franck LAVENNE

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Papers by franck LAVENNE

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

American Journal of Physiology-Heart and Circulatory Physiology, 1996

With the use of[11C]acetate, positron emission tomography (PET) permits exploration of myocardial... more 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...

Imaging Dopamine and Serotonin Systems on MPTP Monkeys: A Longitudinal PET Investigation of Compensatory Mechanisms

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 3, 2016

It is now widely accepted that compensatory mechanisms are involved during the early phase of Par... more It is now widely accepted that compensatory mechanisms are involved during the early phase of Parkinson's disease (PD) to delay the expression of motor symptoms. However, the neurochemical mechanisms underlying this presymptomatic period are still unclear. Here, we measured in vivo longitudinal changes of both the dopaminergic and serotonergic systems in seven asymptomatic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated monkeys (when motor symptoms are less apparent) using PET. We used the progressively MPTP-intoxicated monkey model that expresses recovery from motor symptoms to study the changes in dopamine synthesis ([(18)F]DOPA), dopamine D2/D3 receptors ([(11)C]raclopride), and serotonin transporter (11)C-N,N-dimethyl-2-(-2-amino-4-cyanophenylthio) benzylamine ([(11)C]DASB) and serotonin 1A receptor ([(18)F]MPPF) levels between four different states (baseline, early symptomatic, full symptomatic and recovered). During the early symptomatic state, we observed ...

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A 18F-MPPF PET normative database of 5-HT1A receptor binding in men and women over aging

Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2005

Neurotransmission imaging studies require normative data for the statistical assessment of neurop... more Neurotransmission imaging studies require normative data for the statistical assessment of neurophysiologic dysfunctions. 2'-Methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine (18F-MPPF) is a specific serotonin 5-HT1A antagonist PET tracer recently characterized, modeled, and used for clinical research to explore abnormalities in the serotoninergic system. Our study reports, to our knowledge, the first large normative imaging database of 18F-MPPF binding potential (BP) over aging, for both males and females. Fifty-three healthy volunteers (27 females, 26 males; age, 20-70 y) were selected to undergo structural MRI and single-injection 18F-MPPF multiframe dynamic PET. 18F-MPPF BP values were computed using a nonlinear modeling method with tissue reference. The statistical assessment of the effect of age and sex was performed both at the anatomic structure level, using regions of interest drawn manually on individual MR images, and at the voxel level, using n...

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Quantitative assessment of regional alveolar ventilation and gas volume using 13N-N2 washout and PET

Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2005

Measurement of alveolar volume (Va) and regional ventilation (a) is crucial to understanding the ... more Measurement of alveolar volume (Va) and regional ventilation (a) is crucial to understanding the pathophysiology of acute lung injury and ventilator-induced lung injury. PET has previously been used as a noninvasive, quantitative method to assess a, but formal validation of this technique in experimental lung injury is lacking. This study aims to validate Va and a regional assessment with PET, using inhaled (13)N-N(2) in pigs. Two normal and 2 oleic acid-injured pigs were tracheotomized, mechanically ventilated, and studied in 5 different levels of ventilation by changing respiratory rate. In each experimental condition, lungs were washed-in and then washed-out with (13)N-N(2) through an open circuit in the ventilator. Using this method, multiframe images were acquired with a dedicated PET camera. Regions of interest (ROIs) were drawn on each lung. Regional time-activity curves during washout were generated for each ROI and fitted to a mono- and a bicompartmental model. Validation o...

format_quoteLung density significantly increased in injured pigs (0.72 g/mL) compared to controls (0.59 g/mL), especially in affected dorsal regions.format_quote

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Comparison of PET with radioactive microspheres to assess pulmonary blood flow

Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2002

Microsphere technique is the reference for assessment of pulmonary blood flow (PBF) but is destru... more Microsphere technique is the reference for assessment of pulmonary blood flow (PBF) but is destructive; PET, however, can determine PBF noninvasively. Comparisons of these 2 methods are scanty. Our study aimed at comparing these 2 techniques using a mathematic model taking into account the right ventricle in determining the transit time of a tracer through lung tissue. Ten normal pigs were investigated at baseline, during dobutamine infusion, and during 10 cm H(2)O of positive end-expiratory pressure. Under each condition, PBF was successively measured with PET (PET-PBF) and radioactive microspheres (MS-PBF). For PET-PBF, 2 mCi (74 MBq) (15)O-labeled water were injected intravenously over 20 s and PET scanning was performed for 10 min. The input function was determined noninvasively from PET and invasively from mixed venous blood withdrawals. PET-PBF was computed using a mathematic model taking into account the right ventricle in determining the transit time of the tracer through lu...

format_quoteSignificant correlation (r = 0.79, P < 0.001) found between invasive and noninvasive assessments of PBF using a mathematical model.format_quote

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A PET Monte Carlo simulator from numerical phantom: validation against the EXACT ECAT HR+ scanner

1999 IEEE Nuclear Science Symposium. Conference Record. 1999 Nuclear Science Symposium and Medical Imaging Conference (Cat. No.99CH37019)

The authors have developed a Monte Carlo simulator that uses realistic phantoms defined by the me... more The authors have developed a Monte Carlo simulator that uses realistic phantoms defined by the mean of 3D arrays. One array represents the spatial distribution of the tracer while another defines the attenuating media locations. The simulator allows the user to set the scanner geometric configuration and the acquisitions parameters. Also, effects that degrade the images which are taken into

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

Pain, 2000

Parietal, insular and anterior cingulate cortices are involved in the processing of noxious input... more 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 nonnoxious stimulation.

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Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study

Pain, 1999

Although electrical stimulation of the precentral gyrus (MCS) is emerging as a promising techniqu... more Although electrical stimulation of the precentral gyrus (MCS) is emerging as a promising technique for pain control, its mechanisms of action remain obscure, and its application largely empirical. Using positron emission tomography (PET) we studied regional changes in cerebral¯ood¯ow (rCBF) in 10 patients undergoing motor cortex stimulation for pain control, seven of whom also underwent somatosensory evoked potentials and nociceptive spinal re¯ex recordings. The most signi®cant MCS-related increase in rCBF concerned the ventrallateral thalamus, probably re¯ecting cortico-thalamic connections from motor areas. CBF increases were also observed in medial thalamus, anterior cingulate/orbitofrontal cortex, anterior insula and upper brainstem; conversely, no signi®cant CBF changes appeared in motor areas beneath the stimulating electrode. Somatosensory evoked potentials from SI remained stable during MCS, and no rCBF changes were observed in somatosensory cortex during the procedure. Our results suggest that descending axons, rather than apical dendrites, are primarily activated by MCS, and highlight the thalamus as the key structure mediating functional MCS effects. A model of MCS action is proposed, whereby activation of thalamic nuclei directly connected with motor and premotor cortices would entail a cascade of synaptic events in painrelated structures receiving afferents from these nuclei, including the medial thalamus, anterior cingulate and upper brainstem. MCS could in¯uence the affective-emotional component of chronic pain by way of cingulate/orbitofrontal activation, and lead to descending inhibition of pain impulses by activation of the brainstem, also suggested by attenuation of spinal¯exion re¯exes. In contrast, the hypothesis of somatosensory cortex activation by MCS could not be con®rmed by our results.

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Double dissociation in neural correlates of visual working memory: A PET study

Cognitive Brain Research, 2005

Using positron emission tomography (PET), we investigated the organisation of spatial versus obje... more Using positron emission tomography (PET), we investigated the organisation of spatial versus object-based visual working memory in 11 normal human subjects. The paradigm involved a conditional colour-response association task embedded within two visual working memory tasks. The subject had to remember a position (spatial) or shape (object-based) and then use this to recover the colour of the matching element for the conditional association. Activation of the nucleus accumbens and the anterior cingulate cortex was observed during the conditional associative task, indicating a possible role of these limbic structures in associative memory. When the 2 memory tasks were contrasted, we observed activation of 2 distinct cortical networks: (1) The spatial task activated a dorsal stream network distributed in the right hemisphere in the parieto-occipital cortex and the dorsal prefrontal cortex, and (2) The non spatial task activated a ventral stream network distributed in the left hemisphere in the temporo-occipital cortex, the ventral prefrontal cortex and the striatum. These results support the existence of a domain-specific dissociation with dorsal and ventral cortical systems involved respectively in spatial and non spatial working memory functions.

