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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRo(2)) are major determinants of the contrast in functional magnetic resonance imaging and optical imaging. However, the coupling between CBF and CMRo(2) during cerebral activation remains controversial. Whereas most of the previous models tend to show a nonlinear coupling, experimental studies have led to conflicting conclusions. A physiologic model was developed of oxygen transport through the blood-brain barrier (BBB) for dynamic and stationary states. Common model simplifications are proposed and their implications for the CBF/CMRo(2) relation are studied. The tissue oxygen pool, the BBB permeability, and the hemoglobin dissociation curve are physiologic parameters directly involved in the CBF/CMRo(2) relation. We have been shown that the hypothesis of a negligible tissue oxygen pool, which was admitted by most of the previous models, implies a tight coupling between CBF and CMRo(2). By relaxing this hypothesis, a real uncoupling was allowed that gives a more coherent view of the CBF/CMRo(2) relation, in better agreement with the hypercapnia data and with the variability reported in experimental works for the relative changes of those two variables. This also allows a temporal mismatch between CBF and CMRo(2), which influences the temporal shape of oxygenation at the capillary end.
J Cereb Blood Flow Metab 2003 May
PMID:Relation between cerebral blood flow and metabolism explained by a model of oxygen exchange. 1277 68

Recent blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging studies have shown a reduction of cerebral activation during aging, which may be associated with age-related changes of the cerebral vascular system. The authors used a global hypercapnic breath-holding challenge to define nonneuronal contributions to a significantly reduced activation in the primary sensorimotor cortex during finger tapping in a group of old (n = 6; mean age 65 years) compared with a group of young (n = 6; mean age 27 years) subjects. Within significantly activated voxels in both groups during finger tapping, the mean BOLD signal amplitudes were significantly smaller in the group of older subjects for both tasks. In those voxels showing significant activation only in young subjects during finger tapping, the response to hypercapnia was also greatly diminished in older subjects. The attenuated hypercapnic BOLD signal response in older subjects within this region suggests that age-dependent changes of the cerebral vasculature may alter the neuronal-vascular coupling. In older subjects, cerebral vessels may not react as effectively in response to a vasodilating stimulus, which will lead to differences in the number of voxels that pass a criterion threshold despite similar neuronal activation.
J Cereb Blood Flow Metab 2003 May
PMID:Relation between regional functional MRI activation and vascular reactivity to carbon dioxide during normal aging. 1277 71

Hypercapnia induces cerebral vasodilation and increases cerebral blood flow (CBF), and hypocapnia induces cerebral vasoconstriction and decreases CBF. The relation between changes in CBF and cerebral blood volume (CBV) during hypercapnia and hypocapnia in humans, however, is not clear. Both CBF and CBV were measured at rest and during hypercapnia and hypocapnia in nine healthy subjects by positron emission tomography. The vascular responses to hypercapnia in terms of CBF and CBV were 6.0 +/- 2.6%/mm Hg and 1.8 +/- 1.3%/mm Hg, respectively, and those to hypocapnia were -3.5 +/- 0.6%/mm Hg and -1.3 +/- 1.0%/mm Hg, respectively. The relation between CBF and CBV was CBV = 1.09 CBF0.29. The increase in CBF was greater than that in CBV during hypercapnia, indicating an increase in vascular blood velocity. The degree of decrease in CBF during hypocapnia was greater than that in CBV, indicating a decrease in vascular blood velocity. The relation between changes in CBF and CBV during hypercapnia was similar to that during neural activation; however, the relation during hypocapnia was different from that during neural deactivation observed in crossed cerebellar diaschisis. This suggests that augmentation of CBF and CBV might be governed by a similar microcirculatory mechanism between neural activation and hypercapnia, but diminution of CBF and CBV might be governed by a different mechanism between neural deactivation and hypocapnia.
J Cereb Blood Flow Metab 2003 Jun
PMID:Changes in human cerebral blood flow and cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography. 1279 14

