Influence of nitric oxide synthase and adrenergic inhibition on adenosine-induced myocardial hyperemia.

BACKGROUND: Myocardial perfusion during adenosine-induced hyperemia is used both in clinical diagnosis of coronary heart disease and for scientific investigations of the myocardial microcirculation. The objective of this study was to clarify whether adenosine-induced hyperemia is dependent on endothelial NO production or is influenced by adrenergic mechanisms. METHODS AND RESULTS: In 12 healthy men, myocardial perfusion was measured with PET in 2 protocols performed in random order, each including 3 perfusion measurements. First, perfusion was measured at rest. Second, either saline or the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 4 mg/kg) was infused, and perfusion during adenosine-induced hyperemia was determined. Last, in both protocols, the alpha-receptor blocker phentolamine was infused, and perfusion during adenosine-induced hyperemia was determined again. Resting perfusion was similar in the 2 protocols (0.69+/-0.14 and 0.66+/-0.18 mL. min(-1). g(-1)). L-NAME increased mean arterial blood pressure by 12+/-7 mm Hg (P<0.01) and reduced heart rate by 16+/-7 bpm (P<0.01). Adenosine-induced hyperemia (1.90+/-0.33 mL. min(-1). g(-1)) was attenuated by L-NAME (1.50+/-0.55 mL. min(-1). g(-1), P<0.01). The addition of phentolamine had no effect on the adenosine-induced hyperemia (2.10+/-0.34 mL. min(-1). g(-1), P=NS). In the presence of L-NAME, however, when the adenosine response was attenuated, phentolamine was able to increase hyperemic perfusion (2.05+/-0.44 mL. min(-1). g(-1), P<0.05). CONCLUSIONS: Inhibition of endogenous NO synthesis attenuates myocardial perfusion during adenosine-induced hyperemia, indicating that coronary vasodilation by adenosine is partly endothelium dependent. alpha-Adrenergic blockade has no effect on adenosine-induced hyperemia unless NO synthesis is inhibited.

Abnormalities of cardiac sympathetic innervation in arrhythmogenic right ventricular cardiomyopathy : quantitative assessment of presynaptic norepinephrine reuptake and postsynaptic beta-adrenergic receptor density with positron emission tomography.

BACKGROUND: The frequent provocation of ventricular tachycardia by stress or catecholamines and the efficacy of antiarrhythmic drugs with antiadrenergic properties suggest an involvement of the cardiac adrenergic system in arrhythmogenesis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Previous studies demonstrated abnormalities of the presynaptic uptake-1 assessed by (123)I-MIBG-single-photon emission computed tomography. METHODS AND RESULTS: This study investigated neuronal reuptake of norepinephrine (uptake-1) and beta-adrenergic receptor density in 8 patients with ARVC and 29 age-matched control subjects. All subjects underwent positron emission tomography with the volume of distribution (V(d)) of [(11)C]hydroxyephedrine ((11)C-HED) used to assess presynaptic norepinephrine reuptake, the maximum binding capacity (B(max)) of [(11)C]CGP-12177 ((11)C-CGP-12177) to assess postsynaptic beta-adrenergic receptor density, and [(15)O]H(2)O for quantification of myocardial blood flow. Patients with ARVC demonstrated a highly significant global reduction in postsynaptic beta-adrenergic receptor density compared with that in control subjects (B(max) of (11)C-CGP-12177: 5.9+/-1.3 vs 10.2+/-2.9 pmol/g tissue, P<0.0007), whereas the presynaptic uptake-1 tended toward reduction only (V(d) of (11)C-HED: 59.1+/-25.2 vs 71.0+/-18.8 mL/g tissue, NS). There were no differences in myocardial blood flow between the groups, and plasma norepinephrine was within normal limits in patients and control subjects. CONCLUSIONS: The findings demonstrate a significant reduction of myocardial beta-adrenergic receptor density in patients with ARVC. This may result from a secondary downregulation after increased local synaptic norepinephrine levels caused by increased firing rates of the efferent neurons or as the result of impaired presynaptic catecholamine reuptake. These findings give new insights into the pathophysiology of arrhythmogenesis in ARVC, with potential impact on diagnostic evaluation and therapeutic management.

Electromechanical mapping for detection of myocardial viability in patients with ischemic cardiomyopathy.

