Comparison between human pharmacokinetics and imaging properties of two conjugation methods for 99mTc-annexin A5.

Annexin A5 (AnxA5) is a protein with high affinity for phosphatidyl serine, a phospholipid exposed on the cell surface during apoptosis. This phenomenon has been used for determination of cell death after myocardial infarction. To evaluate the potential of (99m)Tc-AnxA5 for in vivo scintigraphy of apoptotic cells, the pharmacokinetics and imaging properties of two radiopharmaceuticals, (99m)Tc-(n-1-imino-4-mercaptobutyl)-AnxA5 (I-AnxA5) and (99m)Tc-(4,5-bis(thioacetamido)pentanoyl)-AnxA5 (B-AnxA5), were studied. I-AnxA5 was administered intravenously to seven patients and one healthy volunteer, and B-AnxA5 was administered to 12 patients. All patients in the pharmacokinetic study had myocardial disease. Additionally, imaging was performed in a patient with acute myocardial infarction, as well as in three patients with different malignancies. The plasma concentration, excretion and biodistribution of (99m)Tc-AnxA5 were measured, as well as levels of AnxA5 antigen. The kinetic data of both radiopharmaceuticals in plasma fitted a two-compartment model. Both preparations had similar half-lives, but a different distribution over the two compartments. Plasma levels of AnxA5 antigen showed a broad variation. Both radiopharmaceuticals accumulated in the kidney, liver and gut. B-AnxA5 was excreted significantly faster than I-AnxA5. Both compounds can be used for imaging of the head/neck region, the thorax and the extremities. B-AnxA5 has a faster clearance and a lower radiation dose. Imaging of apoptosis in the abdomen will be difficult with both radiopharmaceuticals, and especially with B-AnxA5 because of its faster appearance in the gut.

The role of labeled Annexin A5 in imaging of programmed cell death. From animal to clinical imaging.

Programmed cell death plays a critical role in embryology, homeostasis and disease. However, until recently no non-invasive imaging modality has been able to visualize this process directly. Annexin A5 binds to cells undergoing programmed cell death. When labeling this protein, Annexin A5 becomes a tool for the detection of programmed cell death in vitro and in vivo. Labeled Annexin A5 has enabled our group and others to detect programmed cell death non-invasively in animals and patients. This review will highlight the development of this imaging modality in cellular and animal models. Furthermore, we will discuss Annexin A5 imaging in human disease. We will focus on the clinical applications and their relevance, limitations and future perspectives of non-invasive imaging of programmed cell death using labeled Annexin A5.

Molecular imaging of cell death in intracardiac tumours: A new approach to differential diagnosis in cardiac tumours.

BACKGROUND: Primary endocardial tumours are rare, but may impose a difficult clinical problem. The definite diagnosis regarding the nature of the tumour is often made after surgery. This is due to the fact that current non-invasive imaging techniques are unable to inform us about the nature of the tumour. In addition, invasive techniques can not be used to obtain biological information of the tumour in these cases, because they carry a high risk of embolic complications. OBJECTIVE: To assess the possibility of a novel modality of imaging, molecular imaging, in the diagnosis of primary intracardiac tumours. METHODS: We evaluated two patients with a primary cardiac tumour. Prior to therapy, we infused human recombinant annexin-V Tc99-m and thallium 201. We used a dual isotope single photon emission computed tomography technique. This allowed us to obtain information about the relation between the anatomical position of the left ventricle and the uptake of the labelled annexin-V within the thoracic cavity. RESULTS: The patient with a malignant primary cardiac tumour showed uptake of labelled annexin-V within the area of the tumour. After surgery, the malignant nature was confirmed by histological analysis. The patient with a benignant intracardiac tumour showed no uptake of annexin-V within the area of the tumour. CONCLUSION: This novel imaging technique, molecular imaging, may be of help to differentiate non-invasively between a malignant and benignant primary intracardiac tumour.

Biodistribution and dosimetry of 99mTc-BTAP-annexin-V in humans.

