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BackgroundAdequate blood flow into coronary micro-arteries is essential for myocardial function. Here we assess the mechanisms responsible for amplifying blood flow into myogenically-contracting human and porcine intramyocardial micro-arteries ex vivo using endothelium-dependent and -independent vasodilators.MethodsHuman and porcine atrial and ventricular small intramyocardial coronary arteries (IMCAs) were studied with pressure myography and imaged using confocal microscopy and serial section/3-D reconstruction EM.Results3D rendered ultrastructure images of human right atrial (RA-) IMCAs revealed extensive homo-and hetero-cellular contacts, including to longitudinally-arranged smooth muscle cells (l-SMCs) found between the endothelial cells (ECs) and radially-arranged medial SMCs (r-SMCs). Local and conducted vasodilatation followed focal application of bradykinin in both human and porcine RA-IMCAs, and relied on hyperpolarization of SMCs, but not nitric oxide. Bradykinin initiated asynchronous oscillations in endothelial cell Ca2+ in pressurized RA-IMCAs and, as previously shown in human RA-IMCAs, hyperpolarized porcine arteries. Immunolabelling showed small- and intermediate-conductance Ca2+-activated K+ channels (KCa) present in the endothelium of both species, and concentration-dependent vasodilation to bradykinin followed activation of these KCa channels. Extensive electrical coupling was demonstrated between r-SMCs and l-SMCs, providing an additional pathway to facilitate the well-established myoendothelial coupling. Conducted dilation was still evident in a human RA-IMCA with poor myogenic tone, and heterocellular contacts were visible in the 3D reconstructed artery. Hyperpolarization and conducted vasodilation was also observed to adenosine which, in contrast to bradykinin, was sensitive to combined block of ATP-sensitive (KATP) and inwardly rectifying (KIR) K+ channels.ConclusionsThese data extend our understanding of the mechanisms that coordinate human coronary microvascular blood flow and the mechanistic overlap with porcine IMCAs. The unusual presence of l-SMCs provides an additional pathway for rapid intercellular signaling between cells of the coronary artery wall. Local and conducted vasodilation follow hyperpolarization of the ECs or SMCs, and contact-coupling between l-SMCs and r-SMCs likely facilitates this vasodilation.

Background Cardiac motion results in image artefacts and quantification errors in many cardiovascular magnetic resonance (CMR) techniques, including microstructural assessment using diffusion tensor cardiovascular magnetic resonance (DT-CMR). Here we develop a CMR compatible isolated perfused porcine heart model that allows comparison of data obtained in beating and arrested states. Methods 10 porcine hearts (8/10 for protocol optimisation) were harvested using a donor heart retrieval protocol and transported to the remote CMR facility. Langendorff perfusion in a 3D printed chamber and perfusion circuit re-established contraction. Hearts were imaged using cine, parametric mapping and STEAM DT-CMR at cardiac phases with the minimum and maximum wall thickness. High potassium and lithium perfusates were then used to arrest the heart in a slack and contracted state respectively. Imaging was repeated in both arrested states. After imaging, tissue was removed for subsequent histology in a location matched to the DT-CMR data using fiducial markers. Results Regular sustained contraction was successfully established in 6/10 hearts, including the final 5 hearts. Imaging was performed in 4 hearts and one underwent the full protocol including co-localised histology. Image quality was good and there was good agreement between DT-CMR data in equivalent beating and arrested states. Despite the use of autologous blood and dextran within the perfusate, T2, DT-CMR measures and an increase in mass was consistent with development of myocardial edema resulting in failure to achieve a true diastolic-like state. A contiguous stack of 313 5μm histological sections at and a 100μm thick section showing cell morphology on 3D fluorescent confocal microscopy co-localised to DT-CMR data were obtained. Conclusions A CMR compatible isolated perfused beating heart setup for large animal hearts allows direct comparisons of beating and arrested heart data with subsequent co-localised histology without the need for onsite pre-clinical facilities.

