Are slaughterhouse-obtained livers suitable for use in ex vivo perfusion research?

OBJECTIVES: The success of the ex vivo machine perfusion of pig livers used for preclinical research depends on organ quality and availability. In this study, we investigated whether livers obtained from slaughterhouses are suitable and equivalent to livers obtained from laboratory pigs. METHODS: Livers were obtained from slaughterhouse pigs stunned by electrocution or CO2 inhalation and from laboratory pigs. For the latter group, 45 minutes of warm ischemia was mimicked for a subgroup, ensuring a valid comparison with slaughterhouse-derived livers. RESULTS: Livers from CO2-stunned pigs showed lower indocyanine green clearance and bile production, higher blood lactate and potassium concentrations, and higher alanine aminotransferase activities than electrically stunned pigs. Furthermore, livers from electrically stunned pigs, and livers from laboratory pigs, subjected or not to warm ischemia, showed similar performance in terms of perfusion and metabolism. CONCLUSION: For an ex vivo liver model generated using slaughterhouse pigs, electrical stunning is preferable to CO2 stunning. Livers from electrically stunned slaughterhouse pigs performed similarly to laboratory pig livers. These findings support the use of livers from electrically stunned slaughterhouse pigs, which may therefore provide an alternative to livers obtained from laboratory pigs, consistent with the principle of the 3Rs.

Evaluating the Arteriotomy Size of a New Sutureless Coronary Anastomosis Using a Finite Volume Approach.

OBJECTIVES: The ELANA® Heart Bypass creates a standardized sutureless anastomosis. Hereby, we investigate the influence of arteriotomy and graft size on coronary hemodynamics. METHODS: A computational fluid dynamics (CFD) model was developed. Arteriotomy size (standard 1.43 mm2; varied 0.94 - 3.6 mm2) and graft diameter (standard 2.5 mm; varied 1.5 - 5.0 mm) were independent parameters. Outcome parameters were coronary pressure and flow, and fractional flow reserve (FFR). RESULTS: The current size ELANA (arteriotomy 1.43 mm2) presented an estimated FFR 0.65 (39 mL/min). Enlarging arteriotomy increased FFR, coronary pressure, and flow. All reached a maximum once the arteriotomy (2.80 mm2) surpassed the coronary cross-sectional area (2.69 mm2, i.e. 1.85 mm diameter), presenting an estimated FFR 0.75 (46 mL/min). Increasing graft diameter was positively related to FFR, coronary pressure, and flow. CONCLUSION: The ratio between the required minimal coronary diameter for application and the ELANA arteriotomy size effectuates a pressure drop that could be clinically relevant. Additional research and eventual lengthening of the anastomosis is advised.

Normothermic Ex Vivo Liver Platform Using Porcine Slaughterhouse Livers for Disease Modeling.

Metabolic and toxic liver disorders, such as fatty liver disease (steatosis) and drug-induced liver injury, are highly prevalent and potentially life-threatening. To allow for the study of these disorders from the early stages onward, without using experimental animals, we collected porcine livers in a slaughterhouse and perfused these livers normothermically. With our simplified protocol, the perfused slaughterhouse livers remained viable and functional over five hours of perfusion, as shown by hemodynamics, bile production, indocyanine green clearance, ammonia metabolism, gene expression and histology. As a proof-of-concept to study liver disorders, we show that an infusion of free fatty acids and acetaminophen results in early biochemical signs of liver damage, including reduced functionality. In conclusion, the present platform offers an accessible system to perform research in a functional, relevant large animal model while avoiding using experimental animals. With further improvements to the model, prolonged exposure could make this model a versatile tool for studying liver diseases and potential treatments.

The Impact of Biomedical Engineering on the Development of Minimally Invasive Cardio-Thoracic Surgery.

(1) We describe the boundary conditions for minimally invasive cardiac surgery (MICS) with the aim to reduce procedure-related patient injury and discomfort. (2) The analysis of the MICS work process and its demand for improved tools and devices is followed by a description of the relevant sub-specialties of bio-medical engineering: electronics, biomechanics, and materials sciences. (3) Innovations can represent a desired adaptation of an existing work process or a radical redesign of procedure and devices such as in transcutaneous procedures. Focused interaction between engineers, industry, and surgeons is always mandatory (i.e., a therapeutic alliance for addressing 'unmet patient or professional needs'. (4) Novel techniques in MICS lean heavily on usability and safe and effective use in dedicated hands. Therefore, the use of training and simulation models should enable skills selection, a safe learning curve, and maintenance of proficiency. (5) The critical technical steps and cost-benefit trade-offs during the journey from invention to application will be explained. Business considerations such as time-to-market and returns on investment do shape the cost-benefit room for commercial use of technology. Proof of clinical safety and effectiveness by physicians remains important, but establishing the technical reliability of MICS tools and warranting appropriate surgical skills come first.