BACKGROUND: We evaluated the ability of electromechanical mapping of the left ventricle to distinguish between nonviable and viable myocardium in patients with ischemic cardiomyopathy. METHODS AND RESULTS: Unipolar voltage amplitudes and local endocardial shortening were measured in 31 patients (mean+/-SD age, 62+/-8 years) with ischemic cardiomyopathy (ejection fraction, 30+/-9%). Dysfunctional regions, identified by 3D echocardiography, were characterized as nonviable when PET revealed matched reduction of perfusion and metabolism and as viable when perfusion was reduced or normal and metabolism was preserved. Mean unipolar voltage amplitudes and local shortening differed among normal, nonviable, and viable dysfunctional segments. Coefficient of variation for local shortening exceeded differences between groups and did not allow distinction between normal and dysfunctional myocardium. Optimum nominal discriminatory unipolar voltage amplitude between nonviable and viable dysfunctional myocardium was 6.5 mV, but we observed a great overlap between groups. Individual cutoff levels calculated as a percentage of electrical activity in normal segments were more accurate in the detection of viable dysfunctional myocardium than a general nominal cutoff level. The optimum normalized discriminatory value was 68%. Sensitivity and specificity were 78% for the normalized discriminatory value compared with 69% for the nominal value (P:<0.02). CONCLUSIONS: Endocardial ECG amplitudes in patients with ischemic cardiomyopathy display a wide scatter, complicating the establishment of exact nominal values that allow distinction between viable and nonviable areas. Individual normalization of unipolar voltage amplitudes improves diagnostic accuracy. Electroanatomic mapping may enable identification of myocardial viability.

Cardiac sympathetic innervation in patients with idiopathic right ventricular outflow tract tachycardia.

OBJECTIVES: This study investigated the neuronal reuptake of norepinephrine (uptake-1) and the beta-adrenoceptor density in patients with idiopathic right ventricular outflow tract tachycardia (RVO-VT). BACKGROUND: Clinical findings, such as the inducibility of ventricular tachycardia by stress or catecholamine infusion, and the therapeutic efficacy of antiarrhythmic drugs with antiadrenergic properties suggest abnormalities of cardiac sympathetic innervation in patients with idiopathic RVO-VT. METHODS: Eight patients with idiopathic RVO-VT and a total of 29 age-matched control subjects were investigated by positron emission tomography using [11C]hydroxyephedrine (HED) (volume of distribution of [11C]HED) to assess presynaptic norepinephrine reuptake; [11C]CGP 12177 (maximal binding capacity of [11C]CGP 12177) to measure postsynaptic beta-adrenoceptor density; and oxygen-15-labeled water for quantification of myocardial blood flow (MBF). RESULTS: Both myocardial catecholamine reuptake and beta-adrenoceptor density were significantly reduced in patients with idiopathic RVO-VT. The volume of distribution of [11C]HED in patients with RVO-VT was (mean +/- SD) 41.0 +/- 13.5 versus 71.0 +/- 18.8 ml/g in control subjects (p < 0.002). The maximal binding capacity of the beta-adrenoceptor antagonist [11C] CGP 12177 was 6.8 +/- 1.2 pmol/g in patients with RVO-VT versus 10.2 +/- 2.9 pmol/g in control subjects (p < 0.004). There were no significant differences in MBF at rest (0.98 +/- 0.14 vs. 0.97 +/- 0.24 ml/min per g, p = NS) between patients with RVO-VT and control subjects. CONCLUSIONS: The findings of the present study suggest that myocardial beta-adrenoceptor downregulation in patients with RVO-VT occurs subsequently to increased local synaptic catecholamine levels caused by impaired catecholamine reuptake.

Switching from DXA pencil-beam to fan-beam. II: Studies in vivo.

Switching from the Hologic QDR-1000/W to the QDR-2000 DXA densitometer was critically evaluated with regard to cross-calibration and dosimetry. Studies with bone equivalent humanoid spine phantoms and patient studies were done. Fan-beam scanning with the QDR-2000 is problematic because of magnification. Mean phantom bone mineral content (BMC) and bone mineral density (BMD) were moderately but significantly different. Biological variation disguised differences between the two devices in humans, but significant differences were revealed when individual data were analyzed. Longitudinal assessments of BMC and BMD, initiated with QDR-1000/W and continued with the QDR-2000, should employ single-beam mode only and not fan-beam mode--but even if that is done, significant errors can be introduced. The new QDR-2000 should be properly cross-calibrated with the original densitometer, and one should make sure that the same software, phantom, and type of collimator are used. The radiation dose is substantially higher with QDR-2000 (fan-beam and high-resolution array mode) than with QDR-1000/W (pencil-beam mode) and QDR-2000 (pencil-beam mode), and higher than claimed by the manufacturer. The typical radiation dose given by the manufacturer was half the actual radiation dose measured (e.g., for fan-beam scan 62 microSv versus 33 microSv). High-resolution array mode does not improve precision, but augments the radiation dose to the patient.

