Vascular Beds In Humans Research Articles

Feasibility of Echocardiographic Estimation of Pulmonary Artery Stiffness in Horses

Pulmonary artery stiffness (PAS) is an index of pulmonary artery elasticity that permits to evaluate the pulmonary vascular bed in humans. It can early detect an increase in pulmonary artery stiffness as a consequence of remodeling of the vessel wall caused by chronic pulmonary and congenital heart diseases. This remodeling can occur also in horses with chronic respiratory diseases. Thus, PAS could be a useful echocardiographic parameter also in horses. However, in literature, there are no studies regarding PAS in horses. The aim of this study is to evaluate the feasibility of PAS in horses. Fifteen healthy horses were included in this prospective study. Maximal frequency shift and acceleration time were measured from the pulsed-wave Doppler trace of the pulmonary artery flow, obtained from the right parasternal short-axis view at the level of the pulmonary artery, and then PAS was calculated as the ratio of Maximal frequency shift to acceleration time. The low variability assessed for intra- and inter-observer variability, day-to-day variability and image acquisition variability suggests that PAS can be measured consistently in horses. Further studies could be useful to assess the clinical usefulness of PAS in unhealthy horses, such as those affected by chronic respiratory diseases.

Coronary Collateral Flow Index Is Correlated With the Palmar Collateral Flow Index: Indicating Systemic Collateral Coherence in Individual Patients-Brief Report.

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Abstract TP127: Impact of Smoking on Collateral Blood Flow in Patients With Acute Ischemic Stroke With Large Cerebral Artery Embolic Occlusion

Introduction: Good collateral flow is associated with improved outcomes in acute embolic stroke. There is compelling data linking smoking to all types of stroke, with current smokers at a higher risk than former or never smokers. Smoking has, however, been shown to promote collaterals in coronary vascular bed in humans. It is unknown if there is a similar effect in cerebral collateral flow. We aimed to investigate if cigarette smoking was positively associated with collateral blood flow in a homogenous cohort of patients with acute large vessel occlusive embolic stroke. Methods: We identified all patients aged ≥18 with acute ischemic stroke showing embolic occlusion of ICA terminus/M1 MCA on admission CT angiography (CTA), between 2008 to 2018, through an institutional database. Patients with chronic occlusions and stenotic lesions were excluded. Individual CTAs were independently reviewed by two trained investigators to calculate collateral scores of the affected hemisphere using the modified Tan scale (0-4) as a reference. Details of cigarette smoking history were obtained from the electronic medical records. Patients were grouped into smokers (former and current smokers) and never smokers. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated, and all tests were considered significant when P<0.05. Results: Of the 612 patients identified through the database, 429/612 patients (mean age 71±16 years, 45% [194/429] women) satisfied the inclusion criteria. 64.8% (278/429) had a positive history of smoking with an average of 47±12 pack-years. There was a significant association between good collateral scores (≥2) with smoking history (OR 1.74 CI 1.17-2.61, P=0.006). This trend remained significant even after comparing raw collateral scores (0-4) ( P=0.006, Spearman’s ρ=0.22). However, number of pack-years and collateral scores exhibited no statistically significant relationship (P=0.6). Conclusions: Our study shows that patients who have ever smoked have higher intracranial collateral vessel scores in the event of an acute embolic stroke. Increased impedance and reduced cerebral blood flow resulting from cigarette smoking may stimulate collateral recruitment in cerebral pial circulation, similar to the effect in coronary bed.