Albeit controversial, it has been suggested by several authors that nitric oxide (NO) serves as a permissive factor in the cerebral blood flow response to systemic hypercapnia. Potassium channels are important regulators of cerebrovascular tone and may be modulated by a basal perivascular NO level. To elucidate the functional targets of the proposed NO modulation during hypercapnia-induced vasodilation, the authors performed experiments in isolated, cannulated, and pressurized rat middle cerebral arteries (MCA). Extracellular pH was reduced from 7.4 to 7.0 in the extraluminal bath to induce NO dependent vasodilation. Acidosis increased vessel diameter by 35 +/- 10%. In separate experiments, ATP-sensitive potassium channels (KATP) were blocked by extraluminal application of glibenclamide (Glib), Ca2+-activated potassium channels (KCa) by tetraethylammonium (TEA), voltage-gated potassium channels (Kv) by 4-aminopyridine, and inward rectifier potassium channels (KIR) by BaCl2. Na+-K+-ATP-ase was inhibited by ouabain. Application of TEA slightly constricted the arteries at pH 7.4 and slightly but significantly attenuated the vasodilation to acidosis. Inhibition of the other potassium channels or Na+-K+-ATP-ase had no effect. Combined blockade of KATP and KCa channels further reduced resting diameter, and abolished acidosis induced vasodilation. The authors conclude that mainly KCa channels are active under resting conditions. KATP and KCa channels are responsible for vasodilation to acidosis. Activity of one of these potassium channel families is sufficient for vasodilation to acidosis, and only combined inhibition completely abolishes vasodilation. During NO synthase inhibition, dilation to the KATP channel opener pinacidil or the KCa channel opener NS1619 was attenuated or abolished, respectively. The authors suggest that a basal perivascular NO level is necessary for physiologic KATP and KCa channel function in rat MCA. Future studies have to elucidate whether this NO dependent effect on KATP and KCa channel function is a principle mechanism of NO induced modulation of cerebrovascular reactivity and whether the variability of findings in the literature concerning a modulatory role of NO can be explained by different levels of vascular NO/cGMP concentrations within the cerebrovascular tree.
J Cereb Blood Flow Metab 2003 Oct
PMID:Cerebrovascular vasodilation to extraluminal acidosis occurs via combined activation of ATP-sensitive and Ca2+-activated potassium channels. 1452 33

The functional consequences of increased capillary densities in the brain resulting from vascular endothelial growth factor (VEGF165) overexpression are unknown. Therefore, the authors measured local CBF using the iodo-[14C]antipyrine technique in transgenic mice expressing brain-specifically sixfold higher VEGF165 levels and in nontransgenic littermates. To reveal possible compensatory vasoconstriction, CBF was also measured during severe hypercapnia (Paco2 > 130 mm Hg). Simultaneously, local capillary density, perfusion state, and blood-brain-barrier permeability were assessed. Using the 2-[14C]deoxyglucose method, metabolic effects of VEGF over-expression could be excluded. In transgenic mice all capillaries showed normal morphology and a tight blood-brain barrier. However, 3% nonperfused capillaries in some brain structures indicate ongoing angiogenesis. Capillary density was drastically increased in transgenic mice in white matter structures (70% to 185%), the dentate gyrus (143%), and caudate nucleus (86%). In all other brain structures investigated, capillary densities were moderately increased by approximately 20%. Normocapnic CBF did not differ between transgenic and nontransgenic mice. During maximal hypercapnic vasodilation, CBF was 20% to 30% higher in transgenic mice, although only in brain structures where capillary density was increased more than twofold. These findings suggest that attenuated CBF in transgenic mice during normocapnia is only partly due to a compensatory vasoconstriction, and that microvascular networks in transgenic brains might be ineffectively constructed.
J Cereb Blood Flow Metab 2004 Aug
PMID:Massive inborn angiogenesis in the brain scarcely raises cerebral blood flow. 1536 15

