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Whole body energy expenditure, thermogenic and metabolic changes in the forearm, and intercellular glucose concentrations in subcutaneous adipose tissue on the abdomen determined by microdialysis were measured during epinephrine infusion in healthy subjects. After a control period, epinephrine was infused at rates of 0.2 and 0.4 nmol.kg-1 x min-1. Whole body resting energy expenditure was 4.36 +/- 0.56 (SD) kJ/min. Energy expenditure increased to 5.14 +/- 0.74 and 5.46 +/- 0.79 kJ/min, respectively (P < 0.001), during the epinephrine infusions. Respiratory exchange ratio was 0.80 +/- 0.04 in the resting state and did not change. Local forearm oxygen uptake was 3.9 +/- 1.3 mumol.100 g-1 x min-1 in the basal period. During epinephrine infusion, it increased to 5.8 +/- 2.1 (P < 0.03) and 7.5 +/- 2.3 mumol.100 g-1 x min-1 (P < 0.001). Local forearm glucose uptake was 0.160 +/- 0.105 mumol.100 g-1 x min-1 and increased to 0.586 +/- 0.445 and 0.760 +/- 0.534 mumol.100 g-1 x min-1 (P < 0.025). The intercellular glucose concentration in the subcutaneous adipose tissue on the abdomen was equal to the arterial concentration in the basal period but did not increase as much during infusion of epinephrine, indicating glucose uptake in adipose tissue in this condition. If it is assumed that forearm skeletal muscle is representative for the average skeletal muscle, it can be calculated that on average 40% of the enhanced whole body oxygen uptake induced by infusion of epinephrine is taking place in skeletal muscle. It is proposed that adipose tissue may contribute to epinephrine-induced thermogenesis.

The purpose of this study was to evaluate the usefulness of a microdialysis technique for measurement of substances in the interstitial water space in intact human skin. Glucose was selected to validate the method. The cutaneous glucose concentration was measured by microdialysis and compared to that in venous blood. Single dialysis fibers (length 20 mm, 2,000 Da molecular weight cutoff) were glued to nylon tubings and inserted in forearm skin by means of a fine needle. Dialysis fibers were inserted in duplicate. Seven subjects were investigated after an overnight fast. Intradermal position of the dialysis probes was established by C-mode ultrasound scanning. The implantation trauma lasted 90-135 min as measured by laser Doppler flowmetry. Each dialysis fiber was calibrated in vivo by perfusing it with four to five different glucose concentrations. The perfusion rate was 3 microliters/min. Regression analysis of the calibration curves yielded the relative in vivo recovery of glucose. The skin glucose concentration was calculated as that particular perfusate glucose concentration that resulted in no net glucose transport across the dialysis membrane. Correlation coefficient of the regression lines was 0.93 +/- 0.03 (mean +/- SEM). After the injection trauma had vanished, recovery was 20.5 +/- 0.7%. Coefficient of variation (CV) on recovery was 10.9%. The cutaneous glucose concentration was 99.1 +/- 1.8% of the glucose concentration in venous plasma water (CV 4.1%). These findings suggest that the microdialysis technique accurately and precisely can reflect biochemical events in the interstitial water space in human skin in vivo.

The aim of this study was to estimate bone-marrow blood flow (BMBF) in man and to correlate this with myelosuppression induced by cytostatic treatment dosed as a function of surface area. Twenty-four patients suffering from small-cell lung cancer participated in the study. Blood flow was measured with the xenon-133 washout technique. The 133Xe clearance measurement took place in conjunction with the pre-treatment bone-marrow staging procedure (ad modern Radner). Tissue samples were taken for microscopy and for the determination of the blood-to-tissue partition coefficient lambda. After the bone-marrow aspiration, 0.1-0.2 ml of 133Xe in saline was injected into the bone marrow and the cannula was removed. Following a hyperaemic phase of 12 min (7-16 min), monoexponential washouts were demonstrated. The median washout rate constant was 0.0063 min-1 (0.0038-0.0098 min-1). Lambda values of 0.3-3.5 ml g were found, but microscopy of the bone marrow showed a fairly large admixture of peripheral blood. Therefore, the lambda values should be taken with caution and absolute blood-flow values were not calculated. The results demonstrated no correlation between 133Xe clearance from crista iliaca and leucocyte or platelet suppression.

Subcutaneous adipose tissue blood flow rate was measured in the lower leg of 22 normal human subjects over 12- to 20-h ambulatory conditions. The 133Xe washout technique, portable CdTe(Cl) detectors, and a portable data storage unit were used. The tracer depot was applied on the medial aspect of the right lower leg 10 cm proximal to the malleolar level by means of the epicutaneous, atraumatic labeling technique. The change from upright to supine position from day 1 in the beginning of the night period elicited an instantaneous blood flow rate increment of 30-40% in accordance with a decrease in central and local postural sympathetic vasoconstrictor activity. During sleep, characteristic variations in subcutaneous blood flow were disclosed. The 133Xe washout curve could be divided into three segments with significantly different slopes. Approximately 90 min after the subject went to sleep, an additional blood flow rate increment of considerable magnitude was observed. The mean increase was 84%, but in several cases a greater than 200% increment was measured (maximum 244%). The intra-individual coefficient of variation for the nocturnal blood flow response was in triplicate measurements 25% (n = 9). The hyperemic phase lasted approximately 100 min after which the blood flow rate returned to the level measured at the beginning of the night period. The blood flow rates measured on the second day did not differ from those on the first day. Control measurements performed under similar thermal conditions, but with the subjects kept awake, did not reveal any hyperemic phases. This points toward changes in cardiovascular regulatory mechanisms during sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