format_quoteA significant task effect was found in error rates between NSPA and other tasks, indicating task-dependent cognitive load differences.format_quote

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Neural substrates of levodopa-responsive gait disorders and freezing in advanced Parkinson's disease: A kinesthetic imagery approach

Human Brain Mapping, 2014

Gait disturbances, including freezing of gait, are frequent and disabling symptoms of Parkinson's... more Gait disturbances, including freezing of gait, are frequent and disabling symptoms of Parkinson's disease. They often respond poorly to dopaminergic treatments. Although recent studies have shed some light on their neural correlates, their modulation by dopaminergic treatment remains quite unknown. Specifically, the influence of levodopa on the networks involved in motor imagery (MI) of parkinsonian gait has not been directly studied, comparing the off and on medication states in the same patients. We therefore conducted an [H 2 15 0] Positron emission tomography study in eight advanced parkinsonian patients (mean disease duration: 12.3 6 3.8 years) presenting with levodoparesponsive gait disorders and FoG, and eight age-matched healthy subjects. All participants performed three tasks (MI of gait, visual imagery and a control task). Patients were tested off, after an overnight withdrawal of all antiparkinsonian treatment, and on medication, during consecutive mornings. The order of conditions was counterbalanced between subjects and sessions. Results showed that imagined gait elicited activations within motor and frontal associative areas, thalamus, basal ganglia and

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Effect of sensory stimulus on striatal dopamine release in humans and cats: a [11C]raclopride PET study

Neuroscience Letters, 2004

Background : Sensory stimulation of the forelimb extremities constitutes a well-established exper... more Background : Sensory stimulation of the forelimb extremities constitutes a well-established experimental model that has consistently shown to activate dopamine (DA) neurotransmission in the mammals' forebrain. Objectives : To visualize in vivo this modification of striatal DA release in healthy human volunteers using Positron Emission Tomography (PET) and [ 11 C]raclopride. Experiments in humans were paralled by experiments in anesthetized cats. Changes in endogenous DA release were assessed through its competition with [ 11 C]raclopride binding (BP raclo), a radioligand probing DA D2-receptors. Results : In humans no significant difference of BP raclo in caudate (with sensory stimulation: 2.0 ± 0.3 versus without sensory stimulation: 2.2 ± 0.3; P = 0.3) or putamen (2.6 ± 0.3 versus 2.6 ± 0.2; P = 0.9) ipsilateral to the stimulus was disclosed as a result of sensory stimulation. Similarly, no change of BP raclo was observed contralaterally to the stimulation in the caudate nucleus (with sensory stimulation: 2.0 ± 0.4 versus without sensory stimulation: 2.1 ± 0.2; P = 0.5) and the putamen (2.5 ± 0.4 versus 2.6 ± 0.2; P = 0.4). In cats the same results were obtained in the ipsilateral to stimulation striatum (with sensory stimulation: 2.5 ± 0.03 versus without sensory stimulation: 2.4 ± 0.05; P = 0.7). No change was also observed contralaterally to the stimulation (2.4 ± 0.04 versus 2.5 ± 0.06; P = 0.6). The [ 11 C]raclopride binding remained unchanged by sensory stimuli in both humans and cats. Conclusion : This suggests that the DA release induced by sensory stimulus is mostly extrasynaptic whereas the synaptic DA release is probably small, which fits well with the absence of [ 11 C]raclopride displacement. The mechanism of this extrasynaptic DA release could be related to a local action of glutamate on dopaminergic terminals via a thalamo-cortico-striatal loop. Present results also underline homology between cat and human responses to sensory stimuli and validate the use of cat brain to find physiological concepts in humans.

