Blood Flow In Normal Subjects Research Articles

Assessment of cranial blood flow in cervical spondylosis patients

Background: The effect of rotation of head movement on cerebral artery blood flow in normal subjects has been widely studied. Many factors effect blood flow through the vertebral artery such as rotation of head, variably sized arteries, atheroma, tortuous vertebral arteries, carotid sinus compression etc. Objective: To determine the effect of head and neck movement on the cranial blood flow in cervical spodylosis patients with reticulopathy. Material and methods: Fifty participants (23 male, 27female) with informed consent (20-70 years) participated in this study. Subjects with severe hypertension, cardiovascular, liver, kidney or other life threatening diseases were excluded. The changes in the Anterior, Middle, and Posterior cerebral arteries blood flow between the neutral (face to front) and rotated head positions (flexion and extension) was measured with Trans-cranial Doppler Method in healthy and Cervical Spondylosis with reticulopathy patients. Results: No significant differences in the afferent cerebral blood flow of the neutral and of the changed head positions in cervical spondylosis patient was found. In Cervical Spodylosis patients with reticulopathy, the mean values of cerebral blood flow were insignificantly different as compared to neutral position, however according to the data collected till now, the lowest blood inflow level was recorded during extension of the head. Flow changes were less than 10% considered to be normal. Conclusion: The flow changes in the afferent cerebral arteries of healthy subjects were insignificant. When a person has cervical spondylosis with reticulopathy, flexion and extension of head may diminish blood flow through the vertebral artery in its course through the cervical spine. Further studies and data are required to establish association. Keywords: Cervical spondylosis, Cranial blood flow, TCD

Effects of the acupoints PC 6 Neiguan and LR 3 Taichong on cerebral blood flow in normal subjects and in migraine patients.

Acupuncture has been proven to be effective in the treatment of various cardiovascular disorders; it acts both on the peripheral flow and on the cerebral flow. Our study aimed to evaluate the effects of the insertion of PC 6 Neiguan and LR 3 Taichong acupoints on the cerebral blood flow (CBF) in the middle cerebral artery (MCA). These effects were measured in a group of patients suffering from migraine without aura (Group M) and in a healthy control group (Group C). In the study, we included 16 patients suffering from migraine without aura, classified according to the criteria of the International Headache Society, and 14 healthy subjects as a control group. The subjects took part in the study on two different days, and on each day, the effect of a single acupoint was evaluated. Transcranial Doppler was used to measure the blood flow velocity (BFV) in the MCA. Our study showed that the stimulation of PC 6 Neiguan in both groups results in a significant and longlasting reduction in the average BFV in the MCA. After pricking LR 3 Taichong, instead, the average BFV undergoes a very sudden and marked increase; subsequently, it decreases and tends to stabilize at a slightly higher level compared with the baseline, recorded before needle insertion. Our data seem to suggest that these two acupoints have very different effects on CBF. The insertion of PC 6 Neiguan probably triggers a vasodilation in MCA, while the pricking of LR 3 Taichong determines a rapid and marked vasoconstriction.

Literature search and review related to specific preparatory work in the establishment of Dietary Reference Values for Phosphorus, Sodium and Chloride

Literature search and review related to specific preparatory work in the establishment of Dietary Reference Values for Phosphorus, Sodium and Chloride

The Influence of Posture Change on Ocular Blood Flow in Normal Subjects, Measured by Laser Speckle Flowgraphy

