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Sleep plays an essential role in physiology, allowing the brain and body to restore itself. Despite its critical role, our understanding of the underlying processes in the sleeping human brain is still limited. Sleep comprises several distinct stages with varying depths and temporal compositions. Cerebral blood flow (CBF), which delivers essential nutrients and oxygen to the brain, varies across brain regions throughout these sleep stages, reflecting changes in neuronal function and regulation. This systematic review and meta-analysis assesses global and regional CBF across sleep stages. We included, appraised, and summarized all 38 published sleep studies on CBF in healthy humans that were not or only slightly (< 24 h) sleep deprived. Our main findings are that CBF varies with sleep stage and depth, being generally lowest in NREM sleep and highest in REM sleep. These changes appear to stem from sleep stage-specific regional brain activities that serve particular functions, such as alterations in consciousness and emotional processing. [ABSTRACT FROM AUTHOR]

Liver cirrhosis is characterized by significant circulatory dysregulation, related to an imbalance among several vasodilating agents, mainly nitric oxide. In contrast to portal vein and macrovascular hemodynamic alterations, which have been rather well described, the peripheral microcirculatory and endothelial structure and function in this population are less well studied. Endothelial dysfunction is characterized by an imbalance between endothelium-derived relaxing and contracting factors. A number of methods have been used to assess endothelial and microvascular function in human studies. Venous occlusion plethysmography was used for many years as the gold standard for evaluating endothelial function, but flow-mediated dilatation (FMD) of the forearm is currently the most frequently used method. In patients with cirrhosis, the few existing studies have mainly used FMD, but the relevant results are largely contradictory. In recent years, several noninvasive and easily applicable methods, such as near-infrared spectroscopy, laser speckle contrast imaging, peripheral arterial tonometry, optical coherence tomography and nailfold video-capillaroscopy, have been increasingly used to assess peripheral microvascular function and have demonstrated a number of advantages. In this review, we present functional methods to evaluate peripheral microvascular and endothelial function, and we discuss the existing evidence on circulatory dysfunction in patients with liver cirrhosis. [ABSTRACT FROM AUTHOR]

Short‐term endurance exercise training for 6–8 weeks leads to increases in venous volume and compliance in the limbs. However, it is not known whether these venous vascular properties are improved by acute endurance exercise. We examined the effects of acute endurance exercise involving continuous or interval workloads on venous volume and compliance in the exercising (calf) and non‐exercising (forearm) limbs. Sixteen healthy young volunteers performed cycling exercise involving a continuous workload of 60% heart rate (HR) reserve or an interval workload of 40% HRreserve and 80% HRreserve, alternating every 2 min, for a total of 32 min each. Before and 60 min after acute cycling exercise, venous volume in the calf and forearm was measured by venous occlusion plethysmography during a cuff‐deflation protocol with a venous collecting cuff wrapped to the thigh and upper arm and strain gauges attached to the calf and forearm. The cuff pressure was maintained at 60 mmHg for 8 min and was then deflated to 0 mmHg at a rate of 1 mmHg/s. Venous compliance was calculated as the numerical derivative of the cuff pressure–limb venous volume curve. In both the calf and forearm, the cuff pressure–venous volume curve and the cuff pressure–venous compliance relationship did not differ between before and 60 min after exercise involving continuous or interval workloads. These results suggest that acute exercise does not improve venous volume and compliance in both the exercising and non‐exercising limbs. [ABSTRACT FROM AUTHOR]

Abstract Short‐term endurance exercise training for 6–8 weeks leads to increases in venous volume and compliance in the limbs. However, it is not known whether these venous vascular properties are improved by acute endurance exercise. We examined the effects of acute endurance exercise involving continuous or interval workloads on venous volume and compliance in the exercising (calf) and non‐exercising (forearm) limbs. Sixteen healthy young volunteers performed cycling exercise involving a continuous workload of 60% heart rate (HR) reserve or an interval workload of 40% HRreserve and 80% HRreserve, alternating every 2 min, for a total of 32 min each. Before and 60 min after acute cycling exercise, venous volume in the calf and forearm was measured by venous occlusion plethysmography during a cuff‐deflation protocol with a venous collecting cuff wrapped to the thigh and upper arm and strain gauges attached to the calf and forearm. The cuff pressure was maintained at 60 mmHg for 8 min and was then deflated to 0 mmHg at a rate of 1 mmHg/s. Venous compliance was calculated as the numerical derivative of the cuff pressure–limb venous volume curve. In both the calf and forearm, the cuff pressure–venous volume curve and the cuff pressure–venous compliance relationship did not differ between before and 60 min after exercise involving continuous or interval workloads. These results suggest that acute exercise does not improve venous volume and compliance in both the exercising and non‐exercising limbs.

BACKGROUND: In patients with ischemia and no obstructive coronary artery disease (INOCA), coronary microvascular dysfunction is associated with higher rate of major adverse cardiovascular events. OBJECTIVE: To demonstrate if microvascular dysfunction present in coronary microcirculation of patients with INOCA may be detected noninvasively in their peripheral circulation. METHODS: 25 patients with INOCA and 25 apparently healthy individuals (controls) were subjected to nailfold videocapillaroscopy (NVC) and venous occlusion plethysmography (VOP) to evaluate peripheral microvascular function and blood collection for biomarkers analysis, including soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1) and C-reactive protein (CRP). RESULTS: Red blood cell velocity (RBCV) before and after ischemia (RBCVmax) were significantly lower in patients with INOCA (p = 0.0001). Time to reach maximal red blood cell velocity (TRBCVmax) was significantly longer in INOCA group (p = 0.0004). Concerning VOP, maximal blood flow (p = 0.004) and its relative increment were significantly lower in patients with INOCA (p = 0.0004). RBCVmax showed significant correlations with sVCAM-1 (r = –0.38, p < 0.05), ET-1 (r = –0.73, p < 0.05) and CRP (r = –0.33, p < 0.05). Relative increment of maximal post-ischemic blood flow was significantly correlated with sVCAM-1 (r = –0.42, p < 0.05) and ET-1 (r = –0.48, p < 0.05). CONCLUSIONS: The impairment of microvascular function present in coronary microcirculation of patients with INOCA can be also detected in peripheral microcirculation. [ABSTRACT FROM AUTHOR]

