Arterial Forearm Blood Flow Research Articles

Microangiopathy and forearm arterial blood flow in systemic sclerosis: a controlled study.

The aim of the study was to evaluate the interrelationship between the micro- and macrovasculature. This is a cross-sectional study that examined SSc patients and fibromyalgia (FM) patients as controls. We assessed forearm peripheral vascular status and nailfold capillaroscopy. We evaluated the association between nailfold capillaroscopy pattern of microvasculopathy reflected as microangiopathy evolution score and macrovascular changes in the forearm vessels examined by color Doppler ultrasound. We assessed relevant clinical and laboratory data, as well as intima-media thickness (IMT) and internal diameter (ID) in the radial and ulnararteries in millimeters, and calculated the ratio IMT\ID peak systolic velocity and end-diastolic velocity were used for the calculation of the resistance index. We examined 73 patients: 50 patients with SSc and 23 patients with FM. Ten patients with SSc had arterial occlusions compared to 1 among FM patients (p = 0.082). The SSc group had a statistically significantly higher mean IMT to ID ratio (p < 0.001). There was no correlation between microangiopathy evolution score for both hands, RI, or mean IMT/ID ratio. Total microangiopathy evolution score was not associated with arterial occlusions. Our study demonstrated a high prevalence of macrovascular disease in SSc; no correlation was found between microvasculopathy and macrovascular disease, suggesting that different pathogenic mechanisms might operate in different vessels size. Key Points • This study demonstrated a high prevalence of macrovascular arterial forearm disease in systemic sclerosis patients. • This study found no correlation between capillaroscopic microangiopathy evolution score (MES) and macrovascular abnormalities. • Our findings suggest that different pathogenic mechanisms might operate in different vessels size.

Rotigaptide protects the myocardium and arterial vasculature from ischaemia reperfusion injury.

Ischaemia-reperfusion injury (IRI) causes impaired endothelial function and is a major component of the adverse effects of reperfusion following myocardial infarction. Rotigaptide increases gap junction conductance via connexin-43. We tested the hypothesis that rotigaptide reduces experimental myocardial infarction size and ameliorates endothelial IRI in humans. Myocardial infarction study: porcine myocardial infarction was achieved by catheter-induced occlusion of the left anterior descending artery. In a randomized double-blind study, rotigaptide (n=9) or placebo (n=10) was administered intravenously as a 10min bolus prior to reperfusion and continuously during 2h of reperfusion. Myocardial infarction size (IS) was assessed as proportion of the area at risk (AAR). Human translational study: forearm IRI was induced in the presence or absence of intra-arterial rotigaptide. In a randomized double-blind study, forearm arterial blood flow was measured at rest and during intra-arterial infusion of acetylcholine (5-20μgmin(-1) ; n=11) or sodium nitroprusside (2-8mgmin(-1) ; n=10) before and after intra-arterial infusion of placebo or rotigaptide, and again following IRI. Myocardial infarction study: Rotigaptide treatment was associated with a reduction of infarct size (IS/AAR[%]: 18.7±4.1 [rotigaptide] vs. 43.6±4.2 [placebo], P=0.006). Human translational study: Endothelium-dependent vasodilatation to acetylcholine was attenuated after ischaemia-reperfusion in the presence of placebo (P=0.007), but not in the presence of rotigaptide (P=NS). Endothelium-independent vasodilatation evoked by sodium nitroprusside was unaffected by IRI or rotigaptide (P=NS). Rotigaptide reduces myocardial infarction size in a porcine model and protects from IRI-related endothelial dysfunction in man. Rotigaptide may have therapeutic potential in the treatment of myocardial infarction.

