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1.
Artigo em Inglês | MEDLINE | ID: mdl-38625670

RESUMO

Epicardial interventions have forged new frontiers in cardiac ablation and device therapies. Healthy human hearts typically present with significant adipose tissue layers superficial to the ventricular myocardium and may hinder success or increase the complexities of epicardial interventions. We quantitatively evaluated the distribution of epicardial adipose tissue on the surface of human hearts and provided high-fidelity 3-dimensional reconstructions of these epicardial adipose tissue layers. The regional thickness of adipose tissues was analyzed at 51 anatomical reference points surrounding both ventricles and compared to specific patient demographics. Adipose deposits on the human hearts displayed characteristic patterns, with the thickest accumulations along the interventricular septa (anterior, 9.01 ± 0.50 mm; posterior, 6.78 ± 0.50 mm) and the right ventricular margin (7.44 ± 0.57 mm). We provide one of the most complete characterizations of human epicardial adipose location and relative layer thickness. These results are considered fundamental for an underlying anatomic understanding when performing procedures within the pericardial space.

2.
J Cardiovasc Dev Dis ; 10(12)2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38132658

RESUMO

Electroporation is used in medicine for drug and gene delivery, and as a nonthermal ablation method in tumor treatment and cardiac ablation. Electroporation involves delivering high-voltage electric pulses to target tissue; however, this can cause effects beyond the intended target tissue like nerve stimulation, muscle contractions and pain, requiring use of sedatives or anesthetics. It was previously shown that adjusting pulse parameters may mitigate some of these effects, but not how these adjustments would affect electroporation's efficacy. We investigated the effect of varying pulse parameters such as interphase and interpulse delay while keeping the duration and number of pulses constant on nerve stimulation, muscle contraction and assessing pain and electroporation efficacy, conducting experiments on human volunteers, tissue samples and cell lines in vitro. Our results show that using specific pulse parameters, particularly short high-frequency biphasic pulses with short interphase and long interpulse delays, reduces muscle contractions and pain sensations in healthy individuals. Higher stimulation thresholds were also observed in experiments on isolated swine phrenic nerves and human esophagus tissues. However, changes in the interphase and interpulse delays did not affect the cell permeability and survival, suggesting that modifying the pulse parameters could minimize adverse effects while preserving therapeutic goals in electroporation.

3.
Health Sci Rep ; 6(11): e1704, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38028705

RESUMO

Background and Aims: Modern health care faces a plethora of challenges including the delivery of quality and cost-efficient care. Physicians are first-hand observers of clinical problems but may lack the requisite training and education to develop innovations that improve patient care. Few medical education programs address innovation, leadership, and transdisciplinary collaboration despite being highlighted by national medical and education organizations including the American Medical Association. The University of Minnesota has implemented the Augustine program over the last 10-years to produce physicians that are leaders in medical innovation. Methods: As a novel joint engineering-medical school curriculum to educate medical students, residents, and fellows, the Augustine program incorporates engineering coursework, biomedical research, and a multidisciplinary design and business development experience to produce physicians capable of designing and marketing "disruptive technologies." The Augustine program takes 1-year to complete in addition to the 4-year medical education and provides a Master of Biomedical Engineering upon completion. Results: Augustine program graduates (n = 6) have reported significant contributions related to the joint engineering-medical education including peer-reviewed publications (Median: 13), deployable assets (Median: 2), and intellectual property (Median: 1). Most surveyed graduates (n = 5, 83%) continue to be active contributors to medical innovation and all (n = 6, 100%) utilize their transdisciplinary education to improve patient care. Conclusion: Augustine program graduates impact the entire spectrum of innovation and continue to improve patient care. The program will seek to emphasize the inclusion of physician residents and fellows with position expansion. The addition of a multi-week medical innovation clerkship will provide a more focused experience for students unable to dedicate an entire year to a transdisciplinary experience.

