Relationship between upper and lower limb conduit artery vasodilator function in humans

Brachial artery flow-mediated dilation (FMD) is a strong predictor of future cardiovascular disease and is believed to represent a "barometer" of systemic endothelial health. Although a recent study [Padilla et al. Exp Biol Med (Maywood) 235: 1287-1291, 2010] in pigs confirmed a strong correlation between brachial and femoral artery endothelial function, it is unclear to what extent brachial artery FMD represents a systemic index of endothelial function in humans. We conducted a retrospective analysis of data from our laboratory to evaluate relationships between the upper (i.e., brachial artery) vs. lower limb (superficial femoral n = 75; popliteal artery n = 32) endothelium-dependent FMD and endothelium-independent glyceryl trinitrate (GTN)-mediated dilation in young, healthy individuals. We also examined the relationship between FMD assessed in both brachial arteries (n = 42). There was no correlation between brachial and superficial femoral artery FMD (r(2) = 0.008; P = 0.46) or between brachial and popliteal artery FMD (r(2) = 0.003; P = 0.78). However, a correlation was observed in FMD between both brachial arteries (r(2) = 0.34; P < 0.001). Brachial and superficial femoral artery GTN were modestly correlated (r(2) = 0.13; P = 0.007), but brachial and popliteal artery GTN responses were not (r(2) = 0.08; P = 0.11). Collectively, these data indicate that conduit artery vasodilator function in the upper limbs (of healthy humans) is not predictive of that in the lower limbs, whereas measurement of FMD in one arm appears to be predictive of FMD in the other. These data do not support the hypothesis that brachial artery FMD in healthy humans represents a systemic index of endothelial function.     

Fluid ingestion during exercise increases skin blood flow independent of increases in blood volume.

The purpose of this experiment was to determine whether fluid ingestion attenuates the hyperthermia and cardiovascular drift that occurs during exercise dehydration due to increases in blood volume. In addition, forearm blood flow, which is indicative of skin blood flow, was measured to determine whether the attenuation of hyperthermia and cardiovascular drift during exercise with fluid ingestion is due to higher skin blood flow. On three different occasions, seven trained cyclists [mean age, body weight, and maximum oxygen uptake: 23 +/- 3 yr, 73.9 +/- 10.5 kg, and 4.75 +/- 0.34 (SD) l/min, respectively] cycled at a power output equal to 62-67% maximum oxygen uptake for 2 h in a warm environment (33 degrees C, 50% relative humidity, wind speed 2.5 m/s). During exercise, they randomly received no fluid (NF) or a volume of a carbohydrate-electrolyte fluid replacement solution (FR) sufficient to replace 80 +/- 2% of sweat loss or were intravenously infused with 5.3 ml/kg of a blood volume expander (BVX; 6% dextran in saline). The infusion of 398 +/- 23 ml of BVX maintained blood volume at levels similar to that when 2,404 +/- 103 ml of fluid were ingested during FR and greater than that when no fluid was ingested during the 2nd h of exercise (P less than 0.05). However, BVX and NF resulted in similar esophageal and rectal temperatures, forearm blood flow, and elevations in serum osmolality and sodium concentration during 2 h of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional cerebral artery mean flow velocity and blood flow during dynamic exercise in humans.

Transcranial Doppler ultrasound-determined middle (MCA) and anterior (ACA) cerebral artery mean flow velocities (Vmean) and pulsatility indexes (PI) were measured during "no-load" [21, 60, and 102 revolutions/min (rpm)] and loaded cycling (30, 60, and 149 W) at approximately 60 rpm. At rest Vmean MCA was 51 (36-55) cm/s (median and range; n = 10) and Vmean ACA was 41 (36-49) cm/s (n = 7; P < 0.05). With no load on the cycle Vmean MCA increased 4 (2-36), 10 (0-47), and 27% (4-58) (P < 0.05) at the three pedaling frequencies, respectively; arterial PCO2 (PaCO2) remained constant. During loaded cycling the increases were 19 (6-42), 25 (2-45), and 32% (12-67) (P < 0.01), respectively, with only a minimal change in PaCO2. No significant changes were observed in Vmean ACA. Changes in Vmean MCA were similar to those recorded by the initial slope index (ISI) of the 133Xe clearance method (n = 11), which in turn were smaller than increases recorded by the fast-compartment flow. PI ACA followed PI MCA during no-load as well as loaded exercise and increased with work rate, perhaps reflecting an increase in pulse pressure from 56 (48-63) mmHg at rest to 109 (88-123) mmHg at 149 W (P < 0.01). Data demonstrate a graded increase in regional cerebral perfusion during dynamic exercise corresponding to the MCA territory.     

