Changes In Forearm Blood Flow Research Articles

Aerobic exercise training combined with local strength exercise restores muscle blood flow and maximal aerobic capacity in long-term Hodgkin lymphoma survivors.

It is unclear whether muscle blood flow (MBF) is altered in long-term Hodgkin lymphoma (HL) survivors. We tested the hypothesis that 1) MBF response during mental stress (MS) is impaired in long-term HL survivors and 2) aerobic exercise training combined with local strength exercise (ET) restores MBF responses during MS in these survivors. Eighteen 5-year HL survivors and 10 aged-paired healthy subjects (HC) were studied. Twenty HL survivors were randomly divided into two groups: exercise-trained (HLT, n = 10) and untrained (HLUT, n = 10). Maximal aerobic capacity was evaluated by a cardiopulmonary exercise test and forearm blood flow (FBF) by venous occlusion plethysmography. MS was elicited by Stroop color and word test. ET was conducted for 4 mo, 3/wk for 60 min each session. The aerobic exercise intensity corresponded to anaerobic threshold up to 10% below the respiratory compensation point. The strength exercises consisted of two to three sets of chest press, pulley and squat exercises, 12-15 repetitions each exercise at 30-50% of the maximal voluntary contraction. Baseline was similar in HL survivors and HC, except peak oxygen consumption (peak V̇o2, P = 0.013) and FBF (P = 0.006) that were lower in the HL survivors. FBF responses during MS were lower in HL survivors (P < 0.001). ET increased peak V̇o2 (11.59 ± 3.07%, P = 0.002) and FBF at rest (33.74 ± 5.13%, P < 0.001) and during MS (24 ± 5.31%, P = 0.001). Further analysis showed correlation between the changes in peak V̇o2 and the changes in FBF during MS (r = 0.711, P = 0.001). In conclusion, long-term HL survivors have impaired MBF responses during MS. ET restores MBF responses during MS.NEW & NOTEWORTHY Long-term Hodgkin lymphoma (HL) survivors have impaired muscle blood flow responses during mental stress and decreased maximal aerobic capacity. Supervised aerobic exercise training combined with local strength exercises restores muscle blood flow responses during mental stress and maximal aerobic capacity in these survivors. These findings provide evidence of safety and effectiveness of exercise training in HL survivors. Moreover, they highlight the importance of exercise training in the treatment of this set of patients.

Thermoregulatory Responses to Very Hot and Dry Heat Exposure: Interactions Between Age and Sex

Extreme heat events can cause mass morbidity and mortality. Older adults are more susceptible to the adverse effects of heat. Additionally, sex is known to independently influence the physiological responses to heat stress. However, less is known regarding the interaction between age and sex on thermoregulation. Purpose: This study investigated differences in thermoregulatory responses between males and females in older and younger individuals exposed to a hot and dry environment with accompanying activities of daily living. Methods: Twenty older (70 ± 4 yrs) and twenty younger (29 ± 5 yrs) adults (10 males and 10 females per group) were exposed to 3-hours of ambient heating, replicating peak environmental conditions during the 2018 Los Angeles heat wave (47 °C, 15% relative humidity). Participants performed seven 5-minute periods of light exercise (≍3 METS; metabolic heat production: 2.99 ± 0.33 W/kg) dispersed throughout the heat exposure to simulate heat generation associated with activities of daily living. Participants ingested 3 mL/kg/hr of tap-temperature water throughout the trial. Core temperature, skin temperature, and heart rate changes were assessed from pre-post heat exposure. Whole-body sweat rate and forearm blood flow changes were indexed to changes in core temperature. Data were analyzed using a two-way ANOVA (Age x Sex) Results: Delta core temperature was greater in older individuals (males: 1.43 ± 0.47°C, females: 1.31 ± 0.39°C) than in younger (males: 0.83 ± 0.22°C, females: 0.53 ± 0.24°C, p&lt;0.001) but there was no difference between sex (p = 0.063) nor was there an interaction (p = 0.423). There was an interaction of age and sex on delta heart rate (p = 0.019). Older females (32 ± 9 bpm) had greater increases in heart rate than older males (18 ± 8 bpm), younger males (18 ± 6 bpm), and younger females (18 ± 12 bpm, p ≤ 0.009 for all comparisons). There was no effect of age (p = 0.529), sex (p = 0.670), or interaction (p = 0.422) on delta skin temperature. There was an interaction between age and sex for whole-body sweat loss (WBSL) indexed to changes in core temperature and body surface area (p = 0.009). Younger females (1688 ± 685 mL/m2/°C) had greater WBSL than older females (612 ± 211 mL/m2/°C, p &lt; 0.0001), older males (694 ± 327 mL/m2/°C, p &lt; 0.0001), and younger males (1038 ± 282 mL/m2/°C, p &lt; 0.0001). There was a main effect of sex (p = 0.003) and age (p &lt; 0.0001), but no interaction (p = 0.152) on delta forearm blood flow indexed to changes in core temperature (older males: 116 ± 67 mL/min/°C, older females: 194 ± 73 mL/min/°C, younger males: 263 ± 72 mL/min/°C, younger females: 468 ± 243 mL/min/°C). Conclusion: These data suggest that many thermoregulatory responses to heat stress are influenced by the interaction between age and sex. Supported by NIH R01AG069005 (CGC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Simultaneous measurements of tissue blood flow and oxygenation using a wearable fiber-free optical sensor.