Essential information on surgical heart valve characteristics for optimal valve prosthesis selection: Expert consensus document from the European Association for Cardio-Thoracic Surgery (EACTS)-The Society of Thoracic Surgeons (STS)-American Association for Thoracic Surgery (AATS) Valve Labelling Task Force.

Comprehensive information on the characteristics of surgical heart valves (SHVs) is essential for optimal valve selection. Such information is also important in assessing SHV function after valve replacement. Despite the existing regulatory framework for SHV sizing and labelling, this information is challenging to obtain in a uniform manner for various SHVs. To ensure that clinicians are adequately informed, the European Association for Cardio-Thoracic Surgery (EACTS), The Society of Thoracic Surgeons (STS) and American Association for Thoracic Surgery (AATS) set up a Task Force comprised of cardiac surgeons, cardiologists, engineers, regulatory bodies, representatives of the International Organization for Standardization and major valve manufacturers. Previously, the EACTS-STS-AATS Valve Labelling Task Force identified the most important problems around SHV sizing and labelling. This Expert Consensus Document formulates recommendations for providing SHV physical dimensions, intended implant position and hemodynamic performance in a transparent, uniform manner. Furthermore, the Task Force advocates for the introduction and use of a standardized chart to assess the probability of prosthesis-patient mismatch and calls valve manufacturers to provide essential information required for SHV choice on standardized Valve Charts, uniformly for all SHV models.

Essential Information on Surgical Heart Valve Characteristics for Optimal Valve Prosthesis Selection: Expert Consensus Document From the European Association for Cardio-Thoracic Surgery (EACTS)-The Society of Thoracic Surgeons (STS)-American Association for Thoracic Surgery (AATS) Valve Labelling Task Force.

Comprehensive information on the characteristics of surgical heart valves (SHVs) is essential for optimal valve selection. Such information is also important in assessing SHV function after valve replacement. Despite the existing regulatory framework for SHV sizing and labelling, this information is challenging to obtain in a uniform manner for various SHVs. To ensure that clinicians are adequately informed, the European Association for Cardio-Thoracic Surgery (EACTS), The Society of Thoracic Surgeons (STS) and American Association for Thoracic Surgery (AATS) set up a Task Force comprised of cardiac surgeons, cardiologists, engineers, regulatory bodies, representatives of the International Organization for Standardization and major valve manufacturers. Previously, the EACTS-STS-AATS Valve Labelling Task Force identified the most important problems around SHV sizing and labelling. This Expert Consensus Document formulates recommendations for providing SHV physical dimensions, intended implant position and hemodynamic performance in a transparent, uniform manner. Furthermore, the Task Force advocates for the introduction and use of a standardized chart to assess the probability of prosthesis-patient mismatch and calls valve manufacturers to provide essential information required for SHV choice on standardized Valve Charts, uniformly for all SHV models.

Essential information on surgical heart valve characteristics for optimal valve prosthesis selection: expert consensus document from the European Association for Cardio-Thoracic Surgery (EACTS)-The Society of Thoracic Surgeons (STS)-American Association for Thoracic Surgery (AATS) Valve Labelling Task Force.

Comprehensive information on the characteristics of surgical heart valves (SHVs) is essential for optimal valve selection. Such information is also important in assessing SHV function after valve replacement. Despite the existing regulatory framework for SHV sizing and labelling, this information is challenging to obtain in a uniform manner for various SHVs. To ensure that clinicians are adequately informed, the European Association for Cardio-Thoracic Surgery (EACTS), The Society of Thoracic Surgeons (STS) and American Association for Thoracic Surgery (AATS) set up a Task Force comprised of cardiac surgeons, cardiologists, engineers, regulatory bodies, representatives of the International Organization for Standardization and major valve manufacturers. Previously, the EACTS-STS-AATS Valve Labelling Task Force identified the most important problems around SHV sizing and labelling. This Expert Consensus Document formulates recommendations for providing SHV physical dimensions, intended implant position and haemodynamic performance in a transparent, uniform manner. Furthermore, the Task Force advocates for the introduction and use of a standardized chart to assess the probability of prosthesis-patient mismatch and calls valve manufacturers to provide essential information required for SHV choice on standardized Valve Charts, uniformly for all SHV models.