Middle cerebral artery flow velocity and blood flow during exercise and muscle ischemia in humans.

Changes in middle cerebral artery flow velocity (Vmean), measured by transcranial Doppler ultrasound, were used to determine whether increases in mean arterial pressure (MAP) or brain activation enhance cerebral perfusion during exercise. We also evaluated the role of "central command," mechanoreceptors, and/or muscle "metaboreceptors" on cerebral perfusion. Ten healthy subjects performed two levels of dynamic exercise corresponding to a heart rate of 110 (range 89-134) and 148 (129-170) beats/min, respectively, and exhaustive one-legged static knee extension. Measurements were continued during 2-2.5 min of muscle ischemia. MAP increased similarly during static [114 (102-133) mmHg] and heavy dynamic exercise [121 (104-136) mmHg] and increased during muscle ischemia after dynamic exercise. During heavy dynamic exercise, Vmean increased 24% (10-47%; P less than 0.01) over approximately 3 min despite constant arterial carbon dioxide tension. In contrast, static exercise with a higher rate of perceived exertion [18 (13-20) vs. 15 (12-18) units; P less than 0.01] was associated with no significant change in Vmean. Muscle ischemia after exercise was not associated with an elevation in Vmean, and it did not provoke an increase in Vmean after static exercise. Changes in Vmean during exercise were similar to those recorded with the initial slope index of the 133Xe clearance method. The data show that middle cerebral artery mean flow velocity reflects changes in cerebral perfusion during exercise. Furthermore, they support the hypothesis that cerebral perfusion during exercise reflects an increase in brain activation that is independent of MAP, central command, and muscle metaboreceptors but is likely to depend on influence of mechanoreceptors.     

Heterogeneity in conduit artery function in humans: impact of arterial size

To determine whether conduit artery size affects functional responses, we compared the magnitude, time course, and eliciting shear rate stimulus for flow-mediated dilation (FMD) in healthy men (n = 20; 31 +/- 7 yr). Upper limb (brachial and radial) and lower limb (common and superficial femoral) FMD responses were simultaneously assessed, whereas popliteal responses were measured in the same subjects during a separate visit. Glyceryl trinitrate (GTN)-mediated responses were similarly examined. Edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, were used to calculate conduit artery diameter, blood flow, and shear rate continuously across the cardiac cycle. Baseline artery size correlated inversely with the FMD response (r = -0.57, P < 0.001). Within-artery comparisons revealed a significant inverse correlation between artery size and FMD% for the radial (r = -0.66, P = 0.001), brachial (r = -0.55, P = 0.01), and popliteal artery (r = -0.48, P = 0.03), but not for the superficial and common femoral artery. Normalization of FMD responses for differences in eliciting shear rate did not abolish the between-artery relationship for artery function and size (r = -0.48, P < 0.001), suggesting that differences between artery function responses were not entirely due to size-related differences in shear rate. This was reinforced by a significant between-artery correlation for GTN responses and baseline artery size (r = -0.74, P < 0.001). In summary, systematic differences exist in vascular function responses of conduit arteries that differ in size. This raises the possibility that differences in artery size within or between individuals may influence functional responses.     

