Ultrasound assessment of popliteal vein compliance during a short deflation protocol.

The purpose of the present study was to determine whether ultrasound is a useful tool to measure the venous characteristics of the lower extremity during a standard venous collecting cuff deflation protocol. To accomplish this, lower extremity pressure-cross-sectional area (CSA) and pressure-volume relationships were measured in eight (25 +/- 1 yr) supine subjects. Popliteal vein CSA was assessed by using high-resolution ultrasound, while calf volume changes were simultaneously assessed by using venous occlusion plethysmography (VOP). Pressure-CSA and pressure-volume relationships were assessed at baseline, during the cold pressor (CP) test, and following sublingual nitroglycerin (NTG) administration. Relationships were modeled with a quadratic regression equation, and beta(1) and beta(2) were used as indexes of venous compliance. Popliteal vein regression parameters beta(1) (8.485 +/- 2.616 vs. 7.638 +/- 2.664, baseline vs. CP; 8.485 +/- 2.616 vs. 7.734 +/- 3.076, baseline vs. NTG; both P > 0.05) and beta(2) (-0.0841 +/- 0.0241 vs. -0.0793 +/- 0.0242, baseline vs. CP; -0.0841 +/- 0.0241 vs. -0.0771 +/- 0.0280, baseline vs. NTG; both P > 0.05) were not affected by CP or NTG. Similarly, calf regression parameters beta(1) and beta(2), obtained with VOP, were not altered during either trial. Intraclass correlations for venous compliance assessed with ultrasound and VOP were 0.92 and 0.97, respectively, indicating acceptable reproducibility. These data suggest that ultrasound is a functional and reproducible tool to assess the venous characteristics of the lower extremity, in addition to VOP. Additionally, popliteal vein and calf compliance were not affected by the CP test or NTG.     

Venous smooth muscle tone and responsiveness in older adults.

Venous compliance is lower in older adults compared with younger adults. It is possible that alterations in venous smooth muscle tone and responsiveness may contribute to the age-related differences in venous compliance. To determine the effects of sympathetic activation [cold pressor test (cold pressor test); rhythmic ischemic handgrip (rhythmic ischemic handgrip)] and endothelium-independent decreases in smooth muscle tone [sublingual nitroglycerin (nitroglycerin)] on venous compliance in young and older adults, forearm and calf venous compliance was measured in 12 young (22 +/- 1 yr) and 12 old (65 +/- 1 yr) supine subjects using venous occlusion plethysmography. Venous compliance was assessed at baseline, during the cold pressor test and rhythmic ischemic handgrip tests, and after nitroglycerin administration. All pressure-volume relationships were modeled with a quadratic regression equation, and beta1 and beta2 were used as indexes of venous compliance. A repeated-measures ANOVA was used to determine the effect of the age and trial on venous compliance. Calf regression parameters beta1 (0.0639 +/- 0.0126 vs. 0.0503 +/- 0.0059, young vs. older; P < 0.05) and beta2 (-0.00054 +/- 0.00011 vs. -0.00041 +/- 0.00005, young vs. older; P < 0.05) were significantly less in older adults at baseline. Similarly, forearm regression parameters, beta1 and beta2 were lower in older adults at baseline. Venous compliance was not effected by the cold pressor test test, rhythmic ischemic handgrip, or sublingual nitroglycerin in either group. Data suggest that forearm and calf venous compliance is lower in older adults compared with young. However, this difference probably cannot be explained by alterations in smooth muscle tone or responsiveness.     

Gender affects calf venous compliance at rest and during baroreceptor unloading in humans

Leg venous compliance is a determinant of peripheral venous pooling during orthostatic stress such that high venous compliance could contribute to reduced orthostatic tolerance. We tested the hypotheses that 1) calf venous compliance is reduced during baroreceptor unloading, and 2) calf venous compliance is greater in women than men. Twelve men (27 +/- 2 yr) and 12 women (25 +/- 2 yr) were studied in the supine posture. Calf venous compliance was determined by inflating a thigh venous collecting cuff to 60 mmHg for 8 min and then decreasing cuff pressure at a rate of 1 mmHg/s to 0 mmHg. The slope of the pressure-compliance relation (compliance = beta(1) + 2.beta(2).cuff pressure), which is the first derivative of the quadratic pressure-volume relation [(Deltalimb volume) = beta(0) + beta(1).(cuff pressure) + beta(2).(cuff pressure)(2)] during the reduction in collecting cuff pressure, was used to assess venous compliance at baseline and during one-legged lower body negative pressure (LBNP; -50 mmHg). At baseline, calf venous compliance was 48% lower (P < 0.001) in women than men and decreased in men (Delta-25 +/- 8%; P < 0.05) but not women (Delta1 +/- 11%) during LBNP. Rhythmic ischemic handgrip (Delta6 +/- 9%) and cold pressor testing (Delta-9 +/- 7%) did not alter calf venous compliance in a subgroup of men (n = 6). These data indicate gender-dependent effects on calf venous compliance under conditions associated with low sympathetic outflow (i.e., rest) and high sympathetic outflow (i.e., LBNP). However, they cannot explain gender-associated differences in orthostatic tolerance.     

