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Biomedical subjects

M C Grégoire

Publications and source records attributed to M C Grégoire.

At least 19 recordsLinked to original sources

Functional neuroanatomy of different olfactory judgments.

Humans routinely make judgments about olfactory stimuli. However, few studies have examined the functional neuroanatomy underlying the cognitive operations involved in such judgments. In order to delineate this functional anatomy, we asked 12 normal subjects to perform different judgments about olfactory stimuli while regional cerebral blood flow (rCBF) was measured with PET. In separate conditions, subjects made judgments about the presence (odor detection), intensity, hedonicity, familiarity, or edibility of different odorants. An auditory task served as a control condition. All five olfactory tasks induced rCBF increases in the right orbitofrontal cortex (OFC), but right OFC activity was highest during familiarity judgments and lowest during the detection task. Left OFC activity increased significantly during hedonic and familiarity judgments, but not during other odor judgments. Left OFC activity was significantly higher during hedonicity judgments than during familiarity or other olfactory judgments. These data demonstrate that aspects of odor processing in the OFC are lateralized depending on the type of olfactory task. They support a model of parallel processing in the left and right OFC in which the relative level of activation depends on whether the judgment involves odor recognition or emotion. Primary visual areas also demonstrated a differential involvement in olfactory processing depending on the type of olfactory task: significant rCBF increases were observed in hedonic and edibility judgments, whereas no significant rCBF increases were found in the other three judgments. These data indicate that judgments of hedonicity and edibility engage circuits involved in visual processing, but detection, intensity, and familiarity judgments do not.

Adult↗

Anatomic and biochemical correlates of the dopamine transporter ligand 11C-PE2I in normal and parkinsonian primates: comparison with 6-[18F]fluoro-L-dopa.

Positron emission tomography (PET) coupled to 6-[18F]Fluoro-L-Dopa (18F-Dopa) remains the gold standard for assessing dysfunctionality concerning the dopaminergic nigrostriatal pathway in Parkinson's disease and related disorders. The use of ligands of the dopamine transporters (DAT) is an attractive alternative target; consequently, the current aim was to validate one of them, 11C-PE2I, using a multiinjection modeling approach allowing accurate quantitation of DAT densities in the striatum. Experiments were performed in three controls, three MPTP-treated (parkinsonian) baboons, and one reserpine-treated baboon. 11C-PE2I B'max values obtained with this approach were compared with 18F-Dopa input rate constant values (Ki), in vitro Bmax binding of 125I-PE2I, and the number of dopaminergic neurons in the substantia nigra estimated postmortem by stereology. In the caudate nucleus and putamen, control values for 11C-PE2I B'max were 673 and 658 pmol/mL, respectively, whereas it was strongly reduced in the MPTP-treated (B'max = 26 and 36 pmol/mL) and reserpine-treated animals (B'max = 338 and 483 pmol/mL). In vivo 11C-PE2I B'max values correlated with 18F-Dopa Ki values and in vitro 125I-PE2I Bmax values in the striatum and with the number of nigral dopaminergic neurons. Altogether, these data support the use of 11C-PE2I for monitoring striatal dopaminergic disorders and the effect of potential neuroprotective strategies.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Brain processing of visual sexual stimuli in human males.

Despite its critical sociobiological importance, the brain processing of visual sexual stimuli has not been characterized precisely in human beings. We used Positron Emission Tomography (PET) to investigate responses of regional cerebral blood flow (rCBF) in nine healthy males presented with visual sexual stimuli of graded intensity. Statistical Parametric Mapping was used to locate brain regions whose activation was associated with the presentation of the sexual stimuli and was correlated with markers of sexual arousal. The claustrum, a region whose function had been unclear, displayed one of the highest activations. Additionally, activations were recorded in paralimbic areas (anterior cingulate gyrus, orbito-frontal cortex), in the striatum (head of caudate nucleus, putamen), and in the posterior hypothalamus. By contrast, decreased rCBF was observed in several temporal areas. Based on these results, we propose a model of the brain processes mediating the cognitive, emotional, motivational, and autonomic components of human male sexual arousal.

Adult↗

Parietal and cingulate processes in central pain. A combined positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) study of an unusual case.