Purpose: To investigate, using laser speckle flowgraphy (LSFG), the autoregulation of ocular blood flow (BF) in response to posture change.Methods: This study comprised 20 healthy volunteers (mean age 30.0 ± 8.5). The mean blur rate (MBR) of the ocular circulation in the subjects was assessed in both a sitting and a supine position every 2 min over the course of 10 min. Baseline measurements of the MBR at the optic nerve head (ONH) and the choroid were taken in a sitting position. Increases in the MBR ratio in a supine position were calculated with reference to this baseline. Intraocular pressure (IOP), systemic blood pressure and heart rate in the brachial artery were also recorded.Results: In the ONH, the MBR ratio increased significantly over the baseline after 2 min (104.8 ± 5.0%, p = 0.001) and 4 min (104.4 ± 5.6%, p = 0.005), in a supine position, but decreased to the initial level after only 6 min. In the choroid, on the other hand, while the MBR ratio also increased significantly after 2 min in a supine position (113.7 ± 8.1%, p < 0.001), it kept this significant increase over the time course of 10 min. After 10 min in a supine position, IOP increased significantly (p < 0.001), systolic blood pressure decreased significantly (p < 0.001), but diastolic blood pressure did not change significantly compared to the baseline. (p = 0.07)Conclusions: ONH and choroidal circulation have significantly different hemodynamics in response to posture change in healthy volunteers. This finding suggests that LSFG enables us to assess the autoregulation of BF in the ONH.

Pilot Study of Optical Coherence Tomography Measurement of Retinal Blood Flow in Retinal and Optic Nerve Diseases

To investigate blood flow changes in retinal and optic nerve diseases with Doppler Fourier domain optical coherence tomography (OCT). Sixty-two participants were divided into five groups: normal, glaucoma, nonarteritic ischemic optic neuropathy (NAION), treated proliferative diabetic retinopathy (PDR), and branch retinal vein occlusion (BRVO). Doppler OCT was used to scan concentric circles of 3.4- and 3.75-mm diameters around the optic nerve head. Flow in retinal veins was calculated from the OCT velocity profiles. Arterial and venous diameters were measured from OCT Doppler and reflectance images. Total retinal blood flow in normal subjects averaged 47.6 μL/min. The coefficient of variation of repeated measurements was 11% in normal eyes and 14% in diseased eyes. Eyes with glaucoma, NAION, treated PDR, and BRVO had significantly decreased retinal blood flow compared with normal eyes (P < 0.001). In glaucoma patients, the decrease in blood flow was highly correlated with the severity of visual field loss (P = 0.003). In NAION and BRVO patients, the hemisphere with more severe disease also had lower blood flow. Doppler OCT retinal blood flow measurements showed good repeatability and excellent correlation with visual field and clinical presentations. This approach could enhance our understanding of retinal and optic nerve diseases and facilitate the development of new therapies.

Transcorneal electrical stimulation increases chorioretinal blood flow in normal human subjects

PurposeThe aim of this article is to investigate the effect of transcorneal electrical stimulation (TES) on chorioretinal blood flow in healthy human subjects.MethodsThe chorioretinal blood flow of 10 healthy subjects was measured before and after TES by laser speckle flowgraphy and expressed as the square blur rate (SBR). The chorioretinal blood flow was determined before and immediately after TES and 0.5, 1, 1.5, 2, 2.5, 3, 24, and 40 h after TES in three different areas: the margin of the optic disc, a point located midway between the optic disc and macula, and the macula area. The SBR of the stimulated eye is expressed relative to the value of the fellow eye. The mean standardized blur ratio was calculated as the ratio of the standardized SBR to the baseline SBR. The changes of intraocular pressure (IOP), blood pressure (BP), and pulse rate (PR) were determined after each measurement of the SBR. The ocular perfusion pressure (OPP) was calculated from BP and IOP.ResultsThe mean standardized blur ratio at the optic disc did not change significantly throughout the course of the experiment. However, the mean standardized blur ratio midway between the optic disc and macula and at the macula area were significantly higher after TES than that after sham stimulation at 3 and 24 h (P < 0.05, P < 0.01, respectively). At all times, the mean BP, PR, IOP, and OPP were not significantly different from the prestimulation values.ConclusionsTES increases the chorioretinal blood flow in normal subjects with minimal effects on the systemic blood circulation and the IOP. The increase in chorioretinal blood flow may be one of the beneficial effects that TES has on ischemic retinal diseases.