First Expert Evaluation of a New Steerable Catheter in an Isolated Beating Heart.

PURPOSE: In previous studies we developed two mechanical prototypes of steerable catheters: the Sigma, which uses joysticks to actuate two steerable tip segments, and the Epsilon, which has a handle that is an enlarged version of the tip. In this study, we present a first performance evaluation of the prototypes in the cardiac environment. The evaluation was carried out by an expert user, an electrophysiologist with over 20 years of experience, to obtain insight in clinically relevant factors. METHODS: Two experiments were conducted. In the first experiment, the Sigma was used in a passive beating heart setup connected to pumps with a saline solution and camera visualization, and compared with the expert's past experience with conventional steerable catheters. In the second experiment, the Sigma was used in an active beating heart setup with blood perfusion through the coronary arteries and echo visualization, and compared with the Epsilon prototype. The prototype was evaluated through questionnaires on task performance, catheter usability, and workload. After each of the experiments, the catheter characteristics were evaluated via a survey and followed by an in-depth interview. RESULTS & CONCLUSIONS: The expert user found the passive beating heart setup to more successful than the active beating heart setup for the purpose of this experiment, with insightful visualization while the heart was in beating condition. The steerability of the prototypes was experienced as useful and clinically relevant. Based on the questionnaires and interview we were able to identify future design improvements and developments for the steerable catheter prototypes.

Attenuated cardiac function degradation in ex vivo pig hearts.

Isolated hearts offer the opportunity to evaluate heart function, treatments, and diagnostic tools without in vivo factor interference. However, the early loss of cardiac function and edema occur over time and do limit the duration of the experiment. This research focuses on delaying these limitations using optimal blood control. This study examines whether blood conditioning by means of the combination of blood predilution and hemodialysis can significantly reduce cardiac function degradation. Slaughterhouse porcine hearts were revived in the PhysioHeart™ platform to restore physiological cardiac performance. Twelve hearts were divided into a control group and a dialysis group; in the latter group, hemodialysis was attached to the blood reservoir. Cardiac hemodynamics and blood parameters were recorded and evaluated. Blood conditioning significantly reduced the loss of cardiac pump function (control group vs dialysis group, -14.9 ± 6.3%/h vs -9.7 ± 2.7%/h) and loss of cardiac output (control group vs dialysis group, -11.8 ± 3.4%/h vs -5.9 ± 2.0%/h). Hemodialysis resulted in physiological and stable blood parameters, whereas in the control group ions reached pathological values, while interstitial edema still occurred. The combination of blood predilution and hemodialysis significantly attenuated ex vivo cardiac function degradation and delayed the loss of cardiac hemodynamics. We hypothesized that besides electrolyte and metabolic control, the hemodialysis-accompanied increase in hematocrit resulted in improved oxygen transport. This could have temporarily compensated the deleterious effect of an increased oxygen-diffusion distance due to edema in the dialysis group and resulted in less progression of cell decay. Clinically validated measures delaying edema might improve the effectiveness of the PhysioHeart™ platform.

Development of an ex vivo aneurysm model for vascular device testing.

An ex vivo aneurysm model that closely resembles the in vivo situation can provide an important tool for testing therapies. The model should mimic a variety of conditions, such as in vivo hemodynamics and native arterial structure and characteristics, avoiding animal experimentation.  Therefore, the aim of this study is to develop an ex vivo aneurysm model by vessel wall stiffening to be used to assess treatment strategies. Porcine carotid arteries from slaughterhouse animals were used to evaluate the acute effect of different concentrations of Rose Bengal on distensibility. This sono-sensitive compound was activated by several ultrasound frequencies, resulting in stiffening of the treated arteries of which the most effective combination was selected. In a pulsatile ex vivo vascular bioreactor treated and control porcine carotid arteries were subjected to physiological conditions for 10 days. During culture, hemodynamics showed increased mean pressure and decreased pulsatility in treated arteries compared to controls. Change in vessel morphology and significant increase of distal diameter was observed in the treated arteries but not in the controls. Histology of treated arteries revealed dissection-like lesions distally and aneurysm-like structure proximally. Finally, a stent graft was deployed in one treated artery and cultured demonstrating the feasibility of testing endovascular devices in the model. In conclusion, we developed an ex vivo model reproducing the onset of aneurysm formation. This could represent a promising tool for early stage device testing thereby reducing the need for animal studies.