Parietal, insular and anterior cingulate cortices are involved in the processing of noxious inputs and genesis of pain sensation. Parietal lesions may generate central pain by mechanisms generally assumed to involve the 'medial' pain system (i.e. medial thalamic nuclei and anterior cingulate cortex (ACC)). We report here PET and fMRI data in a patient who developed central pain and allodynia in her left side after a bifocal infarct involving both the right parietal cortex (SI and SII) and the right ACC (Brodmann areas 24 and 32), thus questioning the schematic representation of cortical pain processing. No rCBF increase was found in any part of the residual cingulate cortices, neither in the basal state (which included spontaneous pain and extended hypoperfusion around the infarct), nor during left allodynic pain. Thus, as previously observed in patients with lateral medullary infarct, neither spontaneous pain nor allodynia reproduce the cingulate activation observed after noxious pain in normal subjects. Conversely, both PET and fMRI data argue in favour of plastic changes in the 'lateral discriminative' pain system. Particularly, allodynia was associated with increased activity anteriorly to the infarct in the right insula/SII cortex. This response is likely to be responsible for the strange and very unpleasant allodynic sensation elicited on the left side by a non-noxious stimulation.

Brain Mapping↗

Differential recruitment of the speech processing system in healthy subjects and rehabilitated cochlear implant patients.

Differences in cerebral activation between control subjects and post-lingually deaf rehabilitated cochlear implant patients were identified with PET under various speech conditions of different linguistic complexity. Despite almost similar performance in patients and controls, different brain activation patterns were elicited. In patients, an attentional network including prefrontal and parietal modality-aspecific attentional regions and subcortical auditory regions was over-activated irrespective of the nature of the speech stimuli and during expectancy of speech stimuli. A left temporoparietal semantic region was responsive to meaningless stimuli (vowels). In response to meaningful stimuli (words, sentences, story), left middle and inferior temporal semantic regions and posterior superior temporal phonological regions were under-activated in patients, whereas anterior superior temporal phonological regions were over-activated. These differences in the recruitment of the speech comprehension system reflect the alternative neural strategies that permit speech comprehension after cochlear implantation.

Acoustic Stimulation↗

Iterative crystal efficiency calculation in fully 3-D PET.

The calculation of the intrinsic efficiency of individual crystals is one of the steps needed to obtain accurate images of the radioisotope distribution in positron emission tomography (PET). These efficiencies can be computed by comparing the number of coincidence counts obtained when the crystals are equally illuminated by the same source. However, because the number of coincidence counts acquired for one crystal also depends on the efficiency of the other crystals in coincidence, most methods of crystal efficiency calculation need to assume that the influence of the other crystals is negligible. If there are large crystal efficiency variations, this approximation may lead to systematic errors. We have recently implemented an iterative method for a single ring of detectors that does not rely on this assumption. In this paper, we describe a fully three-dimensional (3-D) iterative method that better exploits the sensitivity of the tomograph and allows reduced acquisition times or the use of narrow energy windows. We compare the performance of the iterative method (single-ring and extended to fully 3-D) with noniterative techniques for different acquisition times of a uniform cylinder. Two different energy windows were used to assess the performance of each method with different levels of variations of crystal efficiency. The results showed that the iterative methods are more accurate when large efficiency variations exist and that only the fully 3-D methods provided good efficiency estimates with very low duration scans. We, thus, conclude that iterative fully 3-D methods provide the best estimations and can be used in a larger range of situations than can the other methods tested.

Algorithms↗

A selective imaging of tinnitus.

We selectively imaged the neural correlates of tinnitus, by contrasting a condition with no phantom auditory sensation with a condition during which tinnitus is present, using a rare form of tinnitus elicited by eye movements. Using positron emission tomography (PET), we demonstrate that phantom auditory sensation increases regional cerebral blood flow bilaterally in temporo-parietal association auditory areas but not in the primary auditory cortex. These results confirm that conscious perception does not necessarily require activation in primary areas and suggest that the perceptual qualities of tinnitus, e.g. intensity, frequency and spatial localization, are represented in temporo-parietal regions. Activation in these regions is compatible with cortical processing of ascending auditory messages generated at subcortical levels.

Adult↗

Neuroanatomical correlates of visually evoked sexual arousal in human males.