Absence of Gravity-Dependent Modulation of Straight Sinus Flow Velocity in Healthy Humans

The influence of whole-body positions on the cerebral blood flow in normal subjects is unclear. Blood flow in cerebral veins and sinuses is continuous, pulsatile and proportional to cerebral blood flow. We examined young healthy volunteers to evaluate peak mean flow velocity (vm) in the straight sinus (SS) assessed by transcranial Doppler sonography in predefined variations of the whole-body pitch position relative to gravity in the presence of a normal (normocarbia) and an impaired (hypercarbia) cerebral autoregulation. A 2 MHz ultrasound probe was fixed with a headband nearby the protuberantia occipitalis externa. Fifteen subjects were seated in a motorized three-dimensional turntable. Vm-SS, blood pressure and heart rate were monitored in five whole-body pitch positions from upright (0°) to “20° head-hanging” (110°): 0, 30, 60, 90 and 110°. The experiment was repeated during the inspiration of 5% CO 2. Of 15 subjects, 14 showed reliable ultrasound data; the results of one subject with movement artifacts were excluded. Vm-SS values under normocarbia (hypercarbia) were 23.9 ± 4.2 cm/s (40.9 ± 6.7 cm/s) at 0°, 23.1 ± 5.0 cm/s (38.0 ± 5.0 cm/s) at 30°, 24.9 ± 5.1 cm/s (39.9 ± 3.3 cm/s) at 60°, 29.2 ± 8.5 cm/s (41.0 ± 4.7 cm/s) at 90° and 27.0 ± 11.6 cm/s (43.6 ± 12.1 cm/s) at 110°. Vm-SS measured under normocarbia ( p = 0.09) and hypercarbia ( p = 0.25) were not affected while subjects were positioned from upright toward “20° head-hanging”, whereas blood pressure and heart rate decreased ( p < 0.01). Our results suggest that changes of whole-body position from upright to “20° head-hanging” do not alter cerebral blood flow in healthy subjects. (E-mail: Ralf.Baumgartner@usz.ch)

Pattern electroretinogram in glaucoma

Several studies have shown that the pattern electroretinogram, a direct, objective method of measuring retinal ganglion cell function, is altered early in ocular hypertension and glaucoma. Renewed interest in the pattern electroretinogram for early detection of pre-perimetric glaucoma has been sparked by noninvasive and reproducible methods of recording using skin electrodes. With the noninvasive pattern electroretinogram, response abnormalities have been detected in up to 50% of glaucoma suspects with normal standard perimetry. In early glaucoma (with either normal or high intraocular pressure), a reduction of intraocular pressure has sometimes yielded improvement in pattern electroretinogram amplitude. A prolonged steady-state stimulus presentation reduces the pattern electroretinogram amplitude and increases optic nerve blood flow in normal subjects, suggesting that sustained activity of retinal ganglion cells is physiologically associated with autoregulatory changes of the neural-vascular system. It is unknown whether this autoregulation is altered in glaucoma. The multifocal pattern electroretinogram does not seem to have an advantage over the pattern electroretinogram in the early detection of glaucoma. The photopic negative response of the diffuse flash electroretinogram has shown changes in glaucoma, but may not be able to detect retinal dysfunction in normal tension glaucoma. The pattern electroretinogram is a noninvasive, direct, objective method that may be useful to clinicians in detecting early retinal ganglion cell dysfunction in glaucoma suspects. The pattern electroretinogram may also optimize treatment strategies based on improvement of retinal ganglion cell function.

Time-resolved 3-dimensional velocity mapping in the thoracic aorta: visualization of 3-directional blood flow patterns in healthy volunteers and patients.

