Decrease In Central Blood Volume Research Articles

A machine-learning based analysis for the recognition of progressive central hypovolemia

Objective: Traditional patient monitoring during surgery includes heart rate (HR), blood pressure (BP) and peripheral oxygen saturation. However, their use as predictors for central hypovolemia is limited, which may lead to cerebral hypoperfusion. The aim of this study was to develop a monitoring model that can indicate a decrease in central blood volume (CBV) at an early stage. Approach: Twenty-eight healthy subjects (aged 18–50 years) were included. Lower body negative pressure (−50 mmHg) was applied to induce central hypovolemia until the onset of pre-syncope. Ten beat-to-beat and four discrete parameters were measured, normalized, and filtered with a 30 s moving window. Time to pre-syncope was scaled from 100%–0%. A total of 100 neural networks with 5, 10, 15, 20, or 25 neurons in their respective hidden layer were trained by 10, 20, 40, 80, 160, or 320 iterations to predict time to pre-syncope for each subject. The network with the lowest average slope of a fitted line over all subjects was chosen as optimal. Main results: The optimal generalized model consisted of 10 hidden neurons, trained using 80 iterations. The slope of the fitted line on the average prediction was −0.64 (SD 0.35). The model recognizes in 75% of the subjects the need for intervention at >200 s before pre-syncope. Significance: We developed a neural network based on a set of physiological variables, which indicates a decrease in CBV even in the absence of HR and BP changes. This should allow timely intervention and prevent the development of symptomatic cerebral hypoperfusion.

Abstract 022: Blood Pressure-Lowering Effect of Local Passive Heat in Autonomic Failure Patients with Supine Hypertension

Primary autonomic failure (AF) is characterized by disabling orthostatic hypotension that is acutely worsened by environmental heat. Given that about half of AF patients have paradoxical supine hypertension, we hypothesized that controlled local passive heat would lower supine blood pressure (BP) in these patients. Fourteen AF patients with supine hypertension (age 71±2 years, 9 men, systolic BP 172±6 mmHg) were randomized to receive passive heat (40-42°C, commercial heating pad over abdomen and pelvis) and sham control for up to 2 hours in a 2-day crossover study. Hemodynamic parameters and core body and skin temperatures were measured in the supine position. The heating pad increased abdominal skin temperature to 40.8±0.4°C and 40.1±0.3°C after 1 and 2 hours of passive heat (vs 35.2±0.2°C and 35.1±0.4°C in sham controls). Core body temperature increased after 1 hour (by 0.2±0.1°C [to 36.9±0.8°C] vs 0.0°C [36.7±0.1°C] in sham controls; P=0.04) and 2 hours (by 0.4±0.1°C [to 37.2±0.1°C] vs 0.1±0.03°C [to 36.8±0.1°C] in sham controls; P=0.04). Systolic BP decreased during heat stress compared to sham control (P<0.01 by mixed-effects model) with a maximal reduction at 1.7 hours of -26±5 mmHg (Figure). This BP drop was due to a decrease in cardiac output (-30±5% vs sham -5±3%; P=0.02) and stroke volume (-29±5% vs sham -6±3%; P<0.01). Systemic vascular resistance and heart rate were similar in both groups. In conclusion, low levels of local passive heat had a BP-lowering effect in AF patients with supine hypertension presumably due to an uncompensated decrease in central blood volume. The therapeutic application of this approach needs to be addressed in future studies.

Manipulation of central blood volume and implications for respiratory control function.

The respiratory operating point (ventilatory or arterial PCO2 response) is determined by the intersection point between the controller and plant subsystem elements within the respiratory control system. However, to what extent changes in central blood volume (CBV) influence these two elements and the corresponding implications for the respiratory operating point remain unclear. To examine this, 17 apparently healthy male participants were exposed to water immersion (WI) or lower body negative pressure (LBNP) challenges to manipulate CBV and determine the corresponding changes. The respiratory controller was characterized by determining the linear relationship between end-tidal PCO2 (PetCO2 ) and minute ventilation (Ve) [Ve = S × (PetCO2 - B)], whereas the plant was determined by the hyperbolic relationship between Ve and PetCO2 (PetCO2 = A/Ve + C). Changes in Ve at the operating point were not observed under either WI or LBNP conditions despite altered PetCO2 (P < 0.01), indicating a moving respiratory operating point. An increase (WI) and a decrease (LBNP) in CBV were shown to reset the controller element (PetCO2 intercept B) rightward and leftward, respectively (P < 0.05), without any change in S, whereas the plant curve remained unaltered at the operating point. Collectively, these findings indicate that modification of the controller element rather than the plant element is the major factor that contributes toward an alteration of the respiratory operating point during CBV shifts.