Objective: Recently, dynamic retinal vessel analysis (DVA) has gained interest for investigation of microvascular function but comparative measurements with standard methods like the forearm blood flow technique (FBF) are uncommon till now. Methods: We recruited 23 high‐risk cardiovascular patients (Risk) and 17 healthy persons (Ctrl). During the FBF experiment, postocclusive reactive hyperaemia (RH) as well as endothelium‐dependent and independent vasodilation was measured by infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) into the brachial artery. The dynamic vessel analyzer was applied for measurement of the retinal arterial and venous response to flickering light during DVA and for determination of the central retinal arterial (CRAE) and venous equivalent (CRVE). Results: Forearm blood flow technique was significantly attenuated in the patient group during postocclusive RH (p <.005). The increase of FBF in response to SNP did not differ significantly between the two groups (p =.09). In contrast, the FBF response to ACh was significantly blunted in the patient group (p <.05), indicating endothelial dysfunction. DVA did not detect any difference of retinal arterial (p =.68) or retinal venous (p =.93) vasodilation between both groups. The CRAE (p =.55) and CRVE (p =.83) did not differ significantly in either group. Conclusions: Forearm blood flow and DVA cannot be regarded as equivalent methods for testing of microvascular function. Possible explanations include differences in the vascular beds and vessel diameters examined as well as differences in the trigger mechanisms applied. Further studies are needed to define the role of DVA in this context. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is associated with morphological and functional changes in both aneurysmal and non-aneurysmal arteries. However, it remains uncertain whether similar changes also exist in the venous vasculature. The aim of this study was to evaluate global venous function in patients with AAA and controls. This experimental study comprised 31 men with AAA (mean ± standard deviation age 70.0 ± 2.8 years) and 29 male controls (aged 70.6 ± 3.4 years). Venous occlusion plethysmography (VOP) was used to evaluate arm venous compliance at venous pressures between 10 and 60 mmHg in steps of 5 mmHg. Compensatory mobilisation of venous capacitance blood (capacitance response) was measured with a volumetric technique during experimental hypovolaemia induced by lower body negative pressure (LBNP). The VOP induced pressure–volume curve was significantly less steep in patients with AAA (interaction, p <.001), indicating lower venous compliance. Accordingly, the corresponding pressure–compliance curves displayed reduced venous compliance at lower venous pressures in patients with AAA vs. controls (interaction, p <.001; AAA vs. control, p =.018). After adjusting for arterial hypertension, diabetes mellitus, hyperlipidaemia, chronic obstructive pulmonary disease, and smoking, VOP detected differences in venous compliance remained significant at low venous pressures, that is, at 10 mmHg (p =.008), 15 mmHg (p =.013), and 20 mmHg (p =.026). Mean venous compliance was negatively correlated with aortic diameter (r = −.332, p =.010). Mobilisation of venous capacitance response during LBNP was reduced by approximately 25% in patients with AAA (p =.030), and the redistribution of venous blood during LBNP was negatively correlated with aortic diameter (r = −.417, p =.007). Men with AAA demonstrated reduced venous compliance and, as a result, a lesser capacity to mobilise peripheral venous blood to the central circulation during hypovolaemic stress. These findings imply that the AAA disease may be accompanied by functional changes in the venous vascular wall. [ABSTRACT FROM AUTHOR]

Purpose: Prompt detection of congestion is an essential target in order to prevent heart failure (HF) related hospitalization, being ambulatory monitoring a promising strategy to do so. A successful non-invasive ambulatory monitoring system requires automatic devices for physiological data recording; these data must give information about HF deterioration early enough to predict HF-related adverse events. This work aims to evaluate seven vascular parameters for the ambulatory monitoring of congestive heart failure patients. Methods: Seven vascular parameters are proposed as indicators of HF deterioration. These parameters are obtained using venous occlusion plethysmography; a technique that uses hardware able of being miniaturized and easily integrated into wearables for ambulatory monitoring. The ability of the proposed vascular parameters to detect congestion is evaluated in eight healthy volunteers and ten congestive heart failure patients with different congestion levels—mild, moderate and severe. Results: Most parameters distinguish between healthy volunteers and heart failure patients, and some of them present significant differences between volunteers and low levels of congestion—mild or moderate. Conclusion: Home monitoring of some of the proposed parameters could detect HF deterioration on its onset and alert to health personnel. [ABSTRACT FROM AUTHOR]

Purpose: We tested whether the values of limb blood flow calculated with strain-gauge venous occlusion plethysmography (VOP) differ when venous occlusion is achieved by automated, or manual inflation, so providing rapid and slower inflation, respectively.Method: In 9 subjects (20-30 years), we calculated forearm blood flows (FBF) values at rest and following isometric handgrip at 70% maximum voluntary contraction (MVC) when rapid, or slower inflation was used.Result: Rapid and slower cuff inflation took 0.23 ± 0.01 (mean ± SEM) and 0.92 ± 0.02 s, respectively, reflecting the range reported in published studies. At rest, FBF calculated from the 1st cardiac cycle after rapid and slower inflation gave similar values: 10.5 ± 1.4 vs. 9.6 ± 1.3 ml dl- 1 min- 1, respectively (P > 0.05). However, immediately post-contraction, FBF was ~ 40% lower with slower inflation: 54.6 ± 5.1 vs. 33.8 ± 4.2 ml dl- 1 min- 1 (P < 0.01). The latter value was similar to that calculated over the 3rd cardiac cycle following rapid inflation: 2nd cardiac cycle: 40.5 ± 4.5; 3rd cycle: 32.6 ± 4.5 ml dl- 1 min- 1. Regression analyses of FBFs recorded at intervals post-contraction showed those calculated over the 1st, 2nd, or 3rd cardiac cycles with rapid inflation correlated well with those from the 1st cardiac cycle with manual inflation (r = 0.79, 0.82, 0.79; P < 0.01). However, only the slope for the 3rd cycle with rapid inflation vs. slower inflation was close to unity (2.07, 1.34, and 0.94, respectively).Conclusion: These findings confirm that the 1st cardiac cycle following venous occlusion should be used when calculating FBF using VOP and, but importantly, indicate that cuff inflation should be almost instantaneous; just ≥ 0.9 s leads to substantial underestimation, especially at high flows. [ABSTRACT FROM AUTHOR]

Purpose: It has recently been shown that venous occlusion plethysmography (VOP) can successfully assess the rate of increase in leg blood flow (LBF) (LBF kinetics) responses during calf exercise, but there is lack of data supporting its validity.Methods: Using Doppler ultrasound (DU) as a criterion standard technique, we tested the hypothesis that VOP would provide similar estimates of LBF kinetics responses as DU during calf plantar-flexion exercise at a range of different intensities. Ten healthy men performed repeated intermittent calf plantar-flexion contractions (3 s duty cycles, 1 s contraction/2 s relaxation) at 30, 50 and 70% maximum voluntary contraction (MVC) on different days.Results: Resting LBF values were significantly (P < 0.05) larger for DU than VOP but the overall mean LBF responses during exercise were not different (P > 0.05) between DU and VOP (30% MVC: 330 ± 78 vs. 313 ± 92 ml/min; 50% MVC: 515 ± 145 vs. 483 ± 164 ml/min; 70% MVC: 733 ± 218 vs. 616 ± 229 ml/min). LBF kinetics analyses revealed that the end-amplitude at the highest intensity (70% MVC) was significantly higher when measured by DU compared with VOP, but all other kinetics parameters were not different between VOP and DU.Conclusions: Given that these slight differences in amplitude observed during exercise can be explained by differences in vascular regions which the two techniques assess, our results suggest that VOP can accurately assess LBF kinetics responses during calf plantar-flexion exercise at intensities between 30 and 70% MVC. [ABSTRACT FROM AUTHOR]