Brain areas activated in human male sexual behavior have not been characterized precisely. For the first time, positron emission tomography (PET) was used to identify the brain areas activated in healthy males experiencing visually evoked sexual arousal. Eight male subjects underwent six measurements of regional brain activity following the administration of [15O]H2O as they viewed three categories of film clips: sexually explicit clips, emotionally neutral control clips, and humorous control clips inducing positive but nonsexual emotions. Statistical Parametric Mapping was used to identify brain regions demonstrating an increased activity associated with the sexual response to the visual stimulus. Visually evoked sexual arousal was characterized by a threefold pattern of activation: the bilateral activation of the inferior temporal cortex, a visual association area; the activation of the right insula and right inferior frontal cortex, which are two paralimbic areas relating highly processed sensory information with motivational states; and the activation of the left anterior cingulate cortex, another paralimbic area known to control autonomic and neuroendocrine functions. Activation of some of these areas was positively correlated with plasma testosterone levels. Although this study should be considered preliminary, it identified brain regions whose activation was correlated with visually evoked sexual arousal in males.

Adult↗

An H(2) (15)O-PET study of cerebral blood flow changes during focal epileptic discharges induced by intracerebral electrical stimulation.

Partial epileptic seizures are known to cause a focal increase in cerebral blood flow (CBF). However, quantified studies of ictal CBF changes under intracranial EEG control are still needed to assess the relationships in time and space between CBF changes and electrical discharges. Ten patients undergoing an intracerebral stereotaxic EEG (stereo-EEG) investigation for epilepsy surgery were prospectively studied for local perfusion changes. These were measured by H(2)(15)O-PET during 12 subclinical or mild symptomatic focal epileptic discharges induced by intracerebral electrical stimulation of the hippocampus (eight), amygdala (two), temporal pole (one) and fusiform gyrus (one). This study aimed to assess whether a significant focal blood flow change reflected the geographical extent of the underlying coincident epileptic discharge, as measured by this method at seizure onset. No significant CBF change was observed on test-retest at rest or during ineffective electrical stimulations outside the epileptogenic area. Compared with the resting condition, a significant focal perfusion increase of 16-55% occurred during eight discharges, there was no CBF change in three and a significant CBF decrease in one. Ictal CBF increases were mostly associated with low-voltage fast activity, but their magnitude had no obvious link with the duration of the discharge (range 8-106 s). Regional analysis of ictal PET was performed in 10 anatomical areas during each of the 12 discharges. Of all the 120 regions, 59 were not explored by intracerebral electrodes and 14 (24%) of these demonstrated ictal CBF changes. In 43 of the 61 regions explored by stereo-EEG (70.5%), PET and depth EEG findings converged, showing either a CBF change in a discharging area or no CBF change in a region unaffected by the discharge. Areas of increased CBF indicated an underlying epileptic discharge in almost 100% of the cases. Conversely, of the 18 regions showing discrepancies between intracerebral recordings and PET data, 17 were discharging regions showing no ictal CBF changes. Thus, a focal CBF increase, when detected at the seizure onset concomitantly with the initial low-voltage fast activity, was a reliable marker of an underlying epileptic discharge. It emphasizes the importance of injecting blood-flow tracers as soon as possible after detection of the discharge in routine clinical studies, even at a subclinical stage of the seizure. However, the extent of significant ictal CBF changes can be more restricted than that of the electrical discharge, thus limiting the reliability of ictal CBF images for outlining the contours of a tailored cortectomy.

Adult↗

Haemodynamic brain responses to acute pain in humans: sensory and attentional networks.

Turning attention towards or away from a painful heat stimulus is known to modify both the subjective intensity of pain and the cortical evoked potentials to noxious stimuli. Using PET, we investigated in 12 volunteers whether pain-related regional cerebral blood flow (rCBF) changes were also modulated by attention. High (mean 46.6 degrees C) or low (mean 39 degrees C) intensity thermal stimuli were applied to the hand under three attentional conditions: (i) attention directed towards the stimuli, (ii) attention diverted from the stimuli, and (iii) no task. Only the insular/second somatosensory cortices were found to respond whatever the attentional context and might, therefore, subserve the sensory-discriminative dimension of pain (intensity coding). In parallel, other rCBF changes previously described as 'pain-related' appeared to depend essentially on the attentional context. Attention to the thermal stimulus involved a large network which was primarily right-sided, including prefrontal, posterior parietal, anterior cingulate cortices and thalamus. Anterior cingulate activity was not found to pertain to the intensity coding network but rather to the attentional neural activity triggered by pain. The attentional network disclosed in this study could be further subdivided into a non-specific arousal component, involving thalamic and upper brainstem regions, and a selective attention and orientating component including prefrontal, posterior parietal and cingulate cortices. A further effect observed in response to high intensity stimuli was a rCBF decrease within the somatosensory cortex ipsilateral to stimulation, which was considered to reflect contrast enhancing and/or anticipation processes. Attentional processes could possibly explain part of the variability observed in previous PET reports and should therefore be considered in further studies on pain in both normal subjects and patients with chronic pain.