The purpose of this study was to determine the biodistribution and the associated radiation dose of technetium-99m 4,5-bis(thioacetamido)pentanoyl-annexin-V (99mTc-Apomate), a tracer proposed for the study of apoptosis. Eight patients (including two females) with normal kidney and liver functions were included in the study. An activity of 580 +/- 90 MBq of 99mTc-Apomate was injected intravenously, immediately followed by a dynamic study of 30 frames of 1 min each. At about 1 h, 4 h and 20 h p.i., whole-body scans were acquired. All activity distributions were measured using a dual-head gamma camera. Before injection of activity, a transmission scan with a cobalt-57 flood source had been performed to determine patient attenuation. Blood samples were taken every 10 min during the first hour after injection, and at about 4 and 20 h. Urine and faeces were collected during the first 20 h. Organ uptake was estimated after correction for body background activity, attenuation and scatter. Residence times were calculated from the dynamic and whole-body studies and used as input in the Mirdose 3.1 program to obtain organ doses and effective dose. It was found that radioactivity strongly accumulated in the kidneys and the liver [at 70 min p.i., 28% +/- 8% and 20% +/- 4% of the injected dose (ID), respectively]. Uptake in the target tissues (lymphomas or heart) was negligible from a dosimetric point of view. Extrapolating data from the first 20 h, one finds that approximately 73% of the ID will be excreted in the urine, and 27% in the faeces. The biological half-life of the activity in the total body was 16 +/- 7 h. Some organ doses +/- standard deviation (SD) in microGy/MBq were: kidneys 63 +/- 22, urinary bladder 20 +/- 6, spleen 15 +/- 3, liver 13 +/- 3, upper large intestine 12 +/- 6, lower large intestine 8 +/- 4, testes 6 +/- 2 and red bone marrow 4 +/- 0.7. The effective dose was 7.6 +/- 0.5 microSv/MBq, corresponding to a total effective dose of 4.6 +/- 0.3 mSv for a nominal injected activity of 600 MBq. In conclusion, 99mTc-Apomate has a high uptake in the kidneys and liver--in fact a factor of 1.3-1.6 higher than that found for the previously studied 99mTc-(n-1-imino-4-mercaptobutyl)-annexin-V. The biological half-life is shorter, however, but still long compared with the physical half-life of 99mTc. The faster appearance of activity in the intestines may preclude imaging of apoptosis in the abdomen. The effective dose is within the lower range of values reported for typical 99mTc compounds.

Patient dosimetry of intravenously administered 99mTc-annexin V.

UNLABELLED: Annexin V labeled with 99mTc is evaluated as a potential in vivo marker for tissue with increased apoptosis. Promising results in patients have been obtained with 99mTc-(n-1-imino-4-mercaptobutyl)-annexin V (99mTc-i-AnxV). Because information on biodistribution and radiation burden is desired for the application of any radiopharmaceutical, a dosimetric study of 99mTc-i-AnxV was undertaken. METHODS: Eight persons with normal kidney and liver functions were included in this study: six patients with myocardial infarction, one with Crohn's disease, and one healthy volunteer. Approximately 600 MBq 99mTc-i-AnxV were injected intravenously immediately before a dynamic study with a dual-head gamma camera in conjugate view mode. In the next 24 h, two to four whole-body scans were acquired. Patient thickness was determined from a transmission scan with a 57Co flood source. Organ uptake was estimated after correction for background, attenuation, and scatter, using a depth-independent buildup factor and an organ-size-dependent attenuation correction. Residence times were calculated from the dynamic and whole-body studies and used as input for the MIRDOSE 3.1 program to obtain organ-absorbed doses and effective dose. RESULTS: Activity strongly accumulated in the kidneys (21% +/- 6% of the injected dose at 4 h postinjection) and the liver (12.8% +/- 2.2%). Uptake in the target tissues (myocardium or colon) was limited and negligible from a dosimetric point of view. The biologic half-life of activity registered over the total body was 62 +/- 13 h. Of the excreted activity, approximately 75% went to the urine and 25% to the feces. The absorbed dose for the more strongly exposed organs was (in microGy/MBq): kidneys, 93 +/- 24; spleen, 22 +/- 6; liver, 17 +/- 2; testes, 15 +/- 3; thyroid, 10 +/- 6; urinary bladder wall, 7.5 +/- 2.6; and red bone marrow, 5.5 +/- 0.8. The effective dose was 9.7 +/- 1.0 microSv/MBq, corresponding to a total effective dose of 5.8 +/- 0.6 mSv for a nominally injected activity of 600 MBq. CONCLUSION: 99mTc-i-AnxV strongly accumulates in the kidneys and to a lesser degree in the liver. The associated effective dose per MBq is in the midrange of values found for routine 99mTc-labeled compounds. From a dosimetric point of view 99mTc-i-AnxV is therefore well suited for the study of apoptosis in patients.