4.
Front Cardiovasc Med ; 10: 1160231, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37424913

RESUMO

Introduction: Pulsed field ablation is an emerging modality for catheter-based cardiac ablation. The main mechanism of action is irreversible electroporation (IRE), a threshold-based phenomenon in which cells die after exposure to intense pulsed electric fields. Lethal electric field threshold for IRE is a tissue property that determines treatment feasibility and enables the development of new devices and therapeutic applications, but it is greatly dependent on the number of pulses and their duration. Methods: In the study, lesions were generated by applying IRE in porcine and human left ventricles using a pair of parallel needle electrodes at different voltages (500-1500 V) and two different pulse waveforms: a proprietary biphasic waveform (Medtronic) and monophasic 48 × 100 µs pulses. The lethal electric field threshold, anisotropy ratio, and conductivity increase by electroporation were determined by numerical modeling, comparing the model outputs with segmented lesion images. Results: The median threshold was 535 V/cm in porcine ((N = 51 lesions in n = 6 hearts) and 416 V/cm in the human donor hearts ((N = 21 lesions in n = 3 hearts) for the biphasic waveform. The median threshold value was 368 V/cm in porcine hearts ((N = 35 lesions in n = 9 hearts) cm for 48 × 100 µs pulses. Discussion: The values obtained are compared with an extensive literature review of published lethal electric field thresholds in other tissues and were found to be lower than most other tissues, except for skeletal muscle. These findings, albeit preliminary, from a limited number of hearts suggest that treatments in humans with parameters optimized in pigs should result in equal or greater lesions.

5.
Echocardiography ; 40(7): 703-710, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37345442

RESUMO

INTRODUCTION: Echocardiography is essential for diagnosing and assessing the severity of perioperative structural and functional heart disease. Yet, educational opportunities to better understand echocardiography-based cardiac anatomy remain limited by the two-dimensional display, lack of anatomic details, variability of heart models, and costs and global access of training. METHODS: We performed micro computed tomography of human heart specimens not suitable for orthotopic transplantation. We created high-resolution computational 3D models of different human hearts, sliced them in the different recommended American Society of Echocardiography views, and 3D printed them using different materials. RESULTS: We scanned, 3D modeled, and 3D printed a variety of human hearts both healthy and diseased. We have made the models available in the cardiac operating rooms and routinely use them for teaching anesthesia residents and cardiothoracic anesthesia fellows about basic and advanced echocardiographic views, cardiopulmonary bypass cannulation strategies, and valvular pathology and planned interventions. CONCLUSION: We have generated a library of 3D printed hearts to display the recommended echocardiographic views as a unique educational tool designed to safely accelerate the understanding of absolute and relative human cardiac anatomy and pathology, especially related to gaining advanced appreciation of clinically employed perioperative echocardiography.


Assuntos
Cardiopatias , Coração , Humanos , Microtomografia por Raio-X , Coração/diagnóstico por imagem , Ecocardiografia , Modelos Anatômicos
6.
J Biomech Eng ; 145(11)2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37382900

RESUMO

While mitral valve (MV) repair remains the preferred clinical option for mitral regurgitation (MR) treatment, long-term outcomes remain suboptimal and difficult to predict. Furthermore, pre-operative optimization is complicated by the heterogeneity of MR presentations and the multiplicity of potential repair configurations. In the present work, we established a patient-specific MV computational pipeline based strictly on standard-of-care pre-operative imaging data to quantitatively predict the post-repair MV functional state. First, we established human mitral valve chordae tendinae (MVCT) geometric characteristics obtained from five CT-imaged excised human hearts. From these data, we developed a finite-element model of the full patient-specific MV apparatus that included MVCT papillary muscle origins obtained from both the in vitro study and the pre-operative three-dimensional echocardiography images. To functionally tune the patient-specific MV mechanical behavior, we simulated pre-operative MV closure and iteratively updated the leaflet and MVCT prestrains to minimize the mismatch between the simulated and target end-systolic geometries. Using the resultant fully calibrated MV model, we simulated undersized ring annuloplasty (URA) by defining the annular geometry directly from the ring geometry. In three human cases, the postoperative geometries were predicted to 1 mm of the target, and the MV leaflet strain fields demonstrated close agreement with noninvasive strain estimation technique targets. Interestingly, our model predicted increased posterior leaflet tethering after URA in two recurrent patients, which is the likely driver of long-term MV repair failure. In summary, the present pipeline was able to predict postoperative outcomes from pre-operative clinical data alone. This approach can thus lay the foundation for optimal tailored surgical planning for more durable repair, as well as development of mitral valve digital twins.