Generation of myocardial factor images directly from the dynamic oxygen-15-water scan without use of an oxygen-15-carbon monoxide blood-pool scan.

UNLABELLED: The measurement of regional myocardial blood flow (MBF) with H2(15)O and PET requires an additional C15O blood-pool scan for the purpose of region of interest (ROI) definition. This additional scan results in a substantially increased radiation dose, study duration and risk of movement artifacts. Therefore, a method was developed to generate myocardial factor images directly from the dynamic H2(15)O study without the need for a C15O scan. METHODS: The factor sinograms were generated by means of linear dimension reduction of the dynamic sinograms, where the required variate and covariate factors (myocardial and blood time-activity curves) were modeled from the lung time-activity curve. The factor images were generated by iterative reconstruction. RESULTS: No significant difference was found between MBF values from ROIs drawn on the traditional images (using the C15O scan) and those drawn on the factor images. CONCLUSION: It is possible to generate myocardial images directly from the dynamic H2(15)O study, so that the C15O scan can be omitted from MBF studies. The proposed method is robust and results in nearly optimal signal-to-noise ratios in the factor images.

Pulmonary permeability in never-smokers between 21 and 67 yr of age.

During the last 5-10 years, measurements of pulmonary clearance (PCl) of aerosolized 99mTc-labeled diethylenetriamine pentaacetic acid (99mTC-DTPA) have become increasingly used as an index of pulmonary epithelial injury. The aim of this study was to apply a carefully defined procedure for measurements of PCl in healthy nonsmoking individuals and analyze whether sex, age, and height are clinically relevant confounders contributing to the range of interindividual variation. Measurements of regional ventilation (V) and perfusion (Q) were included to analyze whether these indexes are influenced by the same confounders. We studied 39 males and females between 21 and 67 yr of age. Average PCl of the lungs was 0.85 +/- 0.25%.min-1. There was a significant difference between PCl of the central and peripheral parts of the lungs (P less than 0.01). Regional V and Q were greater in the lower than in the upper halves of the lungs (P less than 0.01). There was no relation between PCl, V, or Q and the sex, age, and height of the individuals. It is concluded that when measuring PCl in adult individuals anthropometric measurements need not be considered.

The DaNeX study of embryonic mesencephalic, dopaminergic tissue grafted to a minipig model of Parkinson's disease: preliminary findings of effect of MPTP poisoning on striatal dopaminergic markers.

A multicenter study is under way to investigate the efficacy of allografting of embryonic mesencephalic neurons in a pig model of Parkinson's disease. We have first established that a stable parkinsonian syndrome can be established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication of adult male Göttingen minipigs. We are now using positron emission tomography (PET) methods for testing the physiological responses to MPTP intoxication and the time course of the response to several treatment strategies. We now report preliminary results obtained in 11 pigs employed in the initial phase of the study; the completed study shall ultimately include 30 pigs. Animals were randomly assigned to one of five groups: 1) Control, 2) MPTP intoxication, 3) MPTP intoxication followed by allograft, 4) MPTP intoxication followed by allograft with immunosuppression, and 5) MPTP intoxication followed by allograft with immunosuppression and co-grafting of immortalized HiB5 cells, which had been manipulated to secrete glia cell line-derived neurotrophic factor (GDNF) (approximately 2 ng GDNF/h/10(5) cells). MPTP was administered (1 mg/kg/day, SC) for 7-10 days until the pigs had developed mild parkinsonian symptoms of muscle rigidity, hypokinesia, and impaired coordination, especially of the hind limbs. Approximately 2 weeks after the last MPTP dose, animals received a T1-weighted magnetic resonance imaging (MRI) scan, and a series of dynamic PET recordings. After the first series of PET scans, four grafts of porcine embryonic mesencephalic tissue (E28 days) were placed in each striatum of some MPTP-intoxicated pigs, using MRI-based stereotactic techniques. Immunosuppression of some animals with cyclosporin and prednisolone began just prior to surgery. Two more series of PET scans were performed at 4-month intervals after surgery. After the last scans, pigs were killed and the brains were perfused for unbiased stereological examination of cytological and histochemical markers in striatum and substantial nigra. The behavioral impairment of the animals (the "Parkinson's score") had been evaluated throughout the 8-month period. Kinetic analysis of the first set of PET scans has indicated that the rate constant for the decarboxylation of FDOPA in catecholamine fibers was reduced by 33% in striatum of the mildly parkinsonian pigs. The rate of association of [11C]NS-2214 to catecholamine uptake sites was reduced by 62% in the same groups of pigs. No significant difference was found in the binding potential of [11C]raclopride to the dopamine D2-like receptors in striatum of the MPTP-intoxicated versus control pigs. These preliminary results are suggestive that the activity of DOPA decarboxylase may be upregulated in the partially denervated pig striatum.