Objective The relation between venous morphology and venous function in postthrombotic syndrome is poorly understood. The aim of this study was to compare obstruction and collateralization as seen with magnetic resonance venography with variables of venous occlusion plethysmography in patients with postthrombotic syndrome. Methods Medical records, magnetic resonance venography and venous occlusion plethysmography data were analyzed in 28 patients (33 legs). Magnetic resonance venography images were scored for degree of obstruction and collateralization in segments of pelvic and abdominal veins and correlated to venous occlusion plethysmography data. Results Obstruction of the inferior vena cava correlated with an overall increase of collaterals ( p < 0.001). The summary scores of collaterals or obstructions did not correlate with venous occlusion plethysmography variables. Relative expelled volume at 4 s correlated inversely with obstruction of the inferior vena cava ( p = 0.045) and vertebral collateralization ( p = 0.033). Conclusions Modest correlations were found between magnetic resonance venography scores and venous occlusion plethysmography variables. Prospective studies with refined scoring and magnetic resonance venography techniques may increase our knowledge further. [ABSTRACT FROM AUTHOR]

The vasodilatory mechanism of Nntroglycerin (NTG) is similar to sodium nitroprusside (SNP) in regard to action on guanosine 3′5′-monophosphate (cyclic GMP) via nitric oxide. However, it is unknown whether NTG can achieve the same magnitude of vasodilation in the forearm as SNP. Therefore, the purpose of the study was to evaluate the differences in forearm blood flow (FBF) and forearm vascular conductance (FVC) during escalating infusions of NTG vs. SNP at similar concentration doses and rates. We measured FBF using venous occlusion plethysmography (VOP) and Doppler ultrasound in eight young, healthy participants (mean age = 28 ± 2 yr) during four forearm volume (FAV)-specific doses (0.25, 0.5, 1, and 2 µg·100 ml FAV−1·min−1) of SNP and NTG infused via a brachial artery catheter. There was a significant difference in FVC of SNP vs. NTG only at the higher doses, as measured by VOP (14.9 ± 1.4 and 18.3 ± 1.5 vs. 11.6 ± 1.2 and 12.5 ± 1.2 ml/dl FAV−1·min−1·100 mmHg−1). FVC as measured by Doppler ultrasound unadjusted for FAV was significantly different at the lowest and the higher two doses of SNP compared with NTG (202.1 ± 25.8, 329.4 ± 46.7, and 408 ± 63.5 vs. 142.9 ± 22.4, 217.2 ± 18.8, and 247.5 ± 18.2 ml·min−1·100 mmHg−1). SNP induces significantly higher vasodilatory actions compared with NTG. However, NTG is comparable in eliciting equivalent vasodilator effects to SNP during low concentration doses when measured by VOP. Importantly, for forearm pharmacology studies, NTG can elicit marked endothelium-independent forearm vasodilation. NEW & NOTEWORTHY We compared the vasodilatory capacities of NTG vs. SNP at similar concentration doses and rates into the forearm. Based on the results of the study, it may be feasible to use intra-arterial NTG as a measure of endothelial-independent vasodilator in research studies. However, NTG dosing may need to be higher if used as an endothelial-independent vasodilator due to significant differences in the vasodilatory effects during higher doses of SNP compared with NTG. [ABSTRACT FROM AUTHOR]

Introduction: Inorganic nitrate ingestion has been posited to affect arterial blood pressure and vascular function. Purpose: We sought to determine the acute effect of a red spinach extract (RSE) high in inorganic nitrate on vascular reactivity 1-h after ingestion in peripheral conduit and resistance arteries. Methods: Fifteen ( n = 15; males 8, females 7) apparently healthy subjects (aged 23.1 ± 3.3 years; BMI 27.2 ± 3.7 kg/m) participated in this crossover design, double-blinded study. Subjects reported to the lab ≥2-h post-prandial and consumed RSE (1000 mg dose; ~90 mg nitrate) or placebo (PBO). Venipuncture was performed on three occasions: baseline, 30-min post-ingestion and between 65 to 75-min post-ingestion. Baseline vascular measurements [i.e., calf venous occlusion plethysmography, brachial artery flow-mediated dilation (FMD)], 30-min of continuous blood pressure (BP) and heart rate (HR) analysis, and follow-up vascular measurements beginning at 40-min post-ingestion were also performed. Results: Humoral nitrate following RSE ingestion was significantly higher at 30- (+54 %; P = 0.039) and 65 to 75-min post-ingestion compared to baseline (+255 %, P < 0.001) and PBO at the same time points ( P < 0.05). No significant changes in BP or HR occurred in either condition. Peak reactive hyperemia (RH) calf blood flow increased significantly (+13.7 %; P = 0.016) following RSE ingestion, whereas it decreased (−14.0 %; P = 0.008) following PBO ingestion. No significant differential FMD responses were detected ( P > 0.05), though RH was decreased following the baseline measure in both conditions. Conclusions: RSE significantly increased plasma nitrate 30-min post-ingestion, but acute microvascular (i.e., resistance vasculature) reactivity increases were isolated to the lower limb and no appreciable change in brachial artery FMD was observed. [ABSTRACT FROM AUTHOR]

Obesity is associated with the impairment of endothelial function leading to the initiation of the atherosclerotic process. We have hypothesized that an increasing impairment of endothelial and vascular smooth muscle cell functions occurs from lean subjects to severe obese ones. Thus, the present study was carried out to investigate the grade of obesity in which endothelial dysfunction can be detected and if there is an increasing impairment of endothelial and vascular smooth muscle cell functions as body mass index increases. According to body mass index, subjects were allocated into five groups: Lean controls, Overweight, Obese class I, Obese class II, and Obese class III. Endothelial and vascular smooth muscle cell functions were evaluated measuring forearm blood flow responses to increasing intra-arterial infusions of acetylcholine and sodium nitroprusside using venous occlusion plethysmography. We observed that forearm blood flow was progressively impaired from lean controls to severe obese and found no significant differences between Lean controls and Overweight groups. Our data suggests that obesity class I is the first grade of obesity in which endothelial dysfunction can be detected and that body mass index positively correlates with the worsening of endothelium-dependent and independent changes in forearm blood flow.

