Can skin temperature manipulation, with minimal core temperature change, influence plasma volume in resting humans?

We investigated body-fluid distribution in resting humans, during short-term, whole-body skin temperature modification, in which core temperature changes (ΔT_c) were minimal. Seven males participated in hot (36.2°C (s.d. 0.7), 44% relative humidity (rh; s.d. 3)), temperate (22.0°C (s.d. 1.0), 52% rh (s.d. 6)), and cool trials (14.4°C (s.d. 1.6), 74% rh (s.d. 9)), while seated at rest. Total body water (TBW), extracellular fluid (ECF), erythrocyte (RCV) and plasma volumes (PV) were measured using a simultaneous radionuclide dilution technique. In the cold, PV contracted by 205 ml (±60) by the end of exposure (p = 0.04), while in the heat, PV expanded 108 ml (±123; p = 0.02). Both RCV and TBW remained stable, regardless of the environment. Despite fluid movement across the vascular wall, ECF, interstitial and intracellular volumes were relatively unaffected by skin temperature. It was concluded that, at rest, and with minimal ΔT_c, the intravascular fluid volume was dependent on prevailing environmental conditions, and its impact on local skin temperature and venomotor tone. Accepted: 12 July 1999     

Estimation of extracellular space and blood volume using bioelectrical impedance measurements

Summary The bromide-82 dilution space (extracellular space, ECS) and blood volume (BV) were measured in 21 patients with esophageal and gastric cancer and in 27 patients 18–96 months after total gastrectomy. Resistance (R) and reactance (X_c) from bioelectrical impedance measurements were used to obtain multiple regression equations for ECS and BV. The variables weight, gender, and height ²/X_c were independent predictors of ECS (r = 0.767; P < 0.0001). Height 2/R and gender were predictors of blood volume (r = 0.856; P < 0.0001). The mean difference between the Br space and the ECS predicted from impedance measurements was 0 ± 1.54 (mean ± SD). The limits of agreement (± 2 SD) were therefore ±3.081 or 19.6% of the mean Br space of 15.71. The limits of agreement for BV were ±789 ml or ±19.7% of the average BV of 4008 ml. It is concluded that bioelectrical impedance plethysmography using a single frequency can be used for the estimation of ECS and BV The wide limits of agreement, however, may limit its used in clinical practice.Abbreviations ECS extracellular space - BV blood volume - R resistance - X_c reactance - SD standard deviation - LBM lean body mass - TBW total body water - RCM red blood cell mass - cAMA corrected arm muscle area - Z impedance - ANOVA analysis of variance - NS not significant - Na_e/K_c exchangeable sodium to exchangeable potassium ratio - p specific resistivity - PV plasma volume     

Splenic haematopoiesis in patients with cirrhosis of the liver

Summary Hitherto it has generally been assumed that splenic haematopoiesis in adult humans occurs very infrequently and is predominantly associated with haematological disorders. In the present study of patients with cirrhosis of the liver, a marked splenic haematopoiesis was a constant finding. Moreover, low-level splenic erythro- and granulopoiesis was highly prevalent even in haematologically normal controls, while splenic thrombopoiesis was conspicuously absent in both groups. We suggest that splenic haematopoiesis results from entrapment and proliferation of circulating haematopoietic precursor cells in the splenic red pulp. This would account for the presence of splenic haematopoiesis in normal controls as well as in patients with cirrhosis of the liver. In the latter, stimulation of bone marrow haematopoiesis and increased splenic pooling of haematopoietic precursor cells may contribute to the marked increase of splenic haematopoiesis observed.     

The effects of extracellular potassium,ouabain, and prostaglandins on intracellular potassium activity in sheep cardiac Purkinje fibers

(1) Intracellular K activity (a _K ⁱ ) of sheep heart Purkinje fibers was measured using K-selective microelectrodes (liquid ion exchanger).a _K ⁱ in the resting state with an extracellular K of 4 mmol·l^–1 was 112.9±6.1 mmol·l^–1 (n=47) for a membrane potential (V _M) of –73.3±0.9 mV.V _M deviated from the calculated potassium equilibrium potential (E _K=–93 mV). (2) When extracellular K was decreased to 2 mmol·l^–1 or increased to 6 and 10 mmol·l^–1 E _K changed from –114 to –84 and –73 mV, with little change ina _K ⁱ . (3)a _K ⁱ andV _M significantly decreased after administration of 10^–6 mol·l^–1 ouabain. (4) Prostaglandins (PGI₂ 10–100 g·l^–1 and PGE₂ 0.01–1 g·l^–1) decreaseda _K ⁱ without greatly changingV _M. The differences betweenV _M andE _K became smaller. These effects indicate an increase in K permeability and may explain the antiarrhythmic action of prostaglandins.This study was supported by the Deutsche Forschungsgemeinschaft (grant Wi 328). In preliminary form part of the data has been presented (Pflügers Arch. 384: R 13, 1980, and Proc. XXVIII. Int Congr Physiol Sci, Vol XIV: 279, 1980)     