Investigating the physiology of normothermic ex vivo heart perfusion in an isolated slaughterhouse porcine model used for device testing and training.

BACKGROUND: The PhysioHeart™ is a mature acute platform, based isolated slaughterhouse hearts and able to validate cardiac devices and techniques in working mode. Despite perfusion, myocardial edema and time-dependent function degradation are reported. Therefore, monitoring several variables is necessary to identify which of these should be controlled to preserve the heart function. This study presents biochemical, electrophysiological and hemodynamic changes in the PhysioHeart™ to understand the pitfalls of ex vivo slaughterhouse heart hemoperfusion. METHODS: Seven porcine hearts were harvested, arrested and revived using the PhysioHeart™. Cardiac output, SaO2, glucose and pH were maintained at physiological levels. Blood analyses were performed hourly and unipolar epicardial electrograms (UEG), pressures and flows were recorded to assess the physiological performance. RESULTS: Normal cardiac performance was attained in terms of mean cardiac output (5.1 ± 1.7 l/min) and pressures but deteriorated over time. Across the experiments, homeostasis was maintained for 171.4 ± 54 min, osmolarity and blood electrolytes increased significantly between 10 and 80%, heart weight increased by 144 ± 41 g, free fatty acids (- 60%), glucose and lactate diminished, ammonia increased by 273 ± 76% and myocardial necrosis and UEG alterations appeared and aggravated. Progressively deteriorating electrophysiological and hemodynamic functions can be explained by reperfusion injury, waste product intoxication (i.e. hyperammonemia), lack of essential nutrients, ion imbalances and cardiac necrosis as a consequence of hepatological and nephrological plasma clearance absence. CONCLUSIONS: The PhysioHeart™ is an acute model, suitable for cardiac device and therapy assessment, which can precede conventional animal studies. However, observations indicate that ex vivo slaughterhouse hearts resemble cardiac physiology of deteriorating hearts in a multi-organ failure situation and signalize the need for plasma clearance during perfusion to attenuate time-dependent function degradation. The presented study therefore provides an in-dept understanding of the sources and reasons causing the cardiac function loss, as a first step for future effort to prolong cardiac perfusion in the PhysioHeart™. These findings could be also of potential interest for other cardiac platforms.

Biomedical Applications of Photo- and Sono-Activated Rose Bengal: A Review.

Objective: The aim of this review is to discuss and compare the extensive range of biomedical applications of photo- and sono-activated Rose Bengal (RB). Background data: RB is a xanthene dye that due to its interesting photo- and sono-sensitive properties is gaining attention in the scientific field. Methods: This study is a literature review using the database PubMed. Results: As a photosensitizer, RB converts the triplet oxygen molecule into reactive oxygen species after irradiation with green light (532 nm). This mechanism allows for the use of photo-activated RB in photochemical tissue bonding, photodynamic therapy, antimicrobial therapy and cancer treatment, photothrombotic animal models, and other applications, including tissue engineering and treatment of tauopathies. As a sono-sensitive compound, RB is applied for sonodynamic therapy, cancer treatment, and antimicrobial therapy. Conclusions: This review outlines the versatility and effectiveness of photo- and sono-activated RB in numerous biomedical applications.

Characteristics of Surgical Prosthetic Heart Valves and Problems Around Labelling: A Document From the European Association for Cardio-Thoracic Surgery (EACTS)-The Society of Thoracic Surgeons (STS)-American Association for Thoracic Surgery (AATS) Valve Labelling Task Force.