PURPOSE: Metabolic syndrome is an important risk factor for cardiovascular disease. Adipokines interfere with insulin action and endothelial cell function. We investigated the relationship among adipokines, metabolic factors, inflammatory markers, and vascular reactivity in obese subjects with metabolic syndrome and lean controls. METHODS: Cross-sectional study of 19 obese subjects with metabolic syndrome and 8 lean volunteers evaluated as controls. Vascular reactivity was assessed by venous occlusion pletysmography measuring braquial forearm blood flow (FBF) and vascular resistance (VR) responses to intra-arterial infusions of endothelium-dependent (acetylcholine-Ach) and independent (sodium nitroprusside-SNP) vasodilators. Blood samples were obtained to evaluate C reactive protein (CRP), plasminogen activator inhibitor 1 (PAI-1), fibrinogen, adiponectin, resistin, and lipid profile. Patients were classified with regard to insulin resistance through the HOMA-IR index. RESULTS: PAI-1, CRP and fibrinogen were higher and adiponectin was lower in metabolic syndrome subjects compared to controls. Metabolic syndrome subjects had impaired vascular reactivity. Adiponectin and PAI-1 were associated with insulin, HOMA-IR, triglycerides, and HDLc; and resistin with CRP. Adiponectin was associated with VR after Ach in the pooled group and resistin with D FBF after Ach in the metabolic syndrome group. CONCLUSION: Metabolic syndrome subjects exhibited low levels of adiponectin and high levels of CRP, fibrinogen, and PAI-1. Adiponectin and PAI-1 correlated with insulin resistance markers. Adiponectin and resistin correlated with vascular reactivity parameters. An adipocyte-endothelium interaction might be an important mechanism of inflammation and vascular dysfunction.A Síndrome Metabólica é um importante fator de risco para doenças cardiovasculares. As adipocinas interferem com a ação da insulina e com a função endotelial. OBJETIVO: Investigar a relação entre adipocinas, fatores metabólicos, marcadores inflamatórios e reatividade vascular para inferência da função endotelial em pacientes obesos e controles magros. MATERIAL E MÉTODO: Estudo transversal de 19 pacientes obesos com Síndrome Metabólica e 8 controles magros. A reatividade vascular foi avaliada pela pletismografia de oclusão venosa medindo o fluxo sangüíneo da artéria braquial e sua resistência vascular a partir de infusões intra-arteriais de vasodilatadores endotélio-dependente (acetilcolina) e endotélio-independente (nitroprussiato de sódio). Foram também avaliados no sangue a proteína C reativa (PCR), o inibidor do ativador do plasminogênio 1 (PAI-1), fibrinogênio, adiponectina, resistina e o perfil lipídico. Os pacientes foram classificados quanto à resistência insulínica pelo índice HOMA-IR. RESULTADO: PAI-1, PCR e fibrinogênio apresentaram valores mais altos e a adiponectina mais baixos para os pacientes com Síndrome Metabólica do que com os controles. Pacientes com Síndrome Metabólica apresentaram prejuízo da reatividade vascular. A adiponectina e PAI-1 estiveram associadas à insulina, HOMA-IR, triglicerídeos e HDLc; e resistina com o PCR. Adiponectina esteve associada com a resistência vascular e a resistina com o fluxo sangüíneo depois da acetilcolina em pacientes com Síndrome Metabólica. CONCLUSÃO: Pacientes com Síndrome Metabólica exibiram baixas concentrações sangüíneas de adiponectina e altos níveis de PCR, fibrinogênio e PAI-1. Adiponectina e PAI-1 correlacionaram com os marcadores da resistência insulínica. Adiponectina e resistina correlacionaram com a reatividade vascular. A interação adipócito-endotélio vascular pode ser um importante mecanismo de inflamação e disfunção vascular.

Introduction: Exercise promotes cardiovascular health through its direct impact on the vascular endothelium. Conversely, poor sleep quality is associated with endothelial dysfunction, which may explain the increased cardiovascular disease amongst poor sleepers. Yet, the influence of physical activity and poor sleep quality on vascular health is not clear.Purpose: This study examined the relationships between forearm vasodilatory capacity, self-reported sleep quality and free-living, actigraphy-derived energy expenditure in a group of young and older community dwelling adults.Methods: Venous occlusion plethysmography determined baseline and peak forearm blood flow following reactive hyperemia. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Measures of body composition were assessed using dual energy X-ray absorptiometry.Results: A total of 104 (61 young; 43 old) participants completed the study. In general, younger participants were more active, as determined by steps per day and average daily energy expenditure, but reported poorer sleep quality. In the combined sample, those who reported moderate sleep disturbances (PSQI total score; 11-15) had significantly lower vasodilatory capacity (16.8 ± 7.6 ml/100 ml/min) compared to those who reported no sleep disturbance (PSQI total score; 0-5) (22.3 ± 7.2 ml/100 ml/min) or mild sleep disturbance (PSQI total score; 6-10) (22.3 ± 8.1 ml/100 ml/min) (p < 0.01). After adjustment for physical activity, total body fat and age, moderately poor sleep remained an independent predictor of forearm vasodilatory capacity.Conclusions: These findings suggest that any positive vascular benefits accrued through increased physical activity might be offset by the negative consequences of chronically disturbed sleep. [ABSTRACT FROM AUTHOR]

Introduction: External pneumatic compression (EPC) is being employed for a widening range of clinical and non-clinical populations. However, EPC devices vary markedly in treatment pressures, duty cycles and application sites, and the acute effects of whole limb, lower pressure EPC on peripheral vascular function have not been determined. Purpose: The purpose of this study was to determine the acute effects of a single bout of peristaltic pulse EPC on peripheral conduit and resistance artery function. Methods: Twenty ( n = 20; males = 12 and females = 8) young and apparently healthy subjects (aged 26.1 ± 8.2 years) participated in this study. A sequential EPC device with five inflation zones arranged linearly and inflating distal to proximal along the lower limbs was employed with target inflation pressures of 70 mmHg for 1 h. Flow-mediated dilation (FMD) of the brachial and popliteal arteries was evaluated with ultrasound before and after EPC. Venous occlusion plethysmography was employed to evaluate limb blood flow at rest and during reactive hyperemia (RH) in the forearm (FBF) and calf (CBF) before and after EPC. Results: Peak RH CBF was increased by 9 % after EPC ( P < 0.05), whereas peak RH FBF (−10 %) did not change significantly ( P > 0.25). Normalized popliteal artery FMD post-EPC (2.24 ± 1.41) was significantly higher than pre-EPC (1.36 ± 0.67, P = 0.015) and post-sham (1.58 ± 0.86, P = 0.032) values. Similarly, normalized brachial artery FMD post-EPC (1.47 ± 0.32) was significantly higher than pre-EPC (1.11 ± 0.41, P = 0.004) and post-sham (0.99 ± 0.27, P = 0.026) values. Conclusion: Acutely, whole limb, lower pressure EPC improves conduit artery endothelial function systemically, but only improves RH blood flow locally (i.e., compressed limbs). [ABSTRACT FROM AUTHOR]