Sex-related effects on venous compliance and capillary filtration in the lower limb

Recent studies in humans have suggested sex differences in venous compliance of the lower limb, with lower compliance in women. Capillary fluid filtration could, however, be a confounder in the evaluation of venous compliance. The venous capacitance and capillary filtration response in the calves of 12 women (23.2 +/- 0.5 years) and 16 men (22.9 +/- 0.5 years) were studied during 8 min lower body negative pressure (LBNP) of 11, 22, and 44 mmHg. Calf venous compliance is dependent on pressure and was determined using the first derivative of a quadratic regression equation that described the capacitance-pressure relationship [compliance = beta1 + (2 x beta2 x transmural pressure)]. We found a lower venous compliance in women at low transmural pressures, and the venous capacitance in men was increased (P < 0.05). However, the difference in compliance between sexes was reduced and not seen at higher transmural pressures. Net capillary fluid filtration and capillary filtration coefficient (CFC) were greater in women than in men during LBNP (P < 0.05). Furthermore, calf volume increase (capacitance response + total capillary filtration) during LBNP was equivalent in both sexes. When total capillary filtration was not subtracted from the calf capacitance response in the calculation of venous compliance, the sex differences disappeared, emphasizing that venous compliance measurement should be corrected for the contribution of CFC.     

A biphasic model of limb venous compliance: a comparison with linear and exponential models.

Compliance is not linear within the physiological range of pressures, and linear modeling may not describe venous physiology adequately. Forearm and calf venous compliance were assessed in nine subjects. Venous compliance was modeled by using a biphasic model with high- and low-pressure linear phases separated by a breakpoint. This model was compared with a linear model and several exponential models. The biphasic, linear, and two-parameter exponential models best represented the data. The mean coefficient of determination for the biphasic model was greater than for the linear and exponential models in the calf (biphasic 0.94 +/- 0.04, exponential 0.81 +/- 0.16, P = not significant; and linear 0.54 +/- 0.05, P < 0.05) and forearm (biphasic 0.83 +/- 0.17, exponential 0.79 +/- 0.15, P = not significant; and linear 0.51 +/- 0.06, P < 0.05). The breakpoint pressure in the biphasic model was higher in the calf than the forearm, 34.4 +/- 3.9 vs. 29.1 +/- 4.5 mmHg, P < 0.05. A biphasic model can describe limb venous compliance and delineate differences in venous physiology at high and low pressures. The steep low-pressure phase of the compliance curve extends to higher pressures in the calf than in the forearm, thereby enlarging the range of pressures over which hemodynamic regulation by the calf venous circulation occurs.     

Measurement of limb venous compliance in humans: technical considerations and physiological findings.

We conducted a series of studies to develop and test a rapid, noninvasive method to measure limb venous compliance in humans. First, we measured forearm volume (mercury-in-Silastic strain gauges) and antecubital intravenous pressure during inflation of a venous collecting cuff around the upper arm. Intravenous pressure fit the regression line, -0.3 +/- 0.7 + 0.95 +/- 0.02. cuff pressure (r = 0.99 +/- 0.00), indicating cuff pressure is a good index of intravenous pressure. In subsequent studies, we measured forearm and calf venous compliance by inflating the venous collecting cuff to 60 mmHg for 4 min, then decreasing cuff pressure at 1 mmHg/s (over 1 min) to 0 mmHg, using cuff pressure as an estimate of venous pressure. This method produced pressure-volume curves fitting the quadratic regression (Deltalimb volume) = beta(0) + beta(1). (cuff pressure) + beta(2). (cuff pressure)(2), where Delta is change. Curves generated with this method were reproducible from day to day (coefficient of variation: 4.9%). In 11 subjects we measured venous compliance via this method under two conditions: with and without (in random order) superimposed sympathetic activation (ischemic handgrip exercise to fatigue followed by postexercise ischemia). Calf and forearm compliance did not differ between control and sympathetic activation (P > 0.05); however, the data suggest that unstressed volume was reduced by the maneuver. These studies demonstrate that venous pressure-volume curves can be generated both rapidly and noninvasively with this technique. Furthermore, the results suggest that although whole-limb venous compliance is under negligible sympathetic control in humans, unstressed volume can be affected by the sympathetic nervous system.     