Intraoperative surgical prosthetic heart valve (SHV) choice is a key determinant of successful surgery and positive postoperative outcomes. Currently, many controversies exist around the sizing and labelling of SHVs rendering the comparison of different valves difficult. To explore solutions, an expert Valve Labelling Task Force was jointly initiated by the European Association for Cardio-Thoracic Surgery (EACTS), The Society of Thoracic Surgeons (STS) and the American Association for Thoracic Surgery (AATS). The EACTS-STS-AATS Valve Labelling Task Force, comprising cardiac surgeons, cardiologists, engineers, regulators and representatives from the International Organization for Standardization (ISO) and major valve manufacturers, held its first in-person meeting in February 2018 in Paris, France. This article was derived from the meeting's discussions. The Task Force identified the following areas for improvement and clarification: reporting of physical dimensions and characteristics of SHVs determining and labelling of SHV size, in vivo and in vitro testing and reporting of SHV hemodynamic performance and thrombogenicity. Furthermore, a thorough understanding of the regulatory background and the role of the applicable ISO standards, together with close cooperation between all stakeholders (including regulatory and standard-setting bodies), is necessary to improve the current situation. Cardiac surgeons should be provided with appropriate information to allow for optimal SHV choice. This first article from the EACTS-STS-AATS Valve Labelling Task Force summarizes the background of SHV sizing and labelling and identifies the most important elements where further standardization is necessary.

Characteristics of surgical prosthetic heart valves and problems around labeling: A document from the European Association for Cardio-Thoracic Surgery (EACTS)-The Society of Thoracic Surgeons (STS)-American Association for Thoracic Surgery (AATS) Valve Labelling Task Force.

Intraoperative surgical prosthetic heart valve (SHV) choice is a key determinant of successful surgery and positive postoperative outcomes. Currently, many controversies exist around the sizing and labeling of SHVs rendering the comparison of different valves difficult. To explore solutions, an expert Valve Labelling Task Force was jointly initiated by the European Association for Cardio-Thoracic Surgery (EACTS), The Society of Thoracic Surgeons (STS) and the American Association for Thoracic Surgery (AATS). The EACTS-STS-AATS Valve Labelling Task Force, comprising cardiac surgeons, cardiologists, engineers, regulators and representatives from the International Organization for Standardization (ISO), and major valve manufacturers, held its first in-person meeting in February 2018 in Paris, France. This article was derived from the meeting's discussions. The Task Force identified the following areas for improvement and clarification: reporting of physical dimensions and characteristics of SHVs determining and labeling of SHV size, in vivo and in vitro testing, and reporting of SHV hemodynamic performance and thrombogenicity. Furthermore, a thorough understanding of the regulatory background and the role of the applicable ISO standards, together with close cooperation between all stakeholders (including regulatory and standard- setting bodies), is necessary to improve the current situation. Cardiac surgeons should be provided with appropriate information to allow for optimal SHV choice. This first article from the EACTS-STS-AATS Valve Labelling Task Force summarizes the background of SHV sizing and labeling and identifies the most important elements where further standardization is necessary.

Characteristics of surgical prosthetic heart valves and problems around labelling: a document from the European Association for Cardio-Thoracic Surgery (EACTS)-The Society of Thoracic Surgeons (STS)-American Association for Thoracic Surgery (AATS) Valve Labelling Task Force.

Intraoperative surgical prosthetic heart valve (SHV) choice is a key determinant of successful surgery and positive postoperative outcomes. Currently, many controversies exist around the sizing and labelling of SHVs rendering the comparison of different valves difficult. To explore solutions, an expert Valve Labelling Task Force was jointly initiated by the European Association for Cardio-Thoracic Surgery (EACTS), The Society of Thoracic Surgeons (STS) and the American Association for Thoracic Surgery (AATS). The EACTS-STS-AATS Valve Labelling Task Force, comprising cardiac surgeons, cardiologists, engineers, regulators and representatives from the International Organization for Standardization (ISO) and major valve manufacturers, held its first in-person meeting in February 2018 in Paris, France. This article was derived from the meeting's discussions. The Task Force identified the following areas for improvement and clarification: reporting of physical dimensions and characteristics of SHVs determining and labelling of SHV size, in vivo and in vitro testing and reporting of SHV haemodynamic performance and thrombogenicity. Furthermore, a thorough understanding of the regulatory background and the role of the applicable ISO standards, together with close cooperation between all stakeholders (including regulatory and standard-setting bodies), is necessary to improve the current situation. Cardiac surgeons should be provided with appropriate information to allow for optimal SHV choice. This first article from the EACTS-STS-AATS Valve Labelling Task Force summarizes the background of SHV sizing and labelling and identifies the most important elements where further standardization is necessary.