Noninvasive optical characterization of muscle blood flow, oxygenation, and metabolism in women with fibromyalgia

IntroductionWomen with fibromyalgia (FM) have symptoms of increased muscular fatigue and reduced exercise tolerance, which may be associated with alterations in muscle microcirculation and oxygen metabolism. This study used near-infrared diffuse optical spectroscopies to noninvasively evaluate muscle blood flow, blood oxygenation and oxygen metabolism during leg fatiguing exercise and during arm arterial cuff occlusion in post-menopausal women with and without FM.MethodsFourteen women with FM and twenty-three well-matched healthy controls participated in this study. For the fatiguing exercise protocol, the subject was instructed to perform 6 sets of 12 isometric contractions of knee extensor muscles with intensity steadily increasing from 20 to 70% maximal voluntary isometric contraction (MVIC). For the cuff occlusion protocol, forearm arterial blood flow was occluded via a tourniquet on the upper arm for 3 minutes. Leg or arm muscle hemodynamics, including relative blood flow (rBF), oxy- and deoxy-hemoglobin concentration ([HbO2] and [Hb]), total hemoglobin concentration (THC) and blood oxygen saturation (StO2), were continuously monitored throughout protocols using a custom-built hybrid diffuse optical instrument that combined a commercial near-infrared oximeter for tissue oxygenation measurements and a custom-designed diffuse correlation spectroscopy (DCS) flowmeter for tissue blood flow measurements. Relative oxygen extraction fraction (rOEF) and oxygen consumption rate (rVO2) were calculated from the measured blood flow and oxygenation data. Post-manipulation (fatiguing exercise or cuff occlusion) recovery in muscle hemodynamics was characterized by the recovery half-time, a time interval from the end of manipulation to the time that tissue hemodynamics reached a half-maximal value.ResultsSubjects with FM had similar hemodynamic and metabolic response/recovery patterns as healthy controls during exercise and during arterial occlusion. However, tissue rOEF during exercise in subjects with FM was significantly lower than in healthy controls, and the half-times of oxygenation recovery (Δ[HbO2] and Δ[Hb]) were significantly longer following fatiguing exercise and cuff occlusion.ConclusionsOur results suggest an alteration of muscle oxygen utilization in the FM population. This study demonstrates the potential of using combined diffuse optical spectroscopies (i.e., NIRS/DCS) to comprehensively evaluate tissue oxygen and flow kinetics in skeletal muscle.

Role of the Endothelium in the Vascular Effects of the Thrombin Receptor (Protease-Activated Receptor Type 1) in Humans

The purpose of this study was to determine the role of the endothelium in the vascular actions of protease-activated receptor type 1 (PAR-1) activation in vivo in man. Thrombin is central to the pathophysiology of atherothrombosis. Its cellular actions are mediated via PAR-1. Protease-activated receptor type 1 activation causes arterial vasodilation, venoconstriction, platelet activation, and tissue-type plasminogen activator release in man. Dorsal hand vein diameter was measured in 6 healthy volunteers before and after endothelial denudation. Forearm arterial blood flow, plasma fibrinolytic factors, and platelet activation were measured in 24 healthy volunteers during venous occlusion plethysmography. The effects of inhibition of prostacyclin, nitric oxide (NO), and endothelium-derived hyperpolarizing factor on PAR-1 responses were assessed during coadministration of aspirin, the "NO clamp" (L-N(G)-monomethyl arginine and sodium nitroprusside), and tetraethylammonium ion, respectively. Endothelial denudation did not affect PAR-1-evoked venoconstriction (SFLLRN; 0.05 to 15 nmol/min). Although aspirin had no effect, SFLLRN-induced vasodilation (5 to 50 nmol/min) was attenuated by the NO clamp (p < 0.0001) and tetraethylammonium ion (p < 0.05) and abolished by their combination (p < 0.01). The NO clamp augmented SFLLRN-induced tissue-type plasminogen activator and plasminogen activator inhibitor type 1 antigen (p < 0.0001) release, but tetraethylammonium ion and aspirin had no effect. SFLLRN-induced platelet activation was unaffected by NO or prostacyclin inhibition. Acting via PAR-1, thrombin causes contrasting effects in the human vasculature and has a major interaction with the endothelium. This highlights the critical importance of endothelial function during acute arterial injury and intravascular thrombosis, as occurs in cardiovascular events including myocardial infarction and stroke.