Acoustic Stimulation↗

Paradoxical metabolic response of the human brain to a single electroconvulsive shock.

Regional brain protein synthesis was evaluated with positron emission tomography (PET) and L-(S-[11C]methyl)methionine ([11C]MET) in depressive patients, before and 3 h after an electroconvulsive shock (ECS), when energy supply is restored, and in healthy volunteers. Depressive patients presented apparent lower protein synthesis than normals, in agreement with known reduction of cerebral activity. In contrast, ECS resulted in a significant increase (56%, P < 0.05) in global cortical protein synthesis. This paradoxical hyperactivation of cellular protein metabolism in response to seizures and the fact that synaptic activity is further reduced after electroconvulsive therapy (ECT), may provide new insights for understanding the mechanism of action of ECT.

Adult↗

Nursery Neurobiologic Risk Score and outcome at 18 months.

The aim of this study was to confirm the predictive value of the nursery Neurobiologic Risk Score. Prospectively, 121 infants (mean birthweight 961 +/- 179 g, gestation 27.0 +/- 1.2 weeks) were followed at 18 months. The nursery Neurobiologic Risk Score was correlated to the developmental quotient (r = -0.54). From low (scores 0-4), to moderate (scores 5-7) to high (scores > or = 8) risk groups, respectively, significant differences were found in mean developmental quotient (101 +/- 9 vs 92 +/- 19 vs 76 +/- 24) and in prevalence of developmental quotients < 90 (12 vs 24 vs 71%), of cerebral palsy (4 vs 19 vs 41%), of severe disabilities (0 vs 24 vs 50%) and of any disability (16 vs 30 vs 71%). Sensitivity, specificity, positive and negative predictive values for any disability were 81, 54, 49 and 84% for a score > or = 5 and 56, 87, 71 and 78% for a score > or = 8. The nursery Neurobiologic Risk Score was useful in predicting 18 months outcome of very premature infants.

Developmental Disabilities↗

Clinical utility of flumazenil-PET versus [18F]fluorodeoxyglucose-PET and MRI in refractory partial epilepsy. A prospective study in 100 patients.

We assessed the clinical utility of [11C]flumazenil-PET (FMZ-PET) prospectively in 100 epileptic patients undergoing a pre-surgical evaluation, and defined the specific contribution of this neuro-imaging technique with respect to those of MRI and [18F]fluorodeoxyglucose-PET (FDG-PET). All patients benefited from a long term video-EEG monitoring, whereas an intracranial EEG investigation was performed in 40 cases. Most of our patients (73%) demonstrated a FMZ-PET abnormality; this hit rate was significantly higher in temporal lobe epilepsy (94%) than in other types of epilepsy (50%) (P < 0.001). Most FMZ-PET findings coexisted with a MRI abnormality (81%), including hippocampal atrophy (35%) and focal hypometabolism on FDG-PET (89%). The area of decreased FMZ binding was often smaller than that of glucose hypometabolism (48%) or larger than that of the MRI abnormality (28%). FMZ-PET did not prove superior to FDG-PET in assessing the extent of the ictal onset zone, as defined by intracranial EEG recordings. However, it provided useful data which were complementary to those of MRI and FDG-PET in three situations: (i) in temporal lobe epilepsy associated with MRI signs of hippocampal sclerosis, FMZ-PET abnormalities delineated the site of seizure onset precisely, whenever they were coextensive with FDG-PET abnormalities; (ii) in bi-temporal epilepsy, FMZ-PET helped to confirm the bilateral origin of seizures by showing a specific pattern of decreased FMZ binding in both temporal lobes in 33% of cases; (iii) in patients with a unilateral cryptogenic frontal lobe epilepsy, FMZ-PET provided further evidence of the side and site of seizure onset in 55% of cases. Thus, FMZ-PET deserves to be included in the pre-surgical evaluation of these specific categories of epileptic patients, representing approximately half of the population considered for epilepsy surgery.