Cerebral blood flow during static exercise in humans

Cerebral blood flow (CBF) was determined in humans at rest and during four consecutive unilateral static contractions of the knee extensors. Each contraction was maintained for 3 min 15 s with the subjects in a semisupine position. The contractions corresponded to 8, 16, 24, and 32% of the maximal voluntary contraction (MVC) and utilized alternate legs. CBF (measured by the 133Xe clearance technique) was expressed by a noncompartmental flow index (ISI). Heart rate and mean arterial pressure increased from resting values of 73 (55-80) beats/min and 88 (74-104) mmHg to 106 (86-138) beats/min and 124 (102-146) mmHg, respectively (P less than 0.0005), during the contraction at 32% MVC. Arterial PCO2 and central venous pressure did not change. Corrected to the average resting PCO2, CBF during control was 55 (35-73) ml.100 g-1.min-1 and remained constant during contractions. Cerebral vascular resistance increased from 1.5 (1.0-2.2) to 2.4 (1.4-3.0) mmHg. 100 g.min.ml-1 (P less than 0.025) at 32% of MVC. There was no difference in CBF between the two hemispheres at rest or during exercise. In contrast to dynamic leg exercise, static leg exercise is not associated with an increase in global CBF when measured by the 133Xe clearance technique.     

Prior exercise training increases collateral-dependent blood flow in rats after acute femoral artery occlusion

We evaluated whether prior training would improve collateral blood flow (BF) to the calf muscles after acute-onset occlusion of the femoral artery. Exercise training was performed in the absence of any vascular occlusion. Adult male Sprague-Dawley rats ( approximately 325 g) were kept sedentary (n = 14), limited to cage activity, or exercise trained (n = 14) for 6 wk by treadmill running. Early in the day of measurement, animals were surgically prepared for BF determination, and the femoral arteries were occluded bilaterally. Four to five hours later, collateral BF was determined twice during treadmill running with the use of (141)Ce and (85)Sr microspheres: first, at a demanding speed and, second, after a brief rest and at a higher speed. The absence of any further increase in BF at the higher speed indicated that maximal collateral BF was measured. Prior training increased calf muscle BF by approximately 70% compared with sedentary animals; however, absolute BF remained below values previously observed in animals with a well-developed collateral vascular tree. Thus prior training appeared to optimize the use of the existing collateral circuit. This implies that altered vasoresponsiveness induced in normal nonoccluded vessels with exercise training serves to improve collateral BF to the periphery.     

Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans

Rådegran, G. Ultrasound Dopplerestimates of femoral artery blood flow during dynamic knee extensorexercise in humans. J. Appl. Physiol.83(4): 1383-1388, 1997.Ultrasound Doppler has been used tomeasure arterial inflow to a human limb during intermittent staticcontractions. The technique, however, has neither been thoroughlyvalidated nor used during dynamic exercise. In this study, the inherentproblems of the technique have been addressed, and the accuracy wasimproved by storing the velocity tracings continuously and calculatingthe flow in relation to the muscle contraction-relaxation phases. Thefemoral arterial diameter measurements were reproducible with a meancoefficient of variation within the subjects of 1.2 ± 0.2%. Thediameter was the same whether the probe was fixed or repositioned atrest (10.8 ± 0.2 mm) or measured during dynamic exercise. The bloodvelocity was sampled over the width of the diameter and the parabolicvelocity profile, since sampling in the center resulted in anoverestimation by 22.6 ± 9.1% (P < 0.02). The femoral arterial Doppler blood flow increased linearly(r = 0.997, P < 0.001) with increasing load [Doppler blood flow = 0.080 · load (W) + 1.446 l/min] and was correlated positively with simultaneousthermodilution venous outflow measurements(r = 0.996, P < 0.001). The two techniques werelinearly related (Doppler = thermodilution · 0.985 + 0.071 l/min; r = 0.996, P < 0.001), with a coefficient ofvariation of ~6% for both methods.