Effect of graded leg cycling on postischaemic forearm blood flow in healthy subjects

This study assessed in healthy subjects, the effect of leg cycling on the forearm vascular responses to ischaemia to confirm previous results showing that exercise-induced sympathetic activation during leg cycling reduced postischaemic forearm hyperaemia. Seven young healthy subjects performed two bouts of cycling exercises at 50% and 80% of their maximal aerobic capacity (Ex(50), Ex(80) respectively) during which forearm arterial blood flow was successively occluded for 40, 90 and 180 s. Control forearm blood flow (FBF) and postischaemic forearm blood flow (pi-FBF) measured at the release of arterial occlusions were assessed using plethysmography. Digital arterial pressure was continuously monitored allowing calculation of control and postischaemic forearm conductance (FC and pi-FC respectively). At rest, pi-FBF increased with the duration of ischaemia (5 +/- 1, 19 +/- 3, 29 +/- 3, 31 +/- 4 ml min(-1) 100 ml(-1) after 0, 40, 90 and 180 s of ischaemia respectively). During Ex(50), FBF and pi-FBF did not change significantly although pi-FC was significantly reduced (Deltapi-FC = -39%, -33%, -27% for 40, 90, 180 s of ischaemia respectively). During Ex(80), there was a further dramatic decrease in pi-FC (-53%, -66%, -62% from rest) and pi-FBF were largely blunted (13 +/- 4 versus 19 +/- 3, 14 +/- 4 versus 29 +/- 3, 17 +/- 5 versus 31 +/- 4 ml min(-1) 100 ml(-1)). These results demonstrated that forearm responses to ischaemia depended on leg activities. It was suggested that exercise-induced sympathetic activation may have interfered on local vasodilatation because of ischaemia.

Acute effects of haemodialysis on biochemical modulators of endothelial function

To assess the acute effects of haemodialysis (HD) on biochemical factors modulating endothelial function. Academic medical centre. Forty patients (age 63.5 +/- 2.2 years, mean +/- SEM) undergoing HD. Folic acid (F), homocysteine (tHcy), asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (CRP) and malondialdehyde (MDA) were measured pre-HD, 1 h after commencing HD and within the last hour of HD (end-HD). Endothelium-dependent and -independent vasodilatation were measured by applanation tonometry (changes in augmentation index, AIx, postinhaled salbutamol and postsublingual nitroglycerin) in conjunction with biochemical measurements. Marked reductions in serum F (616 +/- 73 vs. 273 +/- 30 nmol L(-1), P < 0.001), tHcy (16.3 +/- 0.7 vs. 11.2 +/- 0.5 micromol L(-1), P < 0.001) and ADMA (0.64 +/- 0.02 vs. 0.47 +/- 0.02 micromol L(-1), P < 0.001) occurred end-HD, whereas CRP and MDA levels did not significantly change. There was no significant change in endothelium-dependent vasodilatation, whereas endothelium-independent vasodilatation improved end-HD (-23.1 +/- 1.9 vs. -17.3 +/- 1.3%, P = 0.018). Regression analysis showed that both higher ADMA (P = 0.029) and lower F levels (P = 0.040) end-HD were determinants of reduced endothelium-dependent vasodilatation end-HD (R(2) = 0.23). HD is associated with significant reductions in F, tHcy and ADMA serum concentrations. The lack of significant effects of HD on endothelium-dependent vasodilatation could be secondary to the concomitant loss of factors either enhancing (F) or impairing (ADMA) endothelial function.