Visualisation of cell death in vivo in patients with acute myocardial infarction.

BACKGROUND: In-vivo visualisation and quantification of the extent and time-frame of cell death after acute myocardial infarction would be of great interest. We studied in-vivo cell death in the hearts of patients with an acute myocardial infarction using imaging with technetium-99m-labelled annexin-V-a protein that binds to cells undergoing apoptosis. METHODS: Seven patients with an acute myocardial infarction and one control were studied. All patients were treated by percutaneous transluminal coronary angioplasty (six primary and one rescue), resulting in thrombolysis in myocardial infarction (TIMI) III flow of the infarct-related artery. 2 h after reperfusion, 1 mg annexin-V labelled with 584 MBq Tc-99m was injected intravenously. Early (mean 3.4 h) and late (mean 20.5 h) single-photon-emission computed tomographic (SPECT) images of the heart were obtained. Routine myocardial resting-perfusion imaging was also done to verify infarct localisation. FINDINGS: In six of the seven patients, increased uptake of Tc-99m-labelled annexin-V was seen in the infarct area of the heart on early and late SPECT images. No increased uptake was seen in the heart outside the infarct area. All patients with increased Tc-99m-labelled annexin-V uptake in the infarct area showed a matching perfusion defect. In a control individual, no increased uptake in the heart was seen. INTERPRETATION: Increased uptake of Tc-99m-labelled annexin-V is present in the infarct area of patients with an acute myocardial infarction, suggesting that programmed cell death occurs in that area. The annexin-V imaging protocol might allow us to study the dynamics of reperfusion-induced cell death in the area at risk and may help to assess interventions that inhibit cell death in patients with an acute myocardial infarction.

Plasma FFA utilization and fatty acid-binding protein content are diminished in type 2 diabetic muscle.

In this study, we investigated the hypothesis that impairments in forearm skeletal muscle free fatty acid (FFA) metabolism are present in patients with type 2 diabetes both in the overnight fasted state and during beta-adrenergic stimulation. Eight obese subjects with type 2 diabetes and eight nonobese controls (Con) were studied using the forearm balance technique and indirect calorimetry during infusion of the stable isotope tracer [U-(13)C]palmitate after an overnight fast and during infusion of the nonselective beta-agonist isoprenaline (Iso, 20 ng. kg lean body mass(-1) x min(-1)). Additionally, activities of mitochondrial enzymes and of cytoplasmatic fatty acid-binding protein (FABP) were determined in biopsies from the vastus lateralis muscle. Both during fasting and Iso infusion, the tracer balance data showed that forearm muscle FFA uptake (Con vs. type 2: fast 449+/-69 vs. 258 +/-42 and Iso 715+/-129 vs. 398+/-70 nmol. 100 ml tissue(-1) x min(-1), P<0.05) and FFA release were lower in type 2 diabetes compared with Con. Also, the oxidation of plasma FFA by skeletal muscle was blunted during Iso infusion in type 2 diabetes (Con vs. type 2: Iso 446 +/- 274 vs. 16+/-70 nmol. 100 ml tissue(-1) x min(-1), P<0.05). The net forearm glycerol release was increased in type 2 diabetic subjects (P< 0.05), which points to an increased forearm lipolysis. Additionally, skeletal muscle cytoplasmatic FABP content and the activity of muscle oxidative enzymes were lowered in type 2 diabetes. We conclude that the uptake and oxidation of plasma FFA are impaired in the forearm muscles of type 2 diabetic subjects in the overnight fasted state with and without Iso stimulation.

Microdialysis assessment of local adipose tissue lipolysis during beta-adrenergic stimulation in upper-body-obese subjects with type II diabetes.