Total immunoreactive angiotensin II,its Hepta-octapeptide fraction,and its hexapeptide in patients with liver disease

Summary Arterial and venous plasma concentrations of total immunoreactive angiotensin II (AT II), its bioactive hepta-octapeptide fraction and its inactive hexapeptide were measured in normal subjects (n=16), in patients with acute viral hepatitis (n=12), and in treated (n=16) and untreated (n=17) patients with cirrhosis of the liver and ascites.Independent of normal or increased values of total immunoreactive AT II, the ratio between the heptaoctapeptides and the hexapeptide remained unchanged. This might indicate continuous octapeptide generation and balanced metabolite turnover throughout the systemic circulation. Morevoer, a significant arterio-venous peptide gradient was lacking. It has to be concluded that total venous plasma AT II sufficiently reflects both the arterial hormone concentration and its major fraction of hepta-octapeptides in arterial (79%) and venous (76%) blood.     

Changes in interstitial pressure during and after blood volume expansion in rats

Summary Interstitial fluid pressure was measured via a chronically implanted capsule before, during and after acute isotonic, iso-oncotic blood volume expansion in normal or in 48-h dehydrated rats. At the same time, the patterns of body fluid distribution, of selected renal responses and of mean arterial and mean central venous pressure responses were studied. Dry tissue weight (DTW) was subsequently determined by freeze drying of the shaved carcass.Dehydration decreased plasma volume and interstitial fluid volume significantly below normal values. The initial intracapsular pressure in dehydrated animals (–3.7±0.6 mm Hg) was not significantly different from that in normal rats (–2.5±0.5), but dehydrated rats showed initially a very significantly lower effective interstitial compliance (0.0005 ml/mm Hg per gram DTW) than did the normal group (0.0704).In the course of the renal response to the volume load, effective interstitial complicance increased to 0.0350 in dehydrated rats but showed no change in normal rats. Neither group completely corrected its elevated blood volume; both returned their central venous pressures to pre-infusion levels; both decreased their interstitial fluid volumes below preinfusion levels and both decreased their intracapsular fluid pressures 1 mm Hg below the level prevailing in non-infused animals at that time.It is concluded that a reduction in interstitial, hydrostatic pressure can be a functionally important influence in the apparent control of central venous pressure following acute blood volume expansion.This study was supported by the Canadian Heart Foundation.     

The effect of posture change on blood volume,serum potassium and whole body electrical impedance

After standing for 1h, ten subjects (7 male, 3 female) assumed a supine position for a further hour. Whole body bioelectrical impedance increased progressively during the hour spent in the supine position: after 60 min supine the increase was 13(6 to 32). Blood and plasma volumes, estimated from haematocrit and haemoglobin concentration, increased by 8.0(6.7 to 12.4)% and 16.7(12.3 to 20.8)% (median(range)) respectively after 60 min supine. Serum potassium concentration had fallen after 10 min supine (4.1(0.1)mmol 1^–1; mean(SEM)) relative to the standing value (4.6(0.1)mmol 1^–1) and was unchanged thereafter. Serum osmolality (P=0.991) and sodium (P=1.000) and chloride (P=0.998) concentrations remained unchanged throughout the study. The fall in serum potassium concentration in the supine position does not appear to be a simple dilutional effect consequent upon increases in blood and plasma volume as there was no effect of postural change on serum sodium or chloride concentrations.     