Purpose: Recent developments in robotics and artificial intelligence (AI) have led to significant advances in healthcare technologies enhancing robot-assisted minimally invasive surgery (RAMIS) in some surgical specialties. However, current human–robot interfaces lack intuitive teleoperation and cannot mimic surgeon’s hand/finger sensing required for fine motion micro-surgeries. These limitations make teleoperated robotic surgery not less suitable for, e.g. cardiac surgery and it can be difficult to learn for established surgeons. We report a pilot study showing an intuitive way of recording and mapping surgeon’s gross hand motion and the fine synergic motion during cardiac micro-surgery as a way to enhance future intuitive teleoperation. Methods: We set to develop a prototype system able to train a Deep Neural Network (DNN) by mapping wrist, hand and surgical tool real-time data acquisition (RTDA) inputs during mock-up heart micro-surgery procedures. The trained network was used to estimate the tools poses from refined hand joint angles. Outputs of the network were surgical tool orientation and jaw angle acquired by an optical motion capture system. Results: Based on surgeon’s feedback during mock micro-surgery, the developed wearable system with light-weight sensors for motion tracking did not interfere with the surgery and instrument handling. The wearable motion tracking system used 12 finger/thumb/wrist joint angle sensors to generate meaningful datasets representing inputs of the DNN network with new hand joint angles added as necessary based on comparing the estimated tool poses against measured tool pose. The DNN architecture was optimized for the highest estimation accuracy and the ability to determine the tool pose with the least mean squared error. This novel approach showed that the surgical instrument’s pose, an essential requirement for teleoperation, can be accurately estimated from recorded surgeon’s hand/finger movements with a mean squared error (MSE) less than 0.3%. Conclusion: We have developed a system to capture fine movements of the surgeon’s hand during micro-surgery that could enhance future remote teleoperation of similar surgical tools during micro-surgery. More work is needed to refine this approach and confirm its potential role in teleoperation.

Aims The co-transmitter neuropeptide-Y (NPY) is released during high sympathetic drive, including ST-elevation myocardial infarction (STEMI), and can be a potent vasoconstrictor. We hypothesized that myocardial NPY levels correlate with reperfusion and subsequent recovery following primary percutaneous coronary intervention (PPCI), and sought to determine if and how NPY constricts the coronary microvasculature. Methods and results Peripheral venous NPY levels were significantly higher in patients with STEMI (n = 45) compared to acute coronary syndromes/stable angina (n = 48) or with normal coronary arteries (NC,n = 16). Overall coronary sinus (CS) and peripheral venous NPY levels were significantly positively correlated (r = 0.79). STEMI patients with the highest CS NPY levels had significantly lower coronary flow reserve, and higher index of microvascular resistance measured with a coronary flow wire. After 2 days they also had significantly higher levels of myocardial oedema and microvascular obstruction on cardiac magnetic resonance imaging, and significantly lower ejection fractions and ventricular dilatation 6 months later. NPY (100–250 nM) caused significant vasoconstriction of rat microvascular coronary arteries via increasing vascular smooth muscle calcium waves, and also significantly increased coronary vascular resistance and infarct size in Langendorff hearts. These effects were blocked by the Y1receptor antagonist BIBO3304 (1 μM). Immunohistochemistry of the human coronary microvasculature demonstrated the presence of vascular smooth muscle Y1receptors. Conclusion High CS NPY levels immediately after reperfusion correlate with microvascular dysfunction, greater myocardial injury, and reduced ejection fraction 6 months after STEMI. NPY constricts the coronary microcirculation via the Y1receptor, and antagonists may be a useful PPCI adjunct therapy.