A 133Xe washout technique for measuring the blood flow in the intestinal mucosa is introduced and evaluated. In 11 anaesthetized pigs a laparotomy was performed and the mucosal blood flow rate in the intestine of the pig was determined by a local epimucosal application of 133Xe. In both the colon and the small intestine the 133Xe washout plotted in a semilogarithmic diagram showed a multiexponential configuration. Histological examination and localization studies showed shunting by diffusion of 133Xe in the intestinal mucosa explaining the multiexponential configuration of the washout curve. Therefore the initial slope of the washout was used for measuring blood flow rate. Blood flow rate was simultaneously measured by microsphere entrapment technique. There was an excellent correlation between the blood flow rate determined by the two techniques the correlation coefficient R being 0.89 in the small intestine and 0.996 in the colon.

Ingestion of carbohydrate results in a diphasic activation of the sympathoadrenal system. One component is an insulin-mediated activation of the sympathetic nervous system (SNS). This activation is partly a haemodynamic reflex, but it may cause a weak thermogenic effect via beta 1-adrenoceptors in white adipose tissue, the liver and the heart. The second thermogenic component of carbohydrate occurs later when the blood glucose concentration decreases towards baseline levels. This elicits an increased secretion of adrenaline from the adrenal medulla, and the circulating level exceeds the physiological threshold for thermogenic effect. The target is mainly skeletal muscle where thermogenesis is stimulated via beta 2-adrenoceptors. Also the basal metabolic rate and the thermogenic responses to cold and heat exposure, mental stress and exercise, have facultative components. Inhibition of facultative thermogenesis by beta-blockers such as propranolol, diminishes the daily energy expenditure and promotes weight gain and obesity. Although thermogenesis mediated by the sympathoadrenal system accounts for only a small part of the daily energy expenditure, it is sufficient to explain the positive energy balance and weight gain reported in patients receiving treatment with beta-adrenoceptor blocking agents.

The effect of a carbohydrate-rich meal on subcutaneous adipose tissue blood flow was studied with and without continuous i.v. infusion of propranolol in healthy volunteers. The subcutaneous adipose tissue blood flow was measured with the 133Xe washout method in three different locations: the forearm, the thigh and the abdomen. The subjects were given a meal consisting of white bread, jam, honey and apple juice (about 2300 kJ). The meal induced a twofold increase in blood flow in the examined tissues. Propranolol abolished the flow increase in the thigh and the abdomen and reduced it in the forearm. This indicates that the mechanism for the flow increase is elicited by a stimulation of vascular beta-adrenoceptors in the subcutaneous adipose tissue, since the beta-adrenoceptor inhibition did not affect the overall metabolic and hormonal responses to the meal.

The purpose of the present study was to investigate regulatory mechanisms for subchondral bone blood flow. A model including elevation of joint cavity pressure in the immature dog knee was applied. The role of prostaglandins in bone blood flow regulation was indirectly examined by indomethacin blockade. In six puppies, both venous tamponade of the joint cavity [50% of the mean arterial blood pressure (MAP)] and arterial tamponade (150% of MAP) resulted in a significant increase in the intraosseous pressure of the distal femoral epiphyses (p less than 0.05). During venous tamponade no changes were registered in pO2, pCO2, pH, potassium, and lactate in blood withdrawn from the distal femoral epiphyses. Arterial tamponade resulted in hypoxia, a decrease in pH, and increased lactate. Inhibition of the prostaglandin synthesis did not alter this response pattern. Thus, the present study suggests the presence of a regulatory mechanism for subchondral bone blood flow since venous tamponade did not significantly alter intraosseous gas tensions, pH, lactate, or potassium in spite of elevated venous outlet resistance. The study does not allow any conclusion as to the exact nature of the regulatory mechanism, but local metabolic regulation is likely to be involved as indicated by accumulation of vasoactive substances at higher tamponade levels. Prostaglandins are probably of minor importance in this regulation.

The blood flow of the dog urinary bladder measured by radioactive microsphere technique was compared to the clearance of locally injected 99mTechnetium pertechnate (99mTc) in the bladder wall. In semilogarithmic plots the 99mTc washout curves showed a multiexponential course. From the initial slopes (median 5.7 min) the bladder blood flow was calculated to be only 30-62% of the results obtained from the radioactive microsphere technique (blood flow in the muscular layer 21.7-44.8 ml/100 g/min). These lower values imply that the rate of removal of the hydrophilic tracer 99mTc at these flow rates is limited by the capillary diffusion capacity. The multiexponential curves reflect recirculation and excretion of 99mTc by the kidneys with accumulation of 99mTc in the bladder. It is concluded, that clearance studies of locally injected 99mTc in the bladder wall are unable to evaluate bladder blood flow.

Subcutaneous, ingvinal adipose tissue from dogs was perfused with blood to which had been added isoprenaline and theophyllamine in order to stimulate lipolysis. The supply of free fatty acid (FFA) carrier to the tissue was varied either by variations in the rate of blood flow or by changes in the albumin concentration of the perfusing blood at constant flow rate. The net production of FFA from the tissue was found to depend on the supply of carrier over a range from 0.1 -- 12 mumoles of albumin x 100 g tissue-1 x min-1. The corresponding molar FFA/albumin ratios in adipose venous blood varied between 12.1 and 1.2. The changes in FFA production appeared to be due to varying degrees of reesterification rather than changes in the rate of lipolysis. The findings suggest that the increase in adipose tissue blood flow demonstrated during various lipolytic conditions is of physiological importance by facilitating the removal of FFA from adipose tissue. Equilibration experiments showed the FFA binding capacity of both dog serum and human plasma to be above than calculated from the association constants of purified human albumin, suggesting the binding of FFA to other plasma carriers than albumin.