Interrelations between age and plasma renin,aldosterone and cortisol,urinary catecholamines,and the body sodium/volume state in normal man

Summary Interrelations between age and plasma renin, aldosterone and cortisol levels, urinary catecholamines, plasma and blood volumes, exchangeable body sodium and blood pressure were studied in 28 young (19 to 29 years), 16 middle-aged (32 to 58 years) and 15 elderly (60 to 74 years) healthy subjects. Supine and upright plasma renin and supine aldosterone levels decreased while urinary noradrenaline excretion rate increased progressively with aging (r0.34;p<0.05), with significant differences in mean values between young and elderly subjects (p<0.02). There was also an age-related decrease in upright plasma aldosterone concentration, although this was not statistically significant. Furthermore, mean plasma cortisol concentrations increased in response to upright posture in elderly (+50%;p<0.02), but not in young (–10%) or middle-aged (–8%) subjects. Blood pressure correlated with age (r=0.35;p<0.05) or noradrenaline excretion rate (r=0.34) in the entire study population and with blood volume in the elderly (r=0.68), but not in the young or middle-aged study groups. There were no significant age-related differences in the body sodium/volume state, basal plasma cortisol levels or urinary adrenaline excretion rate, and plasma renin or aldosterone levels did not correlate with these parameters or with blood pressure. It is concluded that the influence of age on plasma renin or aldosterone levels, plasma cortisol responsiveness to upright posture, and urinary noradrenaline excretion should be taken into consideration, whenever these factors have to be interpreted in patients with arterial hypertension or other clinical disorders. Furthermore, these data are consistent with the possibility that in normal man increases in supine blood pressure with aging may be related at least partly to concomitant changes in free peripheral noradrenaline.This investigation was supported by the Swiss National Science Foundation     

Blood volume and body haematocrit of rats native to a simulated altitude of 3500 m

Circulating blood volume (BV) as the sum of circulating red cell volume (RCV) and plasma volume (PV) was estimated in rats native to a simulated altitude of 3500 m (“natives”), in rats born at sea level and later in life transferred to the simulated high altitude (“newcomers”), and in control sea-level rats. RCV per kg body weight (b.w.) was significantly larger in both “newcomers” and “natives” than in controls. PV per kg b.w. was in the “newcomers” insignificantly and in the “natives” significantly smaller than in the controls. BV per kg b.w. in both high altitude groups tended to be larger than in controls but the difference was not significant. Arterial haematocrit (Ahct) in the “newcomers” was significantly higher than in the controls, and in the “natives” significantly higher than in both other groups. Body haematocrit (the ratio of RCV and BV in per cent) was smaller than Ahct in all groups; this was more pronounced in the “newcomers” than in the controls and even more so in the “natives”. Apparently the haematocrit in the minute vessels of the organs of animals exposed to chronic hypoxic hypoxia increases much less than might be expected from changes of the Ahct. An attempt was made to evaluate the possible error of the more commonly used method of estimating BV, when only RCV, or only PV, is measured, and BV and its complementary fraction are calculated from arterial or venous haematocrit. When, in our results, BV was calculated from RCV and Ahct, the absolute values and also the differences between groups were somewhat underestimated. When BV was calculated from PV and Ahct, the BV itself, and particularly the differences between groups, were overestimated quite considerably. It is suggested that the only safe way to estimate BV is to measure RCV and PV separately.     

Studies on the activity of the renin-angiotensin-aldosterone system (RAAS) in patients with cirrhosis of the liver

Summary Plasma renin activity (PRA), plasma renin concentration (PRC), angiotensinogen, angiotensin II (AT II) and plasma aldosterone were determined by radioimmunoassay in 77 patients with cirrhosis of the liver [group I: with ascites, untreated (n=23); group II: patients with ascites during treatment (n=32); group III: after removal of fluids, but under further spironolactone therapy (n=10); group IV: untreated subjects without ascites (n=12)]. With the exception of decreased angiotensinogen values in all groups ranging between 39% (group IV) and 73% (group III) no significant changes of the other parameters of the RAAS were found in untreated patients. A highly significant increase of PRA, PRC, AT II and plasma aldosterone was observed in treated cirrhotics with (group II) or without (group III) ascites. In the total series of patients AT II was closely related to PRA, PRC and aldosterone emphasizing again the predominant role of AT II to stimulate aldosterone secretion. Plasma sodium was inversely correlated to PRA, PRC, AT II and aldosterone, but no relationship was detected between these parameters of the RAAS and plasma potassium.Our results indicate that hyperaldosteronism in cirrhosis appears unlikely to be the major determinant of avid renal sodium retention and ascites formation. An increased activity of the RAAS is most often initiated by therapeutic factors and/or markedly altered electrolyte metabolism. Therefore, basal conditions of the patients to be studied must be well defined to exclude any artificially induced stimulation of the RAAS.     

