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

Activation of CBF by hypercapnia or functional stimulation has been attributed to multiple mediators, most of which are thought to interfere with cerebrovascular reactivity in a closely time-related manner. Here we describe that brief hypercapnia produces marked up-regulation of somatosensory activation of blood flow that outlasts carbon dioxide exposure for at least 60 min. In chloralose-anesthetized, mechanically ventilated rats, somatosensory activation was carried out by electrical stimulation of the forepaw. Blood flow was measured in the contralateral primary somatosensory cortex by laser-Doppler flowmetry (LDF). Under control conditions, somatosensory stimulation increased LDF by 38.8 +/- 11.0%. Ventilation with 6% CO2 for 3 min caused a rise of LDF by 28.0 +/- 8.7%. Baseline CBF and PaCo2 returned to control values within 20 min. Repetition of somatosensory stimulation after hypercapnia revealed a long-lasting up-regulation of the flow response: 25 min after hypercapnia, functional stimulation increased LDF by 86.0 +/- 18.1%, and 60 min after hypercapnia even by 96.0 +/- 26.0%. This is the first demonstration of CO2-induced up-regulation of functional activation of blood flow and an example of the importance of general physiological variables for the modulation of the coupling process.
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PMID:Brief hypercapnia enhances somatosensory activation of blood flow in rat. 889 5

There is evidence of an intrinsic renin-angiotensin system in the brain. The goal of the study was to determine whether stimulation of endogenous angiotensin production by applying renin to the brain surface has an effect on pial arteriolar caliber and CBF. Pial vessel diameters were measured through a closed cranial window in anesthetized rabbits. Percent changes of blood flow in the cortical area under the cranial window were simultaneously measured by laser-Doppler flowmetry. Topical application of 0.01-0.1 U/ml renin induced maximum dilation of 18.9 +/- 4% (mean +/- SD) of pial arterioles within 2 min. Arteriolar calibers thereafter decreased slowly. Flow gradually increased to peak at 38 +/- 15% 50 min after renin application. Angiotensin I levels in jugular blood, as measured by radioimmunoassay, increased to a peak 40 min after topical renin application. Angiotensin II levels in jugular blood and both angiotensin I and II levels in blood samples from the femoral artery did not change. Diameter and flow changes were inhibited by intravenous pretreatment with the converting enzyme blocker captopril (10 mg/kg body wt i.v.). Captopril did not affect the vasodilation and flow increase in response to hypercapnia. Topically applied captopril (10(-5) M) blocked renin-induced arteriolar dilation. We conclude that renin increases pial arteriolar diameters and cortical blood flow in the rabbit brain. Stimulation of angiotensin production is likely to be a mediator of this response.
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PMID:Effect of renin on brain arterioles and cerebral blood flow in rabbits. 896 12

A new pulse sequence for estimating cerebral blood flow called UNFAIR, which uses a combination of sequential hyperbolic secant preparatory pulses, is introduced. This sequence is based on the same generalized conditions as previously introduced inversion recovery techniques except that the spins in the image slice of interest always have +z magnetization and the in-flowing spins are alternately inverted and uninverted. CBF-weighted images of rat brain under conditions of normocpnia and hypercapnia are presented and demonstrate the expected CBF response. A model describing the signal response to this pulse sequence is also presented and compared with in-vivo data acquired from gray and white matter.
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PMID:Perfusion imaging by un-inverted flow-sensitive alternating inversion recovery (UNFAIR). 910 40

A novel application of laser Doppler flowmetry (LDF) laser Doppler perfusion imaging (LDPI), was used to study cerebral cortical blood flow (CBFcortex). In contrast to the conventional laser Doppler perfusion monitor, LDPI creates two dimensional maps of the tissue perfusion in a well defined area of up to 120 x 120 mm comprising 4096 measurements points. Measurements of CBFcortex were made through an optically transparent polyester film applied to a cranial window preparation in ventilated anaesthetized pigs. Temporal and spatial heterogeneity in CBFcortex were visualized by LDPI during provocations which are known to alter CBF (varying arterial PCO2 or MABP, or infusion of adenosine at constant MABP (concomitant angiotensin administration) or by hyperoxemia). During hypercapnia the recorded CBFcortex increased homogeneously. The adenosine-mediated increase in recorded CBFcortex was concentrated on the lower flow interval, as was the hyperoxemia-caused decline. At decreasing MABP the autoregulatory threshold was found to vary locally within the cortex. The results suggest that LDPI, apart from detecting localized changes in CBFcortex' also visualizes flow changes within different vascular segments. Together with the practical advantages of the system, i.e. not necessitating direct contact with the tissues, this feature makes the technique suitable for studies of CBFcortex distributions.
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PMID:Cerebral blood flow of the exposed brain surface measured by laser Doppler perfusion imaging. 912 66

The roles of nitric oxide, adenosine and cortical arousal in the response to 7.5% CO2 inhalation were investigated by measuring cerebral blood flow bilaterally in the rat somatosensory cortices with laser-Doppler flow probes. Administration of N(omega)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg, i.v.) significantly attenuated the response to hypercapnia (mean decrease of 47%). This effect was partially reversed by a subsequent administration of L-arginine. Caffeine (10 mg/kg, i.v.) also significantly reduced hypercapnic responses (mean decrease of 44%). Caffeine administration was also associated with a tendency for animals to exhibit electrocorticographic signs of arousal; often associated with a reduction in the attenuation of the flow response to CO2 inhalation. 8-(3-Chlorostyryl) caffeine (CSC, 1.0 mg/kg), a selective antagonist at adenosine A2a striatal receptors failed to attenuate CO2-evoked responses, whereas CGS 15943, a less selective A2a receptor antagonist, significantly reduced CO2 responses. These data from the rat suggest (1) that both nitric oxide and adenosine may contribute to pial arteriolar vasodilatation during hypercapnia, and (2) that CO2 inhalation acts as a potent stimulus for cortical arousal, with enhanced neuronal activity contributing to the vascular response. The effects of administration of adenosine antagonists, such as the methylxanthines antagonists caffeine and theophylline, on CBF responses to hypercapnia can potentially be negated by the ability of these agents to facilitate CO2-induced cortical arousal.
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PMID:Hypercapnia-induced increases in cerebral blood flow: roles of adenosine, nitric oxide and cortical arousal. 920 26

Laser-Doppler flowmetry (LDF) is a reliable method for estimation of relative changes of CBF. The measurement depth depends on wavelength of the laser light and the separation distