aim of the study was to develop a versatile hybrid mock circulation (HMC) which can support the development of such implants that have a complex interaction with the circulation. The HMC operates based on the hardware-in-the-loop concept with a hydraulic interface of four pressure-controlled reservoirs allowing the interaction of the implant with a numerical model of the cardiovascular system. Three different conditions were investigated to highlight the versatility and the efficacy of the HMC during the development of such implants: 1) biventricular assist device (BiVAD) support with progressive aortic valve insufficiency, 2) total artificial heart (TAH) support with increasing pulmonary vascular resistance, and 3) flow distribution in a total cavopulmonary connection (TCPC) in a Fontan circulation during exercise. Realistic pathophysiologic waveforms were generated with the HMC and all hemodynamic conditions were simulated just by adapting the software. The results of the experiments indicated the potential of physiologic control during BiVAD or TAH support to prevent suction or congestion events, which may occur during constant-speed operation. The TCPC geometry influenced the flow distribution between the right and the left pulmonary artery, which was 10% higher in the latter and led to higher pressures. Together with rapid prototyping methods, the HMC may enhance the design of implants to achieve better hemodynamics. Validation of the models with clinical recordings is suggested for increasing the reliability of the HMC.

Correction to: Comparison of Flow Estimators for Rotary Blood Pumps: An In Vitro and In Vivo Study.

This erratum is to correct the third row of Table 2, where parameter h2h is missing in the original article.

Long-Term Performance of a Pneumatically Actuated Soft Pump Manufactured by Rubber Compression Molding.

We present a long-term performance study on a pneumatically actuated soft pump (SP). The pump was manufactured by adapting rubber compression technology. Important parameters influencing pump performance (e.g., inflation and deflation times and fluid outlet pressures) were studied. Based on design improvement and material selection, SP durability could be enhanced for over 1 million actuation cycles. This resulted in conveyance of more than 140,000 L of water in less than 12 days. In a next step, we analyzed our SP on a hybrid mock circulation and achieved 1.8 L/min against 10 kPa (75 mmHg). In situ analysis by color Doppler imaging further allowed real-time assessment of the SP's diaphragm motion. We then summarized our findings for future SP development with particular use as a heart replacement therapy. This work demonstrates a new manufacturing approach for future development of long-term stable SPs.

The influence of anesthetic techniques on postoperative cognitive function in elderly patients undergoing hip fracture surgery: General vs spinal anesthesia.

BACKGROUND: Hip fracture is common and morbid in elderly patients. Postoperative cognitive dysfunction (POCD) is also very common in these subjects undergoing surgery with an incidence which exceeds 40% in some reports. To date, the evidence is ambiguous as to whether anesthetic technique may affect the patients' outcome as far as postoperative cognitive function is concerned. OBJECTIVE: The aim of this study was to compare the effect of general and subarachnoid (spinal) anesthesia on the development of POCD up to 30 days after surgery in elderly patients undergoing hip fracture surgery. Methods Subjects over 65 years with hip fracture undergoing surgery were recruited for this study. They were enrolled and randomized to receive either general anesthesia (GA group) or subarachnoid (spinal) anesthesia (S group). Cognitive function was assessed using a battery of neuropsychological tests undertaken preoperatively and at 30 days postoperatively. The incidence of delirium was examined during the same period and their functional status, in terms of activities of daily living was also recorded. RESULTS: A total of seventy patients, 33 men and 37 females, mean age of 76 years were analyzed. Thirty-three patients received general anesthesia (GA group) and 37 subarachnoid (spinal) anesthesia (S group). The two groups of patients were similar with respect to baseline characteristics, comorbidities and perioperative data. The results of neuropsychological testing showed that there were no significant differences between the groups in eight out of ten neurocognitive tests at baseline and 30 days after surgery. There was a statistically significant decline of the Instrumental Activities of Daily Living Scale score in S group compared with group GA on the 30th postoperative day (p = 0.043). A significant decline was also present in Color-Word Task test in S group compared with group GA at baseline (p = 0.014) and 30 days postoperatively (p = 0.003). Postoperative delirium was present in four patients (12%) for the GA group, and in 10 patients (27%) for the group receiving subarachnoid anesthesia. CONCLUSION: We concluded that the choice of anesthesia modality does not appear to influence the emergence of postoperative cognitive dysfunction in elderly patients undergoing hip fracture surgery.

Viscosity Prediction in a Physiologically Controlled Ventricular Assist Device.