Hepatocyte production of modulators of extracellular liver matrix in normal and cirrhotic rat liver

In the present study, we found collagenolytic and gelatinolytic activity in the supernatants of hepatocyte cultures from rats with experimental CCl(4)-induced liver cirrhosis, in levels significantly higher than in comparable supernatants of hepatocyte cultures from normal rats. In addition, we clearly detected the messenger ribonucleic acids (mRNA) of four matrix metalloproteinases (MMP-2, MMP-3, MMP-10, and MMP-13) and of two tissue inhibitors of matrix metalloproteinases (TIMP-1 and TIMP-2) in hepatocytes from both normal and cirrhotic rats by RT-PCR and by in situ hybridization. Finally, we demonstrated MMP-2, MMP-3, and MMP-13 and TIMP-1 and TIMP-2 proteins in the same hepatocyte preparations by immunostaining. We conclude that rat hepatocytes produce the major enzymes and inhibitors involved in liver ECM modulation and therefore suggests that they might participate actively in the pathophysiology of liver cirrhosis in rats.     

The effects of body position and exercise on plasma volume dynamics

Summary We examined the plasma volume changes associated with a protocol of either exercise or controlled rest under identical positional and ambient conditions. Nine healthy adult males rode (E) and on another occasion sat quietly (C) on a cycle ergometer for 30 min. Ten minutes of cycle exercise immediately followed the resting C protocol. Ambient temperature was 30 C (rh=35%) and exercise load was equal to 50% of peak . Venous blood samples were obtained with subjects both in the supine and seated positions prior to all experiments. Additional blood was drawn during minutes 1, 5, 10, and 30 in both experimental conditions. A final sample was taken during C after the 10 min exercise. Moving from the supine to a seated position resulted in an average loss of 162 ml of plasma across all experiments. During the E condition a further reduction in plasma volume (76 ml) occurred by one minute of exercise. Plasma volume stabilized by 5 min of exercise under the E protocol. During the C condition, subsequent fluid loss (98 ml) was not apparent until 10 min after the first seated sample and totalled 176 ml at the end of 30 min of rest. Ten minutes of cycling at the end of the C experiment resulted in a further plasma volume reduction of 137 ml. Plasma protein and albumin contents decreased by 5 min of exercise in E and by 30 min of rest in C. [Na+] and [Cl–] did not change in either condition but a rapid increase in [K+] during exercise indicated an addition of potassium to the vascular volume. An hypothesis concerning the factors involved in postural and exercise body fluid shifts is presented.This work was supported in part by the National Institutes of Health, under Grant H207050-09     

Changes of plasma volume and plasma composition in water-deprived rats

Summary Plasma volume, hematocrit, protein and electrolyte concentrations in plasma were measured in control and water-deprived rats every three days after starting the experiment until the 15th day. Plasma volume variations, as related to body weight, suggest that water loss from plasma was proportional to total body water at three days and after 9 days of water deprivation. Greater plasma water than body water loss was found during the period between 3 and 9 days. Plasma protein and electrolyte variations suggest that during water deprivation there is a loss of protein, sodium and potassium from plasma, which is proportionally less than that of plasma water. Potassium, calcium and inorganic phosphorus were lost proportionally to plasma water. The variations in plasma volume changes were partially explained as due to variations in plasma protein and electrolyte concentrations.     

The effect of pentobarbital anaesthesia upon the extracellular fluid volume in the dog,studied by continuous infusion and single injection methods

The effect of pentobarbital anaesthesia on the volume and ionic composition of the extracellular space was studied in adult male mongrel dogs with permanent catheters in aorta and pulmonary artery. The extracellular fluid volume (Q ^ec ) was determined with: a) methods based on equilibration of the indicator throughoutQ ^ec by continuous infusion; b) methods based on the assumption that after a single injection of indicator the plasma indicator concentration equals extracellular indicator concentration as long as the log plasma indicator concentration-time curve is linear; c) a single injection method based on a closed flow system model with a single inflow and a single outflow orifice. The measurements were made before and 30 and 90 min after induction of anaesthesia. Thirty minutes after induction of anaesthesiaQ ^ec as determined with the method sub a, had decreased by about 10% and remained so during the following 60 min. The values ofQ ^ec as calculated by the method sub c fairly agreed withQ ^ec as determined with the method sub a and also showed a decrease ofQ ^ec during pentobarbital anaesthesia. The procedures sub b overestimatedQ ^ec and yielded a seemingly higherQ ^ec during anaesthesia, because the boundary conditions for these procedures do not apply. The haemoglobin concentration decreased by about 10% and the lactate concentration by about 50%. The phosphate concentration increased by about 25% while the other electrolyte concentrations (Na⁺, K⁺, Mg²⁺, Ca²⁺, Cl^–, HCO ₃ ^– ) did not change. A respiratory acidosis developed during the first 30 min and almost disappeared in the following 60 min. Possible explanations for the pentobarbital-induced concentration ofQ ^ec are discussed.     