H2O2‐Induced Dilation in Human Adipose Arterioles: Role of Smooth Muscle K+ Channels

Hydrogen peroxide (H2O2) induces potent vasodilation in human coronary arterioles from subjects with coronary artery disease (CAD) through the activation of protein kinase G‐large conductance Ca2+‐activated K+ (BKCa) channel pathway. Because the vasodilator effect and mechanism of action of H2O2 vary among different vascular beds and species, it remains unknown whether the K+ channel‐mediated dilation is conserved in other systemic vascular beds in humans. We investigated the vasomotor effect of H2O2 and its underlying mechanism in human adipose arterioles. Arterioles (100‐200 μm) obtained from subjects without CAD were cannulated under 60 mmHg and examined for diameter changes using video microscopy. H2O2 (1‐100 µM) induced concentration‐dependent vasodilation, with maximal dilation of 95±1% at 100 µM. H2O2‐induced dilation was endothelium‐independent and markedly reduced by both paxilline, a BKCa channel blocker, and 4‐AP, a voltage‐gated K+ (KV) channel blocker (dilation at 10 μM, 19±13% vs. 72±9% in control, and 26±5% vs. 66±11% in control, respectively). We further investigated which subtype(s) of the KV1 channels (the major KV family in the vasculature) is responsible to H2O2‐induced dilation. Similar to 4‐AP, DPO‐1 (KV1.5 channel‐specific blocker) reduced dilation to 10 μM H2O2 (12±5% vs. 54±7% in control). In addition, the KV 1.3/1.5‐specific blocker Psora‐4 caused a similar rightward shift in H2O2‐induced dilation, but further reduced the maximal dilation to 100 μM H2O2 (58±5% vs. 83±5% in DPO‐1). In conclusion, H2O2 dilates human adipose arterioles from non‐CAD subjects and the dilation is mediated by both KV and BKCa channels in smooth muscle cells. The mechanism by which H2O2 activates K+ channels (especially KV channel) remains to be determined.

Have we missed that neural vasodilator mechanisms may contribute to exercise hyperemia at onset of voluntary exercise?

Whether neurally-mediated vasodilatation may contribute to exercise hyperemia has not been completely understood. Bülbring and Burn (1935) found for the first time the existence of sympathetic cholinergic nerve to skeletal muscle contributing to vasodilatation in animals. Blair et al. (1959) reported that atropine-sensitive vasodilatation in skeletal muscle appeared during arousal behavior or mental stress in humans. However, such sympathetic vasodilator mechanism for muscle vascular bed in humans is generally denied at present, because surgical sympathectomy, autonomic blockade, and local anesthesia of sympathetic nerves cause no substantial influence on vasodilatation in muscle not only during mental stress but also during exercise. On the other hand, neural mechanisms may play an important role in regulating blood flow to non-contracting muscle. Careful consideration of the neural mechanisms may lead us to an insight about a possible neural mechanism responsible for exercise hyperemia in contracting muscle. Referring to our recent study measuring muscle tissue blood flow with higher time resolution, this review has focused on whether or not central command may transmit vasodilator signal to skeletal muscle especially at the onset of voluntary exercise.

Melatonin differentially affects vascular blood flow in humans

Melatonin is synthesized and released into the circulation by the pineal gland in a circadian rhythm. Melatonin has been demonstrated to differentially alter blood flow to assorted vascular beds by the activation of different melatonin receptors in animal models. The purpose of the present study was to determine the effect of melatonin on blood flow to various vascular beds in humans. Renal (Doppler ultrasound), forearm (venous occlusion plethysmography), and cerebral blood flow (transcranial Doppler), arterial blood pressure, and heart rate were measured in 10 healthy subjects (29±1 yr; 5 men and 5 women) in the supine position for 3 min. The protocol began 45 min after the ingestion of either melatonin (3 mg) or placebo (sucrose). Subjects returned at least 2 days later at the same time of day to repeat the trial after ingesting the other substance. Melatonin did not alter heart rate and mean arterial pressure. Renal blood flow velocity (RBFV) and renal vascular conductance (RVC) were lower during the melatonin trial compared with placebo (RBFV, 40.5±2.9 vs. 45.4±1.5 cm/s; and RVC, 0.47±0.02 vs. 0.54±0.01 cm·s(-1)·mmHg(-1), respectively). In contrast, forearm blood flow (FBF) and forearm vascular conductance (FVC) were greater with melatonin compared with placebo (FBF, 2.4±0.2 vs. 1.9±0.1 ml·100 ml(-1)·min(-1); and FVC, 0.029±0.003 vs. 0.023±0.002 arbitrary units, respectively). Melatonin did not alter cerebral blood flow measurements compared with placebo. Additionally, phentolamine (5-mg bolus) after melatonin reversed the decrease in RVC, suggesting that melatonin increases sympathetic outflow to the kidney to mediate renal vasoconstriction. In summary, exogenous melatonin differentially alters vascular blood flow in humans. These data suggest the complex nature of melatonin on the vasculature in humans.