Assuntos
Doenças das Valvas Cardíacas , Insuficiência da Valva Mitral , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Músculos Papilares , Cordas Tendinosas
7.
IEEE Trans Biomed Eng ; 70(6): 1826-1837, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37022450

RESUMO

OBJECTIVE: The goal of our study was to determine the importance of electric field orientation in an anisotropic muscle tissue for the extent of irreversible electroporation damage by means of an experimentally validated mathematical model. METHODS: Electrical pulses were delivered to porcine skeletal muscle in vivo by inserting needle electrodes so that the electric field was applied in direction either parallel or perpendicular to the direction of the muscle fibres. Triphenyl tetrazolium chloride staining was used to determine the shape of the lesions. Next, we used a single cell model to determine the cell-level conductivity during electroporation, and then generalised the calculated conductivity changes to the bulk tissue. Finally, we compared the experimental lesions with the calculated field strength distributions using the Sørensen-Dice similarity coefficient to find the contours of the electric field strength threshold beyond which irreversible damage is thought to occur. RESULTS: Lesions in the parallel group were consistently smaller and narrower than lesions in the perpendicular group. The determined irreversible threshold of electroporation for the selected pulse protocol was 193.4 V/cm with a standard deviation of 42.1 V/cm, and was not dependent on field orientation. CONCLUSION: Muscle anisotropy is of significant importance when considering electric field distribution in electroporation applications. SIGNIFICANCE: The paper presents an important advancement in building up from the current understanding of single cell electroporation to an in silico multiscale model of bulk muscle tissue. The model accounts for anisotropic electrical conductivity and has been validated through experiments in vivo.


Assuntos
Eletroporação , Músculo Esquelético , Animais , Suínos , Eletroporação/métodos , Terapia com Eletroporação , Eletricidade , Simulação por Computador , Condutividade Elétrica
8.
J Cardiovasc Transl Res ; 16(4): 927-937, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36939960

RESUMO

Percutaneous coronary intervention can be a high-risk procedure that would benefit from optimizing device-tissue interactions between stents and coronary vessels. Using a perfusion-fixed human heart with coronary artery disease, we performed a percutaneous coronary intervention of the left main coronary artery bifurcation. This heart was perfused and multimodal imaging was utilized to view the procedure with direct visualization, fluoroscopy, and optical coherence tomography (OCT). We followed the European Bifurcation Club's guidelines to perform a single-stent bifurcation before transitioning to a two-stent Culotte technique. After each procedural step, the heart was removed from the perfusion apparatus and transferred to a micro-CT scanner to obtain unique scans. We conducted apposition analyses of the computational 3D models from micro-CT DICOM datasets, and compared them to the results from direct visualization and commercial OCT's Apposition Indicator software. Additional measurements of resulting coronary anatomic expansions were taken to determine the potential roles of each step in improving procedural outcomes. Micro-CT images show stent deformation during a percutaneous coronary intervention (provisional to Culotte bifurcation procedure) in an isolated diseased human heart.


Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Microtomografia por Raio-X , Resultado do Tratamento , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Stents , Intervenção Coronária Percutânea/efeitos adversos , Perfusão , Imagem Multimodal , Angiografia Coronária/métodos
9.
Biomed Eng Online ; 22(1): 27, 2023 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-36934270

RESUMO

BACKGROUND: Percutaneous coronary interventions (PCIs) within left main coronary arteries are high-risk procedures that require optimization of interactions between stent(s) and diseased vessels. Optical Coherence Tomography (OCT) is a widely accepted tool that enhances physicians' ability to assess proper stent appositions during clinical procedures. The primary aim of this study was to develop complementary post-procedure imaging methodologies to better assess and interpret outcomes of left main PCI procedures, utilizing both reanimated and perfusion-fixed human hearts. METHODS: PCIs were performed while obtaining OCT scans within the left main anatomies of six human hearts. Subsequently, each heart was scanned with a micro-CT scanner with optimized parameters to achieve resolutions up to 20 µm. Scans were reconstructed and imported into a DICOM segmentation software to generate computational models of implanted stents and associated coronary vessels. 2D images from OCT that were obtained during PCIs were compared to the 3D models generated from micro-CT reconstructions. In addition, the 3D models were utilized to create virtual reality scenes and enlarged 3D prints for development of "mixed reality" tools relative to bifurcation stenting within human left main coronary arteries. RESULTS: We developed reproducible methodologies for post-implant analyses of coronary artery stenting procedures. In addition, we generated high-resolution 3D computational models, with ~ 20-micron resolutions, of PCIs performed within reanimated and perfusion-fixed heart specimens. CONCLUSIONS: Generated computational models of left main PCIs performed in isolated human hearts can be used to obtain detailed measurements that provide further clinical insights on procedural outcomes. The 3D models from these procedures are useful for generating virtual reality scenes and 3D prints for physician training and education.


Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Intervenção Coronária Percutânea/métodos , Angiografia Coronária/métodos , Microtomografia por Raio-X , Resultado do Tratamento , Stents , Perfusão , Tomografia de Coerência Óptica/métodos
10.
Physiol Rep ; 11(5): e15630, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36878878

RESUMO

Preclinical research remains the essential platform in the development and optimization of medical therapies and advancements in translational medicines. However, specifically to animal research, federal laws, and institutional policies require investigators to apply the principles of the 3R's (replacement, reduction, and refinement). The concept of benchtop models utilizing isolated organs, in which multiple variables can be controlled to recreate human function, has been innovative advancements in preclinical research models that adhere to these principles. More specifically, isolated perfused kidney (IPK) models have been invaluable preclinical tools that have led to numerous advancements over the decades, including understanding renal physiology, pharmacologic therapies, and improvements in renal transplantation. However, pre-existing IPK models are not without their own limitations, leaving areas for improvement. An isolated perfused kidney apparatus was designed to best recreate human use conditions as a preclinical tool. Porcine renal blocks were chosen over the more commonly used rodent models, due to their greater similarities to human anatomies. Sixteen porcine kidney pairs obtained en bloc were extracted and placed onto an apparatus where aortic flows, pressures, and overall systemic temperatures were controlled. Organ viability was assessed in 10 renal blocks (n = 8 fresh and n = 2 previously frozen specimens) via both urinary flows and compositions at timepoints up to 180 min. Multimodality imaging, which included fluoroscopy, ultrasound, optical coherence tomography (OCT), and video scopes, was also employed to capture internal and external images to determine renal artery orientations and dimensions. Anatomical measurements and viability assessments of porcine renal blocks were successfully achieved in our perfusion model. Renal main artery diameters averaged smaller in our sample size than in human anatomy while also having more superior takeoff angles. Yet, the average lengths of each main segment were comparable to human anatomy: 32.09 ± 7.97 mm and 42.23 ± 7.33 mm in the left and right renal main artery, respectively. Urine production and urine composition of the fresh renal blocks, when compared to the frozen blocks and baseline perfusate, showed kidney viabilities of up to 3 h via excretion and retention of various metabolites. In this paper, we described a protocol for an isolated perfused kidney apparatus using large mammalian renal blocks. We believe this protocol to be an improvement from similar pre-existing models in better representing human physiologic function while allowing for multimodal imaging. The resulting Visible Kidney™ preclinical model, which has shown viability after isolation and reperfusion, can be a fast and reliable tool for the development of medical devices while also reducing the unnecessary use of animals for research.


