In vitro arterial flow bioreactor systems are widely used in tissue engineering to investigate response of endothelial cells to shear. However, the assumption that such models reproduce physiological flow has not been experimentally tested. Furthermore, shear stresses experienced by the endothelium are generally calculated using a Poiseuille flow assumption. Understanding the performance of flow bioreactor systems is of great importance, since interpretation of biological responses hinges on the fidelity of such systems and the validity of underlying assumptions. Here we test the physiologic reliability of arterial flow bioreactors and the validity of the Poiseuille assumption for a typical system used in tissue engineering. A particle image velocimetry system was employed to experimentally measure the flow within the vessel with high spatial and temporal resolution. Two types of vessels were considered: first, fluorinated ethylene propylene (FEP) tubing representative of a human artery without cells; and second, FEP tubing with a confluent layer of endothelial cells on the vessel lumen. Instantaneous wall shear stress (WSS), time-averaged WSS, and oscillatory shear index were computed from velocity field measurements and compared between cases. The flow patterns and resulting wall shear were quantitatively determined to not accurately reproduce physiological flow, and that the Poiseuille flow assumption was found to be invalid. This work concludes that analysis of cell response to hemodynamic parameters using such bioreactors should be accompanied by corresponding flow measurements for accurate quantification of fluid stresses.

Ventricular assist devices (VADs) have significantly impacted the treatment of adult cardiac failure, but few options exist for pediatric patients. This has motivated our group to develop an implantable magnetically levitated rotodynamic VAD (PediaFlow^®) for 3–20 kg patients. The second prototype design of the PediaFlow (PF2) is 56% smaller than earlier prototypes, and achieves 0.5–1.5 L/min blood flow rates. In vitro hemodynamic performance and hemolysis testing were performed with analog blood and whole ovine blood, respectively. In vivo evaluation was performed in an ovine model to evaluate hemocompatibility and end-organ function. The in vitro normalized index of hemolysis was 0.05–0.14 g/L over the specified operating range. In vivo performance was satisfactory for two of the three implanted animals. A mechanical defect caused early termination at 17 days of the first in vivo study, but two subsequent implants proceeded without complication and electively terminated at 30 and 70 days. Serum chemistries and plasma free hemoglobin were within normal limits. Gross necropsy revealed small, subclinical infarctions in the kidneys of the 30 and 70 day animals (confirmed by histopathology). The results of these experiments, particularly the biocompatibility demonstrated in vivo encourage further development of a miniature magnetically levitated VAD for the pediatric population. Ongoing work including further reduction of size will lead to a design freeze in preparation for of clinical trials.

In this paper, we present a reliable and efficient automatic R-wave detection based on new nonlinear transformation and simple peak-finding strategy. The detection algorithm consists of four stages. In the first stage, the bandpass filtering and differentiation operations are used to enhance QRS complexes and to reduce out-of-band noise. In the second stage, we introduce a new nonlinear transformation based on energy thresholding, Shannon energy computation, and smoothing processes to obtain a positive-valued feature signal which includes large candidate peaks corresponding to the QRS complex regions. The energy thresholding reduces the effect of spurious noise spikes from muscle artifacts. The Shannon energy transformation amplifies medium amplitudes and results in small deviations between successive peaks. Therefore, the proposed nonlinear transformation is capable of reducing the number of false-positives and false-negatives under small-QRS and wide-QRS complexes and noisy ECG signals. In the third stage, we propose a simple peak-finding strategy based on the first-order Gaussian differentiator (FOGD) that accurately identifies locations of candidate R-peaks in a feature signal. This stage computes convolution of the smooth feature signal and FOGD operator. The resultant convolution output has negative zero-crossings (ZCs) around the candidate peaks of feature signal due to the anti-symmetric nature of the FOGD operator. Thus, these negative ZCS are detected and used as guides to find locations of real R-peaks in an original signal at the fourth stage. Unlike other existing algorithms, the proposed algorithm does not use search back algorithm and learning phase. The proposed algorithm is validated using the standard MIT-BIH arrhythmia database and achieves an average sensitivity of 99.94% and a positive predictivity of 99.96%. Experimental results show that the proposed algorithm outperforms other existing algorithms in case of different QRS complex morphologies (negative, low-amplitude, wide), very big change in amplitudes of adjacent R-peaks, irregular heart rates, and noisy ECG signals.