Metabolic disturbances linked to obesity: the role of impaired tissue perfusion

Associated with elevated risk of cardiovascular events and cancer, obesity is a worldwide problem affecting developed and developing countries. Microcirculatory vessels, represented by arterioles, capillaries and venules (mean internal diameter < 100 microm), are the place where blood/tissue nutrition and exchange effectively take place. Microvascular dysfunction is an early event in obesity probably secondary to endothelial dysfunction and capillaries rarefaction. New research techniques allow the investigation of the microcirculation in different vascular beds in humans. Studies suggest a link between endothelial dysfunction and visceral obesity. Oxidative stress, inflammation and renin-angiotensin system are among factors considered to be involved on microvascular dysfunction in obesity. Microcirculatory impairment present in obesity suggests that it could be an important causal factor in obesity-related disorders such as insulin resistance and hypertension.

Differential distribution of vasa vasorum in different vascular beds in humans

Objective Vasa vasorum (VV) have been implicated to play a role in the pathogenesis of atherosclerosis. This study was designed to describe the distribution of VV density in different vascular beds in humans and to investigate the association between VV density and the known distribution of atherosclerosis in human arteries. Methods Forty-two human arteries, harvested at autopsy or after explantation, were analyzed by three-dimensional microscopic-computed tomography (micro-CT). VV density, endothelial-surface-fraction (Σ VV endothelial-surface-area/vessel-wall-volume) and vascular-area-fraction (Σ VV area/vessel-wall-area) were calculated for coronary, renal and femoral arteries. Representatively five coronary, renal and femoral arteries were stained for endothelial cells (von Willebrand-Factor), macrophages (CD68), vascular endothelial growth factor (VEGF) and collagen (Sirius Red). Results Coronary arteries showed a higher VV density compared to renal and femoral arteries (2.12 ± 0.26 n/mm 2 versus 0.61 ± 0.06 n/mm 2 and 0.66 ± 0.11 n/mm 2; P < 0.05 for both) as well as a higher endothelial-surface-fraction and vascular-area-fraction. Histology showed a positive correlation between histologically derived VV density and CD68-positive cells/area ( r = 0.54, P < 0.01), VEGF-immunoreactivity/area ( r = 0.55, P < 0.01) and a negative correlation between VV density and collagen I content ( r = 0.66, P < 0.05). Conclusion This micro-CT study highlights a higher VV density in coronary than in peripheral arteries, supporting the relation between VV density and the susceptibility to atherosclerosis in different vascular beds in humans.

Vascular Reactions of Iodinated X-Ray Contrast Media: Mechanisms and Possible Therapeutic Interventions

Vascular reactions after administration of all classes of iodinated x-ray contrast media are well known side effects of these drugs. Both vasodilation and vasoconstriction have been observed. The manner and extent of the change in vessel tone depends on the type of contrast medium, species, vascular territory and contractile state of the vessels. The mechanisms underlying the vascular reaction induced by contrast media are currently not completely clear and studies on this question are partly contradictory or non-conclusive. Even if these side effects do not vitally compromise the patients, they are mainly responsible for patients discomfort during examinations. To date, there are only a few possibilities to treat this type of side effect. In this review we describe the effects of high osmolar ionic, low osmolar non-ionic and isotonic contrast media on different vascular beds in humans and animals. Data from clinical and in vivo studies as well as from in vitro investigations on isolated organs and isolated vessel segments will be discussed. It will give an overview of the mechanistic explanations of the vascular reactions.

