The CX3C chemokine fractalkine induces vascular dysfunction by generation of superoxide anions.

Objective: The chemokine fractalkine activates platelets and induces leukocyte adhesion to the endothelium. Expression of fractalkine and its receptor, CX3CR1, is elevated in coronary artery disease. We assessed the effects of fractalkine on vascular function in isolated rat aorta.

Soluble guanylyl cyclase activation with HMR1766 attenuates platelet activation in diabetic rats.

Objective: Platelet activation significantly contributes to cardiovascular morbidity and mortality in diabetes. An association between impaired NO-mediated platelet inhibition and platelet activation has recently been demonstrated in experimental diabetes. Guanylyl cyclase activation enhances the reduced signaling via the NO/cGMP pathway.

Medroxyprogesterone acetate but not drospirenone ablates the protective function of 17 beta-estradiol in aldosterone salt-treated rats.

Controversial results obtained from human and animal studies on the prevention of heart disease by estrogens and progestins warrant a better understanding of nuclear hormone receptor function and interaction. To address this issue and taking into account that effects of synthetic progestins are not only referable to action through the progesterone receptor but may also be mediated by other steroid receptors, we characterized cardiovascular function and inflammatory gene expression in aldosterone salt-treated rats on long-term administration of 17beta-estradiol, medroxyprogesterone acetate, and drospirenone, a new progestogen exhibiting antimineralocorticoid activity. The complex pattern of cardiovascular injury in ovariectomized Wistar rats induced by chronic aldosterone infusion plus a high-salt diet was significantly attenuated in sham-ovariectomized rats and by coadministration of 17beta-estradiol in ovariectomized animals after 8 weeks of continuous treatment.

Efficient simulation of magnetic resonance imaging with Bloch-Torrey equations using intra-voxel magnetization gradients.

The process of image formation in magnetic resonance imaging (MRI) can be simulated by means of an iterative solution of Bloch-Torrey equations. This is a useful accessory to analyze the influence of sample properties, sequence parameters and hardware specifications on the MRI signal. In this paper, a computer algorithm is presented which is based on calculating partial derivatives of the magnetization vector.

Functional magnetic resonance imaging with intermolecular double-quantum coherences at 3 T.

Functional magnetic resonance imaging (fMRI) based on the selection of intermolecular double-quantum coherences (iDQC) was performed with a standard birdcage coil at 3 T in a group of normal human volunteers. Suppression of spurious signal contributions from unwanted coherence-transfer pathways was achieved by combining a two-step phase cycle and a long repetition time of 5 s. A gradient-recalled echo iDQC sequence (echo time, T(E) = 80 ms) yielded robust activation with a visual paradigm.

Rosuvastatin reduces platelet activation in heart failure: role of NO bioavailability.

Objectives: Endothelial dysfunction and platelet activation are part of the cardiovascular phenotype in congestive heart failure (CHF). We investigated whether 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibition would beneficially modulate vascular NO bioavailability and platelet activation in experimental CHF.

Methods And Results: Chronic myocardial infarction was induced by coronary ligation in male Wistar rats.

Platelet activation in heart failure.

Heart failure is a common disease in aging western populations. Not only severe but even mild to moderate heart failure is associated with increasing risk for stroke. This can partly be attributed to concomitant atrial fibrillation, a well-known risk factor for stroke.

Endothelial dysfunction in heart failure: mechanisms and therapeutic approaches.

Endothelial dysfunction contributes to the development of impaired coronary and systemic perfusion as well as reduced exercise capacity in patients with congestive heart failure (CHF). Thereby endothelial dysfunction is assumed to have a fundamental impact on morbidity and potential mortality in this disease. Reduced bioavailability of nitric oxide (NO) and abundant formation of reactive oxygen species (ROS) within the vascular wall are the key determinants in endothelial dysfunction.

Reduced vascular NO bioavailability in diabetes increases platelet activation in vivo.

Objective: Platelet activation is a feature of cardiovascular disease that is also characterized by endothelial dysfunction. The direct relationship between impaired endothelium-derived NO bioavailability and platelet activation remains unclear. We investigated whether acute inhibition of NO production modulates platelet activation in mice and whether specific rescue of endothelial function in diabetes modifies platelet activation.

Increased platelet activation in young Zucker rats with impaired glucose tolerance is improved by acarbose.

Patients with diabetes display increased platelet activation. Recent data show a markedly increased risk for cardiovascular events already in pre-diabetic individuals with impaired glucose tolerance (IGT). We investigated whether IGT is associated with platelet activation.

Reduced basal nitric oxide bioavailability and platelet activation in young spontaneously hypertensive rats.

Objective: To investigate the role of basal nitric oxide (NO) bioavailability for platelet activation in young spontaneously hypertensive rats before onset of hypertension. Phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) in platelets was used as a sensitive monitor of in vivo NO bioavailability.

Methods And Results: Whole blood samples were taken from 10-week-old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR).

Rapid regulation of platelet activation in vivo by nitric oxide.

Background: Platelet activation is a feature of many cardiovascular diseases characterized by endothelial dysfunction. The mechanistic relationship between impaired systemic nitric oxide (NO) bioavailability and platelet activation in vivo remains unclear. We investigated whether acute inhibition of NO production in humans modulates platelet activation in vivo and whether exogenous NO would counteract such an effect.

Endothelial dysfunction in congestive heart failure: ACE inhibition vs. angiotensin II antagonism.

Background: Endothelial dysfunction of the vasculature contributes to the elevated peripheral resistance and reduced myocardial perfusion in congestive heart failure (CHF). The present study systematically investigated the effect of angiotensin II (AT(1))- receptor blockade on vascular superoxide (O(2)(-)) production and endothelial dysfunction.