An analysis of thoracic aortic blood flow in normal subjects and patients with aortic pathologic findings is presented. Various visualization tools were used to analyze blood flow patterns within a single 3-component velocity volumetric acquisition of the entire thoracic aorta Time-resolved, 3-dimensional phase-contrast magnetic resonance imaging (3D CINE PC MRI) was employed to obtain complete spatial and temporal coverage of the entire thoracic aorta combined with spatially registered 3-directional pulsatile blood flow velocities. Three-dimensional visualization tools, including time-resolved velocity vector fields reformatted to arbitrary 2-dimensional cut planes, 3D streamlines, and time-resolved 3D particle traces, were applied in a study with 10 normal volunteers. Results from 4 patient examinations with similar scan prescriptions to those of the volunteer scans are presented to illustrate flow features associated with common pathologic findings in the thoracic aorta. Previously reported blood flow patterns in the thoracic aorta, including right-handed helical outflow, late systolic retrograde flow, and accelerated passage through the aortic valve plane, were visualized in all volunteers. The effects of thoracic aortic disease on spatial and temporal blood flow patterns are illustrated in clinical cases, including ascending aortic aneurysms, aortic regurgitation, and aortic dissection. Time-resolved 3D velocity mapping was successfully applied in a study of 10 healthy volunteers and 4 patients with documented aortic pathologic findings and has proven to be a reliable tool for analysis and visualization of normal characteristic as well as pathologic flow features within the entire thoracic aorta.

Chromametric Assessment of Nasal Mucosal Color and Its Application in Patients with Nasal Allergy

The color of the nasal mucosa was evaluated quantitatively in patients with nasal allergy and was compared with that in normal subjects. The chromaticity of the inferior turbinate was measured with the aid of a chromometer coupled with a light projection unit. Chromaticity was indicated by two parameters: the x and y values, which indicate the proportions of the red and green components of a color, respectively. Subjects included patients with Japanese cedar pollinosis (CP; n = 70) and perennial allergic rhinitis (PAR; n = 49), and normal subjects (n = 60). Mucosal blood flow in the inferior turbinate also was measured with a laser Doppler flowmeter in normal subjects. In normal subjects, the x value ranged between 0.4013 and 0.4539, and they value ranged between 0.3065 and 0.3379. The averages of the x and y values were 0.4264 +/- 0.0119 and 0.3204 +/- 0.0067, respectively. Age and sex were not related to the chromaticity value. Application of 0.1% epinephrine (0.12 mL) by aerosol spray decreased the x value significantly, in association with a significant decrease in blood flow in normal subjects. The x value of chromaticity in PAR patients was significantly lower than that in normal subjects; this showed the reduced red component of the color. There was no significant difference in the y value between PAR patients and the normal group. In the CP group, the x and y values were not significantly different from values in normal subjects. However, the x value in the first week after the onset of symptoms was significantly greater than that in the normal group. It subsequently decreased to the normal level in the second week and fell to a significantly lower level thereafter. This study found that the chromaticity of the nasal mucosa reflects local blood flow and that the circulatory dynamics in CP patients changes with time luring the pollinosis season.

Insulin-induced increment of coronary flow reserve is not abolished by dexamethasone in healthy young men.

