Multimodal functional and still imaging of a transplanted human heart reanimated using Visible Heart® methodologies.

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.

Identification of Radiofrequency Ablation Catheter Parameters That May Induce Intracardiac Steam Pops: Direct Visualization of Elicitation in Reanimated Swine Hearts.

Radiofrequency, a common ablation modality, is used clinically to terminate cardiac arrhythmias. With excessive heating, complications sometimes occur when the applied energy generates steam pops, which cause release of energy in the form of tissue and/or air emboli. In this study, we investigated numerous parameters potentially associated with intracardiac steam pops including (1) wattage, (2) catheter tip temperature, (3) catheter irrigation, (4) anatomic site, and (5) repeat ablations at a given site. Using unique Visible Heart® methodologies in reanimated swine hearts, we visualized 539 ablations; steam pops developed in 140 of these ablations. The incidence of steam pops significantly increased for both nonirrigated and irrigated ablations at 40 W (p < 0.005), and for nonirrigated ablations with catheter contact angles perpendicular to the tissue or that encompassed larger surface areas (p < 0.05). To minimize the incidence of steam pops, clinicians performing radiofrequency ablations must consider catheter parameters.

Determination of cryothermal injury thresholds in tissues impacted by cardiac cryoablation.

Despite widespread clinical use of cryoablation, there remain questions regarding dosing and treatment times which may affect efficacy and collateral injury. Dosing and treatment times are directly related to the degree of cooling necessary for effective lesion formation. Human and swine atrial, ventricular, and lung tissues were ablated using two cryoablation systems with concurrent infrared thermography. Post freeze-thaw samples were cultured and stained to differentiate viable and non-viable tissue. Matlab code correlated viability staining to applied freeze-thaw thermal cycles, to determine injury thresholds. Tissue regions were classified as live, injured, or dead based upon staining intensity at the lesion margin. Injury begins at rates of ∼10 °C/min to 0 °C, with non-viable tissue requiring cooling rates close to 100 °C/min to âˆ¼ -22 °C for swine and significantly greater cooling to -26 °C for human tissue (p = 0.041). At similar rates, lung tissue injury began at 0 °C, with human tissue requiring significantly less cooling, to âˆ¼ -15 °C for complete necrosis and -26 °C for swine (p = 0.024). Data suggest that there are no significant differences between swine and human myocardial response, but there may be differences between swine and human lung cryothermal tolerance.

Testing the Efficacy of Pharmacological Agents in a Pericardial Target Delivery Model in the Swine.

To date, many pharmacological agents used to treat or prevent arrhythmias in open-heart cases create undesired systemic side effects. For example, antiarrhythmic drugs administered intravenously can produce drops in systemic pressure in the already compromised cardiac patient. While performing open-heart procedures, surgeons will often either create a small port or form a pericardial cradle to create suitable fields for operation. This access yields opportunities for target pharmacological delivery (antiarrhythmic or ischemic preconditioning agents) directly to the myocardial tissue without undesired side effects. We have developed a swine model for testing pharmacological agents for target delivery within the pericardial fluid. While fully anesthetized, each animal was instrumented with a Swan-Ganz catheter as well as left and right ventricle pressure catheters, and pacing leads were placed in the right atrial appendage and the right ventricle. A medial sternotomy was then performed and a pericardial access cradle was created; a plunge pacing lead was placed in the left atrial appendage and a bipolar pacing lead was placed in the left ventricle. Utilizing a programmer and a cardiac mapping system, the refractory period of the atrioventricular node (AVN), atria and ventricles was determined. In addition, atrial fibrillation (AF) induction was produced utilizing a Grass stimulator and time in AF was observed. These measurements were performed prior to treatment, as well as 30 min and 60 min after pericardial treatment. Additional time points were added for selected studies. The heart was then cardiopleged and reanimated in a four chamber working mode. Pressure measurements and function were recorded for 1 hr after reanimation. This treatment strategy model allowed us to observe the effects of pharmacological agents that may decrease the incidence of cardiac arrhythmias and/or ischemic damage, during and after open-heart surgery.

The novel in vitro reanimation of isolated human and large mammalian heart-lung blocs.

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.

The Effects of Radiofrequency or Cryothermal Ablation on Biomechanical Properties of Isolated Human or Swine Cardiac Tissues.