Obesity is associated with the impairment of endothelial function leading to the initiation of the atherosclerotic process. As obesity is a multiple grade disease, we have hypothesized that an increasing impairment of endothelial and vascular smooth muscle cell functions occurs from lean subjects to severe obese ones, creating a window of opportunities for preventive measures. Thus, the present study was carried out to investigate the grade of obesity in which endothelial dysfunction can be detected and if there is an increasing impairment of endothelial and vascular smooth muscle cell functions as body mass index increases. According to body mass index, subjects were allocated into five groups: Lean controls (n = 9); Overweight (n = 11); Obese class I (n = 26); Obese class II (n = 15); Obese class III (n = 19). Endothelial and vascular smooth muscle cell functions were evaluated measuring forearm blood flow responses to increasing intra-arterial infusions of acetylcholine and sodium nitroprusside using venous occlusion plethysmography. We observed that forearm blood flow was progressively impaired from lean controls to severe obese and found no significant differences between Lean controls and Overweight groups. Known determinants of endothelial dysfunction, such as inflammatory response, insulin resistance, and diagnosis of metabolic syndrome, did not correlate with forearm blood flow response to vasodilators. Moreover, several risk factors for atherosclerosis were excluded as independent predictors after confounder-adjusted analysis. Our data suggests that obesity per se could be sufficient to promote impairment of vascular reactivity, that obesity class I is the first grade of obesity in which endothelial dysfunction can be detected, and that body mass index positively correlates with the worsening of endothelium-dependent and independent changes in forearm blood flow. [ABSTRACT FROM AUTHOR]

Breast cancer-related lymphedema ( BCRL) is a frequent, chronic and debilitating swelling that mainly affects the ipsilateral arm and develops as a complication to breast cancer treatment. The pathophysiology is elusive opposing development of means for prediction and treatment. We have earlier shown that the forearm capillary filtration coefficient ( CFC) is increased bilaterally in BCRL. In this study, we aimed to elucidate if increased CFC is associated with low-grade inflammation and/or vascular endothelial growth factor-c ( VEGF-C) signaling. Fourteen patients with unilateral BCRL and nine matched breast cancer controls without BCRL participated. Forearm CFC was measured by venous congestion strain gauge plethysmography, and suction blisters were induced medially on the upper arms. Concentrations of 17 selected cytokines, VEGF-C, and total protein were measured in blister fluid and in plasma. Forearm CFC was higher bilaterally in BCRL subjects ( P ≤ 0.036). No differences between forearms were found in either group. Plasma VEGF-C concentrations were significantly higher in the BCRL subjects ( P < 0.001). In BCRL subjects, monocyte chemotactic protein 1 ( MCP-1) ( P = 0.009) and total protein ( P = 0.035) concentrations were higher in blister fluid from edematous arms compared with nonedematous arms. No differences were found in interstitial cytokine or total protein concentrations between arms in control subjects. Higher plasma concentration of VEGF-C is a possible cause of bilaterally increased forearm CFC in BCRL subjects. Interstitially increased MCP-1 levels may augment local microvascular protein permeability in BCRL. [ABSTRACT FROM AUTHOR]

Background: There is a functional decline of endothelial- dependent vasodilatation in the aging process. The aims of this study were to investigate if various microcirculatory parameters could correlate to anthropometrical variables, oxidative stress and inflammatory biomarkers in successful aging and compare the results to young healthy controls. Methods: Healthy elderly women (HE, 74.0 ± 8.7 years, n = 11) and young controls (YC, 23.1 ± 3.6 years, n = 24) were evaluated through nailfold videocapillaroscopy (NVC), venous occlusion plethysmography (VOP) and laboratorial analysis. Functional capillary density (FCD) and diameters, maximum red blood cell velocity (RBCVmax) during the reactive hyperemia response/RBCVbaseline after 1 min arterial occlusion at the finger base, time to reach RBCVmax were determined by NVC, peak increment of forearm blood flow (FBF) during the reactive hyperemia response (%Hyper) and after 0.4 mg sublingual nitroglycerin (%Nitro) by VOP and lipidogram, fibrinogen, fasting and postload glucose, oxidized LDL-cholesterol (oxLDL), sICAM, sVCAM, sE-Selectin, interleukines 1 and 6 and TNF-α by laboratorial analysis. Correlations and linear multiple regression (LMR) between %Hyper, %Nitro, microcirculatory parameters, oxidative stress and inflammatory biomarkers were investigated. Results: sVCAM, sE-Selectin and oxLDL were higher and RBCVmax/RBCVbaseline and %Hyper lower in HE, while %Nitro and FCD remained unchanged. Fibrinogen, LDL-cholesterol, oxLDL correlated negatively to %Hyper while sVCAM correlated negatively to %Hyper and RBCVmax/RBCVbaseline. Healthy aged women presented dilated capillaries with sustained perfusion and endothelial dysfunction with preserved vascular smooth muscle reactivity. Fibrinogen, LDL-cholesterol, oxidized-LDL and sVCAM correlated negatively to endothelial function but not to microcirculatory parameters. Oxidized-LDL and sVCAM could determine %Hyper through LMR. Conclusion: Oxidized-LDL and sVCAM might be used as endothelial dysfunction biomarkers for elderly with normal cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Purpose: Calf venous compliance ( C) is commonly evaluated with venous occlusion plethysmography (VOP) during a standard cuff deflation protocol. However, the technique relies on two not previously validated assumptions concerning thigh cuff pressure ( P) transmission and the impact of net fluid filtration ( F) on C. The aim was to validate VOP in the lower limb and to develop a model to correct for F during VOP. Methods: Strain-gauge technique was used to study calf volume changes in 15 women and 10 age-matched men. A thigh cuff was inflated to 60 mmHg for 4 and 8 min with a subsequent decrease of 1 mmHg s. Intravenous pressure ( P) was measured simultaneously. C was determined with the commonly used equation [Compliance = β + 2 β × P] describing the pressure-compliance relationship. A model was developed to identify and correct for F. Results: Transmission of P to P was 100 %. The decrease in P correlated well with P reduction ( r = 0.99, P < 0.001). Overall, our model showed that C was underestimated when F was not accounted for (all P < 0.01). F was higher in women ( P < 0.01) and showed a more pronounced effect on C compared to men ( P < 0.05). The impact of F was similar during 4- and 8-min VOP. Conclusions: P is an adequate substitute for P in the lower limb. F is associated with an underestimation of C and differences in the effect of F during VOP can be accounted for with the correction model. Thus, our model seems to be a valuable tool in future studies of venous wall function. [ABSTRACT FROM AUTHOR]