FDOPA metabolism in the adult porcine brain: influence of tracer circulation time and VOI selection on estimates of striatal DOPA decarboxylation.

Different methodologies for PET data analysis influence the magnitude of estimates of blood-brain transfer coefficients and rate constants for the metabolism of FDOPA in living striatum. We now test the effects on several kinetic parameters of automatic procedures for volume of interest (VOI) selection. We also tested the sensitivity of the estimates to dynamic frame sequence duration, and produced a standard method for minimizing the variations in physiological estimates for FDOPA kinetics in minipig brain. We used minipigs because our previous work has shown them to provide an appropriate animal model for study normal and pathological cerebral DOPA metabolism using PET. Time-activity curves in striatum of adult minipigs were acquired in VOIs defined manually on MR-images, or alternatively on the basis of the radioactivity concentration based on the most radioactive voxel in the last scan frame. For all frame sequences, the relative decarboxylase activity (k(3)(D)) declined significantly (P < 0.006) as the VOI threshold declined from 95 to 70% of the most radioactive voxel. Irrespective of VOI size, the magnitude of k(3)(D) declined significantly (P < 0.001) from 0.074+/-0.008 to 0.045+/-0.005 per min (mean+/-S.E.M.) as total sequence length increased from 60 to 120 min circulation. The method of VOI selection had no significant effect on the striatum decarboxylation index of FDOPA calculated relative to the radioactivity in cerebellum (k(3)(S)).

Linear dimension reduction of sequences of medical images: I. Optimal inner products.

A general theory is presented for minimizing noise in linear dimension reduction of sequences of medical images when the factors and the covariance matrix and mean of the noise are given. A dimension reduction is optimal when all diagonal elements in the covariance matrix of the noise in the signal (factor) space are minimized. This occurs when the noise in the signal space is uncorrelated with the residual noise. Expressions are given for the resulting covariance matrix of the noise in the signal space. Many optimal inner products exist, which all result in the same optimal dimension reduction. Given any pair of inner products for signal space and residual space, a combined inner product exists that is also optimal. If the covariance matrices of the noise in different pixel vectors are not multiples of each other, different pixel vectors may have different optimal inner products. The averaging process in generating images from tomographic projections tends to make the covariance matrices more uniform.

Linear dimension reduction of sequences of medical images: III. Factor analysis in signal space.

A method is presented for improving the precision of factor analysis by utilizing physiological information. The first step is an optimal linear dimension reduction, whereby the data are projected onto a low-dimensional signal space. Then principal component analysis is performed in the signal space rather than in the entire data space. This improves the precision of the principal components. Unlike ordinary principal component analysis, the present method is not degraded when the time intervals are subdivided, provided that the signal space is correct. Alternatively, but with identical results, the covariance matrix can be calculated from the whole data space. The covariance matrix is then transformed and principal component analysis is performed in either a low-rank matrix or a low-dimensional submatrix instead of in the whole covariance matrix. Factor analysis using the intersection method with a theory space may be improved by employing the present method. In simulations based on a [11C]flumazenil study with 27 frames, the proposed method required only 58 per cent of the radioactivity to produce the same precision as the intersection method and only 27 per cent when compared to ordinary principal component analysis.

Noise reduction and convergence of Bayesian algorithms with blobs based on the Huber function and median root prior.

Iterative image reconstruction algorithms have the potential to produce low noise images. Early stopping of the iteration process is problematic because some features of the image may converge slowly. On the other hand, there may be noise build-up with increased number of iterations. Therefore, we examined the stabilizing effect of using two different prior functions as well as image representation by blobs so that the number of iterations could be increased without noise build-up. Reconstruction was performed of simulated phantoms and of real data acquired by positron emission tomography. Image quality measures were calculated for images reconstructed with or without priors. Both priors stabilized the iteration process. The first prior based on the Huber function reduced the noise without significant loss of contrast recovery of small spots, but the drawback of the method was the difficulty in finding optimal values of two free parameters. The second method based on a median root prior has only one Bayesian parameter which was easy to set, but it should be taken into account that the image resolution while using that prior has to be chosen sufficiently high not to cause the complete removal of small spots. In conclusion, the Huber penalty function gives accurate and low noise images, but it may be difficult to determine the parameters. The median root prior method is not quite as accurate but may be used if image resolution is increased.

