Intra-cardiac transfer of fatty acids from capillary to cardiomyocyte.

Blood-borne fatty acids (Fa) are important substrates for energy conversion in the mammalian heart. After release from plasma albumin, Fa traverse the endothelium and the interstitial compartment to cross the sarcolemma prior to oxidation in the cardiomyocytal mitochondria. The aims of the present study were to elucidate the site with lowest Fa permeability (i.

Modeling Fatty Acid Transfer from Artery to Cardiomyocyte.

Despite the importance of oxidation of blood-borne long-chain fatty acids (Fa) in the cardiomyocytes for contractile energy of the heart, the mechanisms underlying the transfer of Fa from the coronary plasma to the cardiomyocyte is still incompletely understood. To obtain detailed insight into this transfer process, we designed a novel model of Fa transfer dynamics from coronary plasma through the endothelial cells and interstitium to the cardiomyocyte, applying standard physicochemical principles on diffusion and on the chemical equilibrium of Fa binding to carrier proteins Cp, like albumin in plasma and interstitium and Fatty Acid-Binding Proteins within endothelium and cardiomyocytes. Applying these principles, the present model strongly suggests that in the heart, binding and release of Fa to and from Cp in the aqueous border zones on both sides of the cell membranes form the major hindrance to Fa transfer.

Dimensions of compartments and membrane surfaces in the intact rabbit heart of importance in studies on intramyocardial transfer of blood-borne substances.

Cardiac studies on the uptake, storage and intramyocardial transfer of blood-borne substances require detailed information on the geometric ultrastructural dimensions of myocardial compartments and parts thereof, and the membranes separating these compartments. Such a specific ultrastructural set of data of the heart is yet lacking. In the present study, we quantitatively assessed these dimensions in glutaraldehyde-perfusion fixed rabbit hearts by means of histological and tailored mathematical techniques.

Echogenic perfluorohexane-loaded macrophages adhere in vivo to activated vascular endothelium in mice, an explorative study.

Background: Macrophages may concentrate ultrasound contrast agents and exhibit selective adhesion to activated endothelium. The present study investigates in mice the potential of perfluorohexane (PFH) loaded macrophages to act as ultrasound contrast agent with high reflectivity and specifically targeted at (atherosclerotic) vascular lesions.

Methods: Lung passage was evaluated with a mouse echo scanner after injection, at a slow pace or as a bolus, of varying doses of PFH-loaded and unloaded bone marrow macrophages (BMM) into the jugular vein.

Arterial stiffness and hypertension in a large population of untreated individuals: the Rotterdam Study.

Objective: We studied whether arterial stiffness measured as aortic pulse wave velocity (aPWV) and carotid distensibility was associated with different subtypes of hypertension in a large population of untreated middle-aged and elderly men and women.

Methods: The study was conducted within the framework of the population-based Rotterdam Study. We included 4088 individuals with information on aPWV, with 3554 individuals with carotid distensibility measurements without use of antihypertensive medication.

The change in arterial stiffness over the cardiac cycle rather than diastolic stiffness is independently associated with left ventricular mass index in healthy middle-aged individuals.

Background: The current standard for arterial stiffness assessment, aortic pulse wave velocity (aPWV), is measured at diastolic pressure. Arterial stiffness, however, is pressure dependent. At the carotid artery level, the degree of this dependency can be quantified as the difference (ΔPWV) between systolic and diastolic (cPWVd) carotid pulse wave velocity.

Common carotid intima-media thickness in cardiovascular risk stratification of older people: the Rotterdam Study.

Aim: Non-invasive measures of atherosclerosis, such as carotid intima-media thickness (cIMT), may improve global cardiovascular risk prediction. The aim of this study was to determine whether common carotid IMT in addition to traditional risk factors improves risk classification in a general population of older people.

Methods And Results: A group of 3580 non-diabetic people aged 55-75 years and free of cardiovascular disease at baseline were followed for a median time of 12.

Does aortic stiffness improve the prediction of coronary heart disease in elderly? The Rotterdam Study.

It has been demonstrated that aortic stiffness is an independent predictor of cardiovascular disease. We investigated whether this measure is of use in cardiovascular risk stratification in clinical practice for elderly subjects (mean age 71.5 years).

Spatial distension variations are associated with focal atherosclerotic plaques.

Background: Alterations in arterial absolute distension (AD) and relative distension (RD) in the common carotid artery (CCA), as observed by ultrasound, may relate to atherosclerotic processes in a nearby vascular segment. The main objective of the study was to establish to what extent these mechanical vascular alterations relate to carotid bulb stenosis.

Methods: The AD, RD and their interrecording variation (Delta AD and Delta RD), representing the spatial inhomogeneity of AD and RD, were evaluated in 308 CCA and associated with the degree of bulb stenosis.