Venous responses to rhythmic exercise in contralateral forearm and calf

Ten normal healthy subjects performed a rhythmic handgrip at 30% MVC (maximal voluntary contraction) with and without arterial occlusion of the same limb. Contralateral forearm and calf venous capacitance were simultaneously measured by venous occlusion plethysmography. During rhythmic handgrip at 30% MVC contralateral venous capacitance decreased by -7.17% in the forearm and by -5.14% in the calf. With arterial occlusion the decreases in venous capacitance were even more pronounced: contralateral forearm -14.4% and calf -13.1%. In a second set of experiments (n = 5) rhythmic handgrip at 30% MVC with arrest of the forearm circulation 5 s prior to the cessation of contraction was applied to examine the influence of chemically sensitive metaboreceptors per se on the evoked limb venoconstriction. During the postexercise arterial occlusion forearm venous volume decreased further to -30.6% whereas calf venous volume increased slightly but remained below the control value. After the cessation of the arterial occlusion both forearm and calf capacitance returned to baseline values. Thus, this study provided evidence that as well as a chemically generated reflex arising from the working muscle, central command was found to be involved in the increase in venomotor tone in the nonexercising limbs during rhythmic handgrip at 30% MVC.     

Smaller age-associated reductions in leg venous compliance in endurance exercise-trained men

We determined the independent and interactive influences of aging and habitual endurance exercise on calf venous compliance in humans. We tested the hypotheses that calf venous compliance is 1) reduced with age in sedentary and endurance-trained men, and 2) elevated in young and older endurance-trained compared with age-matched sedentary men. We studied 8 young (28 +/- 1 yr) and 8 older (65 +/- 1) sedentary, and 8 young (27 +/- 1) and 8 older (63 +/- 2) endurance-trained men. Calf venous compliance was measured in supine subjects by inflating a venous collecting cuff, placed above the knee, to 60 mmHg for 8 min and then decreasing cuff pressure at 1 mmHg/s to 0 mmHg. Calf venous compliance was determined using the first derivative of the pressure-volume relation during cuff pressure reduction (compliance = beta(1) + 2. beta(2). cuff pressure). Calf venous compliance was reduced with age in sedentary (approximately 40%) and endurance-trained men (approximately 20%) (both P < 0.01). Furthermore, calf venous compliance was approximately 70-120% greater in endurance-trained compared with age-matched sedentary men and approximately 30% greater in older endurance-trained compared with young sedentary men (both P < 0.01). These data indicate that calf venous compliance is reduced with age in sedentary and endurance-trained men, but compliance is better preserved in endurance-trained men.     

Adrenergic mechanisms do not contribute to age-related decreases in calf venous compliance

Limb venous compliance decreases with advancing age, even in healthy humans. To test the hypothesis that adrenergic mechanisms contribute to age-associated reductions in limb venous compliance, we measured calf venous compliance before and during acute systemic α- and β-adrenergic blockade in eight young (27 ± 1 yr old, mean ± SE) and eight older healthy men (67 ± 2 yr old). Calf venous compliance was determined in supine subjects by inflating a thigh-collecting cuff to 60 mmHg for 8 min and then decreasing it (1 mmHg/s) to 0 mmHg while calf volume was indexed with a strain gauge. The slope (·10?3) of the pressure-compliance relation (compliance= β? + 2·β?·cuff pressure), which is the first derivative of the quadratic pressure-volume relation [(Δlimb volume) = β?+ β?·(cuff pressure) + β?·(cuff pressure)2] during reductions in cuff pressure, was used to quantify calf venous compliance. Calf venous compliance was ～30% lower (P < 0.01) in older compared with young men before adrenergic blockade. In response to adrenergic blockade calf venous compliance did not increase in young (-2.62 ± 0.14 and -2.29 ± 0.18 ml·dl?1·mmHg?1, before and during blockade, respectively) or older men (-1.78 ± 0.27 and -1.68 ± 0.21 ml·dl?1 ·mmHg?1). Moreover, during adrenergic blockade differences in calf venous compliance between young and older men observed before adrenergic blockade persisted. Collectively, these data strongly suggest that adrenergic mechanisms neither directly restrain calf venous compliance in young or older men nor do they contribute to age-associated reductions in calf venous compliance in healthy men.     