Changes in cardiac tissue properties following the application of various ablation modalities may lead to the development of an array of associated complications. The application of either radio frequency (RF) or cryothermal ablations will alter the biomechanical properties of various cardiac tissues in a differential manner; in some cases, this may be attributable to increased incidences of cardiac tamponade, pulmonary vein stenosis, and/or atrial-esophageal fistula. Thus, a greater understanding of the underlying changes in tissue properties induced by ablative therapies will ultimately promote safer and more efficacious procedures. The effects of applied RF or cryothermal energies on the biomechanical properties of the pulmonary vein, left atrial, or right atrial samples ([Formula: see text]) were examined from fresh excised porcine ([Formula: see text]) and donated human tissue ([Formula: see text]). RF ablations were found to reduce the tensile strength of the porcine cardiac specimens ([Formula: see text]), and a similar trend was noted for human samples. Cryoablations did not have a significant impact on the tissue properties compared with the untreated tissue specimens. Locational and species differences were also observed in this experimental paradigm ([Formula: see text]. Incorporating these findings into cardiac device design and computational modeling should aid to reduce the risks of complications associated with tissue property changes resulting from cardiac ablative procedures.

Tissue properties of the fossa ovalis as they relate to transseptal punctures: a translational approach.

OBJECTIVES: This study focused on how catheter size affects transseptal puncture, what transseptal indication means, and whether the swine model is predictive for humans. BACKGROUND: Transseptal puncture is a common procedure that gains access to the left atrium, allowing percutaneous mitral valve repair, left atrial appendage closure, and left-sided ablations. The basic approach has not changed in many years; however, the frequency of transseptal punctures and the size of devices are increasing with emerging treatments. METHODS: A broad range of devices (4 F to 18 F) were advanced through atrial septa of swine hearts; some devices were inserted in both swine and human hearts using 10 F catheters. RESULTS: Greater forces were required to puncture through the septa of human hearts compared to those of swine. Larger catheters used in swine hearts required greater force to advance them through the septa, causing greater dilation of tissue and sometimes tearing the floor of the fossa ovalis; analyses indicated an exponential increase in the size of the iatrogenic atrial septal defect. Specific tissue property testing of the septum primum showed that this tissue sheared at a lower exerted force in a superior to inferior direction. CONCLUSIONS: Results may provide physicians with important knowledge about what to expect when treating a possible iatrogenic atrial septal defect or help them understand the consequences of transseptal punctures. Comparative data between swine and human atrial septal tissue properties provide critical insights between the species and offer clinicians and device designers important information relative to differences in tissue behaviors.

Optimal contact forces to minimize cardiac perforations before, during, and/or after radiofrequency or cryothermal ablations.

BACKGROUND: Catheter perforations remain a major clinical concern during ablation procedures for treatment of atrial arrhythmias and may lead to life-threatening cardiac tamponade. Radiofrequency (RF) ablation alters the biomechanical properties of cardiac tissue, ultimately allowing for perforation to occur more readily. Studies on the effects of cryoablation on perforation force as well as studies defining the perforation force of human tissue are limited. OBJECTIVE: The purpose of this study was to investigate the required force to elicit perforation of cardiac atrial tissue after or during ablation procedures. METHODS: Effects of RF or cryothermal ablations on catheter perforation forces for both swine (n = 83 animals, 530 treatments) and human (n = 8 specimens, 136 treatments) cardiac tissue were investigated. RESULTS: Overall average forces resulting in perforation of healthy unablated tissue were 406g ± 170g for swine and 591g ± 240g for humans. Post-RF ablation applications considerably reduced these forces to 246g ± 118g for swine and 362 ± 185g for humans (P <.001). Treatments with cryoablation did not significantly alter forces required to induce perforations. Decreasing catheter sizes resulted in a reduction in forces required to perforate the atrial wall (P <.001). Catheter perforations occurred over an array of contact forces with a minimum of 38g being observed. CONCLUSION: The swine model likely underestimates the required perforation forces relative to those of human tissues. We provide novel insights related to the comparative effects of RF and cryothermal ablations on the potential for inducing undesired punctures, with RF ablation reducing perforation force significantly. These data are insightful for physicians performing ablation procedures as well as for medical device designers.

The benefits of the Atlas of Human Cardiac Anatomy website for the design of cardiac devices.

This paper describes how the Atlas of Human Cardiac Anatomy website can be used to improve cardiac device design throughout the process of development. The Atlas is a free-access website featuring novel images of both functional and fixed human cardiac anatomy from over 250 human heart specimens. This website provides numerous educational tutorials on anatomy, physiology and various imaging modalities. For instance, the 'device tutorial' provides examples of devices that were either present at the time of in vitro reanimation or were subsequently delivered, including leads, catheters, valves, annuloplasty rings and stents. Another section of the website displays 3D models of the vasculature, blood volumes and/or tissue volumes reconstructed from computed tomography and magnetic resonance images of various heart specimens. The website shares library images, video clips and computed tomography and MRI DICOM files in honor of the generous gifts received from donors and their families.