Surgical Technique for the Implantation of Tissue Engineered Vascular Grafts and Subsequent In Vivo Monitoring

The development of Tissue Engineered Vessels (TEVs) is advanced by the ability to routinely and effectively implant TEVs (4-5 mm in diameter) into a large animal model. A step by-step protocol for inter-positional placement of the TEV and real-time digital assessment of the TEV and native carotid arteries is described here. In vivo monitoring is made possible by the implantation of flow probes, catheters and ultrasonic crystals (capable of recording dynamic diameter changes of implanted TEVs and native carotid arteries) at the time of surgery. Once implanted, researchers can calculate arterial blood flow patterns, invasive blood pressure and artery diameter yielding parameters such as pulse wave velocity, augmentation index, pulse pressures and compliance. Data acquisition is accomplished using a single computer program for analysis throughout the duration of the experiment. Such invaluable data provides insight into TEV matrix remodeling, its resemblance to native/sham controls and overall TEV performance in vivo.     

Characterization of arteriovenous identity in the developing neonate mouse retina

The murine retina has become an ideal model to study blood vessel formation. Blood vessels in the retina undergo various processes, including remodeling and differentiation, to form a stereotypical network that consists of precisely patterned arteries and veins. This model presents a powerful tool for understanding many different aspects of angiogenesis including artery and vein (AV) cell fate acquisition and differentiation. However, characterization of AV differentiation has been largely unexplored in the mouse retinal model. In this study, we describe the expression of previously established AV markers and assess arteriovenous acquisition and identity in the murine neonatal retina. Using in situ hybridization and immunofluorescent antibody staining techniques, we analyzed numerous AV differentiation markers such as EphB4-EphrinB2 and members of the Notch pathway. We find that at postnatal day 3 (P3), when blood vessels are beginning to populate the retina, AV identity is not immediately established. However, by P5 expression of many molecular identifiers of arteries and veins become restricted to their respective vessel types. This molecular distinction is more obvious at P7 and remains unchanged through P9. Overall, these studies indicate that, similar to the embryo, acquisition of AV identity occurs in a step-wise process and is largely established by P7 during retina development.     

Multi-input deep learning approach for Cardiovascular Disease diagnosis using Myocardial Perfusion Imaging and clinical data

PurposeAccurate detection and treatment of Coronary Artery Disease is mainly based on invasive Coronary Angiography, which could be avoided provided that a robust, non-invasive detection methodology emerged. Despite the progress of computational systems, this remains a challenging issue. The present research investigates Machine Learning and Deep Learning methods in competing with the medical experts' diagnostic yield. Although the highly accurate detection of Coronary Artery Disease, even from the experts, is presently implausible, developing Artificial Intelligence models to compete with the human eye and expertise is the first step towards a state-of-the-art Computer-Aided Diagnostic system.MethodsA set of 566 patient samples is analysed. The dataset contains Polar Maps derived from scintigraphic Myocardial Perfusion Imaging studies, clinical data, and Coronary Angiography results. The latter is considered as reference standard. For the classification of the medical images, the InceptionV3 Convolutional Neural Network is employed, while, for the categorical and continuous features, Neural Networks and Random Forest classifier are proposed.ResultsThe research suggests that an optimal strategy competing with the medical expert's accuracy involves a hybrid multi-input network composed of InceptionV3 and a Random Forest. This method matches the expert's accuracy, which is 79.15% in the particular dataset.ConclusionImage classification using deep learning methods can cooperate with clinical data classification methods to enhance the robustness of the predicting model, aiming to compete with the medical expert's ability to identify Coronary Artery Disease subjects, from a large scale patient dataset.     

Effects of altitude on exercise level and heart rate in patients with coronary artery disease and healthy controls

Background. To evaluate the safety and effects of high altitude on exercise level and heart rate in patients with coronary artery disease compared with healthy controls. Methods. Eight patients with a history of an acute myocardial infarction (ejection fraction >5%) with a low-risk score were compared with seven healthy subjects during the Dutch Heart Expedition at the Aconcagua in Argentina in March 2007. All subjects underwent a maximum exercise test with a cycle ergometer at sea level and base camp, after ten days of acclimatisation, at an altitude of 4200 m. Exercise capacity and maximum heart rate were compared between groups and within subjects. Results. There was a significant decrease in maximum heart rate at high altitude compared with sea level in both the patient and the control group (166 vs. 139 beats/min, p<0.001 and 181 vs. 150 beats/min, p<0.001). There was no significant difference in the decrease of the exercise level and maximum heart rate between patients and healthy controls (-31 vs. -30%, p=0.673). Conclusion. Both patients and healthy controls showed a similar decrease in exercise capacity and maximum heart rate at 4200 m compared with sea level, suggesting that patients with a history of coronary artery disease may tolerate stay and exercise at high altitude similarly to healthy controls. (Neth Heart J 2010;18:118-21.)     