     

Leukotriene D4 increases nasal blood flow in humans

The effect of leukotriene D4 on the nasal mucosal blood flow in humans was measured using a laser doppler flow meter. The leukotriene solution was applied topically to the nasal mucosa in 9 healthy subjects, and changes in blood flow were measured non-traumatically by the laser doppler instrument. The response showed a consistent increase in blood flow. A dose-response was found in the range of 0.063 - 4.0 nanomole. These results confirm an earlier study on the human skin, implicating leukotriene D4 as an important vasodilator in humans. No increase in nasal secretion was noted by the subjects tested.     

Alveolar oxygen uptake and femoral artery blood flow dynamics in upright and supine leg exercise in humans

We tested the hypothesis that the slowerincrease in alveolar oxygen uptake(O₂) at the onset ofsupine, compared with upright, exercise would be accompanied by aslower rate of increase in leg blood flow (LBF). Seven healthy subjectsperformed transitions from rest to 40-W knee extension exercise in theupright and supine positions. LBF was measured continuously with pulsedand echo Doppler methods, andO₂ was measured breath bybreath at the mouth. At rest, a smaller diameter of thefemoral artery in the supine position(P < 0.05) was compensated by agreater mean blood flow velocity (MBV) (P < 0.05) so that LBF was not different in the two positions. At the end of6 min of exercise, femoral artery diameter was larger in the uprightposition and there were no differences inO₂, MBV, or LBF betweenupright and supine positions. The rates of increase ofO₂ and LBF in thetransition between rest and 40 W exercise, as evaluated by the meanresponse time (time to 63% of the increase), were slower in the supine[O₂ = 39.7 ± 3.8 (SE) s, LBF = 27.6 ± 3.9 s] than in the uprightpositions (O₂ = 29.3 ± 3.0 s, LBF = 17.3 ± 4.0 s;P < 0.05). These data support ourhypothesis that slower increases in alveolarO₂ at the onset of exercisein the supine position are accompanied by a slower increase in LBF.

     

Seven days of aerobic exercise training improves conduit artery blood flow following glucose ingestion in patients with type 2 diabetes

The vasodilatory effects of insulin account for up to 40% of insulin-mediated glucose disposal; however, insulin-stimulated vasodilation is impaired in individuals with type 2 diabetes, limiting perfusion and delivery of glucose and insulin to target tissues. To determine whether exercise training improves conduit artery blood flow following glucose ingestion, a stimulus for increasing circulating insulin, we assessed femoral blood flow (FBF; Doppler ultrasound) during an oral glucose tolerance test (OGTT; 75 g glucose) in 11 overweight or obese (body mass index, 34 ± 1 kg/m2), sedentary (peak oxygen consumption, 23 ± 1 ml·kg?1·min?1) individuals (53 ± 2 yr) with non-insulin-dependent type 2 diabetes (HbA1c, 6.63 ± 0.18%) before and after 7 days of supervised treadmill and cycling exercise (60 min/day, 60-75% heart rate reserve). Fasting glucose, insulin, and FBF were not significantly different after 7 days of exercise, nor were glucose or insulin responses to the OGTT. However, estimates of whole body insulin sensitivity (Matsuda insulin sensitivity index) increased (P < 0.05). Before exercise training, FBF did not change significantly during the OGTT (1 ± 7, -7 ± 5, 0 ± 6, and 0 ± 5% of fasting FBF at 75, 90, 105, and 120 min, respectively). In contrast, after exercise training, FBF increased by 33 ± 9, 39 ± 14, 34 ± 7, and 48 ± 18% above fasting levels at 75, 90, 105, and 120 min, respectively (P < 0.05 vs. corresponding preexercise time points). Additionally, postprandial glucose responses to a standardized breakfast meal consumed under "free-living" conditions decreased during the final 3 days of exercise (P < 0.05). In conclusion, 7 days of aerobic exercise training improves conduit artery blood flow during an OGTT in individuals with type 2 diabetes.     

Leg exercise conditioning increases peak forearm blood flow.