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

Neuroscience Letters, 1998

Regional brain protein synthesis was evaluated with positron emission tomography (PET) and L-(S-[... more Regional brain protein synthesis was evaluated with positron emission tomography (PET) and L-(S-[ 11 C]methyl)methionine ([ 11 C]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 Ͻ 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.

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A multi-atlas based method for automated anatomical Macaca fascicularis brain MRI segmentation and PET kinetic extraction

NeuroImage, 2013

MRI templates and digital atlases are needed for automated and reproducible quantitative analysis... more MRI templates and digital atlases are needed for automated and reproducible quantitative analysis of non-human primate PET studies. Segmenting brain images via multiple atlases outperforms single-atlas labelling in humans. We present a set of atlases manually delineated on brain MRI scans of the monkey Macaca fascicularis. We use this multi-atlas dataset to evaluate two automated methods in terms of accuracy, robustness and reliability in segmenting brain structures on MRI and extracting regional PET measures. Methods: Twelve individual Macaca fascicularis high-resolution 3DT1 MR images were acquired. Four individual atlases were created by manually drawing 42 anatomical structures, including cortical and sub-cortical structures, white matter regions, and ventricles. To create the MRI template, we first chose one MRI to define a reference space, and then performed a two-step iterative procedure: affine registration of individual MRIs to the reference MRI, followed by averaging of the twelve resampled MRIs. Automated segmentation in native space was obtained in two ways: 1) Maximum probability atlases were created by decision fusion of two to four individual atlases in the reference space, and transformation back into the individual native space (MAXPROB). 2) One to four individual atlases were registered directly to the individual native space, and combined by decision fusion (PROPAG). Accuracy was evaluated by computing the Dice similarity index and the volume difference. The robustness and reproducibility of PET regional measurements obtained via automated segmentation was evaluated on four co-registered MRI/PET datasets, which included test-retest data. Results: Dice indices were always over 0.7 and reached maximal values of 0.9 for PROPAG with all four individual atlases. There was no significant mean volume bias. The standard deviation of the bias decreased significantly when increasing the number of individual atlases. MAXPROB performed better when increasing the number of atlases used. When all four atlases were used for the MAXPROB creation, the accuracy of morphometric segmentation approached that of the PROPAG method. PET measures extracted either via automatic methods or via the manually defined regions were strongly correlated, with no significant regional differences between methods. Intra-class correlation coefficients for test-retest data were over 0.87. Conclusions: Compared to single atlas extractions, multi-atlas methods improve the accuracy of region definition. They also perform comparably to manually defined regions for PET quantification. Multiple atlases of Macaca fascicularis brains are now available and allow reproducible and simplified analyses.

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Functional anatomy of motor urgency

NeuroImage, 2007

This PET H 2 15 O study uses a reaching task to determine the neural basis of the unconscious mot... more This PET H 2 15 O study uses a reaching task to determine the neural basis of the unconscious motor speed up observed in the context of urgency in healthy subjects. Three conditions were considered: selfinitiated (produce the fastest possible movement toward a large plate, when ready), externally-cued (same as self-initiated but in response to an acoustic cue) and temporally-pressing (same as externally-cued with the plate controlling an electromagnet that prevented a rolling ball from falling at the bottom of a tilted ramp). Results show that: (1) Urgent responses (Temporally-pressing versus Externally-cued) engage the left parasagittal and lateral cerebellar hemisphere and the sensorimotor cortex (SMC) bilaterally; (2) Externally-driven responses (Externally-cued versus Self-initiated) recruit executive areas within the contralateral SMC; (3) Volitional responses (Self-initiated versus Externally-cued) involve prefrontal cortical areas. These observations are discussed with respect to the idea that neuromuscular energy is set to a submaximal threshold in selfdetermined situations. In more challenging tasks, this threshold is raised and the first answer of the nervous system is to optimize the response of the lateral (i.e. crossed) corticospinal tract (contralateral SMC) and ipsilateral cerebellum. In a second step, the anterior (i.e. uncrossed) corticospinal tract (ipsilateral SMC) and the contralateral cerebellum are recruited. This recruitment is akin to the strategy observed during recovery in patients with brain lesions.