.Significance: There is an essential need to develop wearable multimodality technologies that can continuously measure both blood flow and oxygenation in deep tissues to investigate and manage various vascular/cellular diseases.Aim: To develop a wearable dual-wavelength diffuse speckle contrast flow oximetry (DSCFO) for simultaneous measurements of blood flow and oxygenation variations in deep tissues.Approach: A wearable fiber-free DSCFO probe was fabricated using 3D printing to confine two small near-infrared laser diodes and a tiny CMOS camera in positions for DSCFO measurements. The spatial diffuse speckle contrast and light intensity measurements at the two different wavelengths enable quantification of tissue blood flow and oxygenation, respectively. The DSCFO was first calibrated using tissue phantoms and then tested in adult forearms during artery cuff occlusion.Results: Phantom tests determined the largest effective source–detector distance (15 mm) and optimal camera exposure time (10 ms) and verified the accuracy of DSCFO in measuring absorption coefficient variations. The DSCFO detected substantial changes in forearm blood flow and oxygenation resulting from the artery occlusion, which meet physiological expectations and are consistent with previous study results.Conclusions: The wearable DSCFO may be used for continuous and simultaneous monitoring of blood flow and oxygenation variations in freely behaving subjects.

Breast Cancer Survivors Improved Forearm Blood Flow Following a Single Bout of Aerobic Exercise: Preliminary Results

Chemotherapy impairs endothelial and resistance artery function contributing to arterial dysfunction, a cardiovascular disease (CVD) risk factor. In healthy individuals, a bout of aerobic exercise acutely improves arterial function. However, the acute effect of aerobic exercise on resistance artery function has not been examined in breast cancer survivors (BCS).PURPOSETo examine the effect of a single bout of aerobic exercise on forearm blood flow in BCS.METHODSSeven BCS (48 ± 4 yrs; 26.0 ± 2.8 kg/m2), 1–5 year post‐chemotherapy treatments and eight female controls (44 ± 9 yrs; 24.2 ± 5.3 kg/m2) completed 30 minutes of cycling exercise at 65% of their maximal aerobic capacity. Cardiac output (Q), Heart rate (HR), mean arterial pressure (MAP), and forearm blood flow (FBF) were assessed at baseline, 15 and 45 minutes post exercise. Automated ambulatory blood pressure monitor was used to acquire Q, HR, and MAP. FBF and Peak FBF was measured with strain‐gauge plethysmography at rest and following 5 minutes of upper arm occlusion respectively. Reactive hyperemia was calculated as the change between baseline and peak FBF. Area under the curve was calculated by including 13 measurements after the 5 min occlusion. Conductance was estimated as FBF divided by mean arterial blood pressure.RESULTSSee Table. In BCS and control groups baseline FBF and conductance increased 15‐min post‐exercise and returned to baseline at 45 minutes post exercise (p&lt;0.05). MAP decreased at 45‐min post‐exercise in both groups (p&lt;0.05). HR was elevated at 15‐min and 45‐min in both groups (p&lt;0.001), while BCS had an overall higher HR (p&lt;0.05). There were no changes in peak FBF, reactive hyperemia area under the curve, peak conductance and Q following exercise.CONCLUSIONBaseline forearm blood flow increased in breast cancer survivors following a single bout of aerobic exercise likely as a result of acute forearm vasodilation. In addition, breast cancer survivors did not exhibit differences at baseline or following exercise suggesting that arterial function was preserved 1–5 years following chemotherapy.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Elevated extracellular potassium prior to muscle contraction reduces onset and steady-state exercise hyperemia in humans