Brain↗

Allodynia after lateral-medullary (Wallenberg) infarct. A PET study.

We used PET to study regional cerebral blood flow (rCBF) changes in nine patients with unilateral central pain after a lateral medullary infarct (Wallenberg's syndrome). All patients presented, on the abnormal side, a combination of hypaesthesia to noxious and thermal stimuli and allodynia to rubbing of the skin with a cold object (i.e. abnormal pain to innocuous stimulation). The rCBF responses during allodynia were compared with those obtained during stimulation of the normal side using (i) a cold non-noxious stimulus identical to that applied to the painful side, and (ii) an electrical high-frequency stimulus at painful ranges. Statistical analysis disclosed two abnormal patterns of rCBF change during allodynia. First, there is a quantitative change whereby the blood flow response was out of proportion with the actual intensity of the stimulus, i.e. the pattern of activation by innocuous rubbing of the skin was in our patients identical to that previously reported in response to painful stimuli in normal subjects. This pattern concerned primarily the contralateral thalamus in its lateral half and the primary and somatosensory areas, as well as inferior parietal [Brodmann area (BA) 39/40], anterior insular (BA 6) and medial prefrontal (BA 10) cortices. Thalamic over-activity may reflect abnormal transduction and amplification of sensory inputs after spinothalamic deafferentation. This might be responsible for both increased rCBF in multiple cortical targets and the perceived shift of stimulus intensity from innocuous to painful ranges. The second abnormality associated with allodynic sensation was qualitative. It concerned exclusively the contralateral cingulate gyrus, which did not exhibit the usual pain-related rCBF increase reported in normal subjects. This abnormal cingulate response may account for the peculiar response of lateral medullary infarct patients to allodynic pain, which is not simply perceived as an exaggerated pain sensation, but as a new, strange and extremely unpleasant feeling, not previously experienced by the patients.

Adult↗

Health and developmental outcomes at 18 months in very preterm infants with bronchopulmonary dysplasia.

OBJECTIVE: To determine whether very preterm infants who are oxygen-dependent at 28 days of life but not at 36 weeks' gestational age are at high risk of morbidities at 18 months. POPULATION: A total of 217 infants born in a tertiary care center at 24 to 28 weeks' gestation in 1987 to 1992, classified into three groups: neonatal comparison group, O2 <28 days of life (n = 76); bronchopulmonary dysplasia (BPD)-1, O2 >/=28 days but not at 36 weeks' gestational age (n = 48); and BPD-2, O2 >/=36 weeks (n = 93). OUTCOME MEASURES: Growth, persistent respiratory problems (asthma, tracheostomy, home oxygen therapy), surgery, hospitalizations, and neurodevelopmental impairments. RESULTS: Among the three groups, no differences were found in weight, height, head circumference, or total number of days of rehospitalizations for any causes, or in rate of rehospitalizations to the intensive care unit, persistent respiratory problems, cerebral palsy, or sensory impairment. Children with BPD-2 needed more hernia repairs compared with the other two groups (comparison group: 12% vs BPD-1: 10% vs BPD-2: 30%), had more days of readmissions for respiratory problems (comparison group: 2.0 vs BPD-1: 2.0 vs BPD-2 6.3 [BPD-1 vs BPD-2]), had a lower mean developmental quotient (comparison group: 97.4 +/- 15.0 vs BPD-1: 97.9 +/- 11.6 vs BPD-2: 90.7 +/- 19.3). Intraparenchymal cerebral lesions, high family adversity, and prolonged ventilation were the most important factors influencing the developmental outcome. CONCLUSION: Children with BPD-1 are similar in all respect at 18 months to children in the comparison group. Children with BPD-2 are similar to the other groups at 18 months in growth, general health, and neurologic outcome but differ in having a higher number of days of rehospitalizations for respiratory causes, more hernia repairs, and more developmental delays.

Bronchopulmonary Dysplasia↗

Positron emission tomography during motor cortex stimulation for pain control.