Wash-out of 133xenon from a local depot in the subcutaneous adipose tissue in the forefoot was measured continuously during 24 hours on subsequent recordings in 51 feet (normal circulation: 10, intermittent claudication: 22 and ischaemic nocturnal rest pain: 19) with a mean time interval of 26 days (range: 3-90 days). The patients were studied under two different conditions. Firstly, during the day in the erect position, awake (sitting, standing and quiet walking) and secondly, during night hours in the supine position, asleep. The coefficient of variation of nocturnal adipose tissue blood flow was calculated to 10%, and for the ratio of blood flow from day to night to 5%. The method is thus considered apt as a monitor in the treatment of peripheral vascular disease, for example, surgery and medical therapy. As predominant source of error is the formation of oedema.

With the intravenous 133Xe technique we measured cerebral blood flow (CBF) in eight healthy subjects during normal subcutaneous temperatures and during extracranial cooling. This gave rise to the possibility of evaluating the contribution of the extracerebral blood flow to the calculation of CBF values. With a two-compartmental analysis of the wash-out curves during cooling there was a significant reduction of the CBF indices f1, representing mainly fast blood flow in the grey matter and f2, representing blood flow in the slowly perfused white matter and extracerebral structures. The reduction of f1 was due to the 'slippage' phenomenon:calculation of f1 was affected by a reduction in f2 due to a considerably reduced extracerebral blood flow. The initial slope index (ISI) calculated from 30 to 90 s of the first part of the presumed mono-exponential 133Xe wash-out curve was not affected by slippage as the ISI remained unchanged in spite of reduced extracerebral blood flow. It is concluded that CBF was unaffected by extracranial cooling. Extracranial cooling can be used to reduce the extracerebral blood flow contribution to the calculated CBF values.

Using the microsphere technique bone blood flow was measured in different anatomical and functional regions in long bones in conscious dogs. The measurements were performed during physical exercise upon a treadmill, and the bone blood flow values were obtained as prework resting values after 1 and 2 hours of exercise and after 1 hour of rest. The perfusion rates increased 50 per cent from 1.6 to 2.5 ml X 100 g tissue-1 X min-1 in the femoral and tibial cortical bones during work. In the cancellous bone of the femoral head an increase from 12.6 to 20.6 ml X 100 g tissue-1 X min-1 was found. Equal flow responses were determined in the fat-filled tibia-condylar and femoral supracondylar bone. The increase took place after 2 hours' exercise, but nonstatistically verified increased perfusion was found after 1 hour's work. The alternation in bone blood flow suggests that bone has a capability of physical vasodilation during muscular work but the flow response is slow and therefore the vasodilatation seems mediated by a metabolically induced stimulus.

In 6 dogs concentration differences for glycerol and FFA were measured between the aorta and the external pudendal vein, a vein which mainly drains subcutaneous adipose tissue in dogs, during prolonged exercise. It was found that the a-v differences increased about 2-fold for both glycerol and FFA, however great interindividual differences were found. In 4 dogs adipose tissue blood flow, glycerol and FFA a-v differences were measured simultaneously, and the mobilizations of glycerol and FFA as well as the re-esterification of FFA were calculated. After 2 h of exercise the values were in the range of 1-7 umol/(100 g.min) for FFA and glycerol mobilizations while the FFA re-esterification was in the range of 2-14 umol/(100 g.min). It was found that the FFA/albumin ratio in adipose venous blood, on average 3.6 was at a level at which the FFA mobilization has been shown to depend on the adipose tissue blood flow in isolated fat pads. In 11 dogs subcutaneous adipose tissue blood flow rose 2-fold during exercise from about 5-10 ml/(100 g.min). It is concluded that the subcutaneous adipose tissue blood flow response to exercise is equal in man and dog, that lipolysis, FFA mobilization and FFA re-esterification are increased in subcutaneous adipose tissue during exercise, and that the increase in blood flows is of importance for the enhanced FFA mobilization during exercise.

In a double-blind cross-over trial an oral thromboxane synthetase inhibitor (TSI) or placebo was given to 15 patients with severe foot ischaemia. After TSI therapy, rest pain remitted in nine out of 14 legs, while remission during placebo was seen in three out of 11 legs (NS). The ankle and toe systolic blood pressures remained constant during both study periods. Nocturnal adipose tissue blood flow in the forefoot was measured by the xenon wash-out method. A significant increase of the nocturnal perfusion rate constant during TSI therapy was found. A slight oedema developed during TSI therapy. This causes a change of the composition of the tissue under study and thus of lambda-xenon. The perfusion rate in the present study thus merely illustrates the latter and not a true increase in blood flow.

A man aged 33 years developed an arterio-venous fistula following a gunshot wound from behind in the right calf. The quality of the fistula could be demonstrated employing digital subtraction angiographic technique while the quantity was demonstrated employing 99Tc macroaggregated albumin. The localization of the fistula is important in view of the surgical procedure and the haemodynamic amount is important to determine cardiac involvement.