Enhanced external counterpulsation (EECP) improves resistance artery function in coronary artery disease patients. However, whether EECP elicits similar effects in persons with abnormal glucose tolerance (AGT) is unknown. Here we provide novel evidence that EECP significantly improves resistance arterial function in the forearm of persons with AGT, whereas the calf only approached significance ( P ≤ 0.10). These improvements were coincident with greater glycemic control, providing further insight into the potential mechanisms of EECP-mediated alterations in glycemia. [ABSTRACT FROM AUTHOR]

Enhanced external counterpulsation (EECP) increases coronary artery perfusion and improves endothelium-dependent vasodilation in peripheral muscular conduit arteries. It is unknown whether vasodilatory capacity is improved in the peripheral resistance vasculature. Here we provide novel evidence from the first randomized, sham-controlled study that EECP increases peak limb blood flow and improves endothelium-dependent vasodilation in both calf and forearm resistance arteries in patients with coronary artery disease. [ABSTRACT FROM AUTHOR]

Aim To investigate the mechanism of action of intra-arterial histamine in the human forearm vasculature. Methods Three studies were conducted to assess changes in forearm blood flow ( FBF) using venous occlusion plethysmography in response to intra-brachial histamine. First, the dose-response was investigated by assessing FBF throughout a dose-escalating histamine infusion. Next, histamine was infused at a constant dose to assess acute tolerance. Finally, a four way, double-blind, randomized, placebo-controlled crossover study was conducted to assess FBF response to histamine in the presence of H1- and H2-receptor antagonists. Flare and itch were assessed in all studies. Results Histamine caused a dose-dependent increase in FBF, greatest with the highest dose (30 nmol min−1) infused [mean ( SEM) infused arm vs. control: 26.8 (5.3) vs. 2.6 ml min−1 100 ml−1; P < 0.0001]. Dose-dependent flare and itch were demonstrated. Acute tolerance was not observed, with an increased FBF persisting throughout the infusion period. H2-receptor antagonism significantly reduced FBF (mean (95% CI) difference from placebo at 30 nmol min−1 histamine: −11.9 ml min−1 100 ml−1 (−4.0, −19.8), P < 0.0001) and flare (mean (95% CI) difference from placebo: −403.7 cm2 (−231.4, 576.0), P < 0.0001). No reduction in FBF or flare was observed in response to the H1-receptor antagonist. Itch was unaffected by the treatments. Histamine did not stimulate vascular release of tissue plasminogen activator or von Willebrand factor. Conclusion Histamine causes dose-dependent vasodilatation, flare and itch in the human forearm. H2-receptors are important in this process. Our results support further exploration of combined H1- and H2-receptor antagonist therapy in acute allergic syndromes. [ABSTRACT FROM AUTHOR]

The ambulatory monitoring of biosignals involves the use of sensors, electrodes, actuators, processing tools and wireless communication modules. When a garment includes these elements with the purpose of recording vital signs and responding to specific situations it is call a 'Smart Wearable System'. Over the last years several authors have suggested that conductive textile material (e-textiles) could perform as electrode for these systems. This work aims at implementing an electrical characterization of e-textiles and an evaluation of their ability to act as textile electrodes for lower extremity venous occlusion plethysmography (LEVOP). The e-textile electrical characterization is carried out using two experimental set-ups ( in vitro evaluation). Besides, LEVOP records are obtained from healthy volunteers ( in vivo evaluation). Standard Ag/AgCl electrodes are used for comparison in all tests. Results shown that the proposed e-textiles are suitable for LEVOP recording and a good agreement between evaluations ( in vivo and in vitro) is found. [ABSTRACT FROM AUTHOR]

BackgroundPolyphenols in red wine are supposed to improve endothelial function. We investigated whether daily red wine consumption improves in-vivo vascular function by reducing endothelin-1 (ET-1). Additional pathways mediating this effect were studied using porcine coronary arteries (PCAs).MethodsEighteen young healthy women drank red wine daily for 3 weeks. Vascular function was evaluated by determining forearm blood flow (FBF) responses to endothelium-dependent (acetylcholine (ACh)) and endothelium-independent (sodium nitroprusside (SNP)) vasodilators. PCAs were suspended in organ baths and exposed to the endothelium-dependent vasodilator bradykinin, the nitric oxide (NO) donor S-nitroso-N-acetyl-L,L-penicillamine (SNAP) and/or red wine extract (RWE).ResultsACh-induced and SNP-induced FBF increases were equally enhanced after 3 weeks of red wine consumption, but an immediate enhancement (i.e., after drinking the first glass) was not observed. Vice versa, plasma ET-1 levels were not decreased after 3 weeks, but we observed an acute drop after drinking one glass of wine. RWE relaxed preconstricted PCAs in an endothelium-, NO-, and soluble guanylyl cyclase (sGC)/guanosine-3′,5′-cyclic monophosphate (cGMP)-dependent manner. Short RWE exposure reduced the response to bradykinin and SNAP by inactivating sGC. This effect disappeared upon prolonged RWE exposure.ConclusionsThe enhanced FBF response following 3 weeks of red wine consumption, but not after one glass, reflects a change in smooth muscle sensitivity. Alterations in sGC responsiveness/activity, rather than changes in ET-1, appear to underlie this phenomenon.American Journal of Hypertension (2011). doi:10.1038/ajh.2010.227 [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To quantitatively assess local muscle micro-circulation with real-time contrast-enhanced ultrasound (CEUS) during different exercises and compare the results with performed muscle work and global blood flow. Materials and methods: Sixteen low mechanical index CEUS examinations of the right lower leg flexors of healthy volunteers were performed using a continuous infusion of SonoVue® (4.8mL/300s). Several muscle perfusion parameters were extracted from derived CEUS signal intensity time curves during different isometric exercises (10–50% of maximum individual strength for 20–30s) and then correlated with the performed muscle work or force, and the whole lower leg blood flow which we measured simultaneously by venous occlusion plethysmography (VOP). Results: The shapes of the CEUS curve during and after exercise differed individually depending on the performed muscle work. The maximum blood volume MAX was observed only after exercise cessation and was significantly correlated with the performed muscle force (r =0.77, p <0.0001). The blood volume over exercise time was inversely correlated with the spent muscle work (r =−0.60, p =0.006). CEUS and VOP measurements correlated only at rest and after the exercise. During exercise, mean CEUS local blood volume decreased (from 3.48 to 2.19 (∼mL)), while mean VOP global blood flow increased (mean, from 3.96 to 7.71mL/100mg/min). Conclusion: Real-time low-MI CEUS provides complementary information about the local muscle micro-circulation compared to established blood flow measures. CEUS may be used for a better understanding of muscle perfusion physiology and in the diagnosis of micro-circulation alterations such as in peripheral arterial occlusive disease or diabetic angiopathy. [ABSTRACT FROM AUTHOR]