Apoptosis during CABG surgery with the use of cardiopulmonary bypass is prominent in ventricular but not in atrial myocardium

Objectives. We aimed to compare the rate of apoptosis after cardiopulmonary bypass (CPB) and cardioplegic arrest during coronary artery bypass grafting (CABG) surgery between atrial and ventricular tissue. Methods. During CABG surgery with CPB and cardioplegic arrest, sequential biopsies were taken from the right atrial appendage and left ventricular anterior wall before CPB and after aortic cross clamp release. Change in number of apoptotic cells and biochemical markers of myocardial ischaemia and renal dysfunction were assessed. Results. CPB was associated with a transient small, but significant increase in CK (1091±374%), CK-MB (128±38%), troponin-T (102±13%) and NT-proBNP (1308±372%) levels (all: p<0.05). A higher number of apoptotic cells as assessed by caspase-3 staining was found in the ventricular biopsies taken after aortic cross clamp release compared with the biopsies taken before CPB (5.3±0.6 vs. 14.0±1.5 cells/microscopic field, p<0.01). The number of apoptotic cells in the atrial appendage was not altered during CPB. Correlation between the duration of aortic cross clamp time and the change in caspase-3 positive cells in the left ventricular wall was of borderline significance (r of 0.58, p=0.08). Similar results were obtained from TUNEL staining for apoptosis. Conclusion. CABG surgery with CPB and cardioplegic arrest is associated with an elevated rate of apoptosis in ventricular but not in atrial myocardial tissue. Ventricular tissue may be more sensitive to detect changes than atrial tissue, and may be more useful to investigate the protective effects of therapeutic intervention. (Neth Heart J 2010;18:236-42.)     

Towards a noninvasive anatomical and functional diagnostic work-up of patients with suspected coronary artery disease

Combining multidetector computed tomography and cardiovascular magnetic resonance imaging provides the clinician a strategy to comprehensively evaluate coronary morphology and function noninvasively. In the MARCC trial (Magnetic Resonance and CT in suspected CAD) a new noninvasive diagnostic work-up for patients with suspected coronary artery disease will be developed, involving the sequential use of both imaging techniques. (Neth Heart J 2010;18:270-3.)     

Patients with coronary stenosis and a fractional flow reserve of ≥0.75 measured in daily practice at the VU University Medical Center

Objectives. The aim of this study was to analyse the rate of major adverse clinical events in patients with coronary artery disease and a fractional flow reserve (FFR) of ≥0.75 and deferred for coronary intervention in daily practice. Methods. From 1 January to 31 December 2006, FFR measurement was initiated in 122 patients (5%) out of 2444 patients referred for coronary angiography. In two patients FFR measurement failed and in one patient the FFR value could no longer be traced in the documents. Thus, 119 patients (84 men, 64 years, range 41-85) were included in the evaluation (145 lesions). Major adverse clinical events (death, myocardial infarction, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG)) and the presence of angina were evaluated at follow-up. Furthermore a cost-effectiveness analysis was performed. Results. In 93 patients (76%) the FFR value was ≥0.75. Seventy of these 93 patients (76%) were treated with medication alone or underwent PCI for a different lesion (medical treatment group). Average duration of follow-up of all 119 patients was 22 months (range 4 days to 30 months). In the medical treatment group seven patients (10%) experienced a major adverse clinical event related to the FFR-evaluated lesion during follow-up. In this study population, the use of FFR measurement is cost-reducing provided that at least 65% of the patients in the medical treatment group has had a PCI with stent implantation when the use of FFR measurement is impossible. In this case, the decision to use PCI with stent implantation is purely based on the angiogram. Conclusions. In patients with a coronary stenosis based on visual assessment and an FFR of ≥0.75 deferral of PCI or CABG is safe in daily clinical practice and saves money. (Neth Heart J 2010;18:402-7.)     

Assessment of coronary flow reserve in nuclear cardiology

The coronary flow reserve is a quantitative parameter defined by the ratio maximal myocardial blood flow to rest myocardial blood flow, which allows to give functional information on the whole coronary arterial tree, integrating both epicardial arteries and microcirculatory. The coronary flow reserve is a powerful tool to guide therapy and to assess prognosis. Exploratory tools, initially limited to experimental invasive techniques, have evolved over the last 10 years, allowing to envisage its use in daily clinical practice. This article reviews the pathophysiology of the coronary flow reserve and the various invasive and non-invasive exploration tools available to practitioners, integrating them into clinical practice.     

Soluble epoxide hydrolase: Gene structure,expression and deletion

Mammalian soluble epoxide hydrolase (sEH) converts epoxides to their corresponding diols through the addition of a water molecule. sEH readily hydrolyzes lipid signaling molecules, including the epoxyeicosatrienoic acids (EETs), epoxidized lipids produced from arachidonic acid by the action of cytochrome p450s. Through its metabolism of the EETs and other lipid mediators, sEH contributes to the regulation of vascular tone, nociception, angiogenesis and the inflammatory response. Because of its central physiological role in disease states such as cardiac hypertrophy, diabetes, hypertension, and pain sEH is being investigated as a therapeutic target. This review begins with a brief introduction to sEH protein structure and function. sEH evolution and gene structure are then discussed before human small nucleotide polymorphisms and mammalian gene expression are described in the context of several disease models. The review ends with an overview of studies that have employed the sEH knockout mouse model.