Critical appraisal of targeted ultrasound contrast agents for molecular imaging in large arteries.

Molecular imaging may provide new insights into the early detection and development of atherosclerosis before first symptoms occur. One of the techniques in use employs noninvasive ultrasound. In the past decade, experimental and clinical validation studies showed that for the microcirculation targeted ultrasound contrast agents, such as echogenic liposomes, microbubbles and perfluorocarbon emulsions, do improve visualization of specific structures.

Noninvasive assessment of arterial stiffness should discriminate between systolic and diastolic pressure ranges.

Arterial stiffening plays an important role in the development of hypertension and cardiovascular diseases. The intrinsically nonlinear (ie, pressure-dependent) elastic behavior of arteries may have serious consequences for the accuracy and interpretation of arterial stiffness measurements and, ultimately, for individual patient management. We determined aortic pressure and common carotid artery diameter waveforms in 21 patients undergoing cardiac catheterization.

Genetic variation in the renin-angiotensin system and arterial stiffness. The Rotterdam Study.

We studied the associations of three renin-angiotensin system polymorphisms, angiotensin-converting enzyme (ACE) I/D, angiotensinogen 235 M/T, and angiotensin II receptor type I 573 C/T, with arterial stiffness. The study was embedded in the Rotterdam Study, a population-based study older adults. The association of the polymorphisms with pulse wave velocity, the carotid distensibility, and pulse pressure was investigated in 3706 subjects.

The dicrotic notch as alternative time-reference point to measure local pulse wave velocity in the carotid artery by means of ultrasonography.

Objectives: Increased arterial stiffness is associated with cardiovascular disease. Its applicability in individual patient management, however, is limited due to lack of reliable methods. We developed a method to measure arterial stiffness by means of local pulse wave velocity (PWV), using multiple M-mode ultrasound and the dicrotic notch (PWVdn) rather than the systolic foot (PWVsf) as time-reference point.

Genetic variation in the fibrinogen-alpha and fibrinogen-gamma genes in relation to arterial stiffness: the Rotterdam Study.

Objective: Arterial stiffness increases with age and predicts cardiovascular disease. Fibrinogen is an acute-phase protein and some studies showed an association with arterial stiffness. We studied genetic variation in the fibrinogen-alpha (FGA) and fibrinogen-gamma (FGG) genes, by means of single nucleotide polymorphisms (FGA: -58 G/A, 1374 G/A, 1526 T/C, 312 Thr/Ala, and FGG: 4288 G/A, 6326 G/A, 7792 T/C) and resultant haplotypes in relation to arterial stiffness.

Wall irregularity rather than intima-media thickness is associated with nearby atherosclerosis.

In addition to intima-media thickness (IMT), IMT inhomogeneity may carry information about atherosclerosis progression. In 147 vascular diseased patients (mean 66 y, 48% male), we determined the carotid bulb stenosis degree based on local Doppler blood flow velocities. Common carotid artery (CCA) morphologic characteristics, i.

Contribution of vascular and neural segments to baroreflex sensitivity in response to postural stress.

Background/aims: The baroreflex pathway has a vascular and a neural segment, both being modulated by variations in peripheral blood pressure (BP). Besides overall baroreceptor sensitivity (BRS), defined as the spectral relationship between changes in peripheral BP and R-R interval within the frequency band of 0.05-0.

The interleukin-6-174 G/C promoter polymorphism and arterial stiffness; the Rotterdam Study.

Arterial stiffness normally increases with age and has been established as a precursor of cardiovascular disease. Interleukin-6 is a pleiotropic inflammatory cytokine with an important role in the inflammatory cascade, such as up-regulation of C-reactive protein (CRP). The interleukin-6-174-G/C promoter polymorphism appears to influence levels of inflammatory markers, which have been shown to be associated with arterial stiffness.

Confluence of incident and reflected waves interferes with systolic foot detection of the carotid artery distension waveform.

Objectives: Local pulse wave velocity, a direct measure of arterial stiffness, can be measured using the systolic foot of the pressure waveform as the time reference point. The accuracy and precision of systolic foot identification, which may be disturbed by early wave reflections, heavily affects pulse wave transit time measurements. We investigated within subjects the existence of early wave reflections and their interference with systolic foot identification.

Perfluorohexane-loaded macrophages as a novel ultrasound contrast agent: a feasibility study.

Purpose: We investigated in vitro the potential of macrophages to act as targeted vehicle for ultrasound molecular imaging.

Procedures: Murine bone marrow-derived macrophages (BMM), incubated for 3 h with different concentrations of perfluorohexane (PFH) emulsions, were monitored by microscopy, flow cytometry, and ultrasound. Effects of PFH loading on BMM adhesion molecule (PSGL-1, VLA-4, Mac-1, LFA-1) expression were analyzed by flow cytometry.