OBJECTIVE: We present a novel machine learning model to accurately predict the blood-analog viscosity during support of a pathological circulation with a rotary ventricular assist device (VAD). The aim is the continuous monitoring of the hematocrit (HCT) of VAD patients with the benefit of a more reliable pump flow estimation and a possible early detection of adverse events, such as bleeding or pump thrombosis. METHODS: A large dataset was generated with a blood pump connected to a hybrid mock circulation by varying the pump speed, the physiological requirements of the modeled circulation, and the viscosity of the blood-analog. The inlet pressure and the intrinsic signals of the pump were considered as inputs for the model. Gaussian process yielded models with the best performance, which were then combined using a variant of stacked generalization to derive the final model. The final model was evaluated with unseen testing data from the dataset created. RESULTS: For these data, the model yielded a mean absolute deviation of 1.81% from the true HCT, while it proved to correctly predict the direction of the HCT change. It showed to be independent of the set speed and of the condition of the simulated cardiovascular circulation. CONCLUSION: The accuracy of the prediction model allows an improvement of the quality of flow estimators and the detection of adverse events at an early stage. The evaluation of this approach with blood is suggested for further validation. SIGNIFICANCE: Its clinical application could provide the clinicians with reliable and important hemodynamic information of the patient and, thus, enhance patient monitoring and supervision.

Comparison of Flow Estimators for Rotary Blood Pumps: An In Vitro and In Vivo Study.

Various approaches for estimating the flow rate of a rotary blood pump have been proposed for monitoring and control purposes. They have been evaluated under different test conditions and, therefore, a direct comparison among them is difficult. Furthermore, a limited performance has been reported for the areas where the pump flow and motor current present a non-monotonic relationship. In this regard, we selected most approaches that have been presented in literature and added a modified one, resulting in four estimators, which are either non-invasive or invasive, i.e., inlet and outlet pump pressure sensors are used. Data from in vitro and in vivo studies with the Deltastream pump DP2 were used to compare the estimators under the same test conditions. These data included both constant and varying pre- and afterload, contractility, viscosity, as well as pump speed settings. Bland-Altman plots were used to evaluate the performance of the estimators. The mean error of the overall estimated flow in vitro ranged from 0.002 to 0.38 L/min and the limits of agreement (LoA) between ± 2 L/min. During negative flows the mean error decreased by about 25% when the pump inlet pressure was added as an input. In vivo, the mean errors increased, while the LoA remained in the same range. An estimator based on pump pressure difference improves the reliability in areas where flow and current relationship is not monotonic. A trade-off between estimation accuracy and number of sensors was identified. The estimation objective and the potential errors should be considered when selecting an estimation approach and designing the pump systems.

Electroacupuncture for the Treatment of Calcific Tendonitis. A Pilot Study.

Current treatment for calcific tendonitis consists of arm rest, antiinflammatory medications, and corticosteroid injections. If unsuccessful, a lot of clinicians suggest several physiotherapy modalities, such as shockwave therapy and electrotherapy. The purpose of our study was to assess the efficacy of electroacupuncture, as a substitute for failed medical treatment in calcific tendonitis. In a pilot study, we prospectively followed 10 patients treated with electroacupuncture for calcific tendonitis who failed to respond to medical treatment. Its efficacy was assessed by evaluating the level of pain, the Beck Depression Inventory, the range of active elbow mobility, and by repeated radiological evaluation of the course of calcific deposits. All clinical and radiological observations were recorded before and within 6 months after the onset of treatment. After electroacupuncture treatment (2 Hz, 180 mA for 30-60 seconds at GB21, GB34, LI4, LI 14, LI15, TW5, TW14, Chien Chien SI9, SI12, S37, S38), the visual analog score decreased notably, and the range of motion returned to normal. Radiological evaluation demonstrated almost complete absorption of calcific deposits within 6 months, after treatment. We conclude that electroacupuncture relieved skeletal pain, improved the quality of patient's life, and contributed to total regression of the calcific depositions in followed patients. So, electroacupuncture may be a valuable treatment option for calcific tendonitis, when medical treatment fails to relieve symptoms.

Virtual surgical planning, flow simulation, and 3-dimensional electrospinning of patient-specific grafts to optimize Fontan hemodynamics.

BACKGROUND: Despite advances in the Fontan procedure, there is an unmet clinical need for patient-specific graft designs that are optimized for variations in patient anatomy. The objective of this study is to design and produce patient-specific Fontan geometries, with the goal of improving hepatic flow distribution (HFD) and reducing power loss (Ploss), and manufacturing these designs by electrospinning. METHODS: Cardiac magnetic resonance imaging data from patients who previously underwent a Fontan procedure (n = 2) was used to create 3-dimensional models of their native Fontan geometry using standard image segmentation and geometry reconstruction software. For each patient, alternative designs were explored in silico, including tube-shaped and bifurcated conduits, and their performance in terms of Ploss and HFD probed by computational fluid dynamic (CFD) simulations. The best-performing options were then fabricated using electrospinning. RESULTS: CFD simulations showed that the bifurcated conduit improved HFD between the left and right pulmonary arteries, whereas both types of conduits reduced Ploss. In vitro testing with a flow-loop chamber supported the CFD results. The proposed designs were then successfully electrospun into tissue-engineered vascular grafts. CONCLUSIONS: Our unique virtual cardiac surgery approach has the potential to improve the quality of surgery by manufacturing patient-specific designs before surgery, that are also optimized with balanced HFD and minimal Ploss, based on refinement of commercially available options for image segmentation, computer-aided design, and flow simulations.