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  • articleNo Access

    ROLE OF CELLULAR COUPLING AND DISPERSION OF REFRACTORINESS IN CARDIAC ARRHYTHMIAS: A SIMULATION STUDY

    Computer simulation is applied to study the role of cellular coupling, dispersion of refractoriness as well as both of them, in the mechanisms underlying cardiac arrhythmias. We first assumed that local ischemia mainly induces cell to cell dispersion in the coupling resistance (case 1), refractory period (case 2) or both (case 3). Numerical experiments, based on the van Capelle and Durrer model, showed that vortices could not be induced in these conditions. In order to be more realistic about coronary circulation we simulated a patchy dispersion of cellular properties, each patch corresponding to the zone irrigated by a small coronary artery. In these conditions, a single activation wave could give rise to abnormal activities. Probabilities of reentry, estimated for the three cases cited above, showed that a severe alteration of the coupling resistance may be an important factor in the genesis of reentry. Moreover, use of isochronal maps revealed that vortices were both stable and sustained with an alteration of coupling alone or along with reductions of action potential duration. Conversely, simulations with reduction of the refractoriness alone induced only transient patterns.

  • articleNo Access

    BRAIN TEMPERATURE DISTRIBUTION DURING DEEP HYPOTHERMIC CIRCULATORY ARREST IN HUMANS

    This paper analyzes the effect of different cooling and rewarming strategies on the brain temperature distribution before and after circulatory arrest in adults and children. The temperature variations during systemic cooling, circulatory arrest, and rewarming are calculated using a thermal model that incorporates physiological parameters. The calculations presented here explain why sometimes hypothermia does not show the expected neuroprotective effect.

    This work shows the importance of departing from a steady temperature distribution when using deep hypothermic circulatory arrest. In the calculations, the external cooling conditions of the head are varied, and it is observed that hypothermic cardiopulmonary bypass (CPB) together with external head cooling help reduce the temperature gradients within the head during periods of reduced blood flow, and reduces the temperature increase in the deep tissue produced by the residual cerebral metabolic activity. The results presented here agree with previous experimental observations1–3 regarding the duration of systemic cooling using CPB.

  • articleNo Access

    AN ENDOCARDIAL ACCELERATION SENSOR FOR MONITORING CARDIAC FUNCTION OF ISCHEMIC HEARTS

    Previous experimental studies demonstrated that in normal hearts, Peak Endocardial Acceleration (PEA), during isovolumic contraction phase, measured with an endocardial sensor (Best, Sorin) in the right ventricle (RV), tracks changes of left ventricular (LV) contractility. Aim of the study: To assess if PEA also tracks LV contractility changes in ischemic hearts resulting from coronary microembolizations (ME). Methods: Under general anaesthesia, six adult beagle dogs (12 ± 2 kg) were instrumented for chronic monitoring of LV pressure, ECG and PEA. Latex beads mixed with fluoroscopy dye were injected into the circumflex coronary artery to cause LV ischemia. Before and after ME, incremental dobutamine infusions were performed to evaluate the contractile response to adrenergic stimulation. Results: A significant correlation between PEA and LVdP/dtmax was observed before and after ME. Such a strong correlation was maintained even during adrenergic stimulation (r = 0.83 to 0.99, p < 0.001). The sensor PEA appears to be an effective means for the chronic monitoring of the mechanical function of ischemic hearts.

  • articleNo Access

    REVIEW: HEMODYNAMIC STUDIES FOR LOWER LIMB AMPUTATION AND REHABILITATION

    No matter what the reason and level of amputation are, amputees will face many complex postoperative problems and potential complications. From the perioperative stage to lengthy rehabilitation process, patients need comprehensive and cautious therapies to help them rebuild their physical and mental health. Although there is some scattered information, the achievements of hemodynamic study for lower limb amputation and rehabilitation have not been systematically classified and summarized. The purpose of this review is to introduce and discuss the hemodynamic issues in preoperative diagnosis, surgical techniques and postoperative problems in the past two decades. Whether from clinical or biomechanical perspective, the investigations of the former two stages have been relatively mature and gained some clear outcomes, even if some conclusions are conflicting and controversial. While in terms of the postoperative problems, such as the common pressure ulcers, DTI and muscle atrophy, there is a lack of vascular or blood flow state studies specifically for lower residual limb. Therefore, the future research focus of hemodynamics for lower limb amputation should probably be the detailed investigations on the relationships between various blood flow parameters and certain common complications. Although hemodynamic research has made some achievements at this stage, it is believed that more advanced and reliable techniques are pending for further explorations and developments.