Feasibility of mapping and cannulation of the porcine epicardial lymphatic system for sampling and decompression in heart failure research.

BACKGROUND AND AIM: The cardiac lymphatic system drains excess fluid from the cardiac interstitium. Any impairment or dysfunction of the lymph structures can result in the accumulation of interstitial fluid, and may lead to edema and eventually cardiac dysfunction. Lymph originates directly from the interstitium and carries real-time information about the metabolic state of cells in specific regions of the heart. The detailed anatomy of the epicardial lymphatic system in individuals is broadly unknown. Generally, the epicardial lymphatic system is not taken into consideration during heart surgery. This study investigates the feasibility of detailed mapping and cannulation of the porcine epicardial lymphatic system for use in preservation of explanted hearts and heart failure studies in pigs and humans. METHODS: The anatomy of the epicardial lymphatic systems of forty pig hearts was studied and documented. Using a 27 G needle, India ink was introduced directly into the epicardial lymphatic vessels in order to visualise them. Based on the anatomical findings thus obtained, two cannulation regions for the left and right principal trunks were identified. These regions were cannulated with a 26 G intravenous Venflon cannula-over-needle, and a Galeo Hydro Guide F014 wire was used to verify that the lumen was patent. RESULTS: The main epicardial lymphatic collectors were found to follow the main coronary arteries. Most of the lymph vessels drained into the left ventricular trunk, which evacuates fluid from the left heart and also partially from the right heart. The right trunk was often found to drain into the left trunk anterior basally. Right heart drainage was highly variable compared to the left. In addition, the overall cannulation success rate of the selected cannulation sites was only 57%. CONSLUSIONS: Mapping of the porcine epicardial lymphatic anatomy is feasible. The right ventricular drainage system had a higher degree of variability than the left, and the right cardiac lymph system was found to be partially cleared through the left lymphatic trunk. To improve cannulation success rate, we proposed two sites for cannulation based on these findings and the use of Venflon cannulas (26 G) for cannulation and lymph collection. This method might be helpful for future studies that focus on biochemical sample analysis and decompression. RELEVANCE FOR PATIENTS: Real-time biochemical assessment and decompression of lymph may contribute to the understanding of heart failure and eventually result in preventive measures. First its relevance should be established by additional research in both arrested and working porcine hearts. Imaging and mapping of the epicardial lymphatics may enable sampling and drainage and contribute to the prevention or treatment of heart failure. We envision that this approach may be considered in patients with a high risk of postoperative left and right heart failure during open-heart surgery.

Full-field analysis of epicardial strain in an in vitro porcine heart platform.

The quantitative assessment of cardiac strain is increasingly performed to provide valuable insights on heart function. Currently, the most frequently used technique in the clinic is ultrasound-based speckle tracking echocardiography (STE). However, verification and validation of this modality are still under investigation and further reference measurements are required to support this activity. The aim of this work was to enable these reference measurements using a dynamic beating heart simulator to ensure reproducible, controlled, and realistic haemodynamic conditions and to validate the reliability of optical-based three-dimensional digital image correlation (3D-DIC) for a dynamic full-field analysis of epicardial strain. Specifically, performance assessment of 3D-DIC was carried out by evaluating the accuracy and repeatability of the strain measurements across multiple cardiac cycles in a single heart and between five hearts. Moreover, the ability of this optical method to differentiate strain variations when different haemodynamic conditions were imposed in the same heart was examined. Strain measurements were successfully accomplished in a region of the lateral left ventricle surface. Results were highly repeatable over heartbeats and across hearts (intraclass correlation coefficient = 0.99), whilst strain magnitude was significantly different between hearts, due to change in anatomy and wall thickness. Within an individual heart, strain variations between different haemodynamic scenarios were greater than the estimated error of the measurement technique. This study demonstrated the feasibility of applying 3D-DIC in a dynamic passive heart simulator. Most importantly, non-contact measurements were obtained at a high spatial resolution (~ 1.5 mm) allowing resolution of local variation of strain on the epicardial surface during ventricular filling. The experimental framework developed in this paper provides detailed measurement of cardiac strains under controlled conditions, as a reference for validation of clinical cardiac strain imaging modalities.

Beating heart porcine high-fidelity simulator for the training of edge-to-edge mitral valve repair.