Hyperinsulinemia is a risk factor for coronary artery disease. Previous studies have reported that hyperinsulinemia increases cardiac and skeletal muscle sympathetic nerve activity and skeletal muscle blood flow in normal subjects. However, little is known about insulin's effects on myocardial blood flow in humans. The purpose of this study was to investigate whether physiological hyperinsulinemia affects myocardial blood flow and flow reserve in healthy subjects. Additionally, the role of the sympathetic nervous system in regulating insulin's effects on coronary perfusion was tested. We used positron emission tomography and oxygen-15-labeled water to measure myocardial blood flow and coronary flow reserve in 16 healthy nonobese men (age, 34 +/- 4 yr; maximal aerobic capacity, 32 +/- 3 mL x g(-1) x min(-1); blood pressure, 118 +/- 10/65 +/- 8 mm Hg) at fasting and during euglycemic hyperinsulinemic clamp (1 mU x kg(-1) x min(-1) for 80 min). To study the role of the sympathetic nervous system, each subject was studied twice: once after administration of dexamethasone (dexa+) for 2 days (2 mg per day) and once without previous medication (dexa-). All studied subjects had normal left ventricular mass, function, and findings in stress echocardiography. Resting myocardial blood flow was 0.76 +/- 0.19 mL x g(-1) x min(-1), and a significant increase in flow was detected after adenosine infusion (140 microg/kg x min for 5 min i.v.), both in the basal fasting state (P < 0.001) and during hyperinsulinemia (P < 0.001). However, the flow response to adenosine was significantly higher during hyperinsulinemia, thus leading to a higher hyperemic flow (3.38 +/- 0.97 vs. 4.28 +/- 1.57 mL x g(-1) x min(-1), basal vs. hyperinsulinemic, P < 0.01) and higher coronary flow reserve (4.6 +/- 1.2 vs. 5.8 +/- 1.9, respectively, P < 0.05). Pretreatment with dexamethasone did not significantly change the resting blood flow [0.72 +/- 0.22 vs. 0.76 +/- 0.19 mL x g(-1) x min(-1), dexa+ vs. dexa-, not significant (NS)], the adenosine stimulated flow (3.56 +/- 1.49 vs. 3.38 +/- 0.97 mL x g(-1) x min(-1), respectively, NS), or the hyperinsulinemic adenosine-stimulated blood flow (4.68 +/- 1.74 vs. 4.28 +/- 1.57 mL x g(-1) x min(-1), respectively, NS). Coronary flow reserves in the basal state (5.3 +/- 2.7 vs. 4.6 +/- 1.2 mL x g(-1) x min(-1), dexa+ vs. dexa-, NS) and during hyperinsulinemia (6.8 +/- 2.9 vs. 5.8 +/- 1.9 mL x g(-1) x min(-1), respectively, NS) tended to be (but were not) significantly higher after dexamethasone treatment. These results demonstrate that insulin acts as a vasodilatory hormone also in the coronary vasculature. Because the insulin-induced increment of myocardial flow reserve remained unchanged by dexamethasone pretreatment, centrally mediated sympathetic activation seems not to play a major role in regulating insulin action on myocardial perfusion in healthy subjects.

Hand gripping effect on cerebral blood flow in normal subjects

The changes of regional cerebral blood flow (rCBF) related to metabolic demand depend on both integrity of neuronal function and vascular blood flow. Therefore, we assessed the motor stimulus to blood flow velocity (BFv) changes of bilateral middle cerebral arteries (MCA) by transcranial Doppler (TCD) sonography in normal subjects. Eighteen subjects (nine female, aged 48.0±3.8 years; nine male, aged 54.4±4.8 years) were investigated. Bilateral TCD sonography from both MCA were monitored during ten cycles of 20 s when subjects were performing bilateral hand gripping with a frequency of one per second, and subsequently 20 s when they were rest. Bilateral hand gripping showed a significant BFv increase on both MCA ( P<0.001). These values were (19±2)% on both sides. There was no significant side to side difference between the absolute BFv values both at rest and during bilateral hand gripping. Additionally, the absolute BFvs and BFv increases were not significantly different between male and female subjects. This study was based on a small sample size, and the method requires the subject cooperation. Our results suggest that bilateral hand gripping may affect blood flow in both MCA without side to side differences. Finally, our suggestion is that test might be useful to assess the neurovascular integrity.

The Dose-Response Relationship of Acetazolamide on the Cerebral Blood Flow in Normal Subjects