The increase in interstitial potassium (K+) during muscle contractions is thought to be a vasodilatory signal that contributes to exercise hyperemia. To determine the role of extracellular K+ in exercise hyperemia, we perfused skeletal muscle with K+ before contractions, such that the effect of any endogenously-released K+ would be minimized. We tested the hypothesis that local, intra-arterial infusion of potassium chloride (KCl) at rest would impair vasodilation in response to subsequent rhythmic handgrip exercise in humans. In 11 young adults, we determined forearm blood flow (FBF) (Doppler ultrasound) and forearm vascular conductance (FVC) (FBF/mean arterial pressure) during 4 min of rhythmic handgrip exercise at 10% of maximal voluntary contraction during 1) control conditions, 2) infusion of KCl before the initiation of exercise, and 3) infusion of sodium nitroprusside (SNP) as a control vasodilator. Infusion of KCl or SNP elevated resting FVC similarly before the onset of exercise (control: 39 ± 6 vs. KCl: 81 ± 12 and SNP: 82 ± 13 ml·min-1·100 mmHg-1; both P < 0.05 vs. control). Infusion of KCl at rest diminished the hyperemic (ΔFBF) and vasodilatory (ΔFVC) response to subsequent exercise by 22 ± 5% and 30 ± 5%, respectively (both P < 0.05 vs. control), whereas SNP did not affect the change in FBF ( P = 0.74 vs. control) or FVC ( P = 0.61 vs. control) from rest to steady-state exercise. These findings implicate the K+ ion as an essential vasodilator substance contributing to exercise hyperemia in humans. NEW & NOTEWORTHY Our findings support a significant and obligatory role for potassium signaling in the local vasodilatory and hyperemic response to exercise in humans.

Forearm vasodilator responses to environmental stress and reactive hyperaemia are impaired in young South Asian men

PurposePrevalence of cardiovascular disease (CVD) is greater in South Asians (SAs) than White Europeans (WEs). Endothelial dysfunction and blunted forearm vasodilatation to environmental stressors have been implicated in CVD. We investigated whether these features are present in young SA men.MethodsIn 15 SA and 16 WE men (19–23 years), we compared changes in forearm blood flow, arterial blood pressure (ABP), forearm vascular conductance (FVC), heart rate, and electrodermal resistance (EDR; sweating) following release of arterial occlusion (reactive hyperaemia endothelium-dependent) and 5 single sounds at 5–10 min intervals (stressors).ResultsAll were normotensive. Peak reactive hyperaemia was smaller in SAs than WEs (FVC increase: 0.36 ± 0.038 vs 0.44 ± 0.038 units; P < 0.05). Furthermore, in WEs, mean FVC increased at 5, 15, and 20 s of each sound (vasodilatation), but increased at 5 s only in SAs, decreasing by 20 s (vasoconstriction). This reflected a smaller proportion of SAs showing forearm vasodilatation at 15 s (5/15 SAs vs 11/16 WEs: P < 0.01), the remainder showing vasoconstriction. Concomitantly, WEs showed greater bradycardia and EDR changes. Intra-class correlation analyses showed that all responses were highly reproducible over five sounds in both WEs and SAs. Moreover, sound-evoked changes in ABP and FVC were negatively correlated in each ethnicity (P < 0.01). However, WEs showed preponderance of forearm vasodilatation and depressor responses; SAs showed preponderance of vasoconstriction and pressor responses.ConclusionsEndothelium-dependent vasodilatation is blunted in young SA men. This could explain their impaired forearm vasodilatation and greater pressor responses to repeated environmental stressors, so predisposing SAs to hypertension and CVD.