Traumatic brain injury (TBI) is frequently accompanied by a systemic inflammatory response secondary to multiple trauma, shock, or infections. This study investigated the impact of sustained systemic inflammation on cerebral hemodynamics and metabolism in ovine traumatic brain injury. Fifteen sheep were investigated for 14 hours. Head injury was induced with a nonpenetrating stunner in anesthetized, ventilated animals. One group (TBI/Endo, n = 6) subsequently received a continuous endotoxin infusion for 12 hours, whereas a second group (TBI, n = 6) received the carrier. Three instrumented animals served as sham controls. Head impact significantly increased intracranial pressure from 9 +/- 4 mm Hg to 21 +/- 15 mm Hg (TBI/Endo) and from 10 +/- 3 mm Hg to 24 +/- 19 mm Hg (TBI) (means +/- SD). Internal carotid blood flow increased and cerebral vascular resistance decreased (P < 0.05) during the hyperdynamic inflammatory response between 10 and 14 hours in the TBI/Endo group, whereas these parameters were at baseline level in the TBI group. Intracranial pressure remained unchanged during this period, but increased during hypercapnia. The CMRO2, PaCO2, and arterial hematocrit values were identical among the groups between 10 and 14 hours. It is concluded that chronic endotoxemia in ovine traumatic brain injury was associated with cerebral vasodilation uncoupled from global brain metabolism. Different mechanisms appear to induce cerebral vasodilation in response to inflammation and hypercapnia.
J Cereb Blood Flow Metab 2004 Dec
PMID:Cerebral vascular and metabolic response to sustained systemic inflammation in ovine traumatic brain injury. 1562 14

Hypercapnia induces cerebral vasodilation and increases cerebral blood volume (CBV), and hypocapnia induces cerebral vasoconstriction and decreases CBV. Cerebral blood volume measured by positron emission tomography (PET) is the sum of three components, that is, arterial, capillary, and venous blood volumes. Changes in arterial blood volume (V(a)) and CBV during hypercapnia and hypocapnia were investigated in humans using PET with H(2)(15)O and (11)CO. Arterial blood volume was determined from H(2)(15)O PET data by means of a two-compartment model that takes V(a) into account. Baseline CBV and values during hypercapnia and hypocapnia in the cerebral cortex were 0.034+/-0.003, 0.038+/-0.003, and 0.031+/-0.003 mL/mL (mean+/-s.d.), respectively. Baseline V(a) and values during hypercapnia and hypocapnia were 0.015+/-0.003, 0.025+/-0.011, and 0.007+/-0.003 mL/mL, respectively. Cerebral blood volume changed significantly owing to changes in PaCO(2), and V(a) changed significantly in the direction of CBV changes. However, no significant change was observed in venous plus capillary blood volume (=CBV-V(a)). This indicates that changes in CBV during hypercapnia and hypocapnia are caused by changes in arterial blood volume without changes in venous and capillary blood volume.
J Cereb Blood Flow Metab 2005 Jul
PMID:Changes in the arterial fraction of human cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography. 1571 51

The association between recovery of brain function and behavior after transient cerebral ischemia in animals and humans is incompletely characterized. Quantitative diffusion- (DWI), perfusion- (PWI), T(2)-weighted (T(2)WI), and functional magnetic resonance imaging (fMRI) were performed before, during, and up to 1 day after 20-mins transient middle cerebral artery occlusion (tMCAO; n=6) or sham operation (n=6) in male Sprague-Dawley rats. Viability thresholds were employed to calculate diffusion, perfusion, and T(2) lesion volumes. Region of interest analysis was used to evaluate structural and functional MR signal changes within the sensorimotor network, which were then related to corresponding behavioral measures. Post-mortem 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed 24 h after ischemia. Transient middle cerebral artery occlusion produced lesions on DWI and PWI, which fully recovered by 30 mins after reperfusion. Ipsilesional fMRI responses to hypercapnia and forepaw stimulation were significantly impaired after ischemia and did not fully normalize until 3 and 24 h after tMCAO, respectively. No abnormalities were observed on imaging or TTC at 24 h despite significant behavioral dysfunctions including contralesional forelimb impairment and ipsilesional neglect. No MRI, behavioral, or TTC anomalies were observed in sham-operated rats. There were no significant correlations between MRI parameters, behavior, and TTC in either group. Together, these results suggest that normal findings on diffusion, perfusion, and T(2) imaging shortly after transient ischemia may not indicate normal tissue status as indicated by fMRI and behavior, which may help explain the persistence of neurologic deficits in patients with normal conventional MRI after cerebral ischemia.
J Cereb Blood Flow Metab 2006 Nov
PMID:Differential recovery of multimodal MRI and behavior after transient focal cerebral ischemia in rats. 1653 30