N(2) fixation in field-grown maize (Zea mays L.) plants was estimated by a nondestructive acetylene reduction method which permitted the plants to continue growing and produce seeds. Samples from six areas revealed mean nitrogenase activities of 74-2167 nmol of C(2)H(4)/(g of dry roots x hr) for 10 plants. Among 276 S(1) lines planted in two field experiments, 17 lines were selected for further nitrogenase activity assays after prescreening. Variability within lines was high but significant differences among lines were obtained in one experiment. The best lines showed mean nitrogenase activities of 2026, 2315, and 7124 nmol of C(2)H(4)/(g of dry roots x hr), whereas the original cultivar reduced only 313 nmol. The highest value approaches the nitrogenase activity of soybean. If the theoretical 3:1 (C(2)H(4)/N(2) reduced) conversion factor is used, a potential daily N(2) fixation of 2 kg of N(2)/hectare can be calculated. Periodic sampling within a brachytic maize cultivar revealed that maximum nitrogenase activity occurred at about the 75% silking stage. Soil effects also were pronounced. N(2)-fixing Spirillum sp. could be isolated from all active root pieces when they were surface sterilized. These organisms appear to be primarily responsible for root nitrogenase activity in maize.

Subcutaneous adipose tissue blood flow (ATBF) was examined in 8 subjects during 6 h exercise on a bicycle ergometer. The initial work load was 118 W corresponding to about 50% of maximal work capacity. The oxygen uptake increased from 0.261 - min-1 at rest to about 1.61-min-1 during work. In 7 subjects ATBF increased, in 1 it remained constant. After 3 h exercise ATBF at an average reached values 3--4 times the control value. This increase was maintained for the remaining work periods. The increase was significant at the 5% level. Plasma free fatty acids increased 7-, plasma glycerol 10-fold during work.

Subcutaneous adipose tissue blood flow (ATBF) was measured in six male subjects by the 133Xe-washout technique during 3-4 h of exercise at a work load corresponding to an oxygen uptake of about 1.71/min. The measurements were done during control conditions, during blockade of lipolysis by nicotinic acid, during acute i.v. beta-adrenergic blockade by propranolol, and during continuous i.v. infusion of glucose. The most pronounced lipid mobilization and utilization during work was seen in the control experiments where ATBF rose 3-fold on average from the initial rest period to the third hour of work. No increase in lipolysis and no increase in ATBF were found when lipolysis was blocked by nicotinic acid (0.3 g/h). Propranolol treatment (0.15 mg/kg) reduced lipolysis and nearly abolished the increase in ATBF during exercise. Intravenous administration of glucose (about 0.25 g/min) did not influence lipid metabolism (evaluated by the respiratory quotient) nor did it reduce the ATBF response to exercise. These results are inconsistent with the hypothesis that increase in ATBF during exercise is elicited via direct stimulation of vascular beta1-receptors, while they are not in disagreement with the hypothesis that adipose tissue vasodilation during exercise is secondary to metabolic events connected to lipolysis.

A study was carried out of the quality and completeness of articles on adverse drug reactions: 5737 articles from 80 countries published between 1972 and 1979 were studied. Only 61% of the articles included information on the number of patients treated and the number with adverse drug reactions, yet these are essential for calculating the incidence of adverse reactions. In only 55% could the incidence of a particular adverse reaction be calculated. Great importance is placed on articles on adverse reactions, particularly those that report on many patients. Authors and editors should ensure that articles include the following information: drug regimens, numbers of patients treated, numbers of patients developing adverse reactions, and nature and incidence of adverse reactions.

The effect of close intra-arterial administration of pentobarbital in the concentration of about 2 X 10(-4) mol/l on the venous stasis induced arteriolar constriction in the dog hindleg was studied in 6 neurolept anesthetized dogs. It was found that the blood flows and vascular resistances in the legs before pentobarbital infusion were equal and the vasoconstrictor responses to venous stasis were the same. Pentobarbital infusion into the femoral artery in one of the legs increased the total leg blood flow compared to the control leg and abolished the increase in vascular resistance during venous stasis. In another experimental series the effect of general pentobarbital anesthesia on the vasoconstrictor activity in response to venous stasis locally in subcutaneous and muscle tissue in the hind limb was examined in 6 dogs. It was found that during the first 2-3 h of anesthesia the vasoconstrictor response was present in both tissues although the response in muscle tissue exhibited a great variation between the dogs during this period. However, after 4-5 h of anesthesia the response was abolished in both tissues. During neurolept anesthesia with fentanyl/N2O the same vasoconstrictor response was demonstrated in the hindleg 1 h and 5 h after induction of the anesthesia. It is concluded that pentobarbital anesthesia abolishes the arteriolar constriction induced by venous stasis. The mechanism may be blockade of the local sympathetic vasoconstrictor fibres or interference with myogenic vasoconstrictor mechanism of the vascular smooth muscle cells or both. It is suggested that fentanyl/N2O anesthesia is better suited for this kind of studies.

The xenon clearance method was adapted to continuous measurement of interscapular brown adipose tissue (ISBAT) blood flow in anesthetized rats. The ISBAT-blood partition coefficient for xenon was determined to 3.6 ml X g-1. The blood flow values obtained by Xe clearance were compared with flow values obtained concomitantly by the microsphere technique in 17 cold acclimated rats, at ISBAT blood flows between 0.1 and 6 ml X g-1 X min-1. Variations in blood flows were obtained by infusion of noradrenaline at different rates. The blood flow values obtained from the xenon clearance method showed a close correlation to the blood flow values determined with microspheres. Y = 0.98. X + 0.15 (r = 0.96, P less than 0.001). The Xe clearance method has the advantages compared to the microsphere technique that it permits continuous monitoring of the blood flow and does not require the sacrifice of the animal.