Tissue oxygenation index reflects changes in forearm blood flow after brief ischemia.

Whether the near-infrared spectroscopy (NIRS) technology correctly detects the changes in oxygenation related to ischemia and reperfusion of organs and tissues other than brain remains unclear. The present study examined how different tissue oxygenation parameters derived from NIRS reflect the changes in the forearm blood flow (FBF) according to the brief ischemia and the subsequent reperfusion, and whether values of these parameters move in parallel with the medial and lateral sides of FBF. Thirteen volunteers underwent the prospective observational study. The tissue oxygenation index (TOI), regional saturation of oxygen (rSO2), skin tissue oxygenation (StO2), and FBF values were evaluated in the forearm. Medial rSO2 values at 1 to 3 minutes after the termination of brief ischemia were higher than lateral rSO2 and respective TOI values. FBF and StO2 values quickly increased according to the cessation of brief ischemia, whereas the medial and lateral values did not differ during and after the brief ischemia. TOI and StO2, but not rSO2, reflected changes in FBF of both medial and lateral sides simultaneously in response to the reperfusion after brief ischemia. The muscle tissue oxygenation during reperfusion favors the use of TOI and StO2, but not rSO2, as the surrogate parameter. J. Med. Invest. 64: 228-232, August, 2017.

Effect of Hyperhydration on the Cardiovascular Responses to an LBNP Presyncopal Challenge

PURPOSETo determine the effects of hyperhydration on heart rate, blood pressure, leg blood volume and forearm blood flow during a lower body negative challenge to presyncope.METHODSNine subjects (Age = 20.2 ± 1.3 yrs, Weight = 75.3 ± 21.1 kgs) participated in two graded LBNP (Lower Body Negative Pressure) tests to pre‐syncope while forearm blood flow (FBF), heart rate (HR), blood pressure (BP), and leg blood volume were measured. Each subject was tested in a control trial (with no fluid ingestion), and after consumption of a hypervolemia‐inducing beverage (NaCl solution of 4.9g per kg of body weight in 10mL of grape flavored Propel). Treatment order was randomized for all subjects. A cumulative stress index (CSI) was subsequently calculated (minutes completed x box pressure) to assess changes in orthostatic tolerance between the control and fluid ingestion LBNP. For all trials in the LBNP chamber, subjects were tested at LBNP levels of −20 mmHg, −40 mmHg, and −60 mmHg for three minutes at each trial, and then an additional increase of −10 mmHg every three minutes until pre‐syncopal symptoms appeared. Forearm blood flow was measured using venous occlusion plethysmography. Near‐infrared spectroscopy (Portamon, Artinis, Inc.) in the right calf muscle was used to determine lower leg blood volume.RESULTSThere were no significant differences in CSI between the hyperhydration (619.8 ± 55.2mmHg.min) and control conditions (640.0 ± 70.3 mmHg.min). Furthermore, the change in forearm blood flow, lower leg blood volume, and heart rate during the LBNP hyperhydration trial were not different from the control trial.CONCLUSIONIngestion of a hypervolemia‐inducing beverage did not alter orthostatic tolerance or the cardiovascular responses to an orthostatic challenge. This suggests that either a larger volume of fluid or a fluid with a different composition needs to be ingested to improve orthostatic tolerance.

Increment of body mass index is positively correlated with worsening of endothelium-dependent and independent changes in forearm blood flow.