Assuntos
Líquidos Corporais , Transplante de Rim , Humanos , Suínos , Animais , Rim , Diurese , Aorta , Mamíferos
11.
PLoS One ; 18(2): e0263639, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36780442

RESUMO

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.


Assuntos
Caracteres Sexuais , Taquicardia Ventricular , Feminino , Masculino , Humanos , Ventrículos do Coração , Coração , Arritmias Cardíacas , Simulação por Computador , Estimulação Cardíaca Artificial , Eletrocardiografia
12.
Clin Anat ; 36(4): 612-617, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36597994

RESUMO

Aortic valve fenestrations are defined as a loss of aortic valve leaflet tissue. They are a common but overlooked finding with unclear significance. The aim of this study was to investigate the varied functional anatomies of aortic valve fenestrations. A total of 400 formalin-fixed autopsied human hearts were macroscopically assessed and the function of the aortic valve of 16 reanimated human hearts were imaged using Visible Heart® methodologies. Aortic valve leaflet fenestrations were present in 43.0% of autopsied hearts (in one leaflet in 24.0%, in two leaflets 16.0%, in all leaflets 3.0%). Fenestrations were mostly present in left (25.5%) followed by right (23.3%) and noncoronary leaflet (16.3%). In 93.8% of cases, the fenestrations form clusters and were mainly located at the free edge of the leaflet in the commissural area (95.4%). Hearts with aortic valve fenestrations had significantly larger aortic valve diameters and aortic valve areas (p < 0.001). The average surface area sizes of fenestrations were 23.8 ± 16.6 mm2 , and the areas were largest for left followed by right and noncoronary leaflet fenestrations (p < 0.001). The fenestration areas positively correlated with donor age (r = 0.31; p = 0.02). Significant hypermobility and subjective weakening of the leaflet adhesion levels of the fenestrated regions were observed. In conclusion, fenestrations of the aortic leaflets are frequent, and their sizes may be significant. They occur in all age groups, yet their size increase with aging. Fragments of leaflets with fenestrations show different behaviors during the cardiac cycle versus unchanged areas.


Assuntos
Aorta , Valva Aórtica , Humanos , Valva Aórtica/anatomia & histologia , Envelhecimento , Autopsia
13.
Ann Biomed Eng ; 51(3): 538-549, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36088432

RESUMO

Cryosurgery is a minimally invasive approach to the treatment of focal prostate cancer (PCa). A major complication is the cryoinjury to the cavernous nerve in the neurovascular bundle (NVB). This nerve cryoinjury halts conduction of action potentials (APs) and can eventually result in erectile dysfunction and therefore diminished quality of life for the patient. Here, we propose the application of cryoprotective agents (CPA) to the regions of the nerves in the NVB, prior to prostate cryosurgery, to minimize non-recoverable loss of AP conduction. We modeled a cryosurgical procedure based on data taken during a clinical case and applied ex-vivo porcine phrenic nerves and rat sciatic nerve with temperature profile of NVB. The APs were measured before and after the CPA exposures and during 3 h of recovery. Comparisons of AP amplitude recovery with various CPA compositions reveal that certain CPAs (e.g., 5% DMSO + 7.5% Trehalose and 5% M22 for porcine and rat nerves, respectively) showed little or no toxicity and effective cryoprotection from freezing (on average 48% and 30% of recovered AP, respectively). In summary, we demonstrate that neural conduction can be preserved after exposure to freezing conditions if CPAs are properly selected and deployed onto the nerve.


