Cardiac transplant outcomes can be compromised by the effects of global ischemia and associated reperfusion injury. In attempts to alleviate these phenomena, various pharmaceutical agents can be ...administered. Previous reports have shown that adenosine triphosphate (ATP) may act as either a postconditioning (PoC) or supplementary (Sup) therapy with cardiosupportive benefits. To further evaluate ATP’s relative effectiveness, we used an isolated swine heart four-chamber working model to monitor both hemodynamic and metabolic responses. We employed two strategies of ATP administration: (1) a postconditional (PoC) bolus just prior to reanimation, and (2) regular dosing throughout the assessment period (Sup). Ex vivo swine hearts in the Sup group elicited significantly higher left ventricular function during the 2 h monitoring period than controls. In contrast, PoC administration appeared to induce depressed cardiac function. The effects of ATP on cardiac function can have varied effects, dependent on when it is administered.
Impact statement
We employed an isolated swine heart four-chamber working model to investigate two potential strategies for adenosine triphosphate (ATP) administration as an ex vivo therapy: (1) application of a single bolus dose during reperfusion (postconditioning or PoC), and (2) repeated bolus dosing throughout the experiment (supplementary or Sup). Ex vivo swine hearts in the Sup group elicited significantly higher left ventricular function during the 2 h experimental monitoring period. In contrast, ATP administration in the PoC group appeared to induce a degree of depressed hemodynamic function. These data suggest varied functional roles of ATP administration relative to their use in ex vivo perfusion strategies. We consider that both treatment strategies, if appropriately administered and with further investigation of dosing paradigms, may eventually elicit value in various clinical scenarios, including heart transplantation and ex vivo heart perfusion to assess potential organs for transplantation and potentially increase the pool of viable donor hearts.
Summary
Donation after circulatory death (DCD) is an underused source of donor lungs. Normothermic cellular ex vivo lung perfusion (EVLP) is effective in preserving standard donor lungs but may also ...be useful in the preservation and assessment of DCD lungs. Using a model of DCD and prolonged EVLP, the effects of donor warm ischemia and postmortem ventilation on graft recovery were evaluated. Adult male swine underwent general anesthesia and heparinization. In the control group (n = 4), cardioplegic arrest was induced and the lungs were procured immediately. In the four treatment groups, a period of agonal hypoxia was followed by either 1 h of warm ischemia with (n = 4) or without (n = 4) ventilation or 2 h of warm ischemia with (n = 4) or without (n = 4) ventilation. All lungs were studied on an EVLP platform for 24 h. Hemodynamic measures, compliance, and oxygenation on EVLP were worse in all DCD lungs compared with controls. Hemodynamics and compliance normalized in all lungs after 24 h of EVLP, but DCD lungs demonstrated impaired oxygenation. Normothermic cellular EVLP is effective in preserving and monitoring of DCD lungs. Early donor postmortem ventilation and timely procurement lead to improved graft function.
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.
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. Keywords: Autonomic nervous system, Conservation, Heart rate, Hibernation, Respiratory sinus arrhythmia, Stress, Ursus, Wildlife
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.
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.
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.
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 only Cardiac myofiber structure and organizations play critical roles in the electrical and mechanical properties of the heart. Diffusion tensor magnetic resonance imaging (DTMRI) has been a ...useful imaging modality to visualize the myocardial fiber orientation with emerging clinical application. DTMRI takes advantage of the limited diffusion of water along the cardiac fiber’s longitudinal axis and provides the dominant direction of diffusion . Until recently, DTMRI usage was relatively limited to clinical imaging of white matter within the brain. While there are limitations for cardiac use in vivo , due to tissue displacement and non‐rigid deformation, DTMRI is becoming a powerful diagnostic tool to assess structural heart damage. The data can also be the input into numerous computational simulations of the heart’s electrical activities. The Visible Heart ® ; Laboratories at the University of Minnesota, in collaboration with Lifesource, an organ procurement organization, maintains a large collection of human hearts that were donated for research. These organs are received fresh and subsequently preserved with 10% buffered formalin in the approximate end‐diastolic state for future anatomical studies. For the present studies, the hearts were rinsed of formalin and completely submerged in an agarose gel in attitudinally correct positions. The hearts are next scanned in a clinical 3T MRI scanner using a diffusion tensor sequence. The raw DTMRI DICOM files are then reconstructed using Diffusion Toolkit and visualized in TrackVis software . This outputs a 3‐dimensional model that allows for visualization of the relative orientations of the myocardial fibers. Whole heart tissue models can also be generated using Materialise Mimics software from these scans. MRI scans of a heart from a 50 year old male with a history of myocardial infarction can be seen in Figure . The DTMRI axial images (Figure ) provide insights relative to the orientations of the myocardial fibers; which can then be transformed into a 3D diagram (Figure ) of directional eigenvectors. Future work will be done to improve resolutions by extending the number of averages acquired during such scanning. Increasing resolution will allow us to assess structural heart damage stemming from myocardial injuries: e.g. from ablations or due to myocardial infarction. Additionally, we hope to combine DTMRI with cardiac tissue models to create a 3D print that highlight regional myocardial fiber orientations. The fiber orientations from the DTMRI scans can also be incorporated into computer simulations, which may help elucidate the activation pathways of the heart. In some cases today, DTMRI can be utilized clinically to improve one’s understanding of the conduction system of the heart, which has implications in lead placement for pacing and ablation procedures. Researchers and clinicians can learn critical information relative to cardiac anatomy from DTMRI. An overview of the methods used to generate a 3D reconstruction of diffusion tensor MRI data. The resulting image is further refined to remove extraneous data Figure 1
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.
PDF