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 139: Vascular Endothelin-1 Activity Increases with Age in Hypertensive Patients

Background: Vascular endothelin-1 (ET-1) dependent vasoconstriction is elevated in patients with hypertension. The effect of increasing age on ET-1 activity is unknown. This study investigated the hypothesis that age is directly associated with ET-1 activity in hypertensive patients. Methods: Retrospective analysis of data collected in a prospective clinical study that investigated vascular ET-1 activity in patients with essential hypertension (BP&gt;140/90mmHg). Endothelin-1 activity was expressed as forearm blood flow (FBF) responses as measured by strain-gauge plethysmography during the intra-arterial infusion of the selective endothelin type-A receptor antagonist BQ-123 (100 nmol/min) for 60 minutes. Changes in FBF from baseline in response to BQ-123 were assessed by one-way ANOVA for repeated measures. Association analyses were performed with use of the Pearson correlation coefficient. Results: Data from 40 patients were included in the current analyses. The baseline characteristics of the study population are reported in the table. Infusion of BQ-123 induced a significant increase in FBF from baseline (p&lt;0.001). The percent increase in FBF from baseline at 60 minutes of BQ-123 infusion was significantly directly associated with age (r=0.435; p=0.006), but not with blood pressure, parameters of glucose and lipid metabolism, markers of endothelial activation, and adipocytokine levels (p=NS for all). Conclusions: In patients with essential hypertension, ET-1 activity is directly associated with age. Our findings suggest that, in this population, aging may contribute to vascular damage and cardiovascular disease risk through an enhanced activation of the ET-1 system. Further study is needed to elucidate the mechanisms underlying the association between age and vascular ET-1 activity.

Role of aldehyde dehydrogenase in hypoxic vasodilator effects of nitrite in rats and humans.

Background and PurposeHypoxic conditions favour the reduction of nitrite to nitric oxide (NO) to elicit vasodilatation, but the mechanism(s) responsible for bioconversion remains ill defined. In the present study, we assess the role of aldehyde dehydrogenase 2 (ALDH2) in nitrite bioactivation under normoxia and hypoxia in the rat and human vasculature.Experimental ApproachThe role of ALDH2 in vascular responses to nitrite was studied using rat thoracic aorta and gluteal subcutaneous fat resistance vessels from patients with heart failure (HF; 16 patients) in vitro and by measurement of changes in forearm blood flow (FBF) during intra-arterial nitrite infusion (21 patients) in vivo. Specifically, we investigated the effects of (i) ALDH2 inhibition by cyanamide or propionaldehyde and the (ii) tolerance-independent inactivation of ALDH2 by glyceryl trinitrate (GTN) on the vasodilator activity of nitrite. In each setting, nitrite effects were measured via evaluation of the concentration–response relationship under normoxic and hypoxic conditions in the absence or presence of ALDH2 inhibitors.Key ResultsBoth in rat aorta and human resistance vessels, dilatation to nitrite was diminished following ALDH2 inhibition, in particular under hypoxia. In humans there was a non-significant trend towards attenuation of nitrite-mediated increases in FBF.Conclusions and ImplicationsIn human and rat vascular tissue in vitro, hypoxic nitrite-mediated vasodilatation involves ALDH2. In patients with HF in vivo, the role of this enzyme in nitrite bioactivation is at the most, modest, suggesting the involvement of other more important mechanisms.

Endothelium‐Dependent and ‐Independent Vasodilation in Women at Risk of Hypertension