Background: Pulmonary dysfunction is a known complication after cardiac surgery using cardiopulmonary bypass, ranging from subclinical functional changes to prolonged postoperative ventilation, acute lung injury, and acute respiratory distress syndrome. Whether human pulmonary arterial function is compromised is unknown. The aim of the present study was to compare the structure and function of isolated and cannulated human pulmonary arteries obtained from lung biopsies after the chest was opened (pre–cardiopulmonary bypass) to those obtained at the end of cardiopulmonary bypass (post–cardiopulmonary bypass) from patients undergoing coronary artery bypass graft surgery. Methods and Results: Pre‐ and post–cardiopulmonary bypass lung biopsies were received from 12 patients undergoing elective surgery. Intralobular small arteries were dissected, cannulated, pressurized, and imaged using confocal microscopy. Functionally, the thromboxane mimetic U46619 produced concentration‐dependent vasoconstriction in 100% and 75% of pre‐ and post–cardiopulmonary bypass arteries, respectively. The endothelium‐dependent agonist bradykinin stimulated vasodilation in 45% and 33% of arteries pre‐ and post–cardiopulmonary bypass, respectively. Structurally, in most arteries smooth muscle cells aligned circumferentially; live cell viability revealed that although 100% of smooth muscle and 90% of endothelial cells from pre–cardiopulmonary bypass biopsies had intact membranes and were considered viable, only 60% and 58%, respectively, were viable from post–cardiopulmonary bypass biopsies. Conclusions: We successfully investigated isolated pulmonary artery structure and function in fresh lung biopsies from patients undergoing heart surgery. Pulmonary artery contractile tone and endothelium‐dependent dilation were significantly reduced in post–cardiopulmonary bypass biopsies. The decreased functional responses were associated with reduced cell viability. Clinical Trial Registration: URL: http://www.isrctn.com/ISRCTN34428459. Unique identifier: ISRCTN 34428459.

Statistical sampling is a fundamental tool in science, and metrology is no exception. The merit of a sample is its efficiency, i.e. a good trade-off between the information collected and the sample size. Although the sample sites are ordinarily decided prior to the measurements, a different option would be to select them one at a time. This strategy is potentially more informative as the next site can be decided based also on the measurements taken up to that time. The core of the method is to drive the next-site selection by a non-parametric model known as kriging, namely a stationary Gaussian stochastic process with a given autocorrelation structure [1,2]. The main feature of this model is the ability to promptly reconfigure itself, changing the pattern of the predictions and their uncertainty each time a new measurement comes in. Since the model is re-estimated after each added point the sampling procedure is an adaptive one. The next sampling site can be selected via a number of model-based criteria, inspired by the principles of reducing prediction uncertainty or optimizing an objective function, or a combination of the two. The methodology has been applied by the authors [3,4] to design inspection plans for measuring geometric errors using touch-probe Coordinate Measuring Machines (CMM). Results showed that both the non adaptive statistical plans (Random, Latin Hypercube sampling, uniform sampling) and two adaptive deterministic plans from the literature were largely outperformed by the proposed plans both in terms of accuracy and cost. Here we further investigate on a number of important questions related to adaptive kriging: which is the best trade-off between the number of adaptive and non-adaptive points (the latter chosen according to uniform coverage), which next-site selection criteria are more suitable to capturing extreme values of the signal in order to provide a good estimate of the geometric errors.

Objective: A cross sectional study was performed to evaluate the presence, in a sample of subjects in the age of pubertal transition, of those psychological characteristics and abnormal eating behaviours, which are generally considered the predictors of eating disorders (EDs) in adolescence. The primary aim of our study was to evaluate the presence of EDs-related psychological traits and of abnormal eating behaviours, in a wide sample of natural 11-13 year olds population, and to determine if, in this period of transition, there are the same differences between males and females, which are related to the ED psychological characteristics that are often observed and assessed in samples of adolescents or young adults; our secondary aim was to evaluate, in the female sample, if and how the episode of menarche, and the related pubertal body transformation, play a role in the development of ED symptomatology. Method: We screened 2925 school children by means of an ad-hoc socio-demographic schedule, the EDI 2 and the EDI-Symptom Checklist questionnaires. We compared each EDI 2 scales score (Mann-Whitney U) and the abnormal eating behaviours (χ2 analyses) between pre- and post-menarche female subjects, for each age subgroup. Results: Fourteen percent of the entire sample scored higher than the cut-off value at the EDI 2 drive for thinness scale and have to be considered at risk for an ED onset. The EDI 2 scores and the adoption of abnormal eating behaviour increase, in the female population, depending on whether they have had menarche. In the male sample the mean values at EDI-2 scales decrease with increasing age. Discussion: The abnormal eating behaviours and the psychological ED attitude are widespread even among a “cross-pubertal” population. Our data confirm the differences between male and female subjects at the EDs attitude, suggesting a strong relation in the female children between the pubertal body transformation and the risk of ED onset.