To examine whether forearm vascular adaptations could occur after upright-leg exercise training, the reactive hyperemic blood flow after 10 min of forearm circulatory arrest (RHBF10) was studied. RHBF10 was examined in seven subjects before, at 2 wk, and after the completion of 4 wk of bicycle ergometer training. Maximal O2 consumption (VO2max) for leg ergometer work increased 13% (P less than 0.05) over 4 wk. Over that period of time RHBF10 in the forearm increased 50% (P less than 0.05), with a reciprocal drop in minimum vascular resistance. Resting heart rate decreased 15% (P less than 0.05) during the same period. Changes in RHBF10 and VO2max were noted after 2 wk of training. Mean arterial pressure did not change. We conclude that vascular adaptations can occur in the forearm muscle beds, even though the training regimen is designed to condition the lower extremities.     

Sympathetic nerve regulation of cochlear blood flow during increases in blood pressure in humans

The purpose of this work was to show that regulation of the blood flow to the cochlea by the sympathetic nervous system occurs in humans at the level of the cochlear microcirculation during increases in blood pressure and that its involvement depends on the pressure level. Eight anaesthetized patients undergoing tympanoplasty for hearing disease took part in a pharmacological protocol of stimulation and inhibition of the autonomic nervous system (ANS) to provide variations in systolic blood pressure (BP_S) and cochlear blood flow (CBF). The CBF was measured by laser-Doppler flowmetry. Changes in autonomic nerve activity were brought about by changes in baroreceptor activity (BR) initiated by the injection of an α adrenergic agent before and after sympathetic and parasympathetic blockade. The CBF variations (δCBF) were plotted against BP_S increases at each stage of the ANS inhibition. The BR diminished significantly after α blockade, after α and β blockade, and after α and β blockade and atropine, by 50% (P < 0.01), 29% (P < 0.05), and 95% (P < 0.001) respectively. The BP_S increased significantly (P < 0.01) by 36 (SD 9)%, 47 (SD 1)%, and 67 (SD 16)% respectively. The CBF response to an increase in BP_S exhibited two opposing variations in the patients: CBF decreased significantly in one group, and increased significantly in the other group. In both groups, δCBF decrease and δCBF increase, respectively, were significant after ANS blockade; even so the decrease and increase, respectively, levelled off at BP_S around 160 mmHg before ANS blockade. For BP_S below 160 mmHg, correlations between δCBF and BP_S were significant before inhibition and after inhibition of ANS. For BP_S above 160 mmHg, BP_S and δCBF were not correlated before inhibition of ANS, and were significantly correlated after inhibition of ANS. For BP_S below 160 mmHg, CBF response to the BP_S increase was the same before and after ANS blockade, i.e. ANS control did not predominate; even so, for BP_S above 160 mmHg, the CBF response to BP_S increase was different before and after ANS blockade: CBF varied significantly after ANS blockade as it varied for BP_S below 160 mmHg, while it remained constant before ANS blockade that elicited ANS control of CBF. In conclusion, sympathetic nerve regulation via its vasomotor tone at the level of cochlear microcirculation occurred markedly when the blood pressure was above 160 mmHg; the autonomic nervous system would appear to control the cochlear blood flow against large variations in blood flow in response to hypertensive phenomena. Accepted: 7 October 1996     