The evaluation and treatment of acute ischemic stroke patients is a rapidly evolving area in contemporary medical practice that has experienced many recent advances. The interface between physicians and scientists/engineers has become a major driver for these advances. This special issue brings together contributions from physicians and researchers from a broad spectrum of disciplines who work together to solve the challenges in the management of stroke patients.

Cheyne-Stokes breathing (CSB) has been associated with advanced heart failure for two centuries. However, the current conventional method of CSB detection is via a full-night polysomnographic test which is a complex, expensive and inconvenient for the patients. Accordingly, the purpose of the current study was to assess a more practical method for CSB detection in heart failure (HF) patients and investigate its prognostic applications. We describe here risk stratification for mortality and morbidity over 6 months of follow-up by using standard pulse oximeter analyzed with an innovative automated program for CSB detection. A total of 109 consecutive HF out-patients, 93 men and 16 women underwent a full-night sleep studies performed at home, using a standard pulse oximeter for detection of CSB during sleep. Data was analyzed by an innovative algorithm-based system. Of the 109 patients, our analysis identified 46 (42%) patients with episodes of CSB. Within the 6-month follow-up period, 8 (17.4%) of these patients died or were urgently transplanted, and 14 (30.4%) were hospitalized for HF. Multiple regression testing with several known prognostic parameters, showed that CSB was the most significant predictor of mortality or heart failure hospitalizations (p < 0.001). Heart failure patients with CSB have increased mortality and morbidity over the next 6 months. The detection of CSB is feasible via a simple and reliable method using a standard pulse oximeter, which may be more suitable for sick HF patients than the complex and inconvenient full-night polysomnography.

Although there are many studies that focus on understanding the consequence of pumping mode (continuous vs. pulsatile) associated with ventricular assist devices (VADs) on pediatric vascular pulsatility, the impact on local hemodynamics has been largely ignored. Hence, we compare not only the hemodynamic parameters indicative of pulsatility but also the local flow fields in the aorta and the great vessels originating from the aortic arch. A physiologic graft anastomotic model is constructed based on a pediatric, patient specific, aorta with a graft attached on the ascending aorta. The flow is simulated using a previously validated second-order accurate Navier–Stokes flow solver based upon a finite volume approach. The major findings are: (1) pulsatile support provides a greater degree of vascular pulsatility when compared to continuous support, which, however, is still 20% less than pulsatility in the healthy aorta; (2) pulsatile support increases the flow in the great vessels, while continuous support decreases it; (3) complete VAD support results in turbulence in the aorta, with maximum principal Reynolds stresses for pulsatile support and continuous support of 7081 and 249 dyn/cm², respectively; (4) complete pulsatile support results in a significant increase in predicted hemolysis in the aorta; and (5) pulsatile support causes both higher time-averaged wall shear stresses (WSS) and oscillatory shear indices (OSI) in the aorta than does continuous support. These findings will help to identify the risk of graft failure for pediatric patients with pulsatile and continuous VADs.

Myxomatous mitral valve disease is a form of mitral valve prolapse, which is characterized by a disorganized collagen matrix with excessive glycosaminoglycan content. Due to loss of mechanical competence and increased surface area of the mitral valve leaflets, this disease leads to regurgitation and cardiac dysfunction. There is a strong clinical need for percutaneous treatment of patients with myxomatous mitral valve disease and regurgitation as an alternative to open-chest surgery. We have previously examined the efficacy of radiofrequency ablation of the mitral valve leaflets as a strategy to reduce prolapse and regurgitation in a canine model. Prior to testing this strategy further in a large animal model, we sought to determine the ‘therapeutic window’ that should be targeted in vitro. Here, we quantified both the geometrical and biomechanical compliance changes of porcine mitral valve anterior leaflets before and after radiofrequency ablation at various powers (Watts) for 15 s. Following ablation, there was significant shortening in the circumferential direction after 15 and 25 W, which led to significant decreases in surface area at these powers. Under an equibiaxial membrane tension of 90 N/m, which approximates systolic loading of 120 mmHg, axial strain in the radial direction was predominantly affected following ablation with significant decreases following 10, 15, and 25 W. Circumferential strain was not different following any ablation power, except 25 W when it was significantly increased. Areal strain at 90 N/m was significantly decreased following 10 and 15 W ablations, but was increased following 25 W. These data indicate that radiofrequency ablation decreases mitral valve leaflet surface area and compliance, but only achieving both within a narrow therapeutic window. To maximize both of these effects, 15 W appears to be the target power. While 25 W leads to ~25% reduction in tissue area, it results in increased compliance. We speculate that at this power, collagen fibers may be failing due to rupture, either directly from ablation or once they are mechanically loaded.

