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The aim of this work was to analyze the influence of sex hormones and anatomical details (trabeculations and false tendons) on the electrophysiology of healthy human hearts. Additionally, sex- and anatomy-dependent effects of ventricular tachycardia (VT) inducibility are presented. To this end, four anatomically normal, human, biventricular geometries (two male, two female), with identifiable trabeculations, were obtained from high-resolution, ex-vivo MRI and represented by detailed and smoothed geometrical models (with and without the trabeculations). Additionally one model was augmented by a scar. The electrophysiology finite element model (FEM) simulations were carried out, using O'Hara-Rudy human myocyte model with sex phenotypes of Yang and Clancy. A systematic comparison between detailed vs smooth anatomies, male vs female normal hearts was carried out. The heart with a myocardial infarction was subjected to a programmed stimulus protocol to identify the effects of sex and anatomical detail on ventricular tachycardia inducibility. All female hearts presented QT-interval prolongation however the prolongation interval in comparison to the male phenotypes was anatomy-dependent and was not correlated to the size of the heart. Detailed geometries showed QRS fractionation and increased T-wave magnitude in comparison to the corresponding smoothed geometries. A variety of sustained VTs were obtained in the detailed and smoothed male geometries at different pacing locations, which provide evidence of the geometry-dependent differences regarding the prediction of the locations of reentry channels. In the female phenotype, sustained VTs were induced in both detailed and smooth geometries with RV apex pacing, however no consistent reentry channels were identified. Anatomical and physiological cardiac features play an important role defining risk in cardiac disease. These are often excluded from cardiac electrophysiology simulations. The assumption that the cardiac endocardium is smooth may produce inaccurate predictions towards the location of reentry channels in in-silico tachycardia inducibility studies. [ABSTRACT FROM AUTHOR]

Advances in the brain-inspired computing space are growing at a rapid rate, and many of these emerging strategies are in the field of neuromorphic control, robotics, and sensor development, just to name a few. These innovations are disruptive in their own right and have numerous, multi-dimensional medical applications within precision medicine, telematics, device development, and informed clinical decision making. For this discussion, I will define brain-inspired computing in the scope of simulating the architecture of the brain and discuss the realization of integrating hardware and other technologies with the applications of medicine, along with the considerations for the regulatory pathway for approval and evaluating the risk/consequences of failure modes. This perspective is a call for continued discussion of the development of a pathway for translating these technologies into medical treatment and diagnostic strategies. The aim is to align with global regulatory bodies and ensure that regulation does not limit the capacity of these emerging innovations while ensuring patient safety and clinical efficacy. It is my perspective that it is and will continue to be critical that these technologies are correctly perceived and understood in the lens of multiple disciplines in order to reach their full potential for medical applications. [ABSTRACT FROM AUTHOR]

The latest technologies associated with implantable physiological monitoring devices can record multiple channels of data (including: heart rates and rhythms, activity, temperature, impedance and posture), and coupled with powerful software applications, have provided novel insights into the physiology of animals in the wild. This perspective details past challenges and lessons learned from the uses and developments of implanted biologgers designed for human clinical application in our research on free-ranging American black bears (Ursus americanus). In addition, we reference other research by colleagues and collaborators who have leveraged these devices in their work, including: brown bears (Ursus arctos), grey wolves (Canis lupus), moose (Alces alces), maned wolves (Chrysocyon brachyurus) and southern elephant seals (Mirounga leonina). We also discuss the potentials for applications of such devices across a range of other species. To date, the devices described have been used in fifteen different wild species, with publications pending in many instances. We have focused our physiological research on the analyses of heart rates and rhythms and thus special attention will be paid to this topic. We then discuss some major expected step changes such as improvements in sensing algorithms, data storage, and the incorporation of next-generation short-range wireless telemetry. The latter provides new avenues for data transfer, and when combined with cloud-based computing, it not only provides means for big data storage but also the ability to readily leverage high-performance computing platforms using artificial intelligence and machine learning algorithms. These advances will dramatically increase both data quantity and quality and will facilitate the development of automated recognition of extreme physiological events or key behaviours of interest in a broad array of environments, thus further aiding wildlife monitoring and management. [ABSTRACT FROM AUTHOR]

A pioneering surgeon at the University of Minnesota, Dr C. Walton Lillehei, is still considered the "father of open-heart surgery". Dr Lillehei and his surgical team performed the first open-heart operations utilizing cross-circulation, including the first successful ventricular septal defect closure on a 3-year-old boy. Before his death at age 67, this patient arranged to donate his body to the University of Minnesota's Anatomy Bequest program. We describe this patient's medical history, and present unique images of internal/external cardiac anatomies and implanted devices obtained via direct visualizations, computed tomography, and fluoroscopy post-mortem. Additionally, we present computational models and 3-dimensional printed models. [ABSTRACT FROM AUTHOR]