The role of extracellular potassium transport in computer models of the ischemic zone

Ischemic heart disease is associated with large mortality and morbidity. Understanding of the relations between coronary artery occlusion, geometry of the ischemic region, physiology of ischemia, and the resulting changes in electrocardiogram (ECG) leads and catheter signals is important to support diagnosis and treatment. Computer models play an important role in understanding ischemia, by linking experimental to clinical results. In this paper we argue that the observed transport of extracellular potassium should be represented in such models. We used a diffusion equation to describe the transport mechanism. This model reproduced the measured spatial distribution of potassium, and its temporal development. We discuss the role of potassium transport next to other aspects of ischemia: the mechanism of changes in action potential and ECG, cellular coupling, anisotropic bidomain tissue conductivity, and the geometry of the ischemic zone. Computational resources for this work were provided by the Réseau québécois de calcul de haute performance (RQCHP). M. Potse was supported by a postdoctoral research award from the Groupe de recherche en sciences et technologie biomédicale (GRSTB), école Polytechnique and Université de Montréal; and by the Research Center of Sacré-Coeur Hospital, Montréal, QC, Canada.     

Changes in extracellular potassium and calcium in rat cerebellar cortex related to local inhibition of the sodium pump

Extracellular K⁺, Ca²⁺, and Na⁺ ([K⁺]_e, [Ca²⁺]_e, [Na⁺]_e) were recorded with ion selective microelectrodes in the cerebellar cortex of urethane-anesthetized rats. Superfusion of the cerebellum with artificial cerebrospinal fluid containing K-strophanthidin (10^–6–10^–4 mol/l) or other cardioactive steroids, known to be inhibitors of the sodium/potassium pump, had the following effects: elevation of resting [K⁺]₃, reduction of poststimulus K⁺-undershoots, decrease of resting [Ca²⁺]_e and [Na⁺]_e. For instance, at 3×10^–5 mol/l K-strophanthidin within the superfusion solution (the unknown intracerebellar concentration being certainly much smaller), [K⁺]_e was elevated up to 130% and [Ca²⁺]_e reduced to 70% of their resting values. Iontophoretic K⁺-pulses were enhanced in amplitude at the same time. Control experiments with iontophoretic TMA application demonstrated that the glycoside effects were not due (or in higher concentrations only partly due) to shrinkage of the extracellular fluid volume. When tetrodotoxin (10^–7 mol/l) or Mn²⁺ (1–3 mmol/l) were additionally superfused, K-strophanthidin effects were qualitatively similar, though quantitatively smaller. This indicates that part of the effects were indirect via neuronal activity evoked by the blockade of the sodium pump. The experiments show that reduction of sodium pump activity in cerebellar cortex has rapid and serious consequences on the distribution of potassium and calcium in the extracellular space, resulting in an alteration of neuronal circuit excitability.     

The changes in hematocrit,hemoglobin, plasma volume and proteins during and after different types of exercise

Summary A group of 7 healthy males was studied after maximal exercise and during and after prolonged exercise of two types (approximately at 40 and 67% of their O₂ max). Hematocrit, plasma proteins concentration, and hemoglobin were followed. Relative changes of plasma volume and total content of plasma protein were calculated from hematocrit changes. The mean corpuscular hemoglobin concentration was obtained by dividing hemoglobin by hematocrit. After maximal exercise, hemoconcentration with concomitant decrease of plasma volume (–13.0%) was found, with a corresponding increase in protein concentration (+12.9%) and without any protein content changes. Later normalisation at the 30th min of the recovery phase was shown. During prolonged submaximal exercise (67% of O₂ max) the changes in hemoconcentration, plasma volume (–7.1%), and plasma protein concentration (+6.9%) reached the highest changes in the first 15 min of exercise, and no decrease in protein content was observed. After them the spontaneous tendency to the normalisation was found. No changes were registered in prolonged mild exercise (40% of O₂ max). The ratio of hemoglobin to hematocrit remained unchanged during and after all types of exercise.