Background and aim: Adrenaline, administered locally by microdialysis in skeletal muscle, causes vasoconstriction around the microdialysis catheter. This is contrary to the vasodilation that normally occurs when adrenaline is infused intravenously or intra-arterially. The hypothesis was tested that vasoconstriction, measured by microdialysis, would not occur with two interventions causing increased plasma levels of adrenaline, mental stress and intravenous adrenaline infusion (0·1 nmol kg−1 min−1). Methods: Twenty-four men (27 ± 1·6 years) underwent these interventions. Blood flow was determined by the microdialysis ethanol technique and 133Xe clearance (gastrocnemius muscle, medial head) and by venous occlusion plethysmography (calf). Results: The ethanol outflow/inflow ratio, which is inversely related to blood flow, decreased to 92·0 ± 3·4% of basal, P = 0·014 (mean ± SEM, n = 16) during the mental stress test, but increased to 108·3 ± 2·2% of basal, P = 0·001 ( n = 16) during the adrenaline infusion. The latter increase was abolished when adrenaline was infused during α-receptor blockade by phentolamine. On the contrary, by 133Xe clearance and venous occlusion plethysmography, blood flow increased during both interventions; 2·0–1·7-fold (mental stress) and 1·3–1·4-fold (adrenaline infusion), respectively, P<0·05. Conclusion: Adrenaline causes vasoconstriction in skeletal muscle when blood flow is measured with the microdialysis ethanol technique, irrespective of the mode of administration. The discrepant blood flow result obtained with the microdialysis ethanol technique might, at least partly, be explained by differential diffusion properties of ethanol and 133Xe. An additional or alternative explanation might be that an inserted microdialysis catheter shifts the balance of vasoconstrictor and vasodilator effects of adrenaline in skeletal muscle. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Using the technique of venous occlusion plethysmography, endothelin (ET) antagonists have been shown to block the vasoconstrictive effects of intra-brachial ET-1 infusion on forearm blood flow. • Effects have been reported only when significant plasma concentrations of the antagonists are present. WHAT THIS STUDY ADDS • S-0139 is a selective ET antagonist given by intravenous administration. • In this study it is shown to have a prolonged duration of pharmacodynamic activity beyond that expected from its pharmacokinetic profile. AIMS To estimate the pharmacologically active dose range of a new investigational compound S-0139, a selective endothelin A (ETA) receptor antagonist, in man, and to examine the duration of its pharmacodynamic effect. METHODS Venous occlusion plethysmography was performed to assess changes in forearm blood flow following intra-brachial administration of endothelin-1 (ET-1). ETA antagonists have been shown to block ET-1-induced vasoconstriction in this model. The study was conducted in three parts: (1) a pilot study to explore dose–response (dose range 0.08–13.33 µg kg−1 min−1), (2) a randomized study to confirm dose–response (placebo, 2.5, 6.67 and 15 µg kg−1 min−1), and (3) a delayed administration study (15.7 µg kg−1 min−1) to explore the duration of the pharmacodynamic effect. In all studies a 3-h infusion of S-0139 was given and during the last 90 min of the infusion, ET-1 was infused concurrently for 90 min. In study (3) a second ET-1 infusion was given starting 3 h after completion of the first. RESULTS Intravenously administered S-0139 resulted in significant inhibition of ET-1-induced vasoconstriction in the forearm (plasma concentration 800–2000 ng ml−1). In the delayed administration study, the same extent of inhibition was still present when ET-1 was administered 3 h after the end of infusion of S-0139, even though the S-0139 plasma concentrations (mean 17 ng ml−1) were well below pharmacologically active concentrations as determined in studies 1 and 2. CONCLUSIONS S-0139 dose-dependently blocks ET-1-mediated vasoconstriction in the forearm and has a prolonged duration of effect beyond that expected from its pharmacokinetic profile. [ABSTRACT FROM AUTHOR]

Abstract: We developed a real-time low-MI contrast-enhanced ultrasound method (CEUS), compared it with venous occlusion plethysmography (VOP) and evaluated its robustness in the quantification of skeletal muscle perfusion during exercise. Contrast pulse sequencing (7MHz) during continuous intravenous infusion of SonoVue (4.8mL/300s) was used repeatedly in eight healthy volunteers to monitor changes of the muscle perfusion before, during and after isometric exercises (10 to 50% of individual maximum strength for 20 to 30 s) of the gastrocnemius muscle in real time. CEUS was correlated with VOP at different time points, and the exactness of several CEUS parameters obtained from ultrasound-signal-intensity-time curves was evaluated. Real-time CEUS depicted a large variability of the skeletal muscle blood volume at rest (mean, 3.48; range, 0.60 to 9.92 [∼mL]), with a significant reproducibility (r=0.72, p <0.05) and correlation with VOP (r=0.59, p <0.001). Mean blood volume during exercise was 1.58(∼mL), increased to a mean maximum after exercise of 8.88(∼mL), the mean change of the local blood volume during and directly after the exercise was –0.10 and +1.57(∼mL/s). The average CEUS signal during exercise decreased (mean area under the curve, –50.4[∼mL·s]) and subsequently increased post exercise (mean 118.6[∼mL·s]). CEUS parameters could be calculated with mean relative errors between 6 and 36%. Continuous assessment of local muscle microcirculation during exercise is possible with real-time CEUS with an acceptable robustness. Its application may be of particular interest in a better understanding of the role of perfusion during muscle training, and the monitoring of pathological vascular response, such as in diabetic microvessel diseases. (E-mail: martin.krix@kabelbw.de) [Copyright &y& Elsevier]