Calculation of single detector efficiencies and extension of the normalization sinogram in PET.

A fast iterative method is presented for calculating single detector efficiencies for positron emission tomographs. These efficiencies can be used to extend the normalization scan to areas outside that covered by the normalization source. The root mean square (rms) error of the calculated single detector efficiencies decreases exponentially with the number of iterations. Thirty iterations per normalization image are sufficient and take about 1 s on a SUN Classic. The geometry factors are composed of factors which only depend on the distance from the centre of the field-of-view (FOV) and of factors which show a more complex pattern over the normalization sinogram. The geometry factors are specific to each scanner. On the ECAT 931 scanner the complex part of the geometry factors showed a diamond shaped pattern (caused by the varying sensitivity of single detectors in a detector block with varying angle of incidence) and S-shaped curves (representing attenuation caused by supporting rods for the ring source). The coefficient of variation of the diamond-shaped pattern was 4% for detectors farthest from the centre of the FOV. Extensions of the normalization scan may, therefore, contain a relative rms error of about 4% if the applied geometry factors only take the distance from the centre of the FOV into account.

Linear dimension reduction of sequences of medical images: II. Direct sum decomposition.

Using unitary transformations together with a previously described statistical theory for optimal linear dimension reduction it is shown how pixels in a sequence of images can be decomposed into a sum of variates, covariates, and residual vectors, with all covariances equal to zero. It is demonstrated that this decomposition is optimal with respect to noise. In addition, it results in simplified and well conditioned equations for dimension reduction and elimination of covariates. The factor images are not degraded by subdivision of the time intervals. In contrast to traditional factor analysis, the factors can be measured directly or calculated based on physiological models. This procedure not only solves the rotation problem associated with factor analysis, but also eliminates the need for calculation of the principal components altogether. Examples are given of factor images of the heart, generated from a dynamic study using oxygen-15-labelled water and positron emission tomography. As a special application of the method, it is shown that the factor images may reveal any contamination of the blood curve derived from the original dynamic images with myocardial activity.

Pulmonary clearance of inhaled 99Tcm-DTPA: significance of site of aerosol deposition.

The aim of this study was to analyse how changes in the site of 99Tcm-DTPA aerosol deposition between central and peripheral parts of the lung influence routine measurement of pulmonary clearance of 99Tcm-DTPA (PCl). The study was performed in six 'never-smokers' and 10 smokers with bronchial hypersecretion. Changes in aerosol deposition was accomplished by changing the aerosol particle size and the velocity by which the subjects inhaled the particles. In the smokers with bronchial hypersecretion there was a significantly smaller PCl after central deposition (P less than 0.01), than after peripheral deposition, while in the never-smokers, significance was not reached. The smokers with bronchial hypersecretion had a significantly higher PCl than the never-smokers (P less than 0.01) when the 99Tcm-DTPA had been deposited in the peripheral parts of the lung, but at the examination of central deposition, the difference was no longer significant. It is concluded that in smokers with bronchial hypersecretion measurement of regional PCl is influenced by the site of 99Tcm-DTPA deposition in the lung.

Effect of terbutaline on mucociliary clearance in asthmatic and healthy subjects after inhalation from a pressurised inhaler and a dry powder inhaler.

BACKGROUND: beta Agonists have been shown to increase mucociliary clearance in some studies but not all. Whether the formulation of beta agonists affects mucociliary clearance is not known but may be important as the use of dry powder inhalers increases. METHODS: The effect of different methods of administration of inhaled terbutaline on mucociliary clearance and forced expiratory volume in one second (FEV1) was assessed in 10 patients with asthma and 10 healthy subjects. Terbutaline (1 mg) was administered through a metered dose inhaler with a spacer (Nebuhaler) or a dry powder inhaler (Turbuhaler), or both treatments were given, in a four way double blind, double dummy trial. Mucociliary clearance was measured by bronchoscintigraphy. RESULTS: Clearance of radioactivity from the lobar bronchi increased in the asthmatic patients by a median of 32% after terbutaline was given by metered dose inhaler and 55% after a combined dose of 2 mg from both inhalers (1 mg from each) compared with placebo but by only 9% after 1 mg of terbutaline was given by a dry powder inhaler. In the healthy subjects mucociliary clearance increased by 51% when terbutaline was given by a dry powder inhaler, by 66% when given by a metered dose inhaler, and by 66% when given by both inhalers combined. The effect of terbutaline on FEV1 was the same with each of the inhalers. CONCLUSION: Despite similar changes in FEV1 with the two formulations terbutaline increased mucociliary clearance significantly in asthmatic and healthy subjects when inhaled from a metered dose inhaler whereas when it was inhaled from a dry powder inhaler its effect was significant only in healthy subjects. The reason for the difference in asthmatic subjects is unclear, but may be associated with differences in the deposition of terbutaline.