Countermeasures against post‐exercise syncope

Following exercise, a decrease in central blood volume can compromise cerebral perfusion and result in syncope. Breathing through an impedance threshold device (ITD) has been shown to restore central blood volume under several hypovolemic conditions. Therefore, we hypothesized that ITD breathing would prevent post‐exercise syncope following a 1‐min Wingate test. We studied 19 recreationally active men and women, subjecting them to a 60° head‐up tilt during recovery from the Wingate test. Measurements included arterial pressure, heart rate, end‐tidal PCO2, and cerebral tissue oxygenation index on a control and breathing intervention (ITD) day. Mean arterial pressure was greater during the last 30 sec of head‐up tilt on the ITD day compared to the control day (97.1 ± 2.1 vs 91.9 ± 1.8 mm Hg; P &lt; 0.05). Cerebral tissue oxygenation tended to be greater during the last 30 sec of head‐up tilt on the ITD day compared to the control day (71.8 ± 0.6 vs 70.7 ± 0.8 mm Hg; P = 0.07). The length of head‐up tilt was compared between study days for each subject. When contrasting this difference, the ITD lengthened the median tilt time by 7 min 20 sec (P = 0.20). These data suggest that the ITD may be beneficial in preventing post‐exercise syncope induced by a Wingate exercise model.

When filling the glass only leaves it half empty!– Insight into the cardiovascular physiology of haemorrhage under heat stress

When filling the glass only leaves it half empty!– Insight into the cardiovascular physiology of haemorrhage under heat stress

Colloid volume loading does not mitigate decreases in central blood volume during simulated haemorrhage while heat stressed

Heat stress results in profound reductions in the capacity to withstand a simulated haemorrhagic challenge; however, this capacity is normalized if the individual is volume loaded prior to the challenge. The present study tested the hypothesis that volume loading during passive heat stress attenuates the reduction in regional blood volumes during a simulated haemorrhagic challenge imposed via lower-body negative pressure (LBNP). Seven subjects underwent 30 mmHg LBNP while normothermic, during passive heat stress (increased internal temperature ∼1◦C), and while continuing to be heated after intravenous colloid volume loading (11 ml kg⁻¹). Relative changes in torso and regional blood volumes were determined by gamma camera imaging with technetium-99m labelled erythrocytes. Heat stress reduced blood volume in all regions (ranging from 7 to 16%), while subsequent volume loading returned those values to normothermic levels. While normothermic,LBNP reduced blood volume in all regions (torso: 22 ± 8%; heart: 18 ± 6%; spleen: 15 ± 8%). During LBNP while heat stressed, the reductions in blood volume in each region were markedly greater when compared to LBNP while normothermic (torso: 73 ± 2%; heart: 72 ± 3%; spleen: 72 ± 5%, all P<0.001 relative to normothermia). Volume loading during heat stress did not alter the extent of the reduction in these blood volumes to LBNP relative to heat stress alone (torso: 73 ± 1%; heart: 72 ± 2%; spleen: 74 ± 3%, all P>0.05 relative to heat stress alone). These data suggest that blood volume loading during passive heat stress (via 11 ml kg⁻¹ of a colloid solution) normalizes regional blood volumes in the torso, but does not mitigate the reduction in central blood volume during a simulated haemorrhagic challenge combined with heat stress.

Atrial Natriuretic Peptide and Acute Changes in Central Blood Volume by Hyperthermia in Healthy Humans.