Background: Acetazolamide (AA) is used to determine the cerebral vasoreactivity (CVR). To investigate whether the usually applied standard dose of 1 g intravenously will guarantee stable test conditions, the dose-response relationship of AA on cerebral blood flow (CBF) and cerebral blood flow velocity (CBFV) in normal subjects was determined. Methods: In 59 healthy volunteers, rCBF was measured with a ¹³³Xenon inhalation device, and CBFV of the middle cerebral artery (MCA) by transcranial Doppler sonography. The first CBF measurement was taken at rest, the second 15 min after application of AA at a dosage of 5, 10, 13, 15 and 18 mg/kg of body weight, respectively. The CBFV (n = 52) of the middle cerebral artery on the side of the better temporal window was taken 25 min after application of AA 13 mg/kg. In order to determine the side effects of AA, statements of an additional 172 patients were included. Results: A significant dosage dependence of AA on the CBF (fast flow and initial slope index) exists between 5 and 18 mg/kg intravenously. After AA 13 mg/kg, the fast flow increases from 70.8 ± 10.8 to 110.1 ± 13.5 ml/100 g/min, the initial slope index from 46.5 ± 5.4 to 62.8 ± 5.8, and the CBFV from 51.5 ± 8.5 to 85.4 ± 14.2 cm/s. The CVR of CBF and CBFV ascertained that way shows an age dependence equivalent to the situation at rest. Severity and frequency of side effects are dosage-dependent, significantly in part, but reversible without exception. Conclusion: For the determination of CVR of CBF with AA, a dosage related to body weight is required. The usually applied standard dose of 1 g intravenously is not sufficient for standardized test conditions. For evaluation of the results obtained, the apparent age dependence of CVR must be taken into account. Because of the severity of side effects occurring at a higher dose, an AA dosage of 13 mg/kg intravenously is recommended.

Lower extremity volumetric arterial blood flow in normal subjects

The objective of this clinical study was to establish normal values for volumetric blood flow in the leg at rest using Doppler ultrasound, and to determine what biophysical factors influence resting volumetric flow. Arterial blood flow was measured at four sites in the legs of 40 healthy subjects using an ATL Ultramark 9 HDI® system. All subjects were nonhypertensive nonsmokers with ankle brachial index values greater than 1 and no history of vascular disease. The subjects, 20 of each gender, in age ranging from 20 to 64 y were examined. Blood flow was calculated from the time-averaged, intensity-weighted mean velocity Doppler waveforms and vessel cross-sectional area at the same site. Thigh and calf circumference measurements were used to estimate muscle masses. The mean flow and standard error measured in four arteries in the leg were: 284 ± 21 mL/min in the common femoral (CFA); 152 ± 10 mL/min in the superficial femoral (SFA); 72 ± 5 mL/min in the popliteal; and 3 ± 1 mL/min in the dorsalis pedis. Although women tended to have higher time-averaged mean velocities in the CFA and SFA than men ( t-test, p < 0.008), their arterial cross-sectional areas tended to be smaller ( t-test, p < 0.004) and no statistically significant difference was found between men and women in volumetric flow at any site. No correlation was found between age, weight, height, muscle mass and volumetric flow at all four sites. These estimates of lower extremity volumetric flow in healthy subjects provide a baseline for future studies of flow rates in patients with vascular disease.

Effect of salt-loading on blood pressure, insulin sensitivity and limb blood flow in normal subjects

1. The aim of this study was to determine the effects of high (220 mmol/day) and low (40 mmol/day) salt intake for 6 days on blood pressure, leg blood flow and insulin sensitivity in 18 healthy normotensive subjects. 2. Twenty-four-hour ambulatory blood pressure was measured at baseline, during salt-loading and salt-depletion. Insulin sensitivity was determined by a two-step euglycaemic-hyperinsulinaemic clamp (low and high insulin infusion rates: 40 and 600 m-unit.min-1.m-2 respectively) and leg blood flow by plethysmography. 3. Salt-loading resulted in changes in weight [change between salt-loading and salt-restriction: delta=+0.45 (S.D. +/-0.69) kg, P=0.015], plasma renin [delta=-11.5 (S.D.+/-12.9) micro-units/l, P=0.001] and urinary noradrenaline [delta=-8.6 (S.D. +/-18.7) nmol/mmol creatinine, P=0.05]. There were borderline significant increases in 24-h systolic blood pressure [delta=+5.8 (S. D.+/-14.2) mmHg, P=0.06] and plasma volume [delta=+0.29 (S.D.+/-0. 67) litres, P=0.08]. 4. Insulin sensitivity was similar in both salt states. Geometric mean metabolic clearance rate of low-dose insulin: low salt, 5.13 (S.D.x//1.35) dl/min; high salt, 4.94 (S.D.x//1.37) dl/min, P=1.0. Geometric mean metabolic clearance rate of high-dose insulin: low salt, 9.68 dl/min (S.D.x//1.30); high salt, 9.68 (S.D. x//1.27) dl/min, P=0.69. 5. Leg blood flow response to high-dose insulin on high salt increased significantly compared with low salt. Percentage change of blood flow on low salt, delta=+36.6 (S.D.+/-22. 9)% versus high salt, delta=+66.8 (S.D.+/-52.2)%, P=0.03. 6. There were no significant relationships between salt-related changes in limb blood flow and changes in insulin sensitivity at either insulin infusion rate. 7. We conclude that salt-loading, despite changing body weight, the renin-angiotensin-aldosterone system, urinary noradrenaline and the leg blood flow response to insulin, has no significant effect on insulin sensitivity. Salt-loading causes dissociated effects on insulin-induced vasodilatation and glucose disposal.

