The role of F-FDG PET/CT in detecting synchronous regional and distant metastatic disease in patients with an in-breast tumour recurrence.

Background: In line with the trend towards minimally invasive, patient-tailored treatment, a selected group of patients with an in-breast tumour recurrence (IBTR) is treated by repeat breast-conserving treatment (BCT). To select eligible patients for repeat BCT, a reliable pre-operative work-up is essential. This study reports on the role of F-FDG PET/CT in detecting synchronous regional and distant metastases in patients with IBTR.

Salt-sensitive trait of normotensive individuals is associated with altered autonomous cardiac regulation: a randomized controlled intervention study.

Blood pressure (BP) responses to sodium intake show great variation, discriminating salt-sensitive (SS) from salt-resistant (SR) individuals. The pathophysiology behind salt sensitivity is still not fully elucidated. We aimed to investigate salt-induced effects on body fluid, vascular tone, and autonomic cardiac response with regard to BP change in healthy normotensive individuals.

Alkaline phosphatase to treat ischaemia-reperfusion injury in living-donor kidney transplantation: APhIRI I feasibility pilot study.

Aims: Ischemia-reperfusion injury (IRI) during kidney transplant procedures is associated with adverse outcome. Alkaline phosphatase (AP) is an enzyme that has the potential to dampen IRI. Prior to this study, it had not been tested in the setting of kidney transplantation.

Cellular, mitochondrial and molecular alterations associate with early left ventricular diastolic dysfunction in a porcine model of diabetic metabolic derangement.

The prevalence of diabetic metabolic derangement (DMetD) has increased dramatically over the last decades. Although there is increasing evidence that DMetD is associated with cardiac dysfunction, the early DMetD-induced myocardial alterations remain incompletely understood. Here, we studied early DMetD-related cardiac changes in a clinically relevant large animal model.

Perturbations in myocardial perfusion and oxygen balance in swine with multiple risk factors: a novel model of ischemia and no obstructive coronary artery disease.

Comorbidities of ischemic heart disease, including diabetes mellitus (DM), hypercholesterolemia (HC) and chronic kidney disease (CKD), are associated with coronary microvascular dysfunction (CMD). Increasing evidence suggests that CMD may contribute to myocardial 'Ischemia and No Obstructive Coronary Artery disease' (INOCA). In the present study, we tested the hypothesis that CMD results in perturbations in myocardial perfusion and oxygen delivery using a novel swine model with multiple comorbidities.

Endovascular procedures cause transient endothelial injury but do not disrupt mature neointima in Drug Eluting Stents.

Extensive application of coronary intravascular procedures has led to the increased need of understanding the injury inflicted to the coronary arterial wall. We aimed to investigate acute and prolonged coronary endothelial injury as a result of guidewire use, repeated intravascular imaging and stenting. These interventions were performed in swine (N = 37) and injury was assessed per coronary segment (n = 81) using an Evans Blue dye-exclusion-test.

Intervening with the Nitric Oxide Pathway to Alleviate Pulmonary Hypertension in Pulmonary Vein Stenosis.

Pulmonary hypertension (PH) as a result of pulmonary vein stenosis (PVS) is extremely difficult to treat. The ideal therapy should not target the high-pressure/low-flow (HP/LF) vasculature that drains into stenotic veins, but only the high-pressure/high-flow (HP/HF) vasculature draining into unaffected pulmonary veins, reducing vascular resistance and pressure without risk of pulmonary oedema. We aimed to assess the activity of the nitric oxide (NO) pathway in PVS during the development of PH, and investigate whether interventions in the NO pathway differentially affect vasodilation in the HP/HF vs.

Right ventricular oxygen delivery as a determinant of right ventricular functional reserve during exercise in juvenile swine with chronic pulmonary hypertension.

Assessing right ventricular (RV) functional reserve is important for determining clinical status and prognosis in patients with pulmonary hypertension (PH). In this study, we aimed to establish RV oxygen (O) delivery as a determinant for RV functional reserve during exercise in swine with chronic PH. Chronic PH was induced by pulmonary vein banding (PVB), with sham operation serving as control.

Cardiac remodelling in a swine model of chronic thromboembolic pulmonary hypertension: comparison of right vs. left ventricle.