Short-Term oral folic acid supplementation enhances endothelial function in patients with type 2 diabetes

Endothelial dysfunction and arterial stiffening are commonly observed in type 2 diabetes. These abnormalities might be secondary to increased plasma concentrations of homocysteine. We sought to determine whether oral folic acid supplementation, by lowering homocysteine levels, enhanced endothelial function and reduced arterial stiffness in type 2 diabetes. Twenty-six type 2 diabetic patients (age 56.5 +/- 0.9 years, diabetes duration 5.5 +/- 0.6 years, means +/- SEM) with no history of cardiovascular disease received 5 mg/d of oral folic acid or placebo for 4 weeks in a double-blind, randomized controlled, parallel group trial. The following parameters were measured before and after treatment: 1) endothelial function (forearm arterial blood flow during local intra-arterial administration of endothelium-dependent [acetylcholine 1.5, 4.5, and 15 microg/min] and endothelium-independent [sodium nitroprusside 1, 2, and 4 microg/min] vasodilators); and 2) carotid-radial and carotid-femoral pulse wave velocity. Folic acid reduced plasma homocysteine concentrations and enhanced endothelium-dependent vasodilatation during each acetylcholine infusion rate (mean and 95% confidence interval post versus pretreatment differences in forearm arterial blood flow ratio between the infused and control arm +0.19 (0.03-0.35), P < .01; +0.39 (0.02-0.81), P < .05; and +0.40 (0.09-0.89), P < .05, respectively). Endothelium-independent vasodilatation and pulse wave velocity were not affected. No significant changes in forearm arterial blood flow and pulse wave velocity were observed in the placebo group. Multiple regression analysis showed that changes in folic acid, but not homocysteine, concentrations independently described changes in maximal endothelium-dependent vasodilatation. Short-term oral folic acid supplementation significantly enhances endothelial function in type 2 diabetic patients, independent of homocysteine lowering.

Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial

Cigarette smoking is associated with increased plasma homocysteine concentrations, endothelial dysfunction and arterial stiffening. Homocysteine per se induces endothelial dysfunction and arterial stiffening and might account, at least partly, for the vascular abnormalities observed in smokers. We sought to determine whether folic acid supplementation, by reducing plasma homocysteine concentrations, enhanced endothelial function and reduced arterial stiffness in smokers. Double-blind, randomized controlled, parallel-group, trial. Academic medical centre. A consecutive sample of 24 healthy cigarette smokers (age 37.8 +/- 2.5 years, mean +/- SEM). Subjects were randomly assigned to 4-week folic acid 5 mg day-1 or placebo. The following were measured before and after treatment: (i) peripheral vasoreactivity (forearm arterial blood flow, FABF) during intra-arterial administration of endothelium-dependent (acetylcholine 1.5, 4.5 and 15 microg min-1) and endothelium-independent (sodium nitroprusside 1, 2 and 4 microg min-1) vasodilators; (ii) carotid-femoral pulse-wave velocity (PWV); (iii) blood pressure (BP). Folic acid reduced homocysteine concentrations (10.8 +/- 0.6 vs. 8.2 +/- 0.5 micromol L-1, P < 0.001) and enhanced endothelium-dependent vasodilatation during each acetylcholine infusion rate (ratio between the FABF in the infused and control arm during increasing infusion rates at baseline 1.09 +/- 0.03 vs. 1.41 +/- 0.09 after treatment, P < 0.01; 1.39 +/- 0.07 vs. 1.83 +/- 0.12, P < 0.01; 1.65 +/- 0.16 vs. 2.72 +/- 0.36, P < 0.05) whilst endothelium-independent vasodilatation was unaffected. A significant fall in BP was also observed (mean BP 88 +/- 2 vs. 83 +/- 1 mmHg, P < 0.01). By contrast, PWV did not significantly change (8.4 +/- 0.3 vs. 7.8 +/- 0.4 m s-1). No significant changes in plasma homocysteine concentrations, FABF, BP, and PWV were observed in the placebo group. A multiple regression analysis showed that changes in folic acid plasma concentrations independently predicted both FABF changes during maximal acetylcholine-mediated vasodilatation (P < 0.01) and BP changes (P = 0.01). Short-term folic acid supplementation significantly enhanced endothelial function and reduced BP in young chronic smokers. These effects were largely independent from the homocysteine lowering effects. Thus, a simple, nontoxic, and relatively inexpensive vitamin intervention might be useful in primary cardiovascular prevention in this high-risk group.