Methods And Results: Vasodilator responses and O(2)(-) production were determined in aortic rings from Wistar rats with experimental CHF 10 weeks after extensive myocardial infarction and compared with sham-operated animals (Sham).

Novel O-glycosyl amino acid mimetics as building blocks for O-glycopeptides act as inhibitors of galactosidases.

As potential lead structures for a new class of glycosidase inhibitors the novel O-glycosyl amino acid mimetics 3'-O-[2,6-anhydro-D-glycero-L-gluco-heptitol-1-yl]-L-serine 3 and-L-threonine 4 were synthesized, employing regio- and stereoselective aziridine ring opening methodology. They proved to be stable in the presence of glycosidases and showed competitive inhibition of alpha-galactosidase from Aspergillus niger.

Novel role of the membrane-bound chemokine fractalkine in platelet activation and adhesion.

Chemokines released by the endothelium have proaggregatory properties on platelets. Fractalkine, a recently discovered membrane-bound chemokine with a transmembrane domain, is expressed in vascular injury; however, the effects of fractalkine on platelets have not yet been investigated. Blood was taken from healthy Wistar-Kyoto rats and the expression of the fractalkine receptor on platelets was demonstrated.

Addition of the selective aldosterone receptor antagonist eplerenone to ACE inhibition in heart failure: effect on endothelial dysfunction.

Objectives: To investigate the effects of adding the selective aldosterone receptor antagonist eplerenone to ACE inhibition on endothelium-dependent vasodilation in rats with chronic heart failure (CHF).

Background: Addition of the non-selective aldosterone antagonist spironolactone to ACE-inhibitors reduces mortality and morbidity in CHF and improves endothelial vasomotor dysfunction, but is associated with considerable side-effects.

Methods: Starting 10 days after extensive myocardial infarction (MI) or sham-operation, Wistar rats were treated either with placebo, the ACE inhibitor trandolapril (TR, 0.

Shape-persistant macrocycles with terpyridine units: synthesis, characterization, and structure in the crystal.

The synthesis of a variety of shape-persistent macrocycles with either one (1a-d, 2) or two (opposing) terpyridine units (3, 4, 5a-c) and inner diameters of up to 2 nm is described. The sequences are mainly based on transition metal cross-coupling reactions and, whenever appropriate, compared with one another regarding their respective efficiency. Typical overall yields and amounts prepared range from 8% (4) to 27% (3) and 25 mg (1a) to 290 mg (1b), respectively.

Inhibition of platelet activation in congestive heart failure by aldosterone receptor antagonism and ACE inhibition.

An increased risk of thrombembolic events in congestive heart failure (CHF) has been attributed to a hypercoagulable state including vascular endothelial dysfunction and platelet activation. After experimental myocardial infarction, male Wistar rats were treated with placebo, the ACE inhibitor trandolapril, the selective aldosterone receptor antagonist eplerenone or the combination of both, for 10 weeks. Platelet-bound fibrinogen and surface-expressed P-selectin were not modulated in rats without CHF compared with sham-operated animals, but were significantly increased in CHF rats (LVEDP>15 mmHg).

CB(1) cannabinoid receptor antagonism promotes remodeling and cannabinoid treatment prevents endothelial dysfunction and hypotension in rats with myocardial infarction.

1. To study the long-term effects of altered cannabinoid receptor activity on myocardial and vascular function, Wistar rats were treated with the selective CB(1) antagonist AM-251 (0.5 mg kg(-1) d(-1)), the potent synthetic cannabinoid HU-210 (50 micro g kg(-1) d(-1)) or vehicle for 12 weeks after coronary artery ligation or sham operation.

Functional perfusion imaging using continuous arterial spin labeling with separate labeling and imaging coils at 3 T.

Functional perfusion imaging with a separate labeling coil located above the common carotid artery was demonstrated in human volunteers at 3 T. A helmet resonator and a spin-echo echo-planar imaging (EPI) sequence were used for imaging, and a circular surface coil of 6 cm i.d.

Endothelium-dependent and -independent relaxation and VASP serines 157/239 phosphorylation by cyclic nucleotide-elevating vasodilators in rat aorta.

Endothelium-dependent vasodilation is thought to be mediated primarily by the NO/cGMP signaling pathway whereas cAMP-elevating vasodilators are considered to act independent of the endothelial cell layer. However, recent functional data suggest that cAMP-elevating vasodilators such as beta-receptor agonists, adenosine or forskolin may also be endothelium-dependent. Here we used functional and biochemical assays to analyze endothelium-dependent, cGMP- and cAMP-mediated signaling in rat aorta.

Angiotensin-converting enzyme inhibition and endothelin antagonism for endothelial dysfunction in heart failure: mono-or combination therapy.

The effect of angiotensin-converting enzyme (ACE) inhibition and endothelin A (ET ) receptor antagonism alone and in combination on endothelial vasomotor dysfunction in chronic heart failure (CHF) was compared. Vasoreactivity and superoxide anion formation were determined in aortic rings from Wistar rats with experimental CHF 12 weeks after extensive myocardial infarction compared with sham-operated animals. Rats were treated with placebo, with the ET receptor antagonist LU 135252 (30 mg/kg/d), with the ACE inhibitor trandolapril (0.

Effects of decreasing inspiratory flow rate during simulated basic life support ventilation of a cardiac arrest patient on lung and stomach tidal volumes.

If the airway of a cardiac arrest patient is unprotected, basic life support with low rather than high inspiratory flow rates may reduce stomach inflation. Further, if the inspiratory flow rate is fixed such as with a resuscitator performance may improve; especially when used by less experienced rescuers. The purpose of the present study was to assess the effect of limited flow ventilation on respiratory variables, and lung and stomach volumes, when compared with a bag valve device.