Measurements of vascular function using strain-gauge plethysmography: technical considerations, standardization, and physiological findings

The main purpose of the present study was to examine the relationships between measures of fitness [estimated peak oxygen consumption (V(O2) peak) and handgrip strength] and forearm vascular function in 55 young (22.6 +/- 3.5 yr) adults. In addition, the present study considered methodological and technical aspects regarding the examination of the venous system using mercury in-Silastic strain-gauge plethysmography (MSGP). Forearm venous capacitance and outflow were examined using five different [7, 14, 21, 28, and 35 mmHg < diastolic blood pressure (DBP)] venous occlusion pressures and after a 5- and 10-min period of venous occlusion. A pressure of 7 mmHg < DBP and a period of 10 min venous occlusion produced the greatest (P < 0.05) venous capacitance and outflow, without altering arterial indexes. Reproducibility of forearm arterial and venous indexes were evaluated at rest and after 5 min of upper arm arterial occlusion at 240 mmHg on three different occasions within 10 days with the interclass correlation coefficient ranging from 0.70 and 0.94. Estimated V(O2) peak correlated with postocclusion arterial inflow (r = 0.54, P = 0.012) and resting venous outflow (r = 0.56, P = 0.016). Finally, handgrip strength was associated with venous capacitance (r = 0.57, P = 0.007) and outflow (r = 0.67, P = 0.001). These results indicate that the examination of forearm vascular function using MSGP is reproducible. Moreover, the data show the importance of careful consideration of the selection of venous occlusion pressure and period when implementing these measures in longitudinal trials. Finally, the associations between fitness and venous measures suggest a link between venous function and exercise performance.     

Decreased capillary filtration but maintained venous compliance in the lower limb of aging women

There are sex-related differences in venous compliance and capillary filtration in the lower limbs, which to some extent can explain the susceptibility to orthostatic intolerance in young women. With age, venous compliance and capacitance are reduced in men. This study was designed to evaluate age-related changes in venous compliance and capillary filtration in the lower limbs of healthy women. Included in this study were 22 young and 12 elderly women (23.1 +/- 0.4 and 66.4 +/- 1.4 yr). Lower body negative pressure (LBNP) of 11, 22, and 44 mmHg created defined transmural pressure gradients in the lower limbs. A plethysmographic technique was used on the calf to assess venous capacitance and net capillary filtration. Venous compliance was calculated with the aid of a quadratic regression equation. No age-related differences in venous compliance and capacitance were found. Net capillary filtration and capillary filtration coefficient (CFC) were lower in elderly women at a LBNP of 11 and 22 mmHg (0.0032 vs. 0.0044 and 0.0030 vs. 0.0041 ml.100 ml(-1).min(-1).mmHg(-1), P < 0.001). At higher transmural pressure (LBNP, 44 mmHg), CFC increased by approximately 1/3 (0.010 ml.100 ml(-1).min(-1).mmHg(-1)) in the elderly (P < 0.001) but remained unchanged in the young women. In conclusion, no age-related decrease in venous compliance and capacitance was seen in women. However, a decreased CFC was found with age, implying reduced capillary function. Increasing transmural pressure increased CFC in the elderly women, indicating an increased capillary susceptibility to transmural pressure load in dependent regions. These findings differ from earlier studies on age-related effects in men, indicating sex-specific vascular aging both in the venous section and microcirculation.     

