SUMMARY1. We have used non-invasive mercury in a silastic strain gauge system to assess the effect of pressure step size, on the time course of the rapid volume response (RVR) to occlusion pressure. We also obtained values for hydraulic conductance (Kf), isovolumnetric venous pressure (Pvi) and venous pressure (Pv) in thirty-five studies on the legs of twenty-three supine control subjects.2. The initial rapid volume response to small (953 + 045 mmHg, mean +S.E.M.) stepped increases in venous pressure, the rapid volume response, could be described by a single exponential of time constant 15-54 + 114 s.3. Increasing the size of the pressure step, to 49 8+ 1+ mmHg, gave a larger value for the RVR time constant (mean 77-3 + 11P6 s).4. We propose that the pressure-dependent difference in the duration of the rapid volume response, in these two situations, might be due to a vascular smooth musclebased mechanism, e.g. the veni-arteriolar reflex.5. The mean (+ S.E.M.) values for Kf, Pvi and Pv were 427+018 (units, ml min-(100 g)-1 mmHg-1 x 10-3), 21 50+0 81 (units, mmHg) and 9-11 +0-94 (units, mmHg), respectively.6. During simultaneous assessment of these parameters in arms and legs, it was found that they did not differ significantly from one another.7. We propose that the mercury strain gauge system offers a useful, non-invasive means of studying the mechanisms governing fluid filtration in human limbs.

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Venous congestion strain‐gauge plethysmography enables the non‐invasive assessment of arterial blood flow, fluid filtration capacity (Kf), venous pressure (Pv)and isovolumetric venous pressure (Pvi)in man. One of the major assumptions of this technique, that cuff pressure (Peuff) applied to the limb equals Pv at the level of the strain gauge, was tested in this study. In nine healthy male volunteers (mean age, 29.3 ± 1.2 years) the saphenous vein was cannulated with an 18‐gauge catheter proximal to the medial malleolus. The subjects were supine and Pv was continuously measured during the application of small step (8–10 mmHg) increases in congestion Pcuff (up to 70 mm Hg). Pcuff, changes in limb circumference and Pv were recorded by computer for off‐line analysis. Since the determination of Pv is influenced by the changes in plasma oncotic pressure, venous blood samples were obtained at the start of the study, when P& was raised to 30 mmHg and again to 65 mmHg and 4 min after deflation of the cuff. The relationship between Pv and Pcuff was linear over the range of 10–70 mm Hg (n= 9, 69 measurements, slope 0.9.1, r= 0.97, P. <<0.001). The non‐invasively measured calf Pv based on the intercept of the relationship between the vascular compliance component (Vv) and Pcuff, was 8.0±0.4mmHg, which was not significantly different from the corrected invasively measured Pv value of 8.8±0.3 mmHg P= 0.08). Venous blood lactate and haemoglobin concentrations, as well as colloid osmotic pressure, total protein and albumin concentrations were unchanged throughout the protocol, whereas significant decreases in Po2 and blood glucose concentration were observed when Pcuff reached 65 mmHg. Assuming a constant oxygen consumption, this may suggest a reduction in tissue perfusion. This study demonstrates the close correlation between Pcuff and Pvin the saphenous vein. Since the small congestion Pcuff step protocol does not cause significant increase in plasma oncotic pressure, we conclude that Pv as well as Kf can be accurately determined with this venous congestion plethysmography protocol.

We studied human lower limbs to test the hypothesis that the application of small cumulative venous congestion pressure steps is associated with a reduction in precapillary resistance. Strain gauge plethysmography was performed on twenty‐one young subjects (22.7 ± 0.6 years). At each of the small cumulative pressure steps, limb blood flow was estimated from the initial slope of the volume response to transient (10 s duration) elevations of venous congestion pressure to 90 mmHg, after which the congestion pressure was returned to the previous value. The blood flow at each pressure was also expressed as a percentage of the initial control value. Peak tibial arterial blood flux was assessed, in four of the subjects, using colour duplex ultrasonography and the same congestion pressure protocol. We used Darcy's Law to predict the limb arterial blood flow and blood flux at each venous congestion pressure, assuming that both mean arterial blood pressure and precapillary resistance remained constant. The mean ± s.e.m. control arterial blood flow at the lowest venous congestion pressure, 4.8 ± 0.1 mmHg, was 2.77 ± 0.18 ml min−1 (100 ml)−1. At the highest venous congestion pressure, 59.2 ± 0.2 mmHg, arterial blood flow was 2.45 ± 0.35 ml min−1 (100 ml)−1 (121.6 ± 16.9 % of the initial value). This did not differ significantly from the initial control value, but was significantly greater than the predicted value of 0.77 ± 0.13 ml min−1 (100 ml)−1 (28.6 ± 2.1 % of the initial value) calculated assuming constant resistance and sustained mean arterial pressure. The tibial arterial peak blood flux at 58.3 mmHg venous congestion pressure was 102.2 ± 2.3 % of the control value, which was significantly greater than the predicted 17.2 ± 1.3 % of control, calculated for this pressure, assuming constant resistance and sustained mean arterial pressure. Our data show that lower limb arterial blood flow is sustained when venous congestion pressure is raised using small cumulative steps, even at congestion pressures approaching mean arterial blood pressure. These data support the notion that precapillary resistance is influenced by signals generated at the microvascular and post microvascular levels and transmitted via the endothelium.