Early changes in vascular dynamics in relation to twin-twin transfusion syndrome.

A clearer understanding of the early determinants of normal and abnormal vascular development is pivotal in order to identify those at increased risk of later vascular disease, and perhaps to prevent it by early intervention. Measurement of pulse wave velocity(PWV) has been used in the postnatal evaluation of the monochorionic(MC) twins. They are genetically identical and those with twin-twin transfusion syndrome(TTTS) provide an ideal natural model in whom to study the influence of differing haemodynamic stresses on the developing vascular tree. We investigated firstly whether surviving twin pairs with TTTS have altered arterial distensibility in childhood by comparing PWV in the radial arteries of surviving MC twin pairs with TTTS and in two control groups, one cohort of MC twins without TTTS and another dichorionic group (DC) Secondly, we tested a cohort of TTTS twin pair survivors treated with laser photocoagulation. The co-twin pairs in the group managed palliatively with amnioreduction showed increased PWV in the donor and reduced PWV in the recipient twins. This was neither seen in the laser-treated, nor in the control groups. Our studies suggest that a period of haemodynamic imbalance gives rise to changes in a muscular conduit artery that persist at least into infancy and it seems that by correcting the abnormal haemodynamics relatively soon after the disease process had begun, the alterations in elasticity are prevented. These studies are the first to demonstrate fetal programming of the vascular bed in humans, and prevention or reversal of this programming by an intervention in mid-gestation.

Early Changes in Vascular Dynamics in Relation to Twin-Twin Transfusion Syndrome

AbstractAclearer understanding of the early determinants of normal and abnormal vascular development is pivotal in order to identify those at increased risk of later vascular disease, and perhaps to prevent it by early intervention. Measurement of pulse wave velocity(PWV) has been used in the postnatal evaluation of the monochorionic(MC) twins. They are genetically identical and those with twin-twin transfusion syndrome(TTTS) provide an ideal natural model in whom to study the influence of differing haemodynamic stresses on the developing vascular tree. We investigated firstly whether surviving twin pairs with TTTS have altered arterial distensibility in childhood by comparing PWV in the radial arteries of surviving MC twin pairs with TTTS and in two control groups, one cohort of MC twins without TTTS and another dichorionic group (DC) Secondly, we tested a cohort of TTTS twin pair survivors treated with laser photocoagulation. The co-twin pairs in the group managed palliatively with amnioreduction showed increased PWV in the donor and reduced PWV in the recipient twins. This was neither seen in the laser-treated, nor in the control groups. Our studies suggest that a period of haemodynamic imbalance gives rise to changes in a muscular conduit artery that persist at least into infancy and it seems that by correcting the abnormal haemodynamics relatively soon after the disease process had begun, the alterations in elasticity are prevented. These studies are the first to demonstrate fetal programming of the vascular bed in humans, and prevention or reversal of this programming by an intervention in mid-gestation.

Evaluation of Endothelium-Dependent Vasodilation in Humans

Ever since nitric oxide (NO) was discoverd to be a powerful endothelium-derived vasorelaxing substance, a number of methods have been developed to investigate the role of NO in the vasodilatory process in humans. The present review discusses the advantages and limitations of the three most commonly used techniques to assess endothelium-dependent vasodilation (EDV) in the coronary circulation, the brachial artery, and in the forearm circulation. Furthermore, six less established methods for the evaluation of EDV in different vascular beds in humans are presented.

In vitro contractile and relaxant responses of human resistance placental stem villi arteries of healthy parturients: role of endothelium.