Background: Our research team obtained a human heart with the right lung attached from a recent transplantation patient via a research collaboration with LifeSource, a local organ procurement organization. The heart and lungs were not viable for transplant given the patient's medical history and were subsequently offered to the University of Minnesota for research purposes.Methods: Using Visible Heart® methodologies, we reanimated the specimen en bloc and collected multimodal direct visualization from inside the cardiac chambers and great vessels of the functioning heart.Results: Video footage, using videoscopic and fluoroscopic imaging, was captured and is presented in this report as supporting material. Multiple still images highlight the surgical suture sites of the transplantation procedures.Conclusions: This multimodal imaging offers unique educational value for medical students, clinicians, and medical device designers for improving transplantation techniques and patient outcomes. [ABSTRACT FROM AUTHOR]

Many lung donor offers are refused despite increasing demand. Portable normothermic ex vivo lung perfusion (EVLP) could increase donor yield by monitoring and reconditioning extended criteria donor (ECD) lungs. We report its use in human lungs declined for clinical transplantation. Ten sets of such lungs were procured from brain‐dead donors and underwent 24 hours of normothermic EVLP using a perfusate based on donor whole blood. Hemodynamic and ventilatory data and P:F ratios were measured. Advanced donor age and borderline oxygenation (donor mean P:F 228 ± 73) were the most commonly cited reasons for refusal for transplantation. There was no significant worsening of pulmonary hemodynamics or compliance or significant P:F decline during preservation in the overall cohort. Mean P:F ratio in the overall cohort was 315 ± 88 mm Hg after 24 hours EVLP. At EVLP termination 5/10 lung blocks met standard EVLP thresholds for acceptability for transplant. Eventual EVLP performance was poorly predicted by donor P:F ratio but well predicted by data gathered early in EVLP. Portable normothermic EVLP is useful for transportation, monitoring, and reconditioning of ECD lungs. Early EVLP measurements are more effective than preprocurement donor P:F in predicting eventual allograft performance. We advocate an aggressive strategy of evaluation of ECD lungs using blood‐based EVLP. [ABSTRACT FROM AUTHOR]

Data relative to anatomical measurements, spatial relationships, and device–tissue interaction are invaluable to medical device designers. However, obtaining these datasets from a wide range of anatomical specimens can be difficult and time consuming, forcing designers to make decisions on the requisite shapes and sizes of a device from a restricted number of specimens. The Visible Heart® Laboratories have a unique library of over 500 perfusion-fixed human cardiac specimens from organ donors whose hearts (and or lungs) were not deemed viable for transplantation. These hearts encompass a wide variety of pathologies, patient demographics, surgical repairs, and/or interventional procedures. Further, these specimens are an important resource for anatomical study, and their utility may be augmented via generation of 3D computational anatomical models, i.e., from obtained post-fixation magnetic resonance imaging (MRI) scans. In order to optimize device designs and procedural developments, computer generated models of medical devices and delivery tools can be computationally positioned within any of the generated anatomical models. The resulting co-registered 3D models can be 3D printed and analyzed to better understand relative interfaces between a specific device and cardiac tissues within a large number of diverse cardiac specimens that would be otherwise unattainable. [ABSTRACT FROM AUTHOR]

Remarkably, American black bears (Ursus americanus) are capable of varying their heart rates to coincidewith their breathing, creating pauses of 30 s or more, yet they do not appear to suffer from embolic events. We evaluated some features of the clotting cascade of black bears, providing novel insights into the underlying mechanisms they evoke for embolic protection during hibernation. We measured activated clotting time, prothrombin time and activated partial thromboplastin time during early denning (December), late denning (March) and summer (August). Activated clotting time during early hibernation was ~3 times longer than that observed among non-hibernating animals. Clotting time was reduced later in hibernation, when bears were within ~1 month of emerging from dens. Prothrombin time was similar for each seasonal time point, whereas activated partial thromboplastin time was highest during early denning and decreased during late denning and summer. We also examined D-dimer concentration to assess whether the bears were likely to have experienced embolic events. None of the nonparturient bears exceeded a D-dimer concentration of 250 ng ml-1 (considered the clinical threshold for embolism in mammals). Our findings suggest there is unique expression of the clotting cascade in American black bears during hibernation, in which extrinsic pathways are maintained but intrinsic pathways are suppressed. This was evaluated by a significant difference between the activated clotting time and activated partial thromboplastin time during the denning and non-denning periods. These changes are likely adaptive, to avoid clotting events during states of immobilization and/or periods of asystole. However, an intact extrinsic pathway allows for healing of external injuries and/or foreign body responses. [ABSTRACT FROM AUTHOR]