The present study was designed to investigate indicators of abdominal adipose tissue lipolysis (microdialysis), and subcutaneous adipose tissue blood flow and whole-body lipolysis, in obesity-associated type II diabetes during overnight-fasted conditions (baseline) and during intravenous infusion of the non-selective beta-agonist isoprenaline. Basal subcutaneous adipose tissue blood flow and isoprenaline-induced increases in adipose tissue blood flow were not significantly different between subjects with type II diabetes and non-obese, non-diabetic controls. Adipose tissue interstitial glycerol concentrations were significantly higher in subjects with type II diabetes compared with controls (P<0. 01), and during isoprenaline infusion there was a decrease in interstitial glycerol in both groups (P<0.001). Arterial glycerol concentrations were higher in subjects with type II diabetes compared with controls (P<0.05), whereas the increases in arterial glycerol concentration in response to isoprenaline infusion were of a similar magnitude in the two groups. Estimated subcutaneous adipose tissue glycerol release was not significantly different between the groups (controls and subjects with type II diabetes: baseline, -129+/-32 and -97+/-72 micromol.min(-1).100 g(-1) adipose tissue respectively; isoprenaline, -231+/-76 and -286+/-98 micromol. min(-1).100 g(-1) respectively). Values for fat oxidation were not significantly different between groups, whereas the isoprenaline-induced increase in fat oxidation tended to be less pronounced in subjects with type II diabetes compared with controls (0.022+/-0.008 and 0.038+/-0.003 g/min respectively; P=0.058). Thus estimated basal subcutaneous adipose tissue glycerol release, expressed per unit of fat mass, is not different in controls and in subjects with type II diabetes. Additionally, the isoprenaline-induced increases in indicators of local abdominal subcutaneous adipose tissue, systemic lipolysis and abdominal adipose tissue blood flow responses were comparable in obese subjects with type II diabetes and in controls. The last two findings contrast with previous data from obese subjects, indicating that the regulation of lipolysis may differ in obesity and obesity-associated type II diabetes.

Body composition in renal transplant patients: bioimpedance analysis compared to isotope dilution, dual energy X-ray absorptiometry, and anthropometry.

Whether multifrequency bioelectrical impedance analysis (MF-BIA), a relatively new method for measuring body composition, is also applicable for accurate body composition measurements in renal transplant (RTx) patients is not known. Therefore, the use of MF-BIA is validated in 77 RTx patients with a stable renal function at least 2 yr posttransplantation. MF-BIA is compared to isotope dilution techniques for measurement of body water compartments, and to dual energy x-ray absorptiometry (DEXA) and anthropometry for measurement of fat and fat free mass. Finally, DEXA and anthropometry are compared to each other. Method agreement is assessed by intraclass correlation coefficients (ICC) and plotted by Bland and Altman analysis. MF-BIA significantly underestimates total body water (TBW, 0.7+/-2.1 L) and overestimates the extracellular water (ECW, 3.3+/-1.8 L) compared to isotope dilution; the ICC between both techniques is 0.943 for TBW and 0.846 for ECW. The percentage body fat (BF) measured by MF-BIA is significantly higher than both BF measured by DEXA (3.4+/-4.7%) or by anthropometry (5.5+/-5.2%). The ICC between MF-BIA and DEXA is 0.887 and between MF-BIA and anthropometry 0.856. BF measured by DEXA is significantly higher than BF measured by anthropometry (2.1+/-4.4%); their ICC is 0.913. In conclusion, MF-BIA seems to be suitable for measurement of TBW in RTx patients; however, method agreement between isotope dilution and MF-BIA for the measurement of ECW is not satisfactory. In the assessment of fat and fat free mass, the reliability of MF-BIA appears to be questionable. Method agreement between DEXA and anthropometry seems to be slightly better.

Dual-energy X-ray absorptiometry in the clinical evaluation of body composition and bone mineral density in patients with chronic obstructive pulmonary disease.