Regulation of subcutaneous adipose tissue blood flow during exercise in humans

Regulation of subcutaneous adipose tissue blood flow (ATBF) remains poorly elucidated in humans, especially during exercise. In the present study we tested the role of adenosine in the regulation of ATBF adjacent to active and inactive thigh muscles during intermittent isometric knee-extension exercise (1 s contraction followed by 2 s rest with workloads of 50, 100, and 150 N) in six healthy young women. ATBF was measured using positron emission tomography (PET) without and with unspecific adenosine receptor inhibitor theophylline infused intravenously. Adipose regions were localized from fused PET and magnetic resonance images. Blood flow in subcutaneous adipose tissue adjacent to active muscle increased from rest (1.0 ± 0.3 ml·100 g(-1)·min(-1)) to exercise (P < 0.001) and along with increasing exercise intensity (50 N = 4.1 ± 1.4, 100 N = 5.4 ± 1.8, and 150 N = 6.9 ± 3.0 ml·100 g(-1)·min(-1), P = 0.03 for the increase). In contrast, ATBF adjacent to inactive muscle remained at resting levels with all intensities (～1.0 ± 0.5 ml·100 g(-1)·min(-1)). During exercise theophylline prevented the increase in ATBF adjacent to active muscle especially during the highest exercise intensity (50 N = 4.3 ± 1.8 ml·100 g(-1)·min(-1), 100 N = 4.0 ± 1.5 ml·100 g(-1)·min(-1), and 150 N = 4.9 ± 1.8 ml·100 g(-1)·min(-1), P = 0.06 for an overall effect) but had no effect on blood flow adjacent to inactive muscle or adipose blood flow in resting contralateral leg. In conclusion, we report in the present study that 1) blood flow in subcutaneous adipose tissue of the leg is increased from rest to exercise in an exercise intensity-dependent manner, but only in the vicinity of working muscle, and 2) adenosine receptor antagonism attenuates this blood flow enhancement at the highest exercise intensities.     

Effect of cold air inhalation and isometric exercise on coronary blood flow and myocardial function in humans

The effects of cold air inhalation and isometric exercise on coronary blood flow are currently unknown, despite the fact that both cold air and acute exertion trigger angina in clinical populations. In this study, we used transthoracic Doppler echocardiography to measure coronary blood flow velocity (CBV; left anterior descending coronary artery) and myocardial function during cold air inhalation and handgrip exercise. Ten young healthy subjects underwent the following protocols: 5 min of inhaling cold air (cold air protocol), 5 min of inhaling thermoneutral air (sham protocol), 2 min of isometric handgrip at 30% of maximal voluntary contraction (grip protocol), and 5 min of isometric handgrip at 30% maximal voluntary contraction while breathing cold air (cold + grip protocol). Heart rate, blood pressure, inspired air temperature, CBV, myocardial function (tissue Doppler imaging), O(2) saturation, and pulmonary function were measured. The rate-pressure product (RPP) was used as an index of myocardial O(2) demand, whereas CBV was used as an index of myocardial O(2) supply. Compared with the sham protocol, the cold air protocol caused a significantly higher RPP, but there was a significant reduction in CBV. The cold + grip protocol caused a significantly greater increase in RPP compared with the grip protocol (P = 0.045), but the increase in CBV was significantly less (P = 0.039). However, myocardial function was not impaired during the cold + grip protocol relative to the grip protocol alone. Collectively, these data indicate that there is a supply-demand mismatch in the coronary vascular bed when cold ambient air is breathed during acute exertion but myocardial function is preserved, suggesting an adequate redistribution of blood flow.     

Cutaneous blood flow during exercise is higher in endurance-trained humans.

This study determined whether cutaneous blood flow during exercise is different in endurance-trained (Tr) compared with untrained (Untr) subjects. Ten Tr and ten Untr men (62.4 +/- 1.7 and 44.2 +/- 1.8 ml. kg(-1). min(-1), respectively; P < 0.05) underwent three 20-min cycling-exercise bouts at 50, 70, and 90% peak oxygen uptake in this order, with 30 min rest in between. The environmental conditions were neutral ( approximately 23-24 degrees C, 50% relative humidity, front and back fans at 2.5 m/s). Because of technical difficulties, only seven Tr and seven Untr subjects completed all forearm blood flow and laser-Doppler cutaneous blood flow (CBF) measurements. Albeit similar at rest, at the end of all three exercise bouts, forearm blood flow was approximately 40% higher in Tr compared with Untr subjects (50%: 4.64 +/- 0.50 vs. 3. 17 +/- 0.20, 70%: 6.17 +/- 0.61 vs. 4.41 +/- 0.37, 90%: 6.77 +/- 0. 62 vs. 5.01 +/- 0.37 ml. 100 ml(-1). min(-1), respectively; n = 7; all P < 0.05). CBF was also higher in Tr compared with Untr subjects at all relative intensities (n = 7; all P < 0.05). However, esophageal temperature was not different in Tr compared with Untr subjects at the end of any of the aforementioned exercise bouts (50%: 37.8 +/- 0.1 vs. 37.9 +/- 0.1 degrees C, 70%: 38.1 +/- 0.1 vs. 38.1 +/- 0.1 degrees C, and 90%: 38.8 +/- 0.1 vs. 38.6 +/- 0.1 degrees C, respectively). We conclude that a higher CBF may allow Tr subjects to achieve an esophageal temperature similar to that of Untr, despite their higher metabolic rates and thus higher heat production rates, during exercise at 50-90% peak oxygen uptake.     