Bone marrow derived mesenchymal stem cell (BMSCs) therapy can significantly improve cardiac ventricular function following ischemic injury. Their potential can be further enhanced by using genetically modified cells, overexpressing certain therapeutic biomolecules. However, such therapy is limited by low efficiency of transplantation of the cells, secreting inadequate therapeutic proteins. To address these issues, we developed recombinant baculoviruses to genetically modify the BMSCs and investigated the potential of using polyethylene glycol (PEG) integrated alginate–chitosan microcapsules (AC) for efficient myocardial transplantation. The data indicates that the cells encapsulated in AC–PEG microcapsules grew rapidly from 80 cells per capsule to above 100 cells per capsule within a week, reaching a confluency of average 110 cells by day 9 of encapsulation. The microcapsules proved superior to commonly used AC microcapsules in terms of immune protection. After 11 days of co-culture of the encapsulated cells with highly confluent lymphocytes, the viable cell population in AC–PEG microcapsules was reduced by only 20%, whereas in AC microcapsules it was reduced to more than 50%. AC–PEG microcapsules also had significantly higher mechanical (65 vs. 10%) and osmotic (92 vs. 52%) stability than commonly used AC microcapsules as seen after 2 h of external stresses. The entrapped genetically modified cells showed highest transgene expression on day 1, which was gradually reduced to 48% after 1 week and to 14% after 2 weeks. This expression pattern was also dependant on initial viral incubation time, with 8 h incubation being the optimum. The encapsulated cells, transduced with baculovirus, also retained their inherent potential to differentiate into multiple lineages. Because of the above characteristics, the baculovirus transduced microencapsulated BMSCs have immense potential in myocardial cell-based gene therapy, although preclinical studies are needed to be done to establish their functional benefits on myocardial implantation.

A growing number of elderly patients with significant co-morbidities do not meet the inclusion criteria for conventional cardiac surgical therapies, including aortic valve replacement and mechanical circulatory support. To meet this clinical need, an aortic valve bypass (AVB) system is being developed that may be implanted using subcostal or mini-thoracotomy surgical approaches without ventricular coring or cardiopulmonary bypass. The AVB system consists of an apical left ventricular (ALV) cannula made from pyrolytic carbon, a valved conduit with a locking mechanism, and a Nitinol clip for anastomosis to the descending aorta. To define design criteria and demonstrate efficacy, ALV cannulae with different diameters (7–14 mm), number of sideholes (6–12), sidehole size (1.9–4.6 mm wide) and tip shapes (tapered, straight) were designed, fabricated, and tested. Cannula efficacy was determined by quantifying flow rates and pressure drops across the ALV cannula using steady-state and dynamic mock circulation models simulating mild, moderate and severe aortic stenosis test conditions. Blood trauma testing was conducted to demonstrate hemocompatibility using the smallest diameter (7 mm) ALV cannula prototype fabricated from pyrolytic carbon (PYC). In vitro and blood trauma testing demonstrated that (1) the 7 mm PYC cannula did not produce significant hemolysis (<40 mg/dL pfHb), but was unable to achieve bypass flow rates above 1.4 L/min, (2) a minimum cannula diameter of 12 mm was required to produce flow rates >4.5 L/min for <10 mmHg pressure drop across the ALV cannula, and (3) the cannula tip shape did not significantly alter bypass flow rate or pressure drop. The ALV cannula may enable a minimally invasive surgical approach using a modified Seldinger’s technique for implantation in heart failure patients with aortic stenosis.