BACKGROUND: Depletion of fat-free mass (FFM) occurs in a considerable number of patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: The goal of the study was to determine whether dual-energy X-ray absorptiometry (DXA) is an applicable method in the clinical evaluation of body composition in COPD. DESIGN: In a cross-sectional study in 79 COPD patients participating in a pulmonary inpatient program and in 23 healthy volunteers, DXA was compared with deuterium dilution (Deu) in the estimation of FFM. Bone mineral density (BMD), a DXA measurement, was also compared between the 2 groups. RESULTS: FFM(DXA) was highly related to FFM(Deu) in men (R2 = 0.93, P < 0.001) and women (R2 = 0.91, P < 0.001). On average, DXA resulted in higher FFM values than did Deu in COPD patients (3.4 kg; P < 0.001) and in healthy volunteers (2.1 kg; P < 0.001). Furthermore, the intramethod difference in FFM was higher in men than in women in the COPD group (P < 0.05) and in healthy volunteers (P < 0.001). BMD was lower in the COPD group than in the healthy, age-matched volunteers (P < 0.001). In 56% of the COPD patients, there were indications of bone mineral loss, defined as a BMD <1 SD of a matched reference population provided by the software. BMD was <2 SDs in 36% of the COPD patients. CONCLUSIONS: DXA appears to be a suitable alternative method to Deu for assessing body composition and is also of value in identifying bone mineral loss in COPD patients, and is therefore applicable in the clinical evaluation of these patients.

Intense muscle uptake of gallium-67 in a patient with sarcoidosis.

Sarcoidosis has been associated with muscle involvement. In general, this involvement remains asymptomatic. The following case report demonstrates a patient with a 4-mo history of sarcoidosis who reported severe fatigue and slight muscular complaints at a regular checkup. Gallium scintigraphy indicated unexpected and unusually extensive muscular localizations of the disease. The latter findings were confirmed by examination of biopsy specimens. The importance of gallium scintigraphy lies in the possibility of wholebody screening for inflammation localizations, particularly when physical, laboratory, lung function and radiographic examinations fail to provide convincing evidence of active sarcoidosis. Furthermore, it can be helpful in the follow-up of the effect of supportive treatment.

In-111 octreotide imaging in staging of small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) tumors have neuroendocrine features. In vitro and in vivo studies have demonstrated that 50%-75% of SCLC tumors express receptors for somatostatin. This might enable in vivo localization of the primary tumor and its metastases by using scintigraphy with a radiolabeled somatostatin analogue, such as octreotide. PURPOSE AND METHODS: The efficacy of scanning with In-111 labeled octreotide (octreotide scan) was studied in the staging of SCLC patients and compared with the results of conventional staging (liver ECHO, bone scintigraphy, MRI of the brain, spine, and pelvis). Imaging was performed in 29 patients with histologically confirmed SCLC at 4, 24, and 48 hours after intravenous injection of 185 MBq In-111 octreotide. RESULTS: In 24 of 29 patients, the primary tumor was visualized. In these 24 patients, 26 metastases were demonstrated with conventional staging, of which only nine were visualized with octreotide scan. Octreotide scans showed two metastases in the brain that were not visualized by MRI. In the other five patients, five metastases were demonstrated with conventional staging. Only two of these were detected with octreotide scan. However, octreotide scan did show a further metastasis in the brain that was not visualized by MR imaging. CONCLUSION: Octreotide imaging has a limited use in the detection of SCLC metastases compared to conventional staging. It might have some specific value in the detection of brain involvement in patients with limited disease.

The effect of a single rectal dose of cisapride on delayed gastric emptying.

BACKGROUND: Cisapride has an established prokinetic effect in patients with delayed gastric emptying. However, rectal administration of the drug might be preferred in patients with either dysphagia or nausea due to gastroparesis. AIM: To determine the effect of a single rectal dose of cisapride 60 mg on gastric emptying in patients with delayed gastric emptying. METHODS: Thirty-two patients (16 males, 16 females) with demonstrated delayed gastric emptying received a single dose of two suppositories containing either cisapride (2 x 30 mg) or placebo, according to a double-blind randomized crossover design. Three hours after administration of the suppositories, the patients received a radio-labelled test meal and radio-opaque markers for measurement of gastric emptying. RESULTS: The mean t1/2 after cisapride administration (76 min, 95% CI: 68-95) was significantly shorter (P = 0.005: n = 28, per-protocol analysis) than after placebo administration (104 min, 81-126). Four hours after ingestion of the meal significantly fewer radio-opaque markers remained in the stomach after cisapride than after placebo administration (P < 0.05). Mild to moderate adverse events, mainly involving the gastrointestinal tract, were reported in 10 patients (31%) after cisapride treatment and in four patients (13%) after placebo (N.S.: n = 32). CONCLUSION: A single suppository dose of cisapride 60 mg significantly accelerates gastric emptying of the solid phase of a meal and of radio-opaque markers in patients with previously demonstrated delayed gastric emptying.