Assuntos
Criocirurgia , Disfunção Erétil , Neoplasias da Próstata , Masculino , Humanos , Ratos , Animais , Suínos , Próstata/cirurgia , Qualidade de Vida , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Disfunção Erétil/cirurgia
15.
J Cardiothorac Vasc Anesth ; 37(2): 308-313, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36372718

RESUMO

The clinical uses of perioperative transesophageal echocardiography have grown exponentially in recent years for both cardiac and noncardiac surgical patients. Yet, echocardiography is a complex skill that also requires an advanced understanding of human cardiac anatomy. Although simulation has changed the way echocardiography is taught, most available systems are still limited by investment costs, accessibility, and qualities of the input cardiac 3-dimensional models. In this report, the authors discuss the development of an online simulator using a high-resolution human heart scan that accurately represents real cardiac anatomies, and that should be accessible to a wide range of learners without space or time limitations.


Assuntos
Ecocardiografia Tridimensional , Ecocardiografia Transesofagiana , Humanos , Ecocardiografia Transesofagiana/métodos , Ecocardiografia , Coração , Simulação por Computador , Fatores de Tempo
16.
J Cardiovasc Dev Dis ; 9(12)2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36547410

RESUMO

Transcatheter aortic valve replacement (TAVR) has become a popular treatment option for severe aortic stenosis for patients with a high risk for mortality with surgical aortic valve replacement (SAVR). Coronary artery occlusion (CAO) following the implantation of the device is a potential and sometimes devastating complication of this procedure, that provokes a sudden deterioration of hemodynamic status followed by cardiogenic shock and electrical instability. With patients that present a high risk for coronary obstruction, coronary protection with a chimney stenting technique is an effective strategy that can ensure coronary perfusion during TAVR in case of acute CAO. Utilizing Visible Heart® methodologies, a human heart was reanimated. A chimney stenting technique was implemented simultaneously with the deployment of a Medtronic Evolut™ Pro+ valve (Medtronic PLC; Minneapolis, MN, USA). The entire procedure was recorded utilizing endoscopic cameras, fluoroscopy, optical coherence tomography, and echocardiography. In addition to these procedural visualizations, post-procedural micro-computed tomography (micro-CT) was conducted to provide post-implantation imaging with approximately 60-micron resolution. Utilizing these imaging modalities in a reanimated human heart allows for the unique opportunity to collect data for TAVR procedures in real human anatomies for the subsequent educational uses by the physicians treating aortic valvular disease and/or the designers of future TAVR technologies and procedures.

17.
Front Physiol ; 13: 910016, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991166

RESUMO

Background: Paravalvular leak (PVL) is a frequent TAVR complication. Prospective identification of patients who are likely to develop PVL after TAVR would likely lead to improved outcomes. Prior studies have used geometric characteristics to predict the likelihood of PVL development, but prediction and quantification has not been done. One of the reasons is that it is difficult to predict the mechanical deformation of the native diseased aortic valve prior to implantation of the prosthetic valve, as existing calcifications likely contribute to the seal between the prosthetic valve and the aortic annulus. However, the relatively amount the native valve plays in preventing PVL is unknown. Methods: A retrospective chart review was conducted identifying patients with mild or greater PVL. One patient who had substantial PVL was identified and a 3D printed (pre-TAVR) aortic root was created. Balloon-expandable TAVR stent frames were implanted within the 3D printed root and a new model was created. Using this geometry, computational fluid dynamics (CFD) simulations were done to quantify PVL. The PVL flow path was iteratively decreased to simulate the space occupied by a crushed native aortic valve and PVL was quantified. Results: PVL was found to decrease as the space occupying the PVL area increased, demonstrating that the native aortic valve contributes to reducing regurgitation. CFD simulations demonstrated that within the patient analyzed, the native valve occupies between 3-40% of the PVL pathway. Conclusion: A priori techniques that predict the development of post TAVR PVL should account for the native diseased valve as our simulations demonstrate that it plays a role in reducing PVL.