BackgroundHyperthermia induces vasodilatation that reduces central blood volume (CBV), central venous pressure (CVP) and mean arterial pressure (MAP). Inhibition of atrial natriuretic peptide (ANP) could be a relevant homeostatic defense mechanism during hyperthermia with a decrease in CBV. The present study evaluated how changes in plasma ANP reflect the changes in CBV during hyperthermia.MethodsTen healthy subjects provided with a water perfused body suit increased body core temperature 1 °C. In situ labeled autologous red blood cells were used to measure the CBV with a gamma camera. Regions of interest were traced manually on the images of the whole body blood pool scans. Two measures of CBV were used: Heart/whole body ratio and thorax/whole body ratio. CVP and MAP were recorded. Arterial (ANPart) and venous plasma ANP were determined by radioimmunoassay.ResultsThe ratio thorax/whole body and heart/whole body decreased 7 % and 11 %, respectively (p<0.001). MAP and CVP decreased during hyperthermia by 6.8 and 5.0 mmHg, respectively (p<0.05; p<0.001). Changes in both thorax/whole body (R=0.80; p<0.01) and heart/whole body ratios (R=0.78; p<0.01) were correlated with changes in ANPart. However, there was no correlation between venous ANP and changes in CBV, nor between ANPart and MAP or CVP.ConclusionArterial but not venous plasma concentration of ANP, is correlated to changes in CBV, but not to pressures. We suggest that plasma ANPart may be used as a surrogate marker of acute CBV changes.

Central and Peripheral Fatigue during Passive and Exercise-Induced Hyperthermia

Hyperthermia was induced during prolonged exercise (ExH) and passive heating (PaH) to isolate the influence of exercise on neuromuscular function during a maximal voluntary isometric contraction (MVC) of the quadriceps under heat stress. The influence of cardiovascular strain in limiting endurance performance in the heat was also examined. On separate days, eight males cycled to exhaustion at 60% maximal oxygen uptake or were immersed in a water bath (∼41°C) until rectal temperature (Tre) increased to 39.5°C. The ExH and PaH interventions were performed in ambient conditions of 38°C and 60% relative humidity with Tre reaching 39.8°C during exercise. Before (control) and after each intervention, voluntary activation and force production capacity were evaluated by superimposing an electrically stimulated tetanus during a 45-s MVC. Force production decreased immediately after PaH and ExH compared with control, with the magnitude of decline being more pronounced after ExH (P < 0.01). Mean voluntary activation was also significantly depressed after both interventions (P < 0.01 vs control). However, the extent of decline in voluntary activation was maintained at ∼90% during both PaH and ExH MVC. This decline accounted for 41.5% (PaH) and 33.1% (ExH) of the decrease in force production. In addition, exhaustion coincided with a marked increase in HR (∼96% of maximum) and a decline in stroke volume (25%) and mean arterial pressure (10%) (P < 0.05). The loss of force production capacity during hyperthermia originated from central and peripheral fatigue factors, with the combination of heat stress and previous contractile activity exacerbating the rate of decline. Thus, the observed significant rise in thermal strain in ExH and PaH impaired neuromuscular function and was associated with an exercise performance limiting increase in cardiovascular strain.

Orthostatic intolerance in the heat: are the α-adrenergic receptors the culprit?

Orthostatic intolerance in the heat: are the α-adrenergic receptors the culprit?

Effect of volume loading on the Frank-Starling relation during reductions in central blood volume in heat-stressed humans

During reductions in central blood volume while heat stressed, a greater decrease in stroke volume (SV) for a similar decrease in ventricular filling pressure, compared to normothermia, suggests that the heart is operating on a steeper portion of a Frank-Starling curve. If so, volume loading of heat-stressed individuals would shift the operating point to a flatter portion of the heat stress Frank-Starling curve thereby attenuating the reduction in SV during subsequent decreases in central blood volume. To investigate this hypothesis, right heart catheterization was performed in eight males from whom pulmonary capillary wedge pressure (PCWP), central venous pressure and SV (via thermodilution) were obtained while central blood volume was reduced via lower-body negative pressure (LBNP) during normothermia, whole-body heating (increase in blood temperature 1 degrees C), and during whole-body heating after intravascular volume expansion. Volume expansion was accomplished by administration of a combination of a synthetic colloid (HES 130/0.4, Voluven) and saline. Before LBNP, SV was not affected by heating (122 +/- 30 ml; mean +/- s.d.) compared to normothermia (110 +/- 20 ml; P = 0.06). However, subsequent volume loading increased SV to 143 +/- 29 ml (P = 0.003). LBNP provoked a larger decrease in SV relative to the decrease in PCWP during heating (8.6 +/- 1.9 ml mmHg(1)) compared to normothermia (4.5 +/- 3.0 ml mmHg(1), P = 0.02). After volume loading while heat stressed, the reduction in the SV to PCWP ratio during LBNP was comparable to that observed during normothermia (4.8 +/- 2.3 ml mmHg(1); P = 0.78). These data support the hypothesis that a Frank-Starling mechanism contributes to compromised blood pressure control during simulated haemorrhage in heat-stressed individuals, and extend those findings by showing that volume infusion corrects this deficit by shifting the operating point to a flatter portion of the heat stress Frank-Starling curve.