Transcatheter treatment of structural heart disease is becoming an everyday reality for an increasing number of surgeons, and effective training modalities for basic guide-wire skills, catheter handling, and periprocedural imaging are of growing relevance. In this video tutorial we present a beating-heart porcine model used as a high-fidelity training simulator for transcatheter cardiac valve procedures.  We demonstrate a complete transcatheter edge-to-edge mitral valve repair procedure, including periprocedural imaging, clip deployment, and quality control. Various mitral valve pathologies can be simulated, including the demonstrated leaflet prolapse. Trainees practice clip navigation within the left atrium, transmitral passage, and clip orientation as well as grasping mitral valve leaflets to treat mitral regurgitation.  Periprocedural imaging is achieved via epicardial echocardiography and left ventricular cardioscopy, and these imaging modalities are also relied on to guide surgeons during the simulations, as required. The beating heart model enables realistic demonstration of the hemodynamic consequences of valve repair, and we believe that this simulator represents a valuable adjunct to surgical training.

Validation of myocardial perfusion quantification by dynamic CT in an ex-vivo porcine heart model.

To test the accuracy of quantification of myocardial perfusion imaging (MPI) using computed tomography (CT) in ex-vivo porcine models. Five isolated porcine hearts were perfused according to Langendorff. Hearts were perfused using retrograde flow through the aorta and blood flow, blood pressure and heart rate were monitored throughout the experiment. An inflatable cuff was placed around the circumflex (Cx) artery to create stenosis grades which were monitored using a pressure wire, analysing perfusion at several fractional flow reserve values of 1.0, 0.7, 0.5, 0.3, and total occlusion. Second-generation dual-source CT was used to acquire dynamic MPI in shuttle mode with 350 mAs/rot at 100 kVp. CT MPI was performed using VPCT myocardium software, calculating myocardial blood flow (MBF, ml/100 ml/min) for segments perfused by Cx artery and non-Cx myocardial segments. Microspheres were successfully infused at three stenosis grades in three of the five hearts. Heart rate ranged from 75 to 134 beats per minute. Arterial blood flow ranged from 0.5 to 1.4 l min and blood pressure ranged from 54 to 107 mmHg. MBF was determined in 400 myocardial segments of which 115 were classified as 'Cx-territory'. MBF was significantly different between non-Cx and Cx segments at stenosis grades with an FFR ≤0.70 (Mann-Whitney U test, p < 0.05). MBF showed a moderate correlation with microsphere MBF for the three individual hearts (Pearson correlation 0.62-0.76, p < 0.01). CT MPI can be used to determine regional differences in myocardial perfusion parameters, based on severity of coronary stenosis. Significant differences in MBF could be measured between non-ischemic and ischemic segments.

Intracoronary hypothermia for acute myocardial infarction in the isolated beating pig heart.

Hypothermia may attenuate reperfusion injury and thereby improve acute myocardial infarction therapy. Systemic cooling trials failed to reduce infarct size, perhaps because the target temperature was not reached fast enough. The use of selective intracoronary hypothermia combined with intracoronary temperature monitoring allows for titrating to target temperature and optimizing the cooling rate. We aimed to the test the feasibility of intracoronary cooling for controlled, selective myocardial hypothermia in an isolated beating pig heart. In five porcine hearts the left anterior descending artery (LAD) was occluded by an over-the-wire balloon (OTWB). After occlusion, saline at 22°C was infused through the OTWB lumen for 5 minutes into the infarct area at a rate of 30 ml/min. Thereafter the balloon was deflated but infusion continued with saline at 4°C for 5 minutes. Distal coronary temperature was continuously monitored by a pressure/temperature guidewire. Myocardial temperature at several locations in the infarct and control areas was recorded using needle thermistors. In the occlusion phase, coronary temperature decreased by 11.4°C (range 9.4-12.5°C). Myocardial temperature throughout the infarct area decreased by 5.1°C (range 1.8-8.1°C) within three minutes. During the reperfusion phase, coronary temperature decreased by 6.2°C (range 4.1-10.3°C) and myocardial temperature decreased by 4.5°C (range 1.5-7.4°C). Myocardial temperature outside the infarct area was not affected. In the isolated beating pig heart with acute occlusion of the LAD, we were able to rapidly "induce, maintain, and control" a stable intracoronary and myocardial target temperature of at least 4°C below body temperature without side effects and using standard PCI equipment, justifying further studies of this technique in humans.