Changes in microvascular fluid filtration capacity during 120 days of 6 degrees head-down tilt.

We used venous congestion strain gauge plethysmography (VCP) to measure the changes in fluid filtration capacity (K(f)), isovolumetric venous pressure (Pv(i)), and blood flow in six volunteers before, on the 118th day (D118) of head-down tilt (HDT), and 2 days after remobilization (Post). We hypothesized that 120 days of HDT cause significant micro- and macrovascular changes. We observed a significant increase in K(f) from 3.6 +/- 0.4 x 10(-3) to 5.7 +/- 0.9 x 10(-3) ml. min(-1). 100 ml(-1). mmHg(-1) (+51.4%; P < 0.003), which returned to pretilt values (4.0 + 0.4 x 10(-3) ml. min(-1). 100 ml(-1). mmHg(-1)) after remobilization. Similarly, Pv(i) increased from 13.4 +/- 2.1 mmHg to 28.9 +/- 2.8 mmHg (+105.8%; P < 0.001) at D118 and was not significantly different at Post (12.4 +/- 2.6 mmHg). Blood flow decreased significantly from 2.3 +/- 0.3 to 1.3 +/- 0.2 ml. min(-1). 100 ml tissue(-1) at D118 and was found elevated to 3.4 +/- 0.7 ml. min(-1). 100 ml tissue(-1) at Post. We believe that the increased K(f) is caused by a higher microvascular water permeability. Because this may result in edema formation, it could contribute to the alterations in fluid homeostasis after exposure to microgravity.

Noninvasive measurement of microvascular leakage in patients with dengue hemorrhagic fever.

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.

Description and validation of a novel liquid metal-free device for venous congestion plethysmography.

We present a newly developed electromechanical sensor with automated calibration for strain-gauge plethysmography (filtrass) and compare it to a conventional mercury-in-Silastic strain-gauge plethysmograph (MSG). Fluid filtration capacity (K(f)) and isovolumetric venous pressure (Piv) of the limb were assessed noninvasively with both devices in 29 healthy volunteers. We found significantly higher K(f) and Piv values with MSG [4.6 +/- 2.0 x 10(-3) ml. min(-1). mmHg(-1). 100 ml tissue(-1) (K(f) units; K(f)U) and 21.2 +/- 8.1 mmHg for Pvi], than with filtrass, giving values of 3.1 +/- 0.8 K(f)U and 15.1 +/- 7.1 mmHg. Because K(f) and Piv are profoundly influenced by the calibration, we investigated the quality of the calibration signal and its impact on the obtained values. We could show that the reproducibility of repeated calibrations was higher with filtrass (58% lower mean +/- SD). The data were grouped according to the quality of calibration, and we found no significant difference in K(f) and Piv between filtrass (3.0 +/- 0.7 K(f)U and 15.9 +/- 6.9 mmHg, respectively) and MSG with good calibration signal (3.3 +/- 0. 8 K(f)U and 18.6 +/- 7.1 mmHg, respectively; no significant difference). However, we obtained significantly higher MSG values (5. 6 +/- 2.0 K(f)U and 23.1 +/- 8.4 mmHg, respectively; P < 0.001) in the group with a bad calibration signal. We suggest that the filtrass sensor, which performs an automatic, standardized calibration procedure and shows a linear signal response to stretch, gives highly reproducible and reliable results and thus is more suitable for routine application.

Vitamin C modifies the cardiovascular and microvascular responses to cigarette smoke inhalation in man.

Both neutrophil margination and increases in the non-invasively assessed parameter, isovolumetric venous congestion cuff pressure (Pv(i)), are symptomatic of some inflammatory diseases. Neutrophil margination occurs primarily, though not exclusively, at the post-capillary endothelial surface. The local haemodynamic changes resulting from margination may be responsible for the observed increases in Pv(i). Smoke inhalation has been shown in animal studies to cause an increase in post-capillary neutrophil margination by mechanisms that can be blocked by oral vitamin C administration. We looked for indices of a relationship between margination and Pv(i) in man, using cigarette smoke inhalation as a pathophysiological challenge. We also examined the effect of prophylactic vitamin C on the response. Smoke inhalation was associated with highly significant increases in both Pv(i) and heart rate. After vitamin C pre-treatment, no increase in Pv(i) was observed in response to the smoke inhalation; however, whilst heart rate still increased significantly, the duration of this response was attenuated. The results suggest that vitamin C affords protection against some of the cardiovascular and microvascular changes associated with cigarette smoke inhalation in man. They also support the notion that non-invasive assessment of changes in Pv(i) may provide a measurable index of systemic changes in inflammatory conditions.