Early activation of the coagulation system during lower body negative pressure

We considered that a moderate reduction of the central blood volume (CBV) may activate the coagulation system. Lower body negative pressure (LBNP) is a non-invasive means of reducing CBV and, thereby, simulates haemorrhage. We tested the hypothesis that coagulation markers would increase following moderate hypovolemia by exposing 10 healthy male volunteers to 10 min of 30 mmHg LBNP. Thoracic electrical impedance increased during LBNP (by 2.6 +/- 0.7 Omega, mean +/- SD; P < 0.001), signifying a reduced CBV. Heart rate was unchanged during LBNP, while mean arterial pressure decreased (84 +/- 5 to 80 +/- 6 mmHg; P < 0.001) along with stroke volume (114 +/- 22 to 96 +/- 19 ml min(-1); P < 0.001) and cardiac output (6.4 +/- 2.0 to 5.5 +/- 1.7 l min(-1); P < 0.01). Plasma thrombin-antithrombin III complexes increased (TAT, 5 +/- 6 to 19 +/- 20 microg l(-1); P < 0.05), indicating that LBNP activated the thrombin generating part of the coagulation system, while plasma D-dimer was unchanged, signifying that the increased thrombin generation did not cause further intravascular clot formation. The plasma pancreatic polypeptide level decreased (13 +/- 11 to 6 +/- 8 pmol l(-1); P < 0.05), reflecting reduced vagal activity. In conclusion, thrombin generation was activated by a modest decrease in CBV by LBNP in healthy humans independent of the vagal activity.

The influence of thermal factors on post‐exercise haemodynamics in endurance exercise‐trained men

The influence of thermal factors on post‐exercise haemodynamics in endurance exercise‐trained men

Detecting Change in Left Ventricular Ejection Time During Head-Up Tilt-Induced Progressive Central Hypovolemia Using a Finger Photoplethysmographic Pulse Oximetry Wave Form

Change in cardiac preload caused by mild hypovolemia can alter left ventricular ejection time (LVET) without noticeable change in blood pressure (BP). Previously our group has explored a novel method of LVET monitoring using a noninvasive finger photoplethysmographic pulse oximetry wave form. The current study investigated the ability of photoplethysmographic pulse oximetry wave form-derived LVET (LVETp) to identify progressive central hypovolemia induced by head-up tilt and evaluated the potential use of LVETp as an early noninvasive indicator of blood loss. Thirteen healthy subjects underwent graded head-up tilt from 0 degrees to 80 degrees. The response of LVETp to tilt was compared with that of interbeat heart interval (RR) and BP. Least-squares linear regression analysis was performed on an intrasubject basis between various physiologic variables and sine of the tilt angle (which is associated with the decrease in central blood volume). During graded tilt, LVETp had a very strong negative linear correlation with sine of the tilt angle, with correlation coefficients (r) ranging from -0.961 to -0.985. At a very mild hypovolemic state (10 degrees), there was a significant decrease in LVETp compared with baseline (0 degrees) but without a significant change in RR and BP. Gradient analysis showed that LVETp was sensitive to central volume loss at all volume states (0 degrees-80 degrees), whereas RR was only responsive at mild-to-moderate and moderate hypovolemic states (20 degrees-80 degrees) but not mild hypovolemic state (0 degrees-20 degrees). LVETp has a strong association with the change in central blood volume and may be a sensitive early marker of nonhypotensive progressive central hypovolemia. Joint interpretation of LVETp and RR trends may help to characterize the extent of blood volume loss.