Women with uterine fibroids (UF), benign tumors of the myometrium, have a greater prevalence of hypertension than women without UF. The mechanism of this predisposition is unclear. Individuals with borderline hypertension have endothelial dysfunction in the form of decreased endothelium‐dependent vasodilation in response to intra‐arterial acetylcholine infusion. It is possible that women with UF also demonstrate impaired endothelium‐dependent vasodilation prior to overt clinical hypertension. We measured forearm blood flow (FBF) using venous occlusion plethysmography at baseline and during intra‐arterial acetylcholine (ACH; 1.0‐4.0 μg/100 ml tissue/min) and sodium nitroprusside (SNP; 0.25‐2.00 μg/100 ml tissue/min) infusions in 4 normotensive women with UF (41±3 y) and 4 age‐matched normotensive women without UF. These women did not differ in body mass index or mean arterial pressure (97±4 vs. 103±6 mmHg, Control vs. UF; p&gt;0.05). Baseline FBF was not different between the two groups (1.6±0.4 vs. 3.0±1.3 ml/100 ml tissue/min; Control vs. UF; p&gt;0.05). FBF increased significantly from baseline in both groups at the highest doses of ACH and SNP; however, the change in FBF was not significantly different between groups (ACH: Δ8.6±1.6 vs. 9.5±4.1 ml/100 ml tissue/min; SNP: Δ9.8±3.0 vs. 13.1±4.6 ml/100 ml tissue/min; Control vs. UF; p&gt;0.05). Our preliminary results suggest that FBF responses to ACH and SNP do not differ between women with and without UF; thus, impairments in endothelium‐dependent and ‐independent vasodilation do not appear to contribute to hypertension risk in normotensive women with UF.&#x0D; Funded by AHA and NIH.

환경온 변화에 따른 비만 아동의 체온조절 행동

This study investigates thermoregulatory behaviors of obese children for their thermal comfort. Nine normal-weight children (NWC) and nine obese children (OC) participated in the study. All subjects were fourth-graders and sixth-graders in elementary school. An informed consent form was obtained from each child and his or her mother. The questionnaire method was used, and the experiment was conducted to determine the preferred amount of clothing at 17℃ and the preferred temperature at 33 ℃. According to the results, OC were more susceptible to heat than NWC, whereas there was no significant difference in their susceptibility to cold. There were no significant differences of the oral temperature and the mean skin temperature between the two groups, but changes in forearm blood flow were less in OC than in NWC. There was no significant difference in the preferred amount of clothing between OC and NWC, and the preferred temperature was higher in NWC than in OC. The results based on the questionnaire are consistent with those based on the experiment. A compositive study of physical exercise, eating behavior, and wearing behavior should be useful for developing programs for preventing and treating obese children. Keywords: obese children, thermoregulatory behaviors, preferred temperature, heat, cold

The effect of liraglutide on endothelial function in patients with type 2 diabetes

This single-centre, 12-week, double-blind, placebo-controlled trial assessed how the human glucagon-like-peptide 1 analogue liraglutide impacted endothelial function in adult patients (n = 49) with type 2 diabetes and no overt cardiovascular disease. Patients were randomized to liraglutide, placebo or glimepiride. At baseline and Week 12, venous occlusion plethysmography was used to measure forearm blood flow (FBF) in response to acetylcholine (ACh) and sodium nitroprusside (SNP) before and after (L)-N(G)-monomethyl arginine (L-NMMA) infusion. At Week 12, ACh-mediated FBF increased with liraglutide and decreased with placebo; however, the between-treatment difference was not significant (p = 0.055). Inhibition of ACh-mediated FBF after L-NMMA infusion increased with liraglutide and decreased with placebo; this between-treatment difference was also not significant (p = 0.149). No change in FBF was observed with SNP. Liraglutide did not significantly impact endothelium-dependent vasodilation after 12 weeks; however, additional investigations looking at the effect of liraglutide on endothelial function in alternative vasculature and during the postprandial period are warranted.