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Association between triallelic polymorphism of the serotonin transporter and [18F]MPPF binding potential at 5-HT1A receptors in healthy subjects

NeuroImage, 2009

Previous [ 11 C]WAY100-635 PET studies have demonstrated that the short (S) and long (L) alleles ... more Previous [ 11 C]WAY100-635 PET studies have demonstrated that the short (S) and long (L) alleles of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) were associated with distinct patterns of 5-HT 1A receptor distribution in human. However, these studies reported discordant findings and did not take into account the recent description of two functional variants of the L allele (L A /L G). To further explore this issue, we investigated the triallelic functional polymorphism of the 5-HTTLPR in 38 healthy volunteers who underwent a [ 18 F]MPPF PET study of 5-HT1A receptors. We used a simplified reference tissue model to generate parametric images of [ 18 F]MPPF binding potential (BP ND), and compared these data among the different genotypes using statistical parametric mapping and region of interest of the raphe nuclei. Homozygote carriers of the S allele demonstrated greater [ 18 F]MPPF BP ND than carriers of the L A allele, but this association was only found in women. Differences in [ 18 F]MPPF BP ND between women with and without L A allele were observed over large clusters encompassing the right and left temporal lobes, cingulate and perisylvian regions, as well as the right precuneus and frontal dorso-lateral cortex, and the left orbitofrontal cortex. In contrast, no difference was found between groups in the raphe nuclei. The greater [ 18 F]MPPF BP ND observed in women homozygote carriers of the S allele could either reflect a greater 5-HT1A receptor density or a lower extracellular concentration of 5-HT. Our data suggest that any future PET studies of 5-HT1A receptors should incorporate the 5-HTTLPR polymorphism status of the population studied.

format_quoteSignificant association found between 5-HTTLPR polymorphism and [18F]MPPF BP ND, primarily in women, showing greater binding in S/S genotype.format_quote

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Test Retest Reproducibility of 18F-MPPF PET in Healthy Humans: A Reliability Study

Journal of Nuclear Medicine, 2007

The aim of this study was to assess the reliability of 29-methoxyphenyl-(N-29-pyridinyl)-p-18 F-f... more The aim of this study was to assess the reliability of 29-methoxyphenyl-(N-29-pyridinyl)-p-18 F-fluoro-benzamidoethylpiperazine (18 F-MPPF) PET binding parameter's quantification via a testretest study over a long-term period. Methods: Ten healthy volunteers underwent 2 dynamic 18 F-MPPF PET scans in an interval of 6 mo. As a methodologic control, 10 simulated datasets, including interindividual functional and anatomic variabilities, were also used to assess the measurement variations in the absence of intraindividual variability. Indices of tracer binding were computed using 2 different models: (a) the simplified reference tissue model (SRTM) and (b) the Logan graphical model. The SRTM allows computing the binding potential (BP) index and plasma-to-brain transport constants (R 1 , k 2). The Logan model evaluates the distribution volume (DV). For both methods, cerebellum was taken as the reference region. From both models, binding indices were calculated with time-activity curves extracted from regions of interest, on one hand, and for each voxel to perform parametric images on the other hand. Results: Reliability indices-that is, bias, variability, and intraclass correlation (ICC)-indicated a good reproducibility: the BP percentage change in mean between test and retest is close to 1% in rich regions and 2% in poor regions. The typical error is around 7%. Mean ICC is over 0.70. The DV percentage change in the mean is 62.5%, with a typical error close to 6% and an ICC over 0.60. Conclusion: Our results show a good reliability, with a reasonable level of intraindividual biologic variability that allows crossover studies with 18 F-MPPF in which small percentage changes are expected between test and retest measurements, in group studies and for single subject assessment.