Venoconstriction by angiotensin II in the human forearm is inhibited by losartan but not by nicardipine.

Arterial constriction by angiotensin II (Ang II) in the human forearm is inhibited by the infusion of the AT1-receptor antagonist losartan. We investigated venous constriction by Ang II in the forearm of 19 healthy subjects (23 +/- 1 years) and the inhibitory effects of losartan. Furthermore, we investigated, in both the arterial and venous systems, whether the constrictor effects of Ang II are calcium influx dependent by determining the influence of nicardipine. Arterial forearm blood flow (FBF) and maximal venous outflow (MVO) were measured by venous-occlusion plethysmography. Sodium nitroprusside (5-12.5 ng/kg/min) was infused to predilate the forearm vasculature. Ang II (0.1, 1, and 10 ng/kg/min) was infused before and during losartan (0.3 and 3 microg/kg/min) or nicardipine (0.05 and 0.15 microg/kg/min), respectively. Ang II decreased FBF (Emax-FBF) by 79 +/- 4% and MVO (Emax-MVO) by 28 +/- 3% (p < 0.05). Nicardipine at 0.05 and 0.15 microg/kg/min reduced Emax-FBF from -79 +/- 4% to -48 +/- 4% and -6 +/- 2%, respectively (p < 0.05). Losartan in both doses completely inhibited Emax-MVO (p < 0.05), whereas nicardipine did not influence the venoconstriction by Ang II (p > 0.05). In conclusion, Ang II causes a constriction of both arteries and veins in the human forearm, which may be inhibited by losartan. The arterial constriction appears to be caused by an AT1-receptor-mediated calcium influx via L-type calcium channels. In contrast, the venoconstrictor effect of Ang II proved insensitive to the calcium antagonist nicardipine.

814-4 Effect of Administration of Dehydroepiandrosterone on Cyclic-Guanidine-Monophosphate Plasma Levels in Men of Advancing Age

Epidemiologic data suggest beneficial effects of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DS) in atherosclerosis and coronary artery disease. Aging is accompanied by a progressive decline in the secretion of DHEA and DS, paralleling that of growth hormone (GH) insulin like growth factor I (IGF-I) axis. Previous studies reported a significant increase of IGF-I serum levels after replacement therapy with DHEA in advancing age men and IGF-I has been shown to have a potent vasodilator effect in the forearm arterial blood flow in humans and the rat renal afferent microvasculature; an effect that can be blocked by inhibition of endothelial derived relaxing factor (EDRF), nitric oxide (NO). We investigated the effect of administration of DHEA on plasma levels of cyclic guanidine monophosphate (cGMP), the second messenger of NO activity and an indirect assay of NO release. We included 34 nonobese men, body mass index (BMI) 22–26 kg/m. age 47–74 years, normotensive and non insulin resistant in a double blind, placebo controlled, randomized study: 18 were treated with DHEA 150 mg daily for 12 days and 16 with placebo. DHEA increased from 3.7 ± 0.2 to 15.0 ± 1.4 μ m/L (p &lt; 0.001) in the DHEA group. No changes were observed in the placebo group. cGMP plasma levels increased from 3.22 ± 0.2 to 6.05 ± 0.21 Pmol/ml(p &lt; 0.005) after administration of DHEA. In the placebo group no significant changes were observed. BMI, fasting insulin, serum lipids and blood pressure did not change during the study. The increase of cGMP in the DHEA treated patients presumably occurs through increased NO production. We suspect that DHEA increases NO via IGF-I stimulation and this might be one of the mechanisms of the protective action of DHEA against coronary ischemic disease.