Changes in size and compliance of the calf after 30 days of simulated microgravity

Increased leg venous compliance may contribute to postflight orthostatic intolerance in astronauts. We reported that leg compliance was inversely related to the size of the muscle compartment. The purpose of this study was to test the hypothesis that reduced muscle compartment after long-duration exposure to microgravity would cause increased leg compliance. Eight men, 31-45 yr old, were measured for vascular compliance of the calf and serial circumferences of the calf before and after 30 days of continuous 6 degrees head-down bed rest. Cross-sectional areas (CSA) of muscle, fat, and bone compartments in the calf were determined before and after bed rest by computed tomography. From before to after bed rest, calculated calf volume (cm3) decreased (P less than 0.05) from 1,682 +/- 83 to 1,516 +/- 76. Calf muscle compartment CSA (cm2) also decreased (P less than 0.05) from 74.2 +/- 3.6 to 70.6 +/- 3.4; calf compliance (ml.100 ml-1.mmHg-1.100) increased (P less than 0.05) from 3.9 +/- .7 to 4.9 +/- .5. The percent change in calf compliance after bed rest was significantly correlated with changes in calf muscle compartment CSA (r = 0.72, P less than 0.05). The increased leg compliance observed after exposure to simulated microgravity can be partially explained by reduced muscle compartment. Countermeasures designed to minimize muscle atrophy in the lower extremities may be effective in ameliorating increased venous compliance and orthostatic intolerance after spaceflight.     

Lower capacitance response and capillary fluid absorption in women to defend central blood volume in response to acute hypovolemic circulatory stress

Acute hemorrhage is a leading cause of death in trauma, and women are more susceptible to hypovolemic circulatory stress than men. The mechanisms underlying the susceptibility are not clear, however. The aim of the present study was to examine the compensatory mechanisms to defend central blood volume during experimental hypovolemia in women and men. Twenty-two women (23.1 +/- 0.4 yr) and 16 men (23.2 +/- 0.5 yr) were included. A lower body negative pressure (LBNP) of 11-44 mmHg induced experimental hypovolemic circulatory stress. The volumetric technique was used to assess the capacitance response (redistribution of peripheral venous blood to the central circulation) as well as to assess net capillary fluid transfer from tissue to blood in the arm. Plasma norepinephrine (NE) and forearm blood flow were measured before and during hypovolemia, and forearm vascular resistance (FVR) was calculated. LBNP created comparable hypovolemia in women and men. FVR increased less in women during hypovolemic stress, and no association between plasma NE and FVR was seen in women (R(2) = 0.01, not significant), in contrast to men (R(2) = 0.59, P < 0.05). Women demonstrated a good initial capacitance response, but this was not maintained with time, in contrast to men [e.g., decreased by 24 +/- 4% (women) vs. 4 +/- 5% (men), LBNP of 44 mmHg, P < 0.01], and net capillary fluid absorption from tissue to blood was lower in women (0.086 +/- 0.007 vs. 0.115 +/- 0.011 ml.100 ml(-1).min(-1), P < 0.05). In conclusion, women showed impaired vasoconstriction, reduced capacitance response with time, and reduced capillary fluid absorption during acute hypovolemic circulatory stress, indicating less efficiency to defend central blood volume than men.     

Vascular perturbations in the chronic orthostatic intolerance of the postural orthostatic tachycardia syndrome.

Chronic orthostatic intolerance is often related to the postural orthostatic tachycardia syndrome (POTS). POTS is characterized by upright tachycardia. Understanding of its pathophysiology remains incomplete, but edema and acrocyanosis of the lower extremities occur frequently. To determine how arterial and venous vascular properties account for these findings, we compared 13 patients aged 13-18 yr with 10 normal controls. Heart rate and blood pressure were continuously recorded, and strain-gauge plethysmography was used to measure forearm and calf blood flow, venous compliance, and microvascular filtration while the subject was supine and to measure calf blood flow and calf size change during head-up tilt. Resting venous pressure was higher in POTS compared with control (16 vs. 10 mmHg), which gave the appearance of decreased compliance in these patients. The threshold for edema formation decreased in POTS patients compared with controls (8.3 vs. 16.3 mmHg). With tilt, early calf blood flow increased in POTS patients (from 3.4 +/- 0.9 to 12.6 +/- 2.3 ml. 100 ml(-1). min(-1)) but did not increase in controls. Calf volume increased twice as much in POTS patients compared with controls over a shorter time of orthostasis. The data suggest that resting venous pressure is higher and the threshold for edema is lower in POTS patients compared with controls. Such findings make the POTS patients particularly vulnerable for edema fluid collection. This may signify a redistribution of blood to the lower extremities even while supine, accounting for tachycardia through vagal withdrawal.     

Age- and fitness-related differences in limb venous compliance do not affect tolerance to maximal lower body negative pressure in men and women.