Effect of salt-loading on blood pressure, insulin sensitivity and limb blood flow in normal subjects

Effect of salt-loading on blood pressure, insulin sensitivity and limb blood flow in normal subjects

Cutaneous vascular response to calcitonin gene‐related peptide in psoriasis and normal subjects

To determine whether cutaneous blood vessels in subjects with psoriasis possess a generalized inherently abnormal response to neuropeptides, the effect of three doses of intradermally injected calcitonin gene-related peptide (CGRP) on skin blood flow in normal subjects (n = 10), and on clinically normal skin (greater than 5 cm from psoriatic lesions) in subjects with psoriasis (n = 9) was measured using a laser Doppler technique. Calcitonin gene-related peptide caused a dose-dependent increase in local blood flow in both psoriatic and normal subjects, which was not statistically different between the two groups. This study has shown that the cutaneous vasculature at sites distant from lesions of psoriasis (> 5 cm) is not inherently different from normal skin in its response to CGRP.

Postischemic hyperemia in subjects with lower limbs obstructive arteriopathy: role of PGI2 and endothelin.

The physiological basis of postischemic hyperemia is not yet fully understood. The present study investigated the effects of pharmacologic manipulation of the prostaglandin system on local hemodynamics. Strain-gauge plethysmography was used to study 8 normal subjects and 9 patients with obliterating arterial disease of the lower limbs. Hemodynamic evaluations were performed before treatment, after seven days of low-dose acetylsalicylic acid (100 mg/day) to inhibit platelet thromboxane synthesis, and after acute infusion of 1 g of acetylsalicylic acid to inhibit endothelial prostacyclin synthesis. In patients with arterial disease, the hemodynamic study was also carried out after infusion of iloprost, a synthetic prostacyclin analogue. Acute infusion of acetylsalicylic acid significantly reduced basal blood flow in normal subjects, but not in patients with arterial disease. In the latter group, iloprost affected neither basal nor maximal postischemic flow. The study also evaluated the role of endothelin in musculocutaneous hemodynamic regulation, both in physiological conditions and in atherosclerosis. This part of the study addressed the possibility that the hemodynamic effects of vasodilator prostanoids like prostacyclin might affect endothelin release in vivo. During reactive hyperemia, plasma endothelin was reduced in normal subjects (-1.02 pg/mL, 95% CI: -2.23, 0.08), but not in patients with atherosclerosis (-0.35 pg/mL, 95% CI: -1.45, 0.75). In both groups, plasma endothelin was not affected by aspirin. These findings confirm the role of prostacyclin in local hemodynamic regulation. In the normal subject, musculocutaneous blood flow seems to depend at least in part on the action of vasodilator prostanoids and endothelin. This is not the case in patients with arterial disease, in whom plasma endothelin does not seem to be affected by postischemic changes in blood flow. A possible explanation for this difference could be alteration of the endothelial function in patients with arterial disease, related to the functional and structural characteristics of the artery wall in atherosclerosis.

N-acetylcysteine does not influence the activity of endothelium-derived relaxing factor in vivo.