Key Points: Right ventricle (RV) function is the most important determinant of survival and quality of life in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The changes in right and left ventricle gene expression that contribute to ventricular remodelling are incompletely investigated. RV remodelling in our CTEPH swine model is associated with increased expression of the genes involved in inflammation (TGFβ), oxidative stress (ROCK2, NOX1 and NOX4), and apoptosis (BCL2 and caspase-3).

Validation of 4D flow CMR against simultaneous invasive hemodynamic measurements: a swine study.

The purpose of this study was to compare invasively measured aorta flow with 2D phase contrast flow and 4D flow measurements by cardiovascular magnetic resonance (CMR) imaging in a large animal model. Nine swine (mean weight 63 ± 4 kg) were included in the study. 4D flow CMR exams were performed on a 1.

Pulmonary microvascular remodeling in chronic thrombo-embolic pulmonary hypertension.

Pulmonary vascular remodeling in pulmonary arterial hypertension involves perturbations in the nitric oxide (NO) and endothelin-1 (ET-1) pathways. However, the implications of pulmonary vascular remodeling and these pathways remain unclear in chronic thrombo-embolic pulmonary hypertension (CTEPH). The objective of the present study was to characterize changes in microvascular morphology and function, focussing on the ET-1 and NO pathways, in a CTEPH swine model.

Transition from post-capillary pulmonary hypertension to combined pre- and post-capillary pulmonary hypertension in swine: a key role for endothelin.

Key Points: Passive, isolated post-capillary pulmonary hypertension (PH) secondary to left heart disease may progress to combined pre- and post-capillary or 'active' PH This 'activation' of post-capillary PH significantly increases morbidity and mortality, and is still incompletely understood. In this study, pulmonary vein banding gradually produced post-capillary PH with structural and functional microvascular remodelling in swine. Ten weeks after banding, the pulmonary endothelin pathway was upregulated, likely contributing to pre-capillary aspects in the initially isolated post-capillary PH.

Multiple common comorbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress, and myocardial stiffening.

Aims: More than 50% of patients with heart failure have preserved ejection fraction characterized by diastolic dysfunction. The prevalance of diastolic dysfunction is higher in females and associates with multiple comorbidities such as hypertension (HT), obesity, hypercholesterolemia (HC), and diabetes mellitus (DM). Although its pathophysiology remains incompletely understood, it has been proposed that these comorbidities induce systemic inflammation, coronary microvascular dysfunction, and oxidative stress, leading to myocardial fibrosis, myocyte stiffening and, ultimately, diastolic dysfunction.

The effect of bioresorbable vascular scaffold implantation on distal coronary endothelial function in dyslipidemic swine with and without diabetes.

Background: We studied the effect of bioresorbable vascular scaffold (BVS) implantation on distal coronary endothelial function, in swine on a high fat diet without (HFD) or with diabetes (DM+HFD).

Methods: Five DM+HFD and five HFD swine underwent BVS implantation on top of coronary plaques, and were studied six months later. Conduit artery segments >5mm proximal and distal to the scaffold and corresponding segments of non-scaffolded coronary arteries, and segments of small arteries within the flow-territory of scaffolded and non-scaffolded arteries were harvested for in vitro vasoreactivity studies.

Exercise facilitates early recognition of cardiac and vascular remodeling in chronic thromboembolic pulmonary hypertension in swine.

Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 4% of patients after pulmonary embolism and is accompanied by an impaired exercise tolerance, which is ascribed to the increased right ventricular (RV) afterload in combination with a ventilation/perfusion (V/Q) mismatch in the lungs. The present study aimed to investigate changes in arterial Po and hemodynamics in response to graded treadmill exercise during development and progression of CTEPH in a novel swine model. Swine were chronically instrumented and received multiple pulmonary embolisms by 1) microsphere infusion (Spheres) over 5 wk, 2) endothelial dysfunction by administration of the endothelial nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester (L-NAME) for 7 wk, 3) combined pulmonary embolisms and endothelial dysfunction (L-NAME + Spheres), or 4) served as sham-operated controls (sham).

Structural and functional changes of the pulmonary vasculature after hypoxia exposure in the neonatal period: a new swine model of pulmonary vascular disease.

Pulmonary vascular disease (PVD) represents an underestimated and increasing clinical burden not only in the neonatal period but also later in life, when exercise tolerance is decreased. Animal models performing long-term followup after a perinatal insult are lacking. This study aimed to develop and characterize a neonatal swine model with hypoxia-induced PVD during long-term followup after reexposure to normoxia and to investigate the exercise response in this model.