Cerebral blood flow during submaximal and maximal dynamic exercise in humans

Cerebral blood flow (CBF) in humans was measured at rest and during dynamic exercise on a cycle ergometer corresponding to 56% (range 27-85) of maximal O2 uptake (VO2max). Exercise bouts were performed by 16 male and female subjects, lasted 15 min each, and were carried out in a semisupine position. CBF (133Xe clearance) was expressed as the initial slope index (ISI) and as the first compartment flow (F1). CBF at rest [ISI, 58 (range 45-73); F1, 76 (range 55-98) ml.100 g-1.min-1] increased during exercise [ISI to 79 (57-94) and F1 to 118 (75-164) ml.100 g-1.min-1, P less than 0.01]. CBF did not differ significantly between work loads from 32 (24-33) to 86% (74-96) of VO2max (n = 10). During exercise, mean arterial pressure increased from 84 (60-100) to 101 (78-124) Torr (P less than 0.01) and PCO2 remained unchanged [5.1 (4.6-5.6) vs. 5.4 (4.4-6.3) kPa, n = 6]. These results demonstrate a median increase of 31% (0-87) in CBF by ISI and a median increase of 58% (0-133) in CBF by F1 during dynamic exercise in humans.     

Evaluation of muscle metaboreflex function through graded reduction in forearm blood flow during rhythmic handgrip exercise in humans

Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Our aim was to determine the muscle metaboreflex threshold and gain in humans by creating an open-loop relationship between active muscle blood flow and hemodynamic responses during a rhythmic handgrip exercise. Eleven healthy subjects performed the exercise at 5 or 15% of maximal voluntary contraction (MVC) in random order. During the exercise, forearm blood flow (FBF), which was continuously measured using Doppler ultrasound, was reduced in five steps by manipulating the inner pressure of an occlusion cuff on the upper arm. The FBF at each level was maintained for 3 min. The initial reductions in FBF elicited no hemodynamic changes, but once FBF fell below a threshold, mean arterial blood pressure (MAP) and heart rate (HR) increased and total vascular conductance (TVC) decreased in a linear manner. The threshold FBF during the 15% MVC trial was significantly higher than during the 5% MVC trial. The gain was then estimated as the slope of the relationship between the hemodynamic responses and FBFs below the threshold. The gains for the MAP and TVC responses did not differ between workloads, but the gain for the HR response was greater in the 15% MVC trial. Our findings thus indicate that increasing the workload shifts the threshold for the muscle metaboreflex to higher blood flows without changing the gain of the reflex for the MAP and TVC responses, whereas it enhances the gain for the HR response.     

Leukotriene D4 increases nasal blood flow in humans

The effect of leukotriene D₄ on the nassal musocal blood flow in humans was measured using a laser doppler flow meter. The leukotriene solution was applied topically to the nasal mucosa in 9 healthy subjects, and changes in blood flow were measured non-traumatically by the laser doppler instrument. The response showed a consistent increases in blood flow. A dose-response was found in the range of 0.063 – 4.0 nanomole. These results confirm an earlier study on the human skin, implicating leukotriene D₄ as an important vasodilator in humans. No increase in nasal secretion was noted by the subjects tested.