Background: In vitro isolated heart preparations are valuable tools for the study of cardiac anatomy and physiology, as well as for preclinical device testing. Such preparations afford investigators a high level of hemodynamic control, independent of host or systemic interactions. Here we hypothesize that recovered human and swine heart-lung blocs can be reanimated using a clear perfusate and elicit viable cardiodynamic and pulmonic function. Further, this approach will facilitate multimodal imaging, which is particularly valuable for the study of both functional anatomy and device-tissue interactions. Five human and 18 swine heart-lung preparations were procured using techniques analogous to those for cardiac transplant. Specimens were then rewarmed and reperfused using modifications of a closed circuit, isolated, beating and ventilated heart-lung preparation. Positive pressure mechanical ventilation was also employed, and epicardial defibrillation was applied to elicit native cardiac sinus rhythm. Videoscopy, fluoroscopy, ultrasound, and infrared imaging were performed for anatomical and experimental study. Results: Systolic and diastolic left ventricular pressures observed for human and swine specimens were 68/2 ± 11/7 and 74/3 ± 17/5 mmHg, respectively, with associated native heart rates of 80 ± 7 and 96 ± 16 beats per minute. High-resolution imaging within functioning human pulmonary vasculature was obtained among other anatomies of interest. Note that one human specimen elicited poor cardiac performance post defibrillation. Conclusions: We report the first dynamic videoscopic images of the pulmonary vasculature during viable cardiopulmonary function in isolated reanimated heart-lung blocs. This experimental approach provides unique in vitro opportunities for the study of novel medical therapeutics applied to large mammalian, including human, heart-lung specimens. [ABSTRACT FROM AUTHOR]

Biologgers can be used to monitor both human and animal physiology and behaviors, activity patterns, and/or environmental stressors. Monitoring of heart rates and rhythms, respiratory patterns, and activity in free-ranging bears can provide unique insights into physiological mechanisms. Such research can also influence the conservation of wildlife, the management of human–wildlife conflicts, and potentially human medicine. Here we describe our experiences with the development and utilization of three generations of implantable biologgers in American black and Eurasian brown bears (Ursus americanus and Ursus arctos arctos). These devices have enabled novel investigations into the underlying mechanisms for winter survival, including the discovery of an extreme respiratory sinus arrhythmias that acts to conserve energy while providing adequate circulation to maintain alertness (i.e., "fight or flight" behaviors). Extreme variations in heart rate have also been documented, including a 33.8 s asystole and a 261 beats/min sinus tachycardia in black bears and a 39.4 s asystole and a 240 beats/min sinus tachycardia in brown bears. Long-term data recording has also identified annual trends in heart rates and activity in both species. Combining physiological data with concurrent GPS collar locations provided insights into the impacts of human and environmental stressors (hunting, predation by other bears, road crossings, drones), which would not have been apparent through spatial data analysis alone. More recently, short-range wireless telemetry has allowed for real-time streaming of data via telemetry stations placed in remote den locations. Future iterations include transponders for biomonitoring and as an early warning system to aid in the prevention of poaching in free-ranging animals. In this review, we discuss the primary experimental capabilities of the current and next-generation systems. We highlight device evolution in terms of new physiological measurements (e.g., temperature, activity, impedance, posture), increased data storage capacity, improved wireless capabilities, and miniaturization to reduce the invasiveness of implantation procedures. These biologgers are now being applied to other species, and the possibilities seem limitless as technologies continue to advance. [ABSTRACT FROM AUTHOR]

Abstract: Computational modelling plays an important role in right ventricular (RV) haemodynamic analysis. However, current approaches use smoothed ventricular anatomies. The aim of this study is to characterise RV haemodynamics including detailed endocardial structures like trabeculae, moderator band, and papillary muscles. Four paired detailed and smoothed RV endocardium models (2 male and 2 female) were reconstructed from ex vivo human hearts high‐resolution magnetic resonance images. Detailed models include structures with ≥1 mm2 cross‐sectional area. Haemodynamic characterisation was done by computational fluid dynamics simulations with steady and transient inflows, using high‐performance computing. The differences between the flows in smoothed and detailed models were assessed using Q‐criterion for vorticity quantification, the pressure drop between inlet and outlet, and the wall shear stress. Results demonstrated that detailed endocardial structures increase the degree of intra‐ventricular pressure drop, decrease the wall shear stress, and disrupt the dominant vortex creating secondary small vortices. Increasingly turbulent blood flow was observed in the detailed RVs. Female RVs were less trabeculated and presented lower pressure drops than the males. In conclusion, neglecting endocardial structures in RV haemodynamic models may lead to inaccurate conclusions about the pressures, stresses, and blood flow behaviour in the cavity. [ABSTRACT FROM AUTHOR]