The thermic effect of carbohydrate has a component mediated by the sympathoadrenal system but of unknown anatomical localization. We have studied the contribution of skeletal muscle to the thermic effect of a carbohydrate-rich natural meal (115 g of carbohydrate, approximately 80% of energy) by means of the forearm technique on two occasions, with and without intravenous beta-blockade with propranolol. The meal-induced thermogenesis was reduced from 9.6 to 7.1% by beta-blockade (P less than 0.04), the major difference was found 90 to 240 min after the meal. The postprandial increments in plasma glucose and lactate did not change by beta-blockade, but there was a trend toward a decreased insulin response (P = 0.06). The carbohydrate-induced increase in forearm oxygen consumption was reduced by 23% after beta-blockade (P less than 0.05), the entire difference being present 90-180 min postprandially and coinciding with the peak in arterial epinephrine. The present study provides evidence of a facultative thermogenic component in skeletal muscle, mediated by epinephrine via beta 2-adrenoreceptors. However, it also points to a nonmuscle component mediated through beta 1-adrenoceptors by norepinephrine released from the sympathetic nervous system. Consequently, the sympathoadrenal system seems to play a physiological role in the daily energy balance.

Adipose tissue blood flow was measured by the microsphere technique in all major adipose tissue depots in dogs during exercise. The measurements were done during rest, after 1 and 2 h of exercise and after a postexercise rest period. It was found that the blood flow to the inguinal, subcutaneous adipose tissue increased from about 6 ml/(100 g . min) during rest to about 10 ml/(100 g.min) during exercise. This increase in flow was significantly smaller than the increase found in the perirenal, the mesenteric and the pericardial depots. In these depots the resting blood flow was about 10 ml/(100 g . min) increasing to about 30 ml/(100 g . min) during exercise. It is concluded that the increase in adipose tissue blood flow during exercise is a general phenomenon for all major adipose tissue depots. The increase in flow in the inguinal, subcutaneous fat pad was comparable to the previously described increase in flow in abdominal, subcutaneous tissue in man. Blood flow to abdominal skin was constant during exercise, while the flow in tissues from the gastrointestinal canal and in the kidneys decreased. The flow in the tongue and in the Achilles tendon significantly increased during exercise.

Plasma concentrations of insulin, C-peptide, and proinsulin were measured in different vascular beds in order to determine renal, hepatic, and systemic kinetics of the endogenous peptides in the fasting condition. Nineteen nondiabetic subjects were studied, two were normal, nine had minor vascular disorders, four had cirrhosis without organic kidney disease, and four had organic kidney disease with moderately decreased glomerular filtration rate. In subjects without organic kidney disease the arteriorenal venous extraction ratios of insulin, C-peptide, and proinsulin were mean 0.27, 0.20, and 0.21, respectively (n = 14). These values were significantly reduced in kidneys with organic disease. Renal plasma clearance values of insulin, C-peptide, and proinsulin were mean 113, 87, and 90 mL/min, respectively (n = 6). Urinary clearances were substantially lower (0.8, 13, 3.5 mL/min, respectively), indicating that a significant degradation of these peptides also takes place in the normal kidney. In subjects without liver disease the estimated hepatic extraction ratio of insulin was mean 0.48, under the assumption that no C-peptide is removed by the liver. Endogenously released insulin was removed from plasma in kidney, liver, and elsewhere in the approximate proportion 10%:65%:25%, whereas, C-peptide was removed by one half in kidney and the other half elsewhere. The overall metabolic clearance rates of insulin and C-peptide were estimated to be 15 and 4.5 mL/min/kg, respectively. The results indicate that the kidney contributes substantially to removal of insulin, C-peptide, an proinsulin, mainly by degradation, less by urinary excretion.

In addition to the obligatory thermogenesis due to processing and storage, carbohydrate ingestion is accompanied by a facultative thermogenesis mediated by catecholamines via beta-adrenoceptors. The anatomical origin of facultative thermogenesis has hitherto not been determined. The possible involvement of skeletal muscle was examined in lean, healthy subjects by measuring the response in forearm oxygen consumption to an oral glucose load. The study demonstrates an early component of skeletal muscle thermogenesis coinciding with the local glucose uptake, followed by a late facultative thermogenesis. The arterial epinephrine concentration increased to a maximum of 200% above base-line values 4 h after glucose. This value greatly exceeds the physiological threshold for the thermogenic action of epinephrine. In forearm venous blood the corresponding increase in epinephrine was only approximately 50% due to enhanced peripheral extraction, which accompanies an increase in arterial epinephrine levels. Due to venous sampling previous studies have overlooked the magnitude of the late postglucose increase in arterial epinephrine, and its potential thermogenic effect has been disregarded. The facultative thermogenesis in skeletal muscle may be of importance for the regulation of body weight in humans.

From a 7-day food recording in 29 morbidly obese patients two groups of six patients each were selected: a high-energy-intake group (HEI) and a low-energy-intake group (LEI). The groups were otherwise comparable. Five lean subjects served as controls for some observations. Oral glucose tolerance tests showed that all patients in the HEI group and the lean controls had normal glucose tolerance, whereas it was abnormal in all subjects in the LEI group. The fasting metabolic rate did not differ between the obese groups but was significantly lower in the lean group. The glucose-induced thermogenesis during 180 min expressed as a percentage of the energy content of the glucose load was lower in both obese groups compared with the lean controls (lean: +11.5 per cent, HEI: +5.3 per cent and LEI: -4.2 per cent, HEI vs lean: P = 0.04 and LEI vs lean: P = 0.005), and lower in the LEI group compared with the HEI group (P = 0.02). The integrated increase in leg oxygen consumption after glucose was also smaller in the LEI group than in the HEI group (15 +/- 269 vs 987 +/- 356 ml, P less than 0.05). The arterial noradrenaline response to glucose was significantly diminished in both obese groups compared with the lean controls. Glucose induced a similar increase in leg noradrenaline release in both obese groups, whereas the arterial adrenaline level was lower in the LEI group compared with the HEI group and with the lean controls (P = 0.04). Among the obese subjects the degree of glucose intolerance was inversely correlated with the post-glucose arterial adrenaline level (r = -0.55, and P = 0.04), and positively correlated with the fractional leg adrenaline extraction (r = 0.71, and P = 0.003). The results suggest that patients who are obese in spite of a fairly low energy intake have a reduced glucose-induced facultative thermogenesis, and that the defect is at least in part located in skeletal muscle. Since the sympathetic nervous system is partly responsible for the glucose-induced thermogenesis, the reduced thermogenic response in the obese patients may be due to an impaired activation of the sympathetic nervous system. It is hypothesized that the reduced arterial adrenaline level in the LEI group is caused by hyperglycaemic suppression of the adrenomedullary secretion and further that this may be a link connecting deterioration of glucose tolerance and a thermogenic defect in obesity.

Tissue blood flow was measured by the tracer microsphere technique in the juxta-articular bones of the immature knee, knee joint capsule and skeletal muscles of the hind limbs after unilateral bone cannulation of the distal femoral epiphysis, surgical exploration of the popliteal vessels and unilateral isolated increase of venous outlet resistance in the distal femoral epiphysis during Halothane anaesthesia. Pressure registration was performed in a liquid-filled electromanometric pressure recording system. Significant regional differences in bone blood flow was found within the different bone compartments of both control and test limb. Bone cannulation resulted in insignificant hyperaemia in the distal femoral epiphysis. No changes of distribution pattern of bone blood flow followed the surgical procedure. Ligation of the medial genicular vein caused a three fold increase of venous outlet resistance measured after 5 min, while an insignificant decrease of arterial inlet resistance was calculated. After one hour a significant decrease of both arterial inlet resistance and venous outlet resistance was found. In addition evidence of a veno-arterial reflex mechanism causing a significant unilateral decrease of distal skeletal muscle blood flow was found. The results demonstrate the presence of both venous and arterial regulation, predominantly metabolic, of bone blood flow in the knee.

The abdominal subcutaneous adipose tissue blood flow (ATBF) was measured bilaterally by the 133Xe washout method. At one side of the skin (epicutaneous) temperature was varied with a temperature blanket, the other side served as control. There was a significant (P less than 0.001) positive correlation between skin temperature and ATBF. In the range from 25 to 37 degrees CATBF increased 9% of the control flow on average per centigrade increase in skin temperature. ATBF at the control side was uninfluenced by the contralateral variations in skin temperature. Although no better correlation could be demonstrated between ATBF and subcutaneous temperature than between ATBF and skin temperature, arguments are presented in favour of the hypothesis that ATBF is influenced by the subcutaneous temperature rather than via reflexes from the skin. Infiltration of the 133Xe depots with 20 microgram histamine increased ATBF 6 fold on average.

Cooling of the scalp has been found to prevent hair loss following cytostatic treatment, but in order to obtain the hair preserving effect the subcutaneous temperature has to be reduced below 22 degrees C. In order to establish the relationship between epicutaneous and subcutaneous temperatures during cooling and rewarming and to measure the effect of scalp cooling on subcutaneous scalp blood flow, subcutaneous blood flow and epi- and subcutaneous temperatures were measured in the frontal region at the hairline border before and during cooling with a cooling helmet, during spontaneous rewarming of the cooling helmet and after removal of the rewarmed helmet in 10 normal subjects. Subcutaneous blood flow was reduced to about 25% of the postcooling control level during cooling. The flow was constantly reduced until the subcutaneous temperature exceeded 30-32 degrees C. A linear relationship between epicutaneous and subcutaneous temperatures could be demonstrated with the regression equation: s = 0.9 c + 4.9 (r = 0.99). In eight of the 10 subjects the subcutaneous temperature could be reduced below 22 degrees C with the applied technique. It is concluded that the hair preserving effect of scalp cooling during cytostatic treatment is mainly due to the metabolic effect of cooling, and only to a minor extent due to the flow reducing effect.

Subcutaneous and perirenal adipose tissue blood flows (ATBF) were measured by the 133Xe washout method before, during and after 4h exercise on a bicycle ergometer. The load corresponded to about 50% of VO2 max (i.e. about 1.7l/min). Subcutaneous and perirenal ATBF increased at an average to 3--400 and 700% of their initial control values respectively. In six of nine measuring sites ATBF remained increased in the hour following work. During work plasma glycerol concentrations increased 8 fold. The core temperature increased 0.9 degree C, skin temperature did not change significantly. During passive elevation of body temperature (core temperature +1.5 degree C; skin temperature +3 degree C) neither subcutaneous ATBF nor plasma glycerol concentrations changed significantly. It is concluded that the increase in subcutaneous ATBF during exercise is not a reaction to increased body temperature.

The blood flow in the hip joint of puppies was studied by means of the microsphere technique. The flow was determined before, during and after intraarticular pressure increase. A venous tamponade of 50 mmHg resulted in a significantly reduced flow in the femoral head and after an arterial tamponade of 150 mmHg the flow almost ceased. The proximal femoral metaphysis, the acetabulum and the hip joint capsule, on the contrary, showed varying degrees of flow increase. It is suggested that the significantly increased blood flow in the hip joint capsule during the intraarticular pressure increase of 50 mmHg and 150 mmHg is caused by an autoregulatory mechanism tending to restore the blood flow in the suffering femoral head. The demonstrated disturbance of the circulation in the juvenile femoral head after venous tamponade supports the theory that synovitis may be the basic mechanism in the production of Calvé-Legg-Perthes' disease.