  • articleOpen Access

    DEVELOPMENT AND VALIDATION OF A RELATIVE BLOOD FLOW CHANGE MEASUREMENT ALGORITHM USING NEAR-INFRARED LIGHT

    The purpose of this study is to develop a near-infrared blood flow measurement algorithm and verify its performance. The gradient value of the measurement point was determined by using LED lights with wavelengths of 760nm and 850nm. This process involved measuring the gradient value for a significant number of regularly spaced cubic pixels centered around the chosen point. The measured gradient values for each pixel were then averaged to derive the final gradient value. Based on the measurement of the gradation value, when the concentration ratio of blood was altered by 20% between 0% and 100%, the gradation values at 760nm and 850nm changed significantly (more than ±2.5%) in all cases. This study validated the efficacy of a self-developed near-infrared light system for detecting changes in blood flow. The ability to measure alterations in blood flow can be instrumental in predicting peripheral vascular disease (PVD) due to compromised circulatory conditions.

  • articleNo Access

    THE GLOBAL EFFECTS OF STROKE ON THE HUMAN ELECTROENCEPHALOGRAM

    The scaling properties of the fluctuations of EEG time series are used in an investigation of acute stroke in humans. We use detrended fluctuation analysis to characterize the fluctuations in 10-second time series in terms of two dimensionless scaling exponents. The statistics of these scaling exponents across 129 scalp sites define measures which may be used to distinguish normal subjects from those with acute cerebral ischemia. By their nature, these statistics emphasize the global properties of EEG dynamics. Simulation of a focal anomaly which accurately reproduces the mean scaling exponents for stroke subjects contradicts the data for the variances, which we take as evidence that the effect of stroke on EEG is global.

  • articleNo Access

    Task-specific compensation and recovery following focal motor cortex lesion in stressed rats

    One reason for the difficulty to develop effective therapies for stroke is that intrinsic factors, such as stress, may critically influence pathological mechanisms and recovery. In cognitive tasks, stress can both exaggerate and alleviate functional loss after focal ischemia in rodents. Using a comprehensive motor assessment in rats, this study examined if chronic stress and corticosterone treatment affect skill recovery and compensation in a task-specific manner. Groups of rats received daily restraint stress or oral corticosterone supplementation for two weeks prior to a focal motor cortex lesion. After lesion, stress and corticosterone treatments continued for three weeks. Motor performance was assessed in two skilled reaching tasks, skilled walking, forelimb inhibition, forelimb asymmetry and open field behavior. The results revealed that persistent stress and elevated corticosterone levels mainly limit motor recovery. Treated animals dropped larger amounts of food in successful reaches and showed exaggerated loss of forelimb inhibition early after lesion. Stress also caused a moderate, but non-significant increase in infarct size. By contrast, stress and corticosterone treatments promoted reaching success and other quantitative measures in the tray reaching task. Comparative analysis revealed that improvements are due to task-specific development of compensatory strategies. These findings suggest that stress and stress hormones may partially facilitate task-specific and adaptive compensatory movement strategies. The observations support the notion that hypothalamic–pituitary–adrenal axis activation may be a key determinant of recovery and motor system plasticity after ischemic stroke.

  • articleNo Access

    INNOVATION AND TECHNOLOGY TRANSFER OF MEDICAL DEVICES FOSTERED BY CROSS-DISCIPLINARY COMMUNITIES OF PRACTITIONERS

    Commercialisation of emerging technological innovations such as medical devices can be a time-consuming and lengthy process resulting in a market entrance failure. To tackle this general problem, major challenges are being analysed, principally focusing on the role of Communities of Practitioners (CoPs) in the process of effective transfer of high-value emerging technologies from academia to market. Taking a case study approach, this document describes the role of a cross-disciplinary CoP in the technology transfer process within a convergence scenario. The case presented is a sensor array for ischemia detection developed by different practitioners from diverse organisations: university, research institution, hospital, and a scientific park. The analysis also involves the innovation ecosystem where all stakeholders are taken into account. This study contributes to a better understanding of the managerial implications of CoP fostering technology transfer and innovation, principally focused on the current need for new biomedical technologies and tools.