We studied regional changes in cerebral flood flow (rCBF) in 9 patients undergoing motor cortex stimulation (MCS) for pain control. Significant increase in rCBF was observed in the lateral thalamus ipsilateral to MCS probably reflecting corticothalamic connections from motor/premotor areas. Subsignificant increases were observed in the anterior cingulate, left insula and upper brainstem. Mean rCBF in the anterior cingulate increased during MCS in patients with good analgesic efficacy, while it decreased in those with poor clinical outcome; conversely, thalamic rCBF increased in the two groups, albeit to a greater extent in patients with good clinical results. Our results support a model of MCS action whereby activation of thalamic nuclei directly connected with motor and premotor cortices would entail a cascade of synaptic events in other pain-related structures, including the anterior cingulate and the periaqueductal gray. MCS could influence the affective-emotional component of chronic pain by way of cingulate activation, and lead to descending inhibition of pain impulses by activation of the brainstem. Such effects may be obtained only if thalamic activation reaches a 'threshold' level, below which the analgesic cascade would not be successfully triggered.

Adult↗

Source propagation of interictal spikes in temporal lobe epilepsy. Correlations between spike dipole modelling and [18F]fluorodeoxyglucose PET data.

Source localization methods were applied to interictal spikes from scalp EEGs and correlated with metabolic (PET scan) data in eight patients suffering from drug-resistant temporal lobe epilepsy (TLE). Dipolar sources, [18F]fluorodeoxyglucose (18FDG)-PET data and anatomical images (MRI) were projected into the same three-dimensional coordinates system. Averaged spikes were adequately modelled by two or three dipolar sources with different onset time of activation but overlapping activity (mean residual variance 3.4 +/- 2.1%). Although, in all patients, spike modelling demonstrated dipolar sources in both mesial and lateral temporal cortex, dipole propagation was consistent with the early involvement of only one of these two areas (mesio-temporal, five patients; lateral and polar neocortex, three patients). Six patients showed a unilateral interictal decrease in glucose uptake, as measured with 18FDG-PET, in the temporal lobe ipsilateral to the EEG spike focus. Temporal hypometabolism was bilateral in one patient and absent in the remaining case. When projected onto PET-scan slices, the dipolar sources of these patients were always included within the hypometabolic area. However, within the hypometabolic zone, the decrease in glucose uptake was not found to be more pronounced in regions containing dipoles. Therefore the spatio-temporal spread of neuronal hyperactivity underlying interictal spiking suggests the presence of preferential epileptogenic networks inside the hypometabolic temporal lobe. Fusion of bioelectric, metabolic and anatomical data proves to be a convenient way of summarizing multimodal information from non-invasive investigations in TLE patients entering an epilepsy surgery programme, and suggests that both interictal spike dipole modelling and 18FDG-PET data might be useful, as a complement to ictal electro-clinical data, in the presurgical evaluation of such patients.

Adult↗

Perfusion-MVO2 mismatch during inotropic stress in CAD patients with normal contractile function.

With the use of[11C]acetate, positron emission tomography (PET) permits exploration of myocardial blood flow (MBF) and oxidative metabolism (MVo2) coupling. PET imaging was performed at rest and under dobutamine infusion in 8 normal subjects and 10 coronary artery disease (CAD) patients with significant single-vessel left anterior descending (LAD) stenosis (> 70%) and normal regional left contractile function at rest. Resting MBF and MVo2 were similar in remote and LAD regions of normal subjects and patients. During dobutamine infusion, MBF and myocardial flow reserve were lower in LAD regions of patients compared with remote regions (MBF: 1.49 +/- 0.42 and 2.06 +/- 0.57 ml.g-1.min-1, P < 0.01; reserve: 1.73 +/- 0.59 and 2.14 +/- 0.47, P < 0.01, respectively), whereas MVo2 expressed as kmono (an index of MVo2) and metabolic reserve were similar (kmono: 0.106 +/- 0.021 vs. 0.107 +/- 0.017 min-1; reserve: 1.88 +/- 0.32 vs. 1.98 +/- 0.37, respectively). This is the first human study showing that, in normal contractile regions at rest but perfused by stenosed artery, a disparate rise in MVo2 relative to the rise in myocardial perfusion occurs during increased cardiac work induced by dobutamine. This flow-metabolism uncoupling probably reflects an increase in O2 extraction.

Adult↗