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Noninvasive Quantitative Assessment of Pulmonary Blood Flow with 18F-FDG PET

Journal of Nuclear Medicine, 2013

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Functional Anatomy of Perceptual and Semantic Processing for Odors

Journal of Cognitive Neuroscience, 1999

The functional anatomy of perceptual and semantic processings for odors was studied using positro... more The functional anatomy of perceptual and semantic processings for odors was studied using positron emission tomography (PET). The first experiment was a pretest in which 71 normal subjects were asked to rate 185 odorants in terms of intensity, familiarity, hedonicity, and comestibility and to name the odorants. This pretest was necessary to select the most appropriate stimuli for the different cognitive tasks of the second experiment. The second one was a PET experiment in which 15 normal subjects were scanned using the water bolus method to measure regional cerebral blood flow (rCBF) during the performance in three conditions. In the first (perceptual) condition, subjects were asked to judge whether an odor was familiar or not. In the second (semantic) condition, subjects had to decide whether an odor corresponded to a comestible item or not. In the third (detection) condition, subjects had to judge whether the perceived stimulus was made of an odor or was just air. It was hypothet...

Modeling [18F]MPPF Positron Emission Tomography Kinetics for the Determination of 5-Hydroxytryptamine(1A) Receptor Concentration with Multiinjection

Journal of Cerebral Blood Flow & Metabolism, 2002

The selectivity of [18F]MPPF (fluorine-18-labeled 4-(2' -methoxyphenyl)-1-[2' -(N-2“-piry... more The selectivity of [18F]MPPF (fluorine-18-labeled 4-(2' -methoxyphenyl)-1-[2' -(N-2“-pirydynyl)-p-fluorobenzamido]ethylpiperazine) for serotonergic 5-hydroxytryptamine(1A) (5-HT1A) receptors has been established in animals and humans. The authors quantified the parameters of ligand-receptor exchanges using a double-injection protocol. After injection of a tracer and a coinjection dose of [18F]MPPF, dynamic positron emission tomography (PET) data were acquired during a 160-minute session in five healthy males. These PET and magnetic resonance imaging data were coregistered for anatomical identification. A three-compartment model was used to determine six parameters: Fv (vascular fraction), K1, k2 (plasma/free compartment exchange rate), koff, kon/Vr (association and dissociation rate), Bmax (receptor concentration), and to deduce Kd (apparent equilibrium dissociation rate). The model was fitted with regional PET kinetics and arterial input function corrected for metabolites. ...

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Effect of activated protein C on pulmonary blood flow and cytokine production in experimental acute lung injury

Intensive Care Medicine, 2007

In acute lung injury (ALI) activated protein C (APC) may reopen occluded lung vessels and minimiz... more In acute lung injury (ALI) activated protein C (APC) may reopen occluded lung vessels and minimize lung inflammation. We aimed at assessing the effect of APC on regional lung perfusion, aerated lung volume, cytokine production and oxygenation in experimental ALI. Prospective, controlled study in an imaging facility. Pigs tracheotomized and mechanically ventilated. Pigs were randomly given intravenously APC (n = 8) or saline (n = 8). Thirty minutes later, ALI was induced by injecting oleic acid. Lung perfusion and aerated lung volume measured with positron emission tomography, plasma cytokines and arterial blood gas were determined just before ALI and 110 and 290 min thereafter. Lung cytokines were measured at the end of the experiment. PaO2 under F I O2 1 was significantly lower in the APC group before lung injury (473+/-129 vs. 578+/-54 mmHg) and 110 min (342+/-138 vs. 446+/-103 mmHg) and 290 min (303+/-171 vs. 547+/-54 mmHg) thereafter (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Lung perfusion nonsignificantly tended to redistribute towards dorsal lung regions with APC. Total aerated lung volume was not different between APC and control before ALI (10.0+/-1.5 vs. 11.0+/-2.5 ml/kg) (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05) or thereafter. Plasma IL-6 and IL-8 at 110 min were greater with APC (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). In contrast to studies using other models, pretreatment with APC was associated with worsening oxygenation in the present investigation. This might be due to ventilation-perfusion mismatch, with more perfusion to dependent nonaerated areas.

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