B-29 Free Communication/Poster - Concussion

Hyperoxia can cause substantial reductions in the peripheral and coronary blood flow at rest and during exercise. This has been attributed to an increase in reactive oxygen species (ROS) generation during hyperoxia. Indeed, vitamin C has been shown to restore coronary flow during administration of 100% O2. However, this model has not been studied in local exercising skeletal muscle. PURPOSE: The primary aim of this study was to investigate the role of ROS in hyperoxia induced reductions in skeletal muscle blood flow during forearm exercise. METHODS: 12 young healthy adults (28±2 years) performed forearm handgrip exercise under normoxia and hyperoxia with saline or Vitamin C infusions. Forearm blood flow (FBF) was measured using Doppler ultrasound while forearm vascular conductance (FVC) was calculated from FBF and mean arterial pressure (brachial artery catheter). RESULTS: Under the control (saline) condition, the percent change of FBF and FVC during hyperoxic exercise (86.3±5.1% and 86.8±5.2%, respectively) was reduced as compared to normoxia (mean=100%) (P 20%, 10-20%, and 20%), infusion of Vitamin C substantially increased the FBF and FVC responses to hyperoxic exercise (102.0±5.2% and 100.8±6.1% respectively) compared to control (saline) conditions (67.1±4.0% and 66.8±3.6% respectively) (P<0.05). However, this was not observed with individuals in the other 2 sub-groups. CONCLUSIONS: Our data suggests that in participants with the greatest hyperoxia induced vasoconstriction during forearm exercise, ROS generation may be a contributing factor. Hence, when Vitamin C is administered during hyperoxic exercise, the FBF seems to be restored only in the individuals who have a 20% or greater decrease in FBF.

Histamine‐induced vasodilatation in the human forearm vasculature

To investigate the mechanism of action of intra-arterial histamine in the human forearm vasculature. 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. 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 cm(2) (-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. 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.

Roles of nitric oxide and prostaglandins in the hyperemic response to a maximal metabolic stimulus: redundancy prevails

Vasodilatory mechanisms controlling post-exercise or post-ischemic hyperemia are thought to be under redundant control and remain incompletely understood. A maximal metabolic stimulus evoked by ischemic exercise (IE) might limit redundancy by full activation of multiple pathways. We tested whether nitric oxide (NO) and/or prostaglandins contribute to the hyperemic response to IE. 17 subjects were randomized into two groups and performed three trials of IE during control (saline), N (G)-monomethyl-L-arginine (L-NMMA; NOS inhibition) (protocol 1) or ketorolac (cyclooxygenase inhibition) infusion (protocol 2), and combined L-NMMA/ketorolac infusion via a brachial arterial catheter. Forearm blood flow (FBF) was measured with venous occlusion plethysmography following IE trials consisting of 5 min of ischemia and simultaneous rhythmic handgrip exercise (final 2 min). Peak and total (area under the curve) FBF and blood pressure (MAP) were measured for 3 min after each trial. Forearm vascular conductance (FVC) was calculated as FBF/MAP. Change (Δ) in peak FBF and FVC from baseline differed only between peak FBF for the saline and L-NMMA + ketorolac trials in protocol 1. Peak ΔFBF was 26.8 ± 2.5, 30.0 ± 2.8, and 33.9 ± 3.6 ml 100 ml(-1) min(-1) for saline, L-NMMA, and L-NMMA + ketorolac trials (P = 0.04). For protocol 1 (n = 8), total ΔFVC was 59.6 ± 4.3, 57.8 ± 6.0, and 59.9 ± 5.6 ml 100 ml(-1) 100 mmHg(-1) for saline, L-NMMA, and L-NMMA + ketorolac trials, (P = 0.82). For protocol 2 (n = 9), total ΔFVC was 54.2 ± 5.0, 56.9 ± 4.5, and 56.5 ± 5.3 ml 100 ml(-1) 100 mmHg(-1) for saline, ketorolac, and ketorolac + L-NMMA trials, (P = 0.69). These results suggest that NO and PGs are not obligatory for the hyperemic response to IE, and other vasodilator mechanisms predominate.

Impairment of endothelium-dependent and endothelium-independent peripheral vasodilation in patients with chronic heart failure due to nonischemic heart disease