Pulmonary vasodilation by phosphodiesterase 5 inhibition is enhanced and nitric oxide independent in early pulmonary hypertension after myocardial infarction.

Myocardial infarction (MI) may result in pulmonary hypertension (PH). Inhibition of phosphodiesterase 5 (PDE5), the enzyme responsible for the breakdown of cGMP in vascular smooth muscle, has become part of the contemporary therapeutic armamentarium for pulmonary arterial hypertension and may also be beneficial for PH secondary to MI. Nitric oxide (NO) is an important activator of cGMP synthesis and can be enhanced in early PH and decreased in severe PH.

Neoatherosclerosis development following bioresorbable vascular scaffold implantation in diabetic and non-diabetic swine.

Background: DM remains a risk factor for poor outcome after stent-implantation, but little is known if and how DM affects the vascular response to BVS.

Aim: The aim of our study was to examine coronary responses to bioresorbable vascular scaffolds (BVS) in swine with and without diabetes mellitus fed a 'fast-food' diet (FF-DM and FF-NDM, respectively) by sequential optical coherence tomography (OCT)-imaging and histology.

Methods: Fifteen male swine were evaluated.

The microcirculation: a key player in obesity-associated cardiovascular disease.

It is increasingly recognized that obesity is a risk factor for microvascular disease, involving both structural and functional changes in the microvasculature. This review aims to describe how obesity impacts the microvasculature of a variety of tissues, including visceral adipose tissue, skeletal muscle, heart, brain, kidneys, and lungs. These changes involve endothelial dysfunction, which in turn (i) impacts control of vascular tone, (ii) contributes to development of microvascular insulin resistance, (iii) alters secretion of paracrine factors like nitric oxide and endothelin, but (iv) also influences vascular structure and perivascular inflammation.

Coronary microvascular dysfunction after long-term diabetes and hypercholesterolemia.

Coronary microvascular dysfunction (CMD) has been proposed as an important component of diabetes mellitus (DM)- and hypercholesterolemia-associated coronary artery disease (CAD). Previously we observed that 2.5 mo of DM and high-fat diet (HFD) in swine blunted bradykinin (BK)-induced vasodilation and attenuated endothelin (ET)-1-mediated vasoconstriction.

Surgical Placement of Catheters for Long-term Cardiovascular Exercise Testing in Swine.

This protocol describes the surgical procedure to chronically instrument swine and the procedure to exercise swine on a motor-driven treadmill. Early cardiopulmonary dysfunction is difficult to diagnose, particularly in animal models, as cardiopulmonary function is often measured invasively, requiring anesthesia. As many anesthetic agents are cardiodepressive, subtle changes in cardiovascular function may be masked.

Spherical and Hyperbolic Embeddings of Data.

Many computer vision and pattern recognition problems may be posed as the analysis of a set of dissimilarities between objects. For many types of data, these dissimilarities are not euclidean (i.e.

VEGF165A microsphere therapy for myocardial infarction suppresses acute cytokine release and increases microvascular density but does not improve cardiac function.

Angiogenesis induced by growth factor-releasing microspheres can be an off-the-shelf and immediate alternative to stem cell therapy for acute myocardial infarction (AMI), independent of stem cell yield and comorbidity-induced dysfunction. Reliable and prolonged local delivery of intact proteins such as VEGF is, however, notoriously difficult. Our objective was to create a platform for local angiogenesis in human-sized hearts, using polyethylene-glycol/polybutylene-terephthalate (PEG-PBT) microsphere-based VEGF165A delivery.

Serial measurement of hFABP and high-sensitivity troponin I post-PCI in STEMI: how fast and accurate can myocardial infarct size and no-reflow be predicted?

The objective of this study was to compare heart-specific fatty acid binding protein (hFABP) and high-sensitivity troponin I (hsTnI) via serial measurements to identify early time points to accurately quantify infarct size and no-reflow in a preclinical swine model of ST-elevated myocardial infarction (STEMI). Myocardial necrosis, usually confirmed by hsTnI or TnT, takes several hours of ischemia before plasma levels rise in the absence of reperfusion. We evaluated the fast marker hFABP compared with hsTnI to estimate infarct size and no-reflow upon reperfused (2 h occlusion) and nonreperfused (8 h occlusion) STEMI in swine.