Aging and chronic exercise training influence leg venous compliance. Venous compliance affects responses to an orthostatic stress; its effect on tolerance to maximal lower body negative pressure (LBNP) in the elderly is unknown. The purpose of this study was to determine the influence of age and fitness, a surrogate measure of exercise training, on calf venous compliance and tolerance to maximal LBNP in men and women. Forty participants, 10 young fit (YF; age = 22.6 +/- 0.5 yr, peak oxygen uptake = 57.1 +/- 2.0 ml.kg(-1).min(-1)), 10 young unfit (YU; 23.1 +/- 1.0 yr, 41.1 +/- 2.0 ml.kg(-1).min(-1)), 10 older fit (OF; 73.9 +/- 2.0 yr, 39.0 +/- 2.0 ml.kg(-1).min(-1)), and 10 older unfit (OU; 70.9 +/- 1.6 yr, 27.1 +/- 2.0 ml.kg(-1).min(-1)), underwent graded LBNP to presyncope or 4 min at -100 mmHg. By utilizing venous occlusion plethysmography, calf venous compliance was determined by using the first derivative of the pressure-volume relation during cuff pressure reduction. We found that the more fit groups had greater venous compliance than their unfit peers (P < 0.05) as did the young groups compared with their older peers (P < 0.05) such that OU < YU = OF < YF. LBNP tolerance did not differ between groups. In conclusion, these data suggest that aging reduces, and chronic exercise increases, venous compliance. However, these data do not support a significant influence of venous compliance on LBNP tolerance.     

Decreased skeletal muscle pump activity in patients with postural tachycardia syndrome and low peripheral blood flow

Standing translocates thoracic blood volume into the dependent body. The skeletal muscle pump participates in preventing orthostatic intolerance by enhancing venous return. We investigated the hypothesis that skeletal muscle pump function is impaired in postural tachycardia (POTS) associated with low calf blood flow (low-flow POTS) and depends in general on muscle blood flow. We compared 12 subjects that have low-flow POTS with 10 controls and 7 patients that have POTS and normal calf blood flow using strain-gauge plethysmography to measure peripheral blood flow, venous capacitance, and calf muscle pump function. Blood volume was estimated by dye dilution. We found that calf circumference was reduced in low-flow POTS (32 +/- 1 vs. 39 +/- 3 and 43 +/- 3 cm) and, compared with controls and POTS patients with normal blood flow, is related to the reduced fraction of calf venous capacity emptied during voluntary muscle contraction (ejection fraction, 0.52 +/- 0.07 vs. 0.76 +/- 0.07 and 0.80 +/- 0.06). We found that blood flow was linearly correlated (r(p) = 0.69) with calf circumference (used as a surrogate for muscle mass). Blood volume measurements were 2.2 +/- 0.3 in low-flow POTS vs. 2.6 +/- 0.5 in controls (P = 0.17) and 2.4 +/- 0.7 in normal-flow POTS patients. Decreased calf blood flow may reduce calf size in POTS and thereby impair the upright ejective ability of the skeletal muscle pump and further contribute to overall reduced blood flow and orthostatic intolerance in these patients.     

Effects of spaceflight on human calf hemodynamics.

Chronic microgravity may modify adaptations of the leg circulation to gravitational pressures. We measured resting calf compliance and blood flow with venous occlusion plethysmography, and arterial blood pressure with sphygmomanometry, in seven subjects before, during, and after spaceflight. Calf vascular resistance equaled mean arterial pressure divided by calf flow. Compliance equaled the slope of the calf volume change and venous occlusion pressure relationship for thigh cuff pressures of 20, 40, 60, and 80 mmHg held for 1, 2, 3, and 4 min, respectively, with 1-min breaks between occlusions. Calf blood flow decreased 41% in microgravity (to 1.15 +/- 0.16 ml x 100 ml(-1) x min(-1)) relative to 1-G supine conditions (1.94 +/- 0.19 ml x 100 ml(-1) x min(-1), P = 0.01), and arterial pressure tended to increase (P = 0.05), such that calf vascular resistance doubled in microgravity (preflight: 43 +/- 4 units; in-flight: 83 +/- 13 units; P < 0.001) yet returned to preflight levels after flight. Calf compliance remained unchanged in microgravity but tended to increase during the first week postflight (P > 0.2). Calf vasoconstriction in microgravity qualitatively agrees with the "upright set-point" hypothesis: the circulation seeks conditions approximating upright posture on Earth. No calf hemodynamic result exhibited obvious mechanistic implications for postflight orthostatic intolerance.     

beta-Receptor agonist activity of phenylephrine in the human forearm.