Aim: To find evidence that small changes in the positioning of the strain gauge, the environmental temperature (sympathetic activation) and position of the arm (venous pressure) alters the outcome of the venous occlusion plethysmography (VOP) measurement of forearm blood flow and to investigate if the hand circulation influences the results. Methods: Forearm blood flow was measured with VOP ( n = 6) on three occasions with air temperatures of 13, 20 and 38°C, respectively. At each occasion the arm position was varied; raised by 10°, horizontal or lowered by 15°. Strain gauges were placed on the forearm at the maximal circumference; 5 cm distal; and 5 cm proximal to this site, respectively. The hand circulation was excluded in half of the measurements. Results: The simple main effect of temperature was highly significant ( P<0·001). With excluded hand circulation (but not when included), there was a two factor interaction between arm position – strain gauge position ( P<0·05). The highest expansion rate was found in the proximal segment when the arm was elevated, but in the distal segment when the arm was lowered. With hand circulation (but not without) there was a two factor interaction between temperature and strain gauge position ( P<0·01). The highest expansion rate was found in the distal segment at normal and high temperatures, but in the proximal segment at low temperature. Conclusion: The volume expansion rate in a particular segment is dependent not only on arterial inflow. Segmental differences in capacity for venous expansion results in redistribution of blood to and from a segment, thus influencing the results obtained. [ABSTRACT FROM AUTHOR]

Abstract: Endothelial dysfunction is common in patients with chronic kidney disease (CKD) and contributes significantly to the high long-term cardiovascular morbidity and mortality. The short-term cardiovascular effects of recombinant human growth hormone (rhGH) in CKD patients (stages III–V) and healthy controls (n =15 each) were explored in a single-center, non-randomized pilot study. Subjects were investigated before, after a 7 day treatment with rhGH, and after a 7 day wash-out period. Microcirculation was assessed by nailfold capillaroscopy and leg strain gauge plethysmography. Echocardiography was performed and serum concentrations of IGF-I and IGF-binding protein-3 (IGFBP-3) were determined. Before the start of rhGH therapy, mean post-ischemic maximum flow velocity of erythrocytes (V RBC) and leg blood flow (LBF) in CKD patients were significantly reduced to 68% and 75% of that seen in controls, whereas V RBC and LBF under resting conditions were comparable. Treatment with rhGH significantly increased V RBC and LBF under resting conditions. Whereas maximum post-ischemic V RBC was improved by rhGH in patients and controls, maximum post-ischemic LBF increased in controls only. This was paralleled by a non-significant reduction of total vascular resistance, and increased heart rate and cardiac index. In conclusion, CKD patients respond to short-term rhGH treatment with significantly improved capillary blood flow, whereas only minor effects on total peripheral resistance and cardiac output were noted. [Copyright &y& Elsevier]

Peripheral arterial disease may lead to lower limb claudication and increased risk of systemic vascular dysfunction. In this article, the authors have investigated the peripheral vascular dysfunction evaluating forearm blood flow using venous occlusion plethysmography, lipid profile, and C-reactive protein in 60 patients with moderate intermittent claudication treated during 20 weeks with placebo (n = 16), cilostazol (200 mg/d; n = 17), or pentoxifylline (1200 mg/d; n = 15) in a randomized double-blinded clinical trial, taking into account smoking. Forearm blood flow after reactive hyperemia response (FBFh) or oral nitroglycerine spray to evaluate endothelial-dependent and endothelial-independent vasodilation, respectively, pain-free and maximal walking distance, levels of C-reactive protein, triglycerides, cholesterol, low-density lipoprotein, and high-density lipoprotein-cholesterol in plasma were determined. The results showed that there was an improvement in the high-density lipoprotein-cholesterol, pain-free and maximal walking distance, and FBFh independent of treatment in nonsmoking patients. Cilostazol increased high-density lipoprotein-cholesterol level, maximal walking distance, and FBFh, whereas pentoxifylline reduced C-reactive protein level and increased maximal walking distance in total and nonsmoking groups. No treatment was effective in smokers. [ABSTRACT FROM AUTHOR]

During ischaemia, the extracellular concentration of the endogenous nucleoside adenosine increases rapidly. Subsequent adenosine receptor stimulation induces various effects, including vasodilation, which can protect the tissue against the ischaemic insult. Adenosine deaminase (ADA) is an enzyme that catalyzes the irreversible deamination of adenosine. We hypothesized that the 22G>A polymorphism in the ADA gene inhibits its catalytic activity, and potentiates the protective effects of adenosine.In 96 healthy volunteers, blood was drawn to determine the ADA genotype, and the Vmax and Km values of the ADA from isolated erythrocytes. In a subgroup of volunteers (n=40) we measured the forearm vasodilator response to 13 min of forearm ischaemia using venous occlusion plethysmography as a read-out parameter for adenosine receptor stimulation.Although healthy volunteers with the 22GA genotype had a lower Vmax value of ADA than volunteers with the GG genotype (61.6±4.3 ng/min/mg, n=14, vs. 78.0±2.8 ng/min/mg, n=82; P=0.02), this did not potentiate the forearm vasodilator response to 13 min of ischaemia (77.4±8.8 ml/dl in the GA group (n=5) vs. 87.0±5.0 ml/dl (n=35), area under the curve, P=0.3).We conclude that heterozygosity for the 22G>A variant of ADA, although reducing catalytic activity, does not enhance forearm reactive hyperaemia. Therefore, the 22G>A variant probably does not contribute to any variability in the protective cardiovascular effects of adenosine. [ABSTRACT FROM AUTHOR]

Jeremy A. Patterson, Steve E. Selig, Deidre Toia, Voramont Bamroongsuk, David L. Hare. Forearm Blood Flow In Individuals With CHF And Age-Matched Healthy Volunteers: A Study And Historical Review. JEPonline 2007;10(5):1-15. This study examined forearm blood flow (FBF) in individuals with chronic heart failure (CHF) at rest, moderate exercise, and following limb occlusion. FBF was measured by venous occlusion plethysmography in CHF patients (n = 43) and healthy age-matched volunteers (n = 8) at rest and during exercise consisting of intermittent isometric hand squeezing at 15, 30, and 45% of maximum voluntary contraction (MVC). Peak vasodilatory capacity was also determined following the release of an occluding arm cuff. FBF was lower in CHF patients during exercise and during peak reactive hyperemia (PRH) compared to healthy volunteers, but there was no significant difference between groups at rest. Peak vasodilatory capacity was significantly higher in healthy volunteers than the CHF group ((30.6 ± 8.6 ml⋅100 mL-1⋅min-1 and 18.3 ± 6.9 ml⋅100 mL-1⋅min-1, respectively). Local blood flow stimulation in response to exercise or limb occlusion is reduced in individuals with CHF, however, there was no difference in resting flows between the two groups, suggesting vasodilatory medication may restore resting blood flow to healthy values. [ABSTRACT FROM AUTHOR]