Change in pulse transit time and pre-ejection period during head-up tilt-induced progressive central hypovolaemia

Traditional vital signs such as heart rate (HR) and blood pressure (BP) are often regarded as insensitive markers of mild to moderate blood loss. The present study investigated the feasibility of using pulse transit time (PTT) to track variations in pre-ejection period (PEP) during progressive central hypovolaemia induced by head-up tilt and evaluated the potential of PTT as an early non-invasive indicator of blood loss. About 11 healthy subjects underwent graded head-up tilt from 0 to 80 degrees . PTT and PEP were computed from the simultaneous measurement of electrocardiogram (ECG), finger photoplethysmographic pulse oximetry waveform (PPG-POW) and thoracic impedance plethysmogram (IPG). The response of PTT and PEP to tilt was compared with that of interbeat heart interval (RR) and BP. Least-squares linear regression analysis was carried out on an intra-subject basis between PTT and PEP and between various physiological variables and sine of the tilt angle (which is associated with the decrease in central blood volume) and the correlation coefficients (r) were computed. During graded tilt, PEP and PTT were strongly correlated in 10 out of 11 subjects (median r = 0.964) and had strong positive linear correlations with sine of the tilt angle (median r = 0.966 and 0.938 respectively). At a mild hypovolaemic state (20-30 degrees ), there was a significant increase in PTT and PEP compared with baseline (0 degrees ) but without a significant change in RR and BP. Gradient analysis showed that PTT was more responsive to central volume loss than RR during mild hypovolaemia (0-20 degrees ) but not moderate hypovolaemia (50-80 degrees ). PTT may reflect variation in PEP and central blood volume, and is potentially useful for early detection of non-hypotensive progressive central hypovolaemia. Joint interpretation of PTT and RR trends or responses may help to characterize the extent of blood volume loss in critical care patients.

Carotid-Cardiac Baroreflex Function Does Not Influence Blood Pressure Regulation during Head-Up Tilt in Humans

The influence of the carotid-cardiac baroreflex on blood pressure regulation was evaluated during supine rest and 40 degrees head-up tilt (HUT) in 9 healthy young subjects with and without full cardiac vagal blockade. The carotid baroreflex responsiveness, or maximal gain (G(MAX)), was assessed from the beat-to-beat changes in heart rate (HR) and mean arterial pressure (MAP) by the variable neck pressure and suction technique ranging in pressure from +40 to -80 Torr, with and without glycopyrrolate (12.0 +/- 1.0 microg/kg body weight; mean +/- SE). In the supine position, glycopyrrolate increased the HR to 91 +/- 3 bpm, from 54 +/- 3; MAP to 89 +/- 2 mmHg, from 76 +/- 2; and cardiac output to 6.8 +/- 0.3 l.min(-1), from 4.9 +/- 0.3 (P < 0.05). The G(MAX) of the carotid baroreflex control of HR was reduced to -0.06 +/- 0.01 bpm.mmHg(-1), from -0.30 +/- 0.02 (P < 0.05) with no significant effect on the G(MAX) of the carotid baroreflex control of MAP. During HUT the carotid baroreflex control of MAP was unchanged, though the G(MAX) of the carotid baroreflex control of HR was increased (P < 0.05). During HUT, central blood volume, assessed by electrical thoracic admittance, and total vascular conductance were decreased with and without glycopyrrolate. Furthermore, glycopyrrolate reduced G(MAX) of the carotid baroreflex control of HR during HUT (P < 0.05) with no significant effect on G(MAX) of the carotid baroreflex control of MAP. These data suggest that during supine rest and HUT-induced decreases in central blood volume, the carotid baroreflex control of HR is mediated primarily via parasympathetic activity. Furthermore, the maintenance of arterial blood pressure during postural stress is primarily mediated by arterial and cardiopulmonary reflex regulation of sympathetic activity and its effects on the systemic vasculature.

Hemodynamic Instability in Sepsis

Septic shock is associated with important hemodynamic alterations, including absolute or relative decrease in central blood volume (1), systolic alterations of left ventricular (LV) (2, 3) and right ventricular (RV) (4) function, and severe peripheral vasodilatation responsible in part for alterations in regional blood flow distribution and probably linked to outcome (5). Hemodynamic treatment of septic shock requires blood volume expansion, which has proved to enhance survival if not delayed (6), and vasoactive support with catecholamines, according to the hemodynamic status (7). For a long time, assessment of hemodynamic instability in sepsis was based on right heart catheterization at the bedside. Recently, the Task Force of the American College of Critical Care Medicine reiterated the usefulness of right heart catheterization in guiding hemodynamic support in patients requiring more than an initial blood volume expansion (7). Concerns about the data obtained by this technique, and their interpretation in a mechanically ventilated patient, are not new (8). Moreover, this technique has been criticized for its invasiveness and associated specific complications (9). However, large cooperative clinical trials have not demonstrated an increase in mortality carried by right heart catheterization (10, 11). We abandoned right heart catheterization in our unit in 1990 and have replaced it by routine echocardiography. Since then, all patients hospitalized with septic shock have been monitored using echocardiography as a noninvasive bedside procedure. In our daily practice, echocardiography is performed after physical examination in all hemodynamically unstable patients and repeated immediately after each major hemodynamic intervention. For this purpose, the frozen multiplane probe can be kept in the esophagus for the time needed to assess the results of a major hemodynamic intervention (10–20 minutes). This strategy is original, few French teams use it, and no trial has demonstrated the usefulness of echocardiography in severe sepsis. But the quality of the data obtained and the growing demand for training from intensivists have convinced us that this procedure will be widely used in the future. Data from echocardiographic evaluation of a series of 183 patients have been published, emphasizing that a large spectrum of changes in ventricular systolic function can be observed in

Lung function during and after prolonged head-down bed rest.

We determined the effects of prolonged head-down tilt bed rest (HDT) on lung mechanics and gas exchange. Six subjects were studied in supine and upright postures before (control), during [day 113 (D113)], and after (R + number of days of recovery) 120 days of HDT. Peak expiratory flow (PF) never differed between positions at any time and never differed from controls. Maximal midexpiratory flow (FEF(25-75%)) was lower in the supine than in the upright posture before HDT and was reduced in the supine posture by about 20% between baseline and D113, R + 0, and R + 3. The diffusing capacity for carbon monoxide corrected to a standardized alveolar volume (volume-corrected DL(CO)) was lower in the upright than in the supine posture and decreased in both postures by 20% between baseline and R + 0 and by 15% between baseline and R + 15. Pulmonary blood flow (Q(C)) increased from R + 0 to R + 3 by 20 (supine) and 35% (upright). As PF is mostly effort dependent, our data speak against major respiratory muscle deconditioning after 120 days of HDT. The decrease in FEF(25-75%) suggests a reduction in elastic recoil. Time courses of volume-corrected DL(CO) and Q(C) could be explained by a decrease in central blood volume during and immediately after HDT.

Age-related influences of leg vein filling and emptying on blood volume redistribution and sympathetic reflex during lower body negative pressure in humans.

To test the hypothesis that leg vein filling and emptying functions could be impaired with advancing age, which would produce less blood volume redistribution toward the lower body and smaller sympathetic reflex response during mild gravitational stress, 9 young and 10 elderly healthy males were exposed to a lower body negative pressure (LBNP) of 15 mmHg. Venous occlusion plethysmography was used to determine the functions of the leg veins. We found that the baseline venous distensibility index (VDI) was lower (0.057 +/- 0.004 vs. 0.048 +/- 0.003 ml x 100 ml(-1) x mmHg(-1), young vs. elderly; p < 0.05), and half-emptying time (T(1/2)) was shorter (1.6 +/- 0.1 vs. 1.3 +/- 0.1 s, young vs. elderly; p < 0.05) in the elderly. At 15 mmHg-LBNP, VDI was decreased and T(1/2) was shortened significantly in the young group, but only slightly in the elderly group. Neither blood pressure nor heart rate changed significantly in either group. The reduction in peripheral venous pressure, which was recorded from the left antecubital vein at the cubital fossa, was less in the elderly, indicating a smaller decrease in central blood volume during LBNP; however, the enhancement of muscle sympathetic nerve activity was nearly the same as that in the young. We conclude that leg vein filling and emptying functions are impaired in elderly people, producing less blood pooling in the legs and smaller reduction in peripheral venous pressure during LBNP; the maintained sympathetic reflex response might be attributable to the well-preserved baroreflex function control of sympathetic outflow to the muscle in the elderly.

Effects of ANF infusion on the renal responses to lower-body negative pressure in humans.

To investigate the role of atrial natriuretic factor (ANF) in renal responses to a decrease in central blood volume, we examined the effects of ANF infusion on renal function and hormones during prolonged lower-body negative pressure (LBNP). Ten healthy volunteers participated in two experimental sequences, each comprising a 120-min baseline period followed by the application of -20 mm Hg LBNP for 90 min. During one of the two sequences, ANF was infused throughout LBNP application at the constant rate of 2.5 ng/kg/min. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by using inulin and p-aminohippuric acid clearance techniques. LBNP induced a significant decrease in ERPF (534 +/- 28 to 457 +/- 26 ml/min; p < 0.05), GFR (120 +/- 2.5 to 112 +/- 2.5 ml/min; p < or = 0.01), in urine excretion (12 +/- 0.9 to 5.6 +/- 0.5 ml/min; p < 0.001), in sodium excretion (0.36 +/- 0.03 to 0.30 +/- 0.02 mmol/min; p < 0.05), and in plasma ANF (19 +/- 3 to 11 +/- 2 pg/ml; p = 0.001) concomitant with an increase in plasma renin activity (PRA; 0.48 +/- 0.09 to 0.87 +/- 0.16 ng/ml/h; p = 0.01) and of forearm vascular resistance (FVR; p < 0.05). The combination of ANF infusion with LBNP led to a slight increase in plasma ANF from baseline (from 20 +/- 2 to 28 +/- 3 pg/ml; p < 0.05). Compared with values obtained during LBNP with saline vehicle infusion, values obtained during LBNP with ANF infusion were similar for ERPF (463 +/- 23 vs. 457 +/- 26 ml/min), for GFR (111 +/- 2 vs. 112 +/- 2 ml/min), and for urine excretion (7 +/- 0.6 vs. 5.6 +/- 0.5 ml/min; p = 0.07), but greater for fractional excretion of sodium (2.38 +/- 0.25% vs. 1.91 +/- 0.11%; p < 0.05) and FVR (p < 0.05), and smaller for PRA (0.49 +/- 0.1 vs. 0.87 +/- 0.16 ng/ml/h; p < 0.01). These data show that ANF infusion attenuates the antinatriuretic effect of low-level LBNP and its PRA-increasing effects without altering renal hemodynamic responses to LBNP, although there is a decrease in the LBNP-induced forearm vasoconstriction. These results were obtained with plasma ANF levels slightly higher than those in baseline. They support the hypothesis that a decrease in ANF secretion might contribute to the antinatriuretic effect of LBNP.

Decreased capacitance response with age in lower limbs of humans – a potential error in the study of cardiovascular reflexes in ageing

The cardiovascular regulation in humans depends to a major extent on sympathetic reflexes originating from volume receptors in the arterial as well as the cardiopulmonary region. With experimental approaches, such as lower body negative pressure (LBNP) and tilting, signs of reduced efficiency with ageing have been shown. However, a confounding factor may be an age-related decline in venous capacitance response of the lower limbs, reducing the decrease in central blood volume and thus the deactivation of baro/cardiopulmonary receptors. This potential error was addressed in the present study. Central hypovolaemic stress was produced by LBNP 60 cmH2O in 10 young (mean age 23, range 20-25 years) and 10 old males (mean age 65, range 61-70 years). Changes in tissue volume of the calf were studied by strain gauge volumetric technique. Transmission of negative pressure to the calf muscle was studied in two young and two old volunteers. The haemodynamic response to hypovolaemic circulatory stress was attenuated in the old as compared with the young subjects, with a less marked increase in heart rate and peripheral resistance. Further, in the old subjects, the decrease in systolic blood pressure, pulse pressure and forearm blood flow was attenuated. Transmission of negative pressure to the calf was equal in both groups. The capacitance response was reduced with age from 2.27 +/- 0.14 to 1.64 +/- 0.13 mL 100 mL-1 (P < 0.005). However, the net capillary fluid filtration was unchanged. The reduced capacitance function might partly explain the declining reflex responses with age in humans, and thus seems to be of considerable importance when studying cardiovascular sympathetic reflex responses in ageing.