In order to investigate pathogenetic factors in growth abnormalities of the knee in hemophilic arthropathy and juvenile rheumatoid arthritis, the hemodynamic changes of the knee following chronic synovial inflammation and elevated joint pressure were studied in puppies. Unilateral arthritis was induced by intraarticular injections of carrageenan solution. Regional blood flow (RBF) was measured by tracer microsphere technique. Microvascular volume (VV) was estimated from the distribution volumes of Cr51-labelled erythrocytes and I125 fibrinogen. Mean transit times (TT) of blood components were calculated from volume/flow ratios. The arthritic joint capsules were characterized by high RBF rates, increased VV, low tissue hematocrit (HCT) and short TT of blood. In the juxtaarticular epiphyses and the patella, RBF was largely unchanged, whereas VV was significantly elevated and TT of blood prolonged. The growth plates formed borders for the extension of these changes. The increased permeability and surface area between blood and bone in arthritis may accelerate the resorption and subsequent destruction of subchondral bone in chronic arthropathies of the juvenile knee.

Tissue/blood partition coefficients (lambda) for xenon were calculated for subcutaneous adipose tissue from the abdominal wall and the thigh, and for the perirenal adipose tissue after chemical analysis of the tissues for lipid, water and protein content. The lambda in the perirenal tissue was found to correlate linearly to the relative body weight (RBW) in per cent with the regression equation lambda = 0.045 . RBW + 0.99. The subcutaneous lambda on the abdomen correlated linearly to the local skinfold thickness (SFT) with the equation lambda = 0.22 SFT + 2.99. Similarly lambda on the thigh correlated to SFT with the equation lambda = 0.20 . SFT + 4.63. It is concluded that the previously accepted lambda value of 10 is generally too high in perirenal as well as in subcutaneous tissue. Thus, by application of the present regression equations, it is possible to obtain more exact estimates of the adipose tissue blood flow measured with the 133Xe wash-out method.

Blood flow to the forearm, and the subcutaneous tissue and skin in the forearm were measured by strain gauge plethysmography, 133Xe-elimination and Laser Doppler flowmetry during an oral glucose load (I g glucose kg-1 lean body mass) and during control conditions. The forearm blood flow remained constant during both experiments. Glucose induced a two-fold vasodilatation in subcutaneous tissue. In skin, glucose induced a relative vasodilatation and later a relative vasoconstriction compared with control experiments. When estimated from forearm blood flow and subcutaneous and skin blood flows, muscle blood flow decreased about 20-30% during both experiments. Proximal nervous blockade did not abolish the glucose-induced vasodilatation in subcutaneous tissue. In the glucose experiment, arterial glucose concentration increased to 7.8 +/- 1.17 mmol l-1 30 min after the load was given and then decreased to 4.5 +/- 0.34 mmol l-1 at the end of the experiment. In the control experiments glucose concentration was constant. Arterial noradrenaline concentration increased significantly from 1.0 +/- 0.13 to about 1.5 +/- 0.3 nmol l-1 120 min after glucose and remained at this level during the experiment. Similarly adrenaline increased from 0.16 +/- 0.11 to about 0.4 +/- 0.16 nmol l-1 180 min after glucose. It is hypothesized that the vasodilating effect of glucose in subcutaneous tissue is secondary to metabolic events connected to glucose uptake and energy deposition in adipose tissue.

The classical forearm technique widely used for studies of skeletal muscle metabolism requires arterial cannulation. To avoid arterial puncture it is becoming more common to arterialize blood from a contralateral hand vein by local heating. This modification and the classical method have produced contradictory results regarding the contribution of skeletal muscle to glucose-induced thermogenesis. The effect on forearm circulation and the metabolism of heating the contralateral hand was examined before and after an oral glucose load. The results suggest that contralateral heating increases subcutaneous blood flow and decreases skeletal muscle blood flow. This facilitates mixing of superficial blood with deep venous blood. Contralateral heating increased deep venous oxygen saturation and abolished the pronounced glucose-induced increase in oxygen consumption observed in the control experiments after glucose. Heating increased rectal temperature by 0.6 degrees C, and plasma norepinephrine levels were increased compared with the control experiments. The present study explains the conflicting reports on glucose-induced thermogenesis in skeletal muscle and warns against heating the contralateral hand when using the forearm technique.

Subcutaneous or perirenal adipose tissue blood flow was measured with the 133Xe-washout technique before and after intravenous injection or infusion of Intralipid in six anesthetized, otherwise intact mongrel dogs. In four anesthetized mongrel puppies adipose tissue blood flow was measured with the radioactive microsphere method in seven different adipose tissue depots before a bolus injection of Intralipid and at the time after the injection when the thermogenic effect of the Intralipid was maximal. The results showed that the vascular resistance increased in all the examined adipose depots in adult as well as in young dogs after this treatment. The administration of Intralipid did not per se induce the vasoconstriction. The vasoconstriction took place simultaneously with increasing FFA/albumin molar ratios. The results support our previous findings in perfused fat pads that high molar FFA/albumin ratios increase vascular resistance in adipose tissue and they give further support to our suggestion that this vasoconstriction may be a link in a negative-feedback mechanism regulating FFA-mobilization in relation to FFA utilization.