Energy expenditure and physical activity in relation to bone mineral density in women with anorexia nervosa.

OBJECTIVES: To assess sleeping metabolic rate (SMR), average daily metabolic rate (ADMR), and total bone mineral density (TBMD) in women with anorexia nervosa, and to evaluate the effect of daily physical activity on TBMD. DESIGN: We compared women with anorexia nervosa and controls using measurements on body composition, and energy expenditure. Relations between these measurements were investigated. SETTING: Daily living environments in The Netherlands, and body composition and energy expenditure laboratory of the Department of Human Biology. SUBJECTS: Twelve adult, non-hospitalized women with anorexia nervosa, and sixteen adult normal weight women. INTERVENTIONS: Average daily metabolic rate was measured with the doubly labeled water method and sleeping metabolic rate in a respiration chamber. TBMD was measured by dual energy X-ray absorptiometry, and percentage body fat was calculated combining the results from underwater weighing and deuterium dilution. RESULTS: TBMD was significantly lower in anorexia than in controls (0.989 +/- 0.081 vs 1.144 +/- 0.054 g/cm2). Also ADMR and SMR were reduced in anorexia. The physical activity index (PAI = ADMR/SMR) was not significantly different from PAI in controls. In anorexia, TBMD was related to the PAI (R2 = 0.35, P < 0.05). Finally, stepwise multiple regression revealed that PAI together with the study groups as dummy variables could explain 69% of the variation in TBMD. CONCLUSION: These findings show that in anorexia TBMD is reduced, but that nonetheless physical activity has a significant positive effect on bone density.

Baseline and postcaptopril renal blood flow measurements in hypertensives suspected of renal artery stenosis.

UNLABELLED: Renal blood flow (RBF) measurements using first-pass radionuclide angiography with DTPA, a glomerularly filtered agent, failed to show significant differences between normal and stenotic kidneys. Since MAG3 is an ideal agent for the study of RBF, this agent might be an attractive alternative tracer to detect differences in RBF. METHODS: An angiographically controlled prospective study was performed in 48 hypertensive patients, in whom a diagnosis of renovascular hypertension was suspected on clinical grounds. The study was done to determine whether RBF measurements using first-pass radionuclide angiography with 99mTc-MAG3 could be helpful in the diagnostic work-up of the patients. Additionally, the study was done before and after ACE-inhibition. RESULTS: On renal angiography, 29 patients showed to have normal renal arteries (50 patients had normal kidneys and 8 patients had small kidneys). Nineteen patients had renal artery stenosis (13 uni- and 6 bilateral disease). In the patients with normal kidneys, the mean value of RBF measurements ranged from 10.5% to 10.9% of cardiac output. Only small stenotic and small kidneys with normal renal arteries showed a significant reduced baseline RBF as compared with normal kidneys (both p < 0.05); this difference disappeared after ACE-inhibition only for the small kidneys with normal renal arteries. In patients with stenosed kidneys, RBF tended to be reduced both at baseline and after captopril, but the differences with normal kidneys were not statistically significant. After ACE-inhibition RBF increased in the majority of kidneys, but postcaptopril RBF data did not differ significantly from those at baseline. CONCLUSION: RBF measurements using first-pass radionuclide angiography with 99mTc-MAG3, either before or after ACE-inhibition, cannot reliably discriminate between patients with essential hypertension and patients with renal artery stenosis.

Lung and gastric uptake in bone scintigraphy of sarcoidosis.

We report on 99mTc-MDP uptake in lungs and stomach in a patient with hypercalcaemia and renal failure due to elevated 1,25(OH)2vitD3 because of sarcoidosis. Presently, this typical scan pattern has only been described in patients with malignancies, parathyroid adenoma and drug-induced vitamin D intoxication. We offer possible explanations for the findings in our patient.