Age-related changes in microvascular permeability: a significant factor in the susceptibility of children to shock?

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.

Increased microvascular water permeability in patients with septic shock, assessed with venous congestion plethysmography (VCP).

OBJECTIVES: To investigate microvascular water permeability (filtration capacity, Kf) in patients with septic and non-septic shock using a new non-invasive method for studying microvascular parameters in man. SETTING: Intensive Care Unit of a university hospital. PATIENTS AND METHODS: We investigated 28 patients, presenting with cardio-vascular instability due to either septic shock, or non-septic shock (haemorrhage, multiple trauma, respiratory and/or cardiac failure). INTERVENTIONS: We used standard invasive methods of monitoring (in-dwelling arterial lines and pulmonary artery flotation catheters) in combination with computer assisted venous congestion plethysmography (VCP) measurements, for a parallel assessment of peripheral microcirculatory parameters. RESULTS: On admission to the ICU, patients with septic shock revealed a significantly higher mean value of filtration capacity Kf = 6.1 +/- 0.4 x 10(-3) (mean value +/- standard error of the mean, ml.min-1.100 ml tissue-1.mmHg-1 = KfU) than non-septic patients Kf = 3.5 +/- 0.3 KfU (p < 0.02). The Kf values of the septic patients were significantly higher than those from age-matched patients with peripheral vascular disease (4.1 +/- 0.2 KfU, p < 0.001) and those of healthy controls (4.3 +/- 0.2 KfU, p < 0.001); the Kf values of the non-septic patients, however, were not significantly different. The highest mean Kf value observed during the stay on ICU was Kfmax 11.6 +/- 0.2 KfU in the septic group and 5.7 +/- 0.1 KfU in the non-septic group (p < 0.001). Pvi, a value reflecting the balance of hydrostatic and oncotic forces in the microcirculation, was elevated in both patient groups. On admission, in septic patients Pvi was 39.2 +/- 3.3 mmHg and in non-septic patients 35.1 +/- 2.7 mmHg, these values were not significantly different, but significantly higher than the Pvi value of healthy controls (Pvi 21.5 +/- 0.8) (p < 0.001). A weak, however significant, positive correlation was found between Kf and Pvi in both patient groups. No correlations were found between Kf, as well as Pvi, and cardiac index (CI), oxygen delivery index (DO2I), oxygen consumption index (VO2I) and systemic vascular resistance index (SVRI). CONCLUSIONS: An increase in permeability of microvessels will cause a loss of intravascular fluid and may therefore partially explain the large fluid requirements of patients in shock. It will also favour the development of oedema, which is often found in septic patients. We propose that changes in Kf are useful indices of microvascular malfunction and that VCP allows the non-invasive assessment of these parameters.

Human calf precapillary resistance decreases in response to small cumulative increases in venous congestion pressure.

1. 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. 2. 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. 3. 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. 4. 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. 5. 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.

Relationship between venous pressure and tissue volume during venous congestion plethysmography in man.

1. 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 (Pcuff) applied to the limb equals Pv at the level of the strain gauge, was tested in this study. 2. 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 mmHg). Pcuff, changes in limb circumference and Pv were recorded by computer for off-line analysis. Since the determination of Kf is influenced by the changes in plasma oncotic pressure, venous blood samples were obtained at the start of the study, when Pcuff was raised to 30 mmHg and again to 65 mmHg and 4 min after deflation of the cuff. 3. The relationship between Pv and Pcuff was linear over the range of 10-70 mmHg (n = 9, 69 measurements, slope 0.91, r = 0.97, P << 0.001). The non-invasively measured calf Pv, based on the intercept of the relationship between the vascular compliance component (Va) and Pcuff, was 8.0 +/- 0.4 mmHg, which was not significantly different from the corrected invasively measured Pv value of 8.8 +/- 0.3 mmHg (P = 0.08). 4. 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. 5. This study demonstrates the close correlation between Pcuff and Pv in 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.