Interpretation of lumbar spine densitometry in women with fractures.

Identification of postmenopausal women at risk of developing osteoporotic fractures is a major clinical problem. In this study the use of projected planar lumbar bone density values for individual fracture risk assessment was questioned. Osteodensitometry (DXA) results from 415 normal women, 62 women with previous vertebral compressions, and 76 women with previous low-energy fractures were analyzed, together with their body size and lumbar vertebral body size variables. The following were found: (1) Lumbar vertebral projected bone mineral areal density (BMD) and bone mineral content (BMC) of normal women correlated with body size variables (p < 0.001). (2) Lumbar vertebral body size variables also correlated with body size variables (p < 0.001). Logistic regression analysis of measured and derived physical variables from women without and with vertebral compression fractures (n = 477) showed: (3) The best compression fracture discriminator, significantly better than BMD, was BMC divided by (Hmax/165 cm)1.5 x (D/4.35 cm)1.5, where Hmax is the body height (cm) at the menopause, and D the mean lumbar vertebral diameter of the three mid-lumbar vertebral bodies (cm). This parameter was termed BMCcorr.. ROC analysis showed: (4) At a BMCcorr. true positive ratio of 80% the corresponding uncorrected BMC or BMD true positive ratio was only 60%. The corresponding false positive ratio was 6%. Lumbar osteodensitometry could not be used to identify women with a history of peripheral low-energy fractures. (5) BMCcorr. did not, unlike BMC and BMD, correlate with body size and vertebral size variables. (6) Likewise, an observed correlation between BMC and lean body mass in a subpopulation of 116 normal women was abolished when BMCcorr. replaced BMC.(ABSTRACT TRUNCATED AT 250 WORDS)

Mucociliary clearance in early simple chronic bronchitis.

Tracheobronchial mucociliary clearance was measured in 37 patients with early simple chronic bronchitis. A non-invasive radio-aerosol technique with inhalation of 99Tcm labelled 5-microns polystyrene particles followed by assessment of radio-nuclide distribution by posterior gamma-camera scans was employed. The mucociliary clearance of the bronchitics was significantly lower than clearance of a non-smoker control group. An interim analysis of the effect of treatment with a surfactant stimulating drug, ambroxol, suggested a dosage-dependent tendency to a faster mucociliary clearance than seen in placebo-treated bronchitics.

Local forearm and whole-body respiratory quotient in humans after an oral glucose load: methodological problems.

The effects of an oral glucose load of 75 g on the local forearm and whole-body energy thermogenesis were measured in normal subjects during the 4 h after the glucose intake. Simultaneous assessment of substrate metabolism in the forearm was performed. Energy expenditure (EE) increased after the glucose load and had not returned to baseline level at the end of the experiment. Whole-body respiratory quotient (RQ) was, on average, 0.80 (SD 0.05) in the baseline condition and increased to a maximum of 0.91 (0.03) and then decreased to baseline level at the end of the experiment. The local forearm oxygen uptake increased 30 min after the glucose intake and remained elevated during the rest of the experiment. The carbon dioxide output from the forearm did not increase before 90 min after the glucose load. Consequently the local forearm RQ decreased significantly from a baseline value of 0.86 (0.17) to 0.63 (0.17) 30 min after the glucose load (P < 0.05). Ninety min after the glucose load RQ increased to a maximum level at 0.95 (0.22) and decreased then gradually to baseline level. The experiments emphasize several methodological problems in the measurement of local forearm RQ. The whole-body RQ and local forearm RQ are not significantly different in the fasting state. The finding of a decrease in local forearm RQ below 0.70 30 min after the glucose load probably indicates a non-steady state in the carbon dioxide exchange. Thus, indirect calorimetry cannot be applied locally during short time periods.