The authors have examined changes in forearm blood flow during local intra-arterial infusion of acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct dilator of smooth muscle) in patients with heart failure due to nonischemic heart disease. Incremental step-up doses of acetylcholine and nitroprusside were infused locally into the brachial artery in 10 healthy controls (group 1), 13 patients with no history of decompensated congestive heart failure (group 2), and 13 patients who exhibited congestive heart failure before admission (group 3). Forearm blood flow was measured by venous occlusion plethysmography. Systemic blood pressure and heart rate were not affected significantly by either infusion in any of the three groups. Groups 1 and 2 showed similar changes in forearm blood flow after endothelium-dependent and endothelium-independent vasodilation, but these changes were attenuated significantly in group 3 (both p<0.05). Although there were no significant differences in clinical characteristics including hemodynamic parameters between groups 2 and 3, plasma noradrenaline concentration was elevated in group 3 (p<0.01). A significant negative correlation was found between plasma noradrenaline level and nitroprusside- or acetylcholine-induced change in forearm blood flow (nitroprusside: r=−0.36, p<0.05; acetylcholine: r=−0.42, p<0.05). These observations demonstrate that the attenuation of the response to vasodilatory stimuli in the peripheral vasculature may persist in the convalescent phase after decompensated heart failure and that the vascular dysfunction may be due not only to endothelial dysfunction but also to an endothelium-independent mechanism such as neurohormonal activation.

Comparison of VOP and Doppler ultrasound in measuring forearm blood flow during direct heating

PURPOSE Venous occlusion plethysmography (VOP) is the gold standard for measuring forearm blood flow to obtain maximal skin blood flow. We sought to compare this method to Doppler ultrasound. METHODS Seven subjects (four female, three male; BMI = 23±3 kg.m−1) underwent a ramped local heating protocol. Local heating was achieved by heating the forearm with a water spray device. Doppler ultrasound of the brachial artery and forearm VOP were measured during five stages: under thermoneutral conditions (33oC), after 15 minutes of heating at 36oC, 39oC, and 42oC, and after 30 minutes of heating at 42oC. The protocol aimed to produce a linear rise in blood flow with each subsequent stage. Doppler ultrasound and VOP blood flow measurements were compared by linear regression analysis. RESULTS The protocol was successful in covering a wide range of blood flow, from normal baseline to near maximal values. Measurement of forearm blood flow using Doppler ultrasound and VOP were shown to be highly correlated, with a regression coefficient of R2 = 0.773. CONCLUSION Comparable changes in forearm blood flow can be measured using either Doppler ultrasound or VOP.

Endothelial Dysfunction and Subsequent Decline in Glomerular Filtration Rate in Hypertensive Patients

Chronic kidney disease is a risk factor for cardiovascular disease, increasing all-cause mortality. Some evidence suggests that endothelial dysfunction is present in the early stages of renal insufficiency, but no data exist about its possible role in the progression of renal disease. Thus, we prospectively evaluated the effect of endothelial function on estimated glomerular filtration rate (eGFR) in essential hypertension. We enrolled 500 never-treated uncomplicated hypertensive subjects with serum creatinine < or =1.5 mg/dL. Endothelial function was measured by strain-gauge plethysmography during intra-arterial infusion of acetylcholine and sodium nitroprusside. eGFR was calculated by use of the Chronic Kidney Disease Epidemiology Collaboration equation. The annual rate of decline of eGFR (DeltaeGFR/y) was determined as the difference between the follow-up and baseline eGFR values, with this value divided by the time interval in years. During follow-up (92.3+/-36.2 months), mean DeltaeGFR/y was 1.49+/-1.65 mL . min(-1) . 1.73 m(-)(2), with no significant differences between men and women (1.55+/-1.72 versus 1.43+/-1.58 mL . min(-1) . 1.73 m(-)(2), respectively; P=0.455). This was correlated with acetylcholine-stimulated forearm blood flow (r=-0.256, P<0.0001), creatinine (r=0.141, P=0.001), systolic blood pressure (r=-0.103, P=0.01), and eGFR (r=0.092, P=0.020). In multivariable regression analysis, forearm blood flow and systolic blood pressure remained associated with change in eGFR. On average, eGFR changed by 0.37 mL . min(-1) . 1.73 m(-)(2) for each 100% change in forearm blood flow (P<0.001) and by 0.1 mL . min(-1) . 1.73 m(-)(2) for each difference of 10 mm Hg in systolic blood pressure (P=0.032). We demonstrated that acetylcholine-stimulated vasodilation and systolic blood pressure were associated with eGFR loss after adjustment for other cardiovascular risk factors and antihypertensive treatment.