Beta-adrenergic stimulation and abdominal subcutaneous fat blood flow in lean, obese, and reduced-obese subjects.

The present study was designed to investigate whether the beta-adrenergically mediated blood flow response of abdominal subcutaneous adipose tissue (per unit adipose tissue weight) was altered in obesity and to study the effect of weight reduction on this response. Body composition (underwater weighing) and fat blood flow were determined in a group of lean (n = 9; % body fat, 11.6 +/- 3.9) and obese (n = 9; % body fat, 28.3 +/- 1.8) subjects. In seven obese subjects, measurements were also performed after a 4-week period of weight reduction induced by a very-low calorie diet (% body fat after diet 23.4 +/- 3.3). After an overnight fast, abdominal subcutaneous fat blood flow was determined by the 133xenon washout technique during a 30-minute period of supine rest and during 30-minute periods of infusion of the beta-agonist isoprenaline (ISO) with and without simultaneous infusion of the beta 1-blocker atenolol (AT). Basal abdominal fat blood flow was significantly higher in lean as compared with obese subjects, whereas weight reduction significantly increased basal fat blood flow (obese v reduced-obese, P < .05). There was a significant increase in abdominal fat blood flow as a result of ISO infusion in lean and obese subjects before and after weight reduction. During ISO+AT infusion, abdominal fat blood flow was still significantly increased as compared with control values in lean and obese subjects. The increase in blood flow during ISO was significantly higher in lean subjects than in obese subjects, whereas the ISO+AT-induced blood flow response was comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

Total forearm blood flow as an indicator of skeletal muscle blood flow: effect of subcutaneous adipose tissue blood flow.

1. In studying forearm skeletal muscle substrate exchange, an often applied method for estimating skeletal muscle blood flow is strain gauge plethysmography. A disadvantage of this method is that it only measures total blood flow through a segment of forearm and not the flow through the individual parts such as skin, adipose tissue and muscle. 2. In the present study the contribution of forearm subcutaneous adipose tissue blood flow to total forearm blood flow was evaluated in lean (% body fat 17.0 +/- 2.2) and obese males (% body fat 30.9 +/- 1.6) during rest and during infusion of the non-selective beta-agonist isoprenaline. Measurements were obtained of body composition (hydrostatic weighing), forearm composition (magnetic resonance imaging) and of total forearm (venous occlusion plethysmography), skin (skin blood flow, laser Doppler), and subcutaneous adipose tissue blood flow (133Xe washout technique). 3. The absolute forearm area and the relative amount of fat (% of forearm area) were significantly higher in obese as compared to lean subjects, whereas the relative amounts of muscle and skin were similar. 4. During rest, the percentage contribution of adipose tissue blood flow to total forearm blood flow was significantly higher in lean compared with obese subjects (19 vs 12%, P < 0.05), whereas there were no differences in percentage contribution between both groups during isoprenaline infusion (10 vs 13%). Furthermore, the contribution of adipose tissue blood flow to total forearm blood flow was significantly lower during isoprenaline infusion than during rest in lean subjects (P < 0.05), whereas in the obese this value was similar during rest and during isoprenaline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of anterior-posterior diameter of inferior vena cava by ultrasonography: a new non-invasive method to assess acute changes in vascular filling state.

OBJECTIVE: The aim was to determine whether measurement of the anterior-posterior diameter of the inferior vena cava (IVC) by ultrasonography, before and during deep inspiration, allows indirect information on baseline blood volume and changes in vascular filling state to be obtained in healthy subjects. METHODS: Blood volume was measured in 12 volunteers by a standard radioactive isotope method. The IVC dimensions were measured by ultrasound in various positions. In addition, in 10 male subjects the effect on the IVC dimensions of volume loading was evaluated by rapid infusion of plasma expander. During and immediately following volume loading, the IVC dimensions and blood volume were remeasured. RESULTS: Neither the baseline IVC diameters nor any combination of these variables correlated with the concomitant blood volume. Volume loading increased the anterior-posterior IVC dimensions linearly, the largest increase being observed with the maximum IVC diameter and the subject in supine position. CONCLUSIONS: It follows that ultrasonic IVC indices cannot be used as accurate indirect estimate of baseline blood volume, but provide reliable information on acute changes of the subjects' vascular filling state.