Elizabeth Irene Reiser, By And Through Her Guardian, Richard E. Reiser And Eleanor Reiser v. Richard Lohner And Howard Francis, Medical Doctors, And Provo Obstetrical And Gynecology Clinic, Inc., A Professional Corporation : Brief of Defendants-Respondents

Appeal from a Verdict of the Fourth Judicial District Court of Utah County, State of Utah Honorable James S. Sawaya, Presidin

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 to test therapeutic approaches while avoiding animal experimentation. The model should mimic a variety of conditions, such as in vivo hemodynamics and native arterial structure and characteristics. The aim of this study was to develop an ex vivo aneurysm model by stiffening vessel walls 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 vessel distensibility. Rose Bengal is a sono-sensitive compound that is activated by several ultrasound frequencies, resulting in stiffening of the treated arteries; the most effective combination of concentration and frequency was determined. In a pulsatile ex vivo vascular bioreactor, treated and control porcine carotid arteries were subjected to physiological conditions for 10 days. Treated arteries showed increased mean pressure and decreased pulsatility compared to controls. Changes in vessel morphology and a significant increase of distal diameter were observed in the treated arteries but not in the controls. Histology revealed distal dissection-like lesions and proximal aneurysm-like structure in the treated arteries. Finally, a stent graft was deployed and cultured in one treated artery, 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 represents a promising tool for early stage device testing, thereby reducing the need for animal studies

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

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

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. Graphical abstract: [Figure not available: see fulltext.

Analysis of myocardial perfusion parameters in an ex-vivo porcine heart model using third generation dual-source CT

PURPOSE: To evaluate the relationship between fractional flow reserve (FFR)-determined coronary artery stenosis severity and myocardial perfusion parameters derived from dynamic myocardial CT perfusion imaging (CTP) in an ex-vivo porcine heart model. METHODS: Six porcine hearts were perfused according to Langendorff. Circulatory parameters such as arterial blood flow (ABF) (L/min), mean arterial pressure (MAP) (mmHg) and heart rate (bpm) were monitored. Using an inflatable cuff and monitored via a pressure wire, coronary artery stenoses of different FFR grades were created (no stenosis, FFR = 0.80, FFR = 0.70, FFR = 0.60, and FFR = 0.50). Third generation dual-source CT was used to perform dynamic CTP in shuttle mode at 70 kV. Using the AHA-16-segment model, myocardial blood flow (MBF) (mL/100 mL/min) and volume (MBV) (mL/100 mL) were analyzed using dedicated software for all ischaemic and non-ischaemic segments. RESULTS: During five successful experiments, ABF ranged from 0.8 to 1.2 L/min, MAP from 73 to 90 mmHg and heart rate from 83 to 115 bpm. Non-ischaemic and ischaemic segments showed significant differences in MBF for stenosis grades of FFR ≤ 0.70. At this degree of obstruction, median MBF was 79 (interquartile range [IQR]: 66-90) for non-ischaemic segments versus 56 mL/100 mL/min (IQR: 46-73) for ischaemic segments (p < 0.05). For MBV, a significant difference was found at FFR ≤ 0.80 with median MBV values of 7.6 (IQR: 7.0-8.3) and 7.1 mL/100 mL (IQR: 6.0-8.2) for non-ischaemic and ischaemic myocardial segments, respectively (p < 0.05). CONCLUSION: Artificial flow alterations in a Langendorff porcine heart model could be detected and measured by CTP-derived myocardial perfusion parameters and showed significant systematic correlation with stepwise flow reduction that permitted early detection of ischaemic myocardium. Additional research in clinical setting is required to develop absolute quantitative CTP

Intermodel disagreement of myocardial blood flow estimation from dynamic CT perfusion imaging

Purpose: To assess the intermodel agreement of different tracer kinetic models to determine myocardial blood flow (MBF) and their diagnostic accuracy in coronary artery disease (CAD) at dynamic CT myocardial perfusion imaging (CTMPI). Methods: Three porcine hearts perfused in Langendorff mode and 15 patients with suspected CAD and perfusion single photon emission CT (SPECT) were included. Dynamic CTMPI was performed in shuffle-mode (70 kVp, 350mAs/rot) on 3rd generation dual-source CT. In porcine hearts and patients, myocardial segments (AHA-16-segment model) were drawn. Tissue attenuation curves were constructed per segment and arterial input functions were derived from the aorta. True MBF was calculated with input flow and weight of the porcine hearts. In patients, ischemic segments were based on SPECT results. MBF quantification was performed using the VPCT-software, Upslope, Extended Toft (ET), Two-compartment (TC) and Fermi models. Results: In porcine hearts, true MBF was 1.88 (interquartile range [IQR]:1.80-2.80)mL/g/min. Diagnostic accuracy was similar for all models: 0.96, 0.99, 0.92, 0.93 and 0.96 for VPCT software, Upslope method, Fermi, ET and TC model. The VPCT software and Upslope method resulted in lower MBF (median 1.44 [1.29-1.58] and 1.39 [1.25-1.59]mL/g/min) compared to the Fermi, ET, and TC model (median values of 1.76 mL/g/min [1.36-2.44], 2.55 mL/g/min [2.20-2.92], and 1.98 mL/g/min [1.60-2.60], respectively [p <0.001]). In patients, all models showed a significant difference in MBF between the 34 ischemic and 206 non-ischemic segments (p-value <0.001). Conclusion: Absolute MBF values are significantly different between the models and a uniform threshold could not be determined; however, diagnostic accuracy for detecting ischemia is similar

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

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

peer reviewedIntraoperative 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