18.
Adv Mater Technol ; 7(3)2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35668819

RESUMO

To extend the preservation of donor hearts beyond the current 4-6 h, this paper explores heart cryopreservation by vitrification-cryogenic storage in a glass-like state. While organ vitrification is made possible by using cryoprotective agents (CPA) that inhibit ice during cooling, failure occurs during convective rewarming due to slow and non-uniform rewarming which causes ice crystallization and/or cracking. Here an alternative, "nanowarming", which uses silica-coated iron oxide nanoparticles (sIONPs) perfusion loaded through the vasculature is explored, that allows a radiofrequency coil to rewarm the organ quickly and uniformly to avoid convective failures. Nanowarming has been applied to cells and tissues, and a proof of principle study suggests it is possible in the heart, but proper physical and biological characterization especially in organs is still lacking. Here, using a rat heart model, controlled machine perfusion loading and unloading of CPA and sIONPs, cooling to a vitrified state, and fast and uniform nanowarming without crystallization or cracking is demonstrated. Further, nanowarmed hearts maintain histologic appearance and endothelial integrity superior to convective rewarming and indistinguishable from CPA load/unload control hearts while showing some promising organ-level (electrical) functional activity. This work demonstrates physically successful heart vitrification and nanowarming and that biological outcomes can be expected to improve by reducing or eliminating CPA toxicity during loading and unloading.

19.
Exp Biol Med (Maywood) ; 247(7): 584-597, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35068214

RESUMO

The isolated tissue bath research methodology was first developed in 1904. Since then, it has been recognized as an important tool in pharmacology and physiology research, including investigations into neuromuscular disorders. The tissue bath is still used routinely as the instrument for performing the "gold standard" test for clinical diagnosis of malignant hyperthermia susceptibility - the caffeine-halothane contracture test. Our research group has utilized this tool for several decades for a range of research studies, and we are currently one of four North American diagnostic centers for determining susceptibility for malignant hyperthermia. This review provides a brief summary of some of the historical uses of the tissue bath. Important experimental considerations for the operation of the tissue bath are further described. Finally, we discuss the different studies our group has performed using isolated tissue baths to highlight the broad potential applications.


Assuntos
Hipertermia Maligna , Banhos , Cafeína/farmacologia , Humanos , Técnicas In Vitro , Laboratórios , Hipertermia Maligna/diagnóstico , Contração Muscular/fisiologia , Projetos de Pesquisa , Pesquisa Translacional Biomédica
20.
Struct Heart ; 6(2): 100033, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37273741

RESUMO

Background: Transcatheter-based annuloplasty therapies for tricuspid regurgitation have demonstrated significant development over recent years. However, the tricuspid valve and neighboring vasculature and conductive tissue regions can present anatomical and device deployment challenges. This present study investigated the anatomical dimensions and spatial relationships of the cardiac structures essential to percutaneous annuloplasty procedures: the tricuspid annulus (TA), right coronary artery (RCA), and triangle of Koch border region. Methods: Measurements were derived from computational three-dimensional reconstructions of static magnetic resonance imaging scans of perfusion-fixed human hearts (n = 82) with preserved right-sided heart anatomies. This specimen set included heart samples presenting with prediagnosed atrioventricular valvular regurgitation. Results: Our anatomical assessments demonstrated that the TA to RCA proximities were intensified with the presence of atrioventricular valvular regurgitation, compared with healthy heart specimens. The minimal distances were frequently located between the lateral and posterior annular points. This annular region corresponds to the RCA distal segments and posterior descending branch origins. Greater portions and incidences of the RCA coursing parallel or inferior to the TA plane were recorded for these diseased hearts. Patient demographic variables (gender, age, and body mass index) were insignificant determinants of change for a majority of our results. Conclusions: These three-dimensional reconstructions provide insights to guide the development and future iterations of transcatheter tricuspid valve annuloplasty systems with regards to device anchoring, annular geometry, tissue proximities, and implantation considerations.

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