Nitric oxide forms complexes with an array of biomolecular carriers that retain biological activity. This reactivity of nitric oxide in physiological systems has led to some dispute as to whether endothelium-derived relaxing factors nitric oxide or a closely related adduct thereof, such as a nitrosothiol. In vitro bioassays used to address this question are limited by the exclusion of biological thiols that are requisite for nitrosothiol formation. Thus, the purpose of this study was to obtain insight into the identity of endothelium-derived relaxing factor in vivo. We reasoned that if endothelium-derived relaxing factor in nitric oxide, infusion of physiological concentrations of thiol would potentiate its bioactivity by analogy with effects seen in vitro, whereas nitrosothiol would be resistant to such modulation. We used venous-occlusion plethysmography to study forearm blood flow in normal subjects. Methacholine (0.3 to 10 micrograms/min) and nitroglycerin (1 to 30 micrograms/min) were infused via the brachial artery to elicit endothelium-dependent and endothelium-independent vasodilation, respectively. Dose-response determinations were made for each drug before and after an intra-arterial infusion of the reduced thiol, N-acetylcysteine, at rates estimated to achieve a physiological concentration of 1 mmol/L. Methacholine increased forearm blood flow in a dose-dependent manner. Infusion of N-acetylcysteine did not change the sensitivity (ED50, 1.7 versus 1.7 micrograms/min, P = NS) or maximal response to methacholine. In contrast, thiol increased the sensitivity to nitroglycerin (ED50, 4.7 versus 2.8 micrograms/min, P < .01). Thus, conflicting with reports in vitro, thiol does not modulate endothelium-derived relaxing factor responses in vivo. These data indicate that sulfhydryl groups are not a limiting factor for endothelium-derived relaxing factor responses in forearm resistance vessels in normal humans and are in keeping with reports that nitrosothiol contributes to endothelium-derived relaxing factor bioactivity in plasma and vascular smooth muscle. Potentiation of the effects of nitroglycerin by N-acetylcysteine can be attributed to its enhanced biotransformation to an endothelium-derived relaxing factor equivalent, such as nitrosothiol. These observations support the notion of an equilibrium between nitric oxide and nitrosothiol in biological systems that may be influenced by redox state.

Physical fitness and endothelial function (nitric oxide synthesis) are independent determinants of insulin-stimulated blood flow in normal subjects.

Insulin induces vasodilation via stimulation of nitric oxide (NO) synthesis. This action of insulin exhibits considerable interindividual variation. We determined whether the response of blood flow to endothelium-dependent vasoactive agents correlates with that to insulin or whether other factors, such as physical fitness, limb muscularity, or vasodilatory capacity, better explain variations in insulin-stimulated blood flow. Direct measurements of the forearm blood flow response to three 2-h sequential doses of insulin (1, 2, and 5 mU/ kg.min), endothelium-dependent (acetylcholine and NG-monomethyl-L-arginine) and endothelium-independent (sodium nitroprusside) vasoactive agents, and ischemia (reactive hyperemic forearm blood flow) were performed in 22 normal subjects (age, 24 +/- 1 yr; body mass index, 22.2 +/- 0.6 kg/m2; maximal aerobic power, 40 +/- 2 mL/kg.min). The highest insulin dose increased blood flow by 111 +/- 17%. The fraction of basal blood flow inhibited by NG-monomethyl-L-arginine (NO synthesis-dependent flow) varied from 6-47%. Maximal aerobic power (r = 0.52; P < 0.02), the percentage of forearm muscle (r = 0.50; P < 0.02), and the NO synthesis-dependent flow (r = 0.42; P < 0.05), but not reactive hyperemic, acetylcholine-stimulated, or sodium nitroprusside-stimulated flow, were significantly correlated with insulin-stimulated (5 mU/kg.min) blood flow. In multiple linear regression analysis, 52% of the variation (multiple R = 0.72; P < 0.001) in insulin-stimulated blood flow was explained by NO synthesis-dependent flow (P < 0.005) and the percentage of forearm muscle (P < 0.005). We conclude that endothelial function (NO synthesis-dependent basal blood flow) and forearm muscularity are independent determinants of insulin-stimulated blood flow.