The effect of passive tilting on microvascular parameters in the human calf: a strain gauge plethysmography study.

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.

Investigating the origin of cyclic changes in limb volume using mercury-in-silastic strain gauge plethysmography in man.

1. Vasomotion, a phenomen frequently observed in skeletal muscle microcirculation, has been observed under physiological conditions and found enhanced during critical reduction of tissue perfusion due to hypoxic hypoxia, haemorrhage and local hypotension. We used a computer assisted non-invasive plethysmographic method to investigate periodic changes of limb volume (volumotion), which we previously found in critically ill patients. The current study was designed to investigate the origin of volumotion. 2. Simultaneous recordings of limb circumference of both calves were obtained. In patients with peripheral vascular disease and patients with minor surgery the cross-correlation with spontaneous breathing was investigated. In patients who had undergone major abdominal or vascular surgery we analysed for cross-correlations between MSG plethysmography signals of both legs and changes in central venous, arterial and ventilation pressures. In this group the effects of positive-pressure ventilation and positive end-expiratory pressure (PEEP) were also studied. 3. No ventilation-related volumotion was observed during spontaneous breathing. During positive-pressure ventilation a ventilation-related peak was found in the Fourier transform in agreement with the ventilation frequency applied. The amplitude of ventilation-related volumotion decreased significantly after a pressure cuff applied to the thigh was inflated above central venous pressure. We observed a significant increase in the amplitude of ventilation-related volumotion when PEEP was applied. 4. Ventilation-related volumotion showed significant cross-correlation between both legs. Slow wave volumotion (0.5-7 cycles min-1) was frequently observed, but always appeared unilaterally. Whilst we looked for correlations between slow wave volumotion and changes in central venous pressure and arterial blood pressure, respectively, significant cross-correlation with the MSG plethysmography recordings was only observed at the frequency of the positive-pressure ventilation. 5. The fact that periodic changes of limb circumference matching the frequency of the positive-pressure ventilation were detectable with the MSG plethysmography system demonstrates that small volume changes (less than 0.02 ml (100 ml tissue)-1) can be assessed using this system. As slow wave volumotion was observed unilaterally and revealed no correlation either with breathing, ventilation or arterial and central venous pressure, we suggest that slow wave volumotion is a local event most likely reflecting arteriolar vasomotion.

Prevalence of cyclic changes in limb volume (volumotion) of male patients with knee injury and the effects of ischemia/reperfusion due to tourniquet.

During surgery of limbs tourniquet up to a maximum of 2 h is frequently applied which may cause ischemia/reperfusion injury (IRI). During this condition the presence of vasomotion may have consequences for the perfusion and nutritive state of the tissues. We used a noninvasive plethysmographic method to investigate periodic changes in limb circumference (volumotion) in healthy male patients (n = 24) undergoing surgery for knee injury. To facilitate surgery a tourniquet was applied to the thigh, which caused an IRI of the leg. Results are given as mean of all values +/- SEM. Immediately after tourniquet release (duration 57.75 +/- 5.19 min) blood lactate levels in the femoral vein increased significantly from 1.40 +/- 0.08 to 2.59 +/- 0.20 mmol/l (p < 0.001) and pH fell from 7.39 +/- 0.01 to 7.32 +/- 0.01 (p < 0.001). Preoperatively 10 out of 24 patients (42%) showed signs of volumotion on the injured leg with a periodicity ranging from 0.8 to 6.9 cycles/min, whereas none showed volumotion in the control leg (p < 0.001). In the second measurement, taken after surgery and reperfusion while peripheral sympathetic nerves were blocked, 7 out of 18 patients (39%) showed volumotion on the injured leg and 0 on the control leg (p < 0.004). 6 h after IRI, volumotion was observed in 11 out of 17 patients (65%) on the injured leg and in 1 patient (6%) on the control leg (p < 0.001). The mean volume change in the patients with volumotion on the injured leg was 0.057 +/- 0.007 ml/100 ml tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Capillary filtration coefficient in type II (non-insulin-dependent) diabetes.