Phenylephrine is generally regarded as a "pure" alpha(1)-agonist. However, after treatment of the forearm with the alpha-adrenergic-blocking drug phentolamine, brachial artery infusion of phenylephrine can cause transient forearm vasodilation. To determine whether this response was beta-receptor mediated, phenylephrine, phentolamine, and propranolol were infused into the brachial arteries of six healthy volunteers. Forearm vascular conductance (FVC) was also calculated and expressed as arbitrary units (units). Infusion of phenylephrine by itself (0.5 microg. dl forearm volume(-1). min(-1)) caused a sustained decrease (P < 0.05) in FVC from 3.5 +/- 0.7 to 0.9 +/- 0.2 units (P < 0.05). Infusion of the alpha-blocker phentolamine increased (P < 0.05) baseline FVC to 5.7 +/- 1.3 units. Subsequent infusion of phenylephrine after alpha-blockade caused FVC to increase (P < 0.05) for ~1 min from 5.7 +/- 1.3 to a peak of 13.1 +/- 1.8 units. Propranolol had no effect on baseline flow, and subsequent phenylephrine infusion after alpha- and beta-blockade caused a small, but significant, sustained decrease in FVC from 5.1 +/- 1.0 to 3.6 +/- 0.8 units. There were no systemic effects from the infusions, and saline infusion at the same rate (1-2 ml/min) had no forearm vasoconstrictor or dilator effects. These data indicate that in humans phenylephrine can exert transient beta(2)-vasodilator activity when its predominant alpha-constrictor effects are blocked.     

Sustained venoconstriction in man supplemented with CO2 at high altitude.

Venoconstriction occurs at high altitude. This study sought to determine whether hypoxia or hypocapnia is the cause of the venoconstriction. Five male subjects were exposed to 4,000-4,400 m (PB 440-465 mmHg) with supplemental 3.77 +/- 0.02% CO2 in a hypobaric chamber for 4 days. Similar alveolar O2 tensions were obtained in four control subjects exposed to 3,500-4,100 m (PB 455-492 mmHg) without CO2. A water-filled plethysmograph was used to determine forearm flow and venous compliance. Systemic blood pressure was measured with the cuff procedure. Catecholamines were measured in 24-h urine collections. Venous compliance fell at high altitude in both groups and was less (P less than 0.01) than control values. Forearm flow and resistance were unaltered at altitude in the group with CO2 supplementation while forearm flow decreased and resistance increased in the hypocapnic group at 72 h of exposure. Urinary catecholamines increased in the group with CO2 and remained unaltered in the hypocapnic group. It is concluded that hypoxia is responsible for decreasing venous compliance, and hypocapnia for increasing resistance and decreasing flow. Group differences observed in urinary catecholamines may be explained by differences in arterial pH.     

Cardiac homeostasis is independent of calf venous compliance in subjects with paraplegia

The purpose of this study was to examine cardiac hemodynamics during acute head-up tilt (HUT) and calf venous function during acute head-down tilt (HDT) in subjects with paraplegia compared with sedentary nondisabled controls. Nineteen paraplegic males (below T6) and nine age-, height-, and weight-matched control subjects participated. Heart rate, stroke volume, and cardiac output were assessed using the noninvasive acetylene uptake method. Venous vascular function of the calf was assessed using venous occlusion plethysmography. After supine measurements were collected, the table was moved to 10 degrees HDT followed by the three levels of HUT (10, 35, and 75 degrees ) in random order. Cardiac hemodynamics were similar between the groups at all positions. Calf circumference was significantly reduced in the paraplegic group compared with the control group (P < 0.001). Venous capacitance and compliance were significantly reduced in the paraplegic compared with control group at supine and HDT. Neither venous capacitance (P = 0.37) nor compliance (P = 0.19) increased from supine with 10 degrees HDT in the paraplegic group. A significant linear relationship was established between supine venous compliance and supine cardiac output in the control group (r = 0.80, P < 0.02) but not in the paraplegic group. The findings of reduced calf circumference and similar venous capacitance at supine rest and 10 degrees HDT in the paraplegic group imply that structural changes may have limited venous dispensability in individuals with chronic paraplegia. Furthermore, the lack of a relationship between supine venous compliance and supine cardiac output suggests that cardiac homeostasis does not rely on venous compliance in subjects with paraplegia.