This investigation was performed to examine the role of brown adipose tissue (BAT) in thermogenesis induced by ephedrine in man. Light microscopy of biopsies from necropsy cases showed BAT to occur most frequently in the perirenal fat. Perirenal BAT thermogenesis was investigated in five lean men before and during stimulation with 1 mg ephedrine orally X kg body wt-1. Perirenal BAT thermogenesis was assessed by continuous measurements of local temperature and blood flow with the 133xenon clearance method. In the same study the effect of ephedrine on skeletal muscle oxygen consumption was estimated by measurements of leg blood flow and arteriovenous oxygen difference. The perirenal adipose tissue blood flow increased approximately twofold, whereas the local temperature increased approximately 0.1 degrees C on an average. Assuming that man possesses 700 g of BAT with a similar thermogenic capacity, this tissue contributed only 10 ml X min-1 to the 40 ml X min-1 increase in oxygen consumption in the subject whose perirenal BAT showed the most pronounced response to ephedrine. The leg oxygen consumption increased on an average 60% after ephedrine. By extrapolation of this value to whole body skeletal muscle, approximately 50% of the increase in oxygen consumption induced by ephedrine may take place in skeletal muscle. It is concluded that skeletal muscle is a tissue of importance with respect to the thermogenic effect of sympathomimetics in man, whereas the results do not support a major role for perirenal BAT.

By the use of invasive techniques, skeletal muscle has been shown to contribute to thermogenesis induced by glucose in humans. In an attempt to study this phenomenon by a non-invasive method, this study investigated intracellular high-energy phosphorous compounds in calf muscle by 31P MR spectroscopy during an oral glucose load in healthy lean subjects. The inorganic phosphate concentration increased gradually (P less than 0.05) after glucose intake. The phosphocreatine/inorganic phosphate rate decreased (P less than 0.05) and the estimated ADP concentration increased. ATP and intracellular pH remained unchanged after the glucose administration. No changes were seen in the control experiments. The processes responsible for the decreased energy state of the skeletal muscle cell may be an obligatory conversion of glucose to glycogen. Also, facultative processes, such as sodium/potassium pumping and substrate cycles stimulated by the sympatho-adrenal system, may be partly responsible.

Rhythmical variations in blood cell flux in human skin have been studied using laser Doppler flowmetry. The fluctuations in blood cell flux could be divided into two different categories named alpha- and beta-oscillations with a median frequency of 6.8 min-1 and 1.5 min-1, respectively. The amplitude of beta-oscillations was approximately two to four times the amplitude of alpha-oscillations. Simultaneous registration from different skin regions showed periods with synchronous and non-synchronous fluctuations for both alpha- and beta-oscillations. alpha-oscillations were unchanged during local and ganglionic nerve blockade and were preserved in chronically sympathectomized tissue. In contrast, beta-oscillations disappeared completely after the three types of denervation. We suggest alpha-oscillations to be local non-neurogenic vasomotion and beta-oscillations to be a vascular reaction of pure neurogenic origin. A method for induction of regular amplified alpha-oscillations was discovered and evaluated. When heating the skin locally to 42 degrees C the blood cell flux increased and the pre-heating alpha- and beta-oscillations disappeared. During the post-heating period, amplified regular rhythmic alpha-oscillations appeared. At the end of the post-heating period beta-oscillations re-appeared.

In order to evaluate if elevation of the ischaemic limb above heart level is an alternative to the conventionally applied method with external counterpressure for estimation of skin perfusion pressure, femoral and popliteal artery pressures were measured directly in eight patients with occlusion of the superficial femoral artery. The measurements were done in the horizontal position and during elevation of the calf above heart level. During elevation relative blood flow, measured by arterio-venous oxygen saturation differences, decreased compared with the horizontal position. In contrast the popliteal arterial pressure decreased only by 20% of the value expected from the degree of elevation of the calf above the level of the heart. Thus, it could be calculated that calf vascular resistance increased two- to three-fold on average during elevation. Four patients were reexamined with the venous pressure kept at 10 mmHg during elevation. In these patients, the increase in vascular resistance was significantly less compared with the situation in which venous pressure was 0 mmHg during elevation. The arterial pressure still did not decrease. It is concluded that perfusion pressure in the ischaemic lower extremity cannot be determined non-invasively by elevation of the extremity, probably due to collapse of segments of the vascular bed increasing the vascular resistance considerably.

The plasma concentration of pancreatic polypeptide (PP-like immunoreactivity) was measured in different vascular beds in order to determine regional kinetics of endogenous PP in fasting, supine subjects with normal or moderately decreased kidney function. Patients with kidney disease (n = 10) had a significantly higher level of circulating PP than controls (n = 10): median PP = 52 (range 21 to 352) v 20 (6 to 143) pmol/L, respectively (P less than 0.02). Circulating PP was inversely correlated to 51Cr-EDTA plasma clearance (r = -0.57, P less than 0.02, n = 14) and directly correlated to serum creatinine concentration (r = 0.70, P less than 0.01). Hepatic venous PP was significantly higher than systemic PP in both controls and patients with kidney disease (P less than 0.001, n = 15). The values were positively correlated (r = 0.98, P less than 0.001; slope = 1.37 +/- 0.05, P less than 0.001), indicating a progressively increasing rate of PP secretion in subjects with raised circulating PP. No statistically significant difference could be detected between systemic and renal venous PP or across the lung, left adrenal gland, or lower limb. Assuming steady state between secretion and biodegradation, the metabolic clearance rate of the peptide was estimated to be approximately 600 to 800 mL/min in controls and slightly below this value in patients with nephropathy. These results suggest that the raised circulating PP found in patients with decreased kidney function is due to both increased secretion and decreased degradation.(ABSTRACT TRUNCATED AT 250 WORDS)