Changes in microvascular permeability may be important in the pathogenesis of diabetic microangiopathy. In order to assess microvascular fluid permeability, the capillary filtration coefficient was determined in the forearm of 24 normotensive type II diabetic patients with minimal evidence of microangiopathy and satisfactory glycemic control, and 24 age- and sex-matched control subjects, using a sensitive strain gauge plethysmographic system. The median capillary filtration coefficient was not significantly different in the type II diabetic patients and control subjects [5.3 (3.2 - 9.1) x 10(-3) mL.min-1.100 g tissue-1.mm Hg-1 versus 5.4 (3.5 - 8.0) x 10(-3) mL.min-1.100 g tissue-1.mm Hg-1, p = 0.98)]. There were no correlations between capillary filtration coefficient and age, blood pressure, body mass index, duration of diabetes, glycemic control, or the presence of microvascular complications. These findings contrast with type I diabetes, where capillary filtration coefficient is elevated at an early stage in the disease, and lend support to the theory that there are differences in early microvascular functional abnormalities between type I and type II diabetes.

The abnormal quinine drinking aversion in the Brattleboro rat with diabetes insipidus is reversed by the vasopressin agonist DDAVP: a possible role for vasopressin in the motivation to drink.

The Brattleboro rat with hypothalamic diabetes insipidus (BDI) has an abnormal aversion to drinking quinine-adulterated water compared with normal rats of the parent Long Evans (LE) strain. This BDI animal tolerates marked hypovolemia and decreased body weight in preference to drinking the quinine-adulterated fluid, indicative of a reduced motivation to drink. Acute or chronic treatment of BDI rats with desamino-8D arginine vasopressin (DDAVP) restored to normal their drinking response to quinine solution. Partial restoration of fluid turnover in BDI rats with hydrochlorothiazide, which has an antidiuretic effect in diabetes insipidus (when vasopressin is absent), failed to abolish the abnormal drinking response to quinine-adulterated solution in 8 out of 12 animals. In contrast, induction of diabetes mellitus in LE rats, which resulted in a marked polydipsia and polyuria even though vasopressin was still present, did not impair the drinking response to quinine solutions. These results suggest that the abnormal drinking response to quinine-adulterated fluid in BDI rats is reversed by treatment with the vasopressin V2-receptor agonist DDAVP but is unlikely to be a consequence of the restoration of fluid turnover to normal levels by a renal action. A possible central action involving vasopressin and the motivation to drink is discussed.

[Microvascular monitoring using mercury in silastic strain gauge plethysmography (MSG)]. / Mikrovaskuläres Monitoring mit Hilfe der Mercury-in-Silastic-Strain-Gauge-Plethysmographie (MSG).

Mercury in silastic strain gauge plethysmography (MSG) is a noninvasive method for assessing microvascular parameters in peripheral limbs. MSG allows measurement of capillary filtration coefficient (Kf), isovolumetric venous pressure (Pvi), venous pressure (Pv) and arterial inflow (Qa) into the limb, respectively. We used MSG in combination with invasive monitoring techniques (pulmonary artery flotation catheters and arterial catheters) to study 36 critically ill patients in either hemorrhagic or septic shock. We observed marked increases in Pvi in both patient groups which correlated with outcome. On admission, both groups showed elevated values for Pvi, survivors 37.7 +/- 2.6, nonsurvivors 33.7 +/- 3.5 mm Hg (mean +/- SEM) when compared with a control group of young healthy students (22.1 +/- 0.82 mm Hg). Survivors showed a decrease in Pvi to 27.3 +/- 1.7 mm Hg, whereas in nonsurvivors Pvi increased to 39.5 +/- 3.0 at the last measurement taken. The changes in Pvi depended on the resuscitation regime used. On admission, patients requiring only fluid replacement (F) had a lower Pvi (31.3 +/- 2.9 mm Hg) than patients needing inotropic support with dobutamine (D, Pvi = 38.2 +/- 2.4 mm Hg) to fulfill our therapeutic goals (DO2 > 550 ml.min-1 x m-2, VO2 > 150 ml.min-1 x m-2 and mixed venous lactate < 1.5 mmol/l). After treatment Pvi did not change significantly in the F group (31.3 +/- 1.8), the D group however showed a significant decrease in Pvi to 25.4 +/- 2.42, which did not differ from the normal value. We regard Pvi as an indicator of insufficient microvascular flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased microvascular fluid permeability in young type 1 (insulin-dependent) diabetic patients.