  • articleFree Access

    FLUORESCENT IMAGES OF MITOCHONDRIAL REDOX STATES IN IN SITU MOUSE HYPOXIC ISCHEMIC INTESTINES

    We have imaged mitochondrial oxidation–reduction states by taking a ratio of mitochondrial fluorophores: NADH (reduced nicotinamide adenine dinucleotide) to Fp (oxidized flavoprotein). Although NADH has been investigated for tissue metabolic state in cancer and in oxygen deprived tissues, it alone is not an adequate measure of mitochondrial metabolic state since the NADH signal is altered by dependence on the number of mitochondria and by blood absorption. The redox ratio, NADH/(Fp + NADH), gives a more accurate measure of steady-state tissue metabolism since it is less dependent on mitochondrial number and it compensates effectively for hemodynamic changes. This ratio provides important diagnostic information in living tissues. In this study, the emitted fluorescence of mouse colon in situ is passed through an emission filter wheel and imaged on a CCD camera. Redox ratio images of the healthy and hypoxic mouse intestines clearly showed significant differences. Furthermore, the corrected redox ratio indicated an increase from an average value of 0.51 ± 0.10 in the healthy state to 0.92 ± 0.03 in dead tissue due to severe ischemia (N = 5). We show that the CCD imaging system is capable of displaying the metabolic differences in normal and ischemic tissues as well as quantifying the redox ratio in vivo as a marker of these changes.

  • articleNo Access

    A novel model for ex situ reperfusion of the human liver following subnormothermic machine perfusion

    TECHNOLOGY01 Dec 2017

    Machine perfusion-based organ preservation techniques are prudently transitioning into clinical practice. Although experimental data is compelling, the outcomes in the highly variable clinical donation-transplantation setting are unpredictable. Here, we offer an intermediate tool for pre-clinical assessment of human donor livers. We present a model for ex situ reperfusion of discarded human livers and report on its application in three human livers that have undergone subnormothermic (21C) machine perfusion as an experimental preservation method. During reperfusion, the livers macroscopically reperfused in the first 15 minutes, and remained visually well-perfused for 3 hours of ex situ reperfusion. Bile production and oxygen consumption were observed throughout ex situ reperfusion. ATP levels increased 4.25-fold during SNMP. Between the end of SNMP and the end of reperfusion ATP levels dropped 45%. ALT levels in blood increased rapidly in the first 30 minutes and ALT release continued to taper off towards the end of perfusion. Release of CRP, TNF-α, IL-1β, and IL-12, IFN-γ was sustained during reperfusion. These findings support the use of this model for the evaluation of novel human liver preservation techniques.

  • chapterNo Access

    CHAPTER 4: Cell therapy for critical limb ischemia: Current progress and future prospects

    Stem Cells31 Mar 2020

    In spite of the current notable advances in surgical management of critical limb ischemia (CLI), the most severe form of peripheral artery disease, it is still associated with the high frequency of amputations, lethality and low quality of life. Although the compensatory opportunities are mainly exhausted in the treatment of CLI, an efficient medical intervention remains possible. The purpose of this intervention is to eliminate a pronounced imbalance between the blood supply of the ischemic tissues and their metabolic needs. The physiological compensatory arteriogenesis, which actively proceeds at the initial stages of limb ischemia, almost ceases to the beginning of its transition into the final stages. Therefore, research efforts are focused on those technologies for tissue repair which are directed at the activation and expansion of the microvascular bed (angiogenesis) in the affected limb. Cell therapy, having been actively studied from the beginning of 2000s, is one of such approaches. This review discusses in-depth the advantages of different cell types for the CLI therapy, including peripheral bone marrow-derived mononuclear cells (BMMNCs) and mesenchymal stem cells (BMMSCs). The results of the most important pre-clinical and clinical studies, including the ongoing clinical trials, involving cell-based approach for CLI therapy have also been discussed besides optimization of the cell delivery techniques with or without the use of biomaterials as cell carriers.