As feto-placental vessels in humans are not innervated, regulation of vascular tone in the fetal extracorporeal circulation most likely depends on either circulating hormones or local paracrine mechanisms. However, the latter have not yet been fully investigated. The aim of our study was to characterize vasomotor behaviour of resistance stem villi arteries when challenged with various constrictor and dilator agents, with special emphasis on the physiological importance of endothelium. The latter is poorly characterized in this particular vascular bed in humans. Villous stem arterial rings (internal diameter 182 +/- 6 microns) were isolated under microscopy from term human placentae obtained after cesarean section. The vessels were mounted as ring preparations in an isometric myograph for tension measurements. Endothelium was removed from some of the rings by gentle insertion of a knotted human hair into the vascular lumen. Of the three vasoconstrictors tested, endothelin-1 (ET-1) showed the greatest potency, being 1,000 times more potent than serotonin and phenylephrine. The classical endothelium-dependent vasodilators, acetylcholine, adenosine diphosphate (ADP) and histamine, caused dose-dependent relaxation of the rings; an effect which was completely abolished by the removal of endothelium. Pre-treatment with the nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine, also markedly reduced the endothelium dependent relaxant responses to ADP. By contrast, the vasodilatory response to sodium nitroprusside was not affected by endothelial removal. We conclude that i) ET-1 is a potent vasoconstrictor of the human placental vascular bed and ii) placental villous endothelial cells synthesize and release relaxing factor(s) which could possibly be NO.

Doppler continuous-wave analysis of grafted mammary artery as a non-invasive technique for static and dynamic assessment of coronary flow in man

In this paper, Doppler continuous-wave analysis of blood velocity in the internal mammary artery, anastomosed to the left coronary vascular bed in humans who have undergone myocardial revascularization, is proposed as a non-invasive technique to study coronary blood flow during physiological procedures which cause it to change. Blood velocity curves obtained in normal and anastomosed internal mammary arteries were compared during hyperventilation and the Valsalva manoeuvre. During hyperventilation, blood velocity increased in the normal mammary but not in the anastomosed artery. During the expiratory effort of the Valsalva manoeuvre, the mean blood velocity decreased in the normal mammary artery but it did not change significantly in the anastomosed artery. Variations in the mean velocity were largely prevented by simultaneous and well-balanced increases and decreases in the diastolic and systolic velocities, respectively.

Estimation of regional metabolism and production of angiotensins in hypertensive subjects.

1. We attempted to collect information on the metabolism and production of angiotensins (ANG) in different vascular beds in humans by constant i.v. infusion of mono-iodinated [125I]-ANG I into subjects with essential hypertension, at the time of renal vein catheterization as part of the diagnostic work-up for renovascular hypertension. 2. Blood samples were taken from the aorta and the renal, antecubital, femoral and hepatic veins. ANG I, ANG II, [125I]-ANG I and [125I]-ANG II were extracted from plasma, separated by h.p.l.c. and quantitated by radio-immunoassay or gamma counting. 3. Our studies so far are restricted to subjects on captopril 50 mg twice daily. Under ACE inhibition (4-6 h after dosing of captopril) no differences in elimination half-life and regional extraction were found between infused [125I]-ANG and unlabelled ANG I. Extraction of arterially delivered [125I]-ANG I was 80% in the kidney, 45% in the forearm, 58% in the leg and 95% in the hepato-mesenteric vascular bed. 4. Measurements of arterial and venous [125I]-ANG II levels indicated that [125I]-ANG I-II conversion had occurred in the cardio-pulmonary vascular bed. 5. ANG I production in the hepato-mesenteric region could be largely accounted for by the renin activity of circulating plasma, but in kidney and limbs only 20-30% of regionally produced ANG I could be accounted for by plasma renin activity. 6. Thus, a major fraction of regionally produced ANG I appears to be formed locally, i.e. not in circulating plasma.(ABSTRACT TRUNCATED AT 250 WORDS)