Microvascular fluid permeability was assessed by determination of the capillary filtration coefficient in the forearm of ten young Type 1 (insulin-dependent) diabetic patients with a short duration of diabetes, satisfactory glycaemic control and minimal evidence of microangiopathy, and ten age- and sex-matched control subjects. A strain gauge plethysmographic method with a computer based logging and analysis system was used. This enabled differentiation between the volume filling and fluid filtration components of the response to venous pressure elevation. The median capillary filtration coefficient was found to be significantly higher in the young diabetic patients in comparison with control subjects (9.2 x 10(-3) ml.min-1.100 g tissue-1.mmHg-1 vs 3.8 x 10(-3) ml.min-1.100 g tissue-1.mmHg-1, p < 0.001). There were no significant correlations between capillary filtration coefficient and either plasma glucose concentration, haemoglobin A1c or duration of diabetes. As there is no evidence from other studies to support an increase in capillary surface area in the forearms of young Type 1 diabetic patients, these results may reflect a primary change in microvascular fluid permeability.

A reassessment of mercury in silastic strain gauge plethysmography for microvascular permeability assessment in man.

1. 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), isovolumetric 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 (9.53 +/- 0.45 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 +/- 1.14 s. 3. Increasing the size of the pressure step, to 49.8 +/- 1.1 mmHg, gave a larger value for the RVR time constant (mean 77.3 +/- 11.6 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 muscle-based mechanism, e.g. the veni-arteriolar reflex. 5. The mean (+/- S.E.M.) values for Kf, Pvi and Pv were 4.27 +/- 0.18 (units, ml min-1 (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.

Mercury in silastic strain gauge plethysmography for the clinical assessment of the microcirculation.

We have used the mercury in silastic strain gauge plethysmography (MSG) system, which is wholly non-invasive, to obtain values (mean +/- s.e.m.) for the following parameters in the legs of supine control subjects: venous pressure (Pv) 9.89 +/- 0.88 mmHg, vascular compliance (Comp) 3.50 +/- 0.29 ml 100 g-1 mmHg-1 x 10(-2), microvascular hydraulic conductivity (Kf) 4.10 +/- 0.16 ml min-1 100 g-1 mmHg-1 x 10(-3) and isovolumetric venous pressure (Pvi) 22.12 +/- 0.82 mmHg. On passive foot-down tilting of control subjects through about 45 degrees, both Pv and Pvi rose to 28.00 +/- 2.33 and 36.58 +/- 2.29 mmHg respectively. The increases in both parameters were highly significant, P < 0.0001. We found that the time course of the vascular compliance component was short if small pressure steps were used. The value increased markedly if large steps were used. We also observed that none of the microvascular parameters studied in the arms differed from those in the legs of the same subjects. We observed that the mean value Kf in the arms of 12 young, non-neuropathic diabetics (9.08 +/- 6.12 x 10(-3)) was significantly greater than that of age and sex-matched controls (P < 0.001). Studies on 14 venous ulceration patients indicated that the values for Kf and Pv were unchanged, whilst those of vascular compliance (5.60 +/- 0.58 x 10(-2) ml 100 g-1 mmHg-1) and Pvi (37.30 +/- 2.25 mmHg) were significantly greater than those found in age-matched controls (P < 0.002 and 0.001, respectively). We feel that Pvi is a useful index of microvascular perfusion. We attribute the pressure-dependent difference, in the time course of the vascular compliance response, to the veni-arteriolar reflex. We feel that the pressure dependency of this response might form the basis for the assessment of peripheral autonomic neuropathy. We believe that the MSG system offers a means of monitoring the development of pathologies resulting from microvascular under-perfusion and, of course, the improvement in response to therapeutic interventions.

The assessment of the microcirculatory effects of dobutamine using mercury in silastic strain gauge plethysmography in man.