Opioid binding to the cerebral blood vessels may affect vascular responsiveness and hence confound interpretation of blood oxygen level-dependent (BOLD) responses, which are usually interpreted as neuronal in origin. Opioid binding varies in different brain regions. It is unclear whether opioids alter neurovascular coupling, or whether their effects are purely neuronal. This study used BOLD functional magnetic resonance imaging (FMRI) to investigate the effect of a mu-opioid agonist remifentanil, on cerebrovascular CO(2) reactivity (being one component of neurovascular coupling). Hypercapnic challenges were delivered to human volunteers, while controlling potential opioid-induced respiratory depression. The BOLD signal increase to hypercapnia was compared before and during remifentanil administration. Remifentanil was shown not to have a generalised effect on CO(2) responsiveness in the cerebral vasculature. However, it caused a significant reduction in the positive BOLD response to hypercapnia in the bilateral primary sensorimotor cortices, bilateral extrastriate visual areas, left insula, left caudate nucleus, and left inferior temporal gyrus. We conclude that remifentanil does not modulate cerebrovascular CO(2) reactivity, as we saw no difference in BOLD response to hypercapnia in areas with high opioid receptor densities. We did however see a focal reduction in areas related to motor control and putative task activation, which we conclude to be related to changes in neuronal activity related to the sedative effects of remifentanil. Our method of controlling CO(2) levels effectively mitigated the potential confound of respiratory depression and allowed comparison over a similar range of CO(2) levels. We suggest that similar methodology should be used when investigating other potentially vasoactive compounds with FMRI.
J Cereb Blood Flow Metab 2007 Feb
PMID:Pharmacological FMRI: measuring opioid effects on the BOLD response to hypercapnia. 1673 39

This paper describes a new rapid steady-state T(1) (RSST(1)) method for mapping the cerebral blood volume fraction (CBVf) by magnetic resonance imaging (MRI). The principle is based on a two-compartment model of the brain (intra- and extravascular), and the effects of paramagnetic contrast agents on the intravascular longitudinal relaxation time T(1). Using appropriate parameters, an Inversion-Recovery-Fast-Low-Angle-Shot sequence acts like a low pass T(1) filter, suppressing signals from tissues with T(1)>>TR (TR=repetition time). It was shown in vivo that, exceeding a particular contrast agent dose, the signal reaches its maximum (corresponding to the intravascular equilibrium magnetization), and is maintained for a duration related to the dose. Acquisitions during this steady state divided by an additional measure of the overall (intra- and extravascular) magnetization at thermal equilibrium provides the CBVf. Experiments were performed on healthy rats at 2.35 T using P760 (Gd(3+)-compound from Guerbet Laboratories) and Gd-DOTA. Because of its high longitudinal relaxivity, P760 is more convenient, and was used to show the feasibility of the method. The CBVf in different structures of the rat brain was compared. The average CBVf for the whole brain slice is 3.29%+/-0.69% (n=15). The influence of transendothelial water exchange was quantified and transversal relaxation effects were found negligible in microvasculature. Finally, the sensitivity of the method to CBVf increases under hypercapnia was evaluated (1%/mm Hg PaCO(2)), demonstrating its potential for longitudinal studies and functional MRI. Clinical applications are feasible since equivalent results were obtained with Gd-DOTA.
J Cereb Blood Flow Metab 2007 Mar
PMID:A new Magnetic Resonance Imaging method for mapping the cerebral blood volume fraction: the rapid steady-state T1 method. 1685 31


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