During studies of the pathogenesis of dengue shock syndrome, a condition largely confined to childhood and characterized by a systemic increase in vascular permeability, we observed that healthy controls, age-matched to children with dengue shock syndrome, gave high values of filtration capacity (K(f)), a factor describing vascular permeability. We hypothesized that K(f) might be age dependent. Calf K(f) was studied in 89 healthy Vietnamese subjects aged 5 to 77 years. The K(f) was highest in the youngest children [7. 53 (1.96-15.46) K(f)U; median (range); where the units of K(f), K(f)U=ml.min(-1).100 ml(-1).mmHg(-1)]. Values were 3- to 4-fold lower towards the end of the second decade [4.69 (1.91-7.06) K(f)U]. Young mammals are known to have a larger microvascular surface area per unit volume of skeletal muscle than adults. During development the proportion of developing vessels is greater. Moreover, the novel microvessels are known to be more permeable to water and plasma proteins than when mature. These factors may explain why children more readily develop hypovolaemic shock than adults in dengue haemorrhagic fever and other conditions characterized by increased microvascular permeability.

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1. Cumulative small steps in venous congestion pressure were used to study the effect of passive tilt on vascular parameters in dependent tissues. Using this protocol we have non‐invasively assessed venous pressure (Pv,est), isovolumetric cuff pressure (Pv,i), which is the congestion cuff pressure (Pcuff) that has to be exceeded to induce fluid filtration. We have also assessed microvascular filtration capacity (Kf), which is the linear relationship between filtration rate (Jv) and Pcuff, when Pcuff > Pv,i, and is the product of the available exchange vessel surface area and wall conductance. 2. Subjects were passively tilted to increase the venous pressure at the level of the calf by 47.4 +/‐ 2.4 mmHg (mean +/‐ S.E.M.). The value of Pv,i increased from 20.6 +/‐ 1.8 to 48.5 +/‐ 3.8 mmHg after the imposition of the tilt. This change may reflect the increased colloid osmotic pressure at the microvascular interface that is known to occur in response to this manoeuvre. 3. The pre‐tilt value of Kf did not change after the imposition of the passive tilt, the values being 3.2 +/‐ 0.4 x 10(‐3) and 3.6 +/‐ 0.4 x 10(‐3) ml min‐1 (100 ml‐1) mmHg‐1, respectively, (n = 13). 4. These results support the notion that passive postural change alters the pre‐capillary resistance, thereby altering the pressure and flow characteristics within the exchange vessels, but does not alter the surface area available for fluid exchange in the calf, contrary to previous findings in the dependent human foot using a single‐step venous occlusion protocol.

Dengue shock syndrome (DSS) is a potentially lethal complication of dengue virus infection associated with hypotension and leakage of plasma water into the extravascular space. To determine whether the underlying pathophysiology of DSS is distinct from that in milder forms of the disease, we assessed microvascular permeability, by use of strain gauge plethysmography, in Vietnamese children with DSS (n=19), or dengue hemorrhagic fever (DHF) without shock (n=16), and in healthy control children (n=15). At admission and after fluid resuscitation, the mean coefficient of microvascular permeability (K(f)) for the patients with dengue was approximately 50% higher than that for the control patients (P=.02). There was no significant difference in K(f) between the 2 groups of patients with dengue; this suggests the same underlying pathophysiology. We hypothesize that in patients with DSS, the fluctuations in K(f) are larger than those in patients with DHF, which leads to short-lived peaks of markedly increased microvascular permeability and consequent hemodynamic shock.