Adverse changes in the microcirculation are currently considered as the most likely common pathway of organ failure, dramatically manifest in the multiple organ failure syndrome. We have investigated 28 patients presenting with gross cardiovascular instability due to septic shock or haemorrhage, using standard invasive methods of monitoring (Physiological Profile). We combined this study with a computer assisted mercury-in-rubber strain gauge plethysmography (MSG) measurement, for a parallel (non-invasive) assessment of peripheral microcirculatory function. We started the investigation on patient arrival in ICU and continued it during their resuscitation regime, which essentially consisted of fluid loading together with inotropic support, where necessary. We found highly significant changes in isovolumetric venous pressure (Pvi), determined by the MSG technique, when we compared survivors (27.29 +/- 1.65 mmHg, mean +/- s.e.m.) with non-survivors (39.5 +/- 2.97 mmHg, P less than 0.001). To investigate the role of dobutamine in patient improvement we compared the Pvi values obtained from the MSG studies and demonstrated a significant decrease from the initial value (38.2 +/- 2.4 mmHg) to the final one (25.4 +/- 2.4 mmHg), obtained after weaning the patients off dobutamine. Marked cyclic changes in limb circumference (vasomotion) were also observed and their appearance correlated well with accepted parameters of cardiovascular instability. We propose that changes in both Pvi and Vm are useful indices of microvascular hypoperfusion which is probably the underlying cause of pathology in both patient groups.

A role for vasopressin in the stress-induced inhibition of gonadotrophin secretion: studies in the brattleboro rat.

Abstract The effects of stress on the secretion of adrenocorticotrophin, corticosterone and luteinizing hormone (LH) in rats congenially lacking hypothalamic vasopressin (Brattleboro rats) and in normal controls of the parent strain (Long Evans) have been compared in an attempt to examine the role of vasopressin in the stress-induced depression of gonadotrophin secretion. In the Long Evans rats, stress (0.6 mg/100g histamine, ip) initiated, within 5 and 20 min respectively, significant (P <0.01, Student's t-test) increases in the plasma adrenocorticotrophin and corticosterone concentrations. It also caused a reduction in the serum LH concentration which was maximal at 5 min. By contrast, in the vasopressin deficient Brattleboro rats, stress had no effect on the serum LH concentration and produced only modest increases in pituitary adrenocortical activity compared with those in Long Evans controls. Pretreatment of both Long Evans and Brattleboro rats with dexamethasone (20mug/100 g ip, daily for 3 days) effectively abolished the pituitary-adrenal response to stress. The steroid treatment also prevented the stress-induced suppression of LH in the Long Evans rats; indeed, these animals, unlike the vehicle-treated controls, exhibited a rise in serum LH concentration within 5 min of exposure to stress. Stress did not affect the serum LH concentrations in steroid-treated Brattleboro rats. The results confirm previous reports that vasopressin is required for the full expression of the pituitary-adrenocortical response stress. They also provide novel evidence which suggests that vasopressin released in stress contributes to the impairment of gonadotrophin secretion.

Increased aversion to bitter-tasting fluids in the Brattleboro rat.

The large daily water intake of Brattleboro rats with diabetes insipidus (BDI) is believed to be due to the volume of depletion caused by their lack of circulating anti-diuretic hormone. However an increased fluid consumption cannot necessarily be interpreted as an increased behavioural drive to drink. In order to examine these rats' motivation to drink, quinine at various concentrations was given in the drinking water as sole fluid source to BDI rats and rats of the parent Long Evans (LE) strain, and their fluid balance after twenty-four hours was determined. Brattleboro rats reduced their fluid intakes significantly more than the control LE rats at the highest concentration of drug used (100 mg/l), suggesting a decreased motivation to drink. A two bottle preference test for quinine showed that the BDI rats actually have a higher taste threshold for the drug in solution in drinking water than the control LE rats. This suggests that the increased aversion to quinine in solution when it is the sole drinking source cannot be due to the BDI rats tasting the quinine at a lower concentration than the LE animals. Nor are greater toxic effects of quinine in BDI rats likely to account for the different drinking responses when presented with quinine solutions, since intragastric administration of the drug had no effect on water consumption in these animals. When BDI rats were given bitter-tasting sucrose octa-acetate solutions as their sole drinking source, drinking was again drastically reduced. However LE rats actually increased their fluid consumption when given sucrose octa-acetate showing a preference for this substance in solution to tap water.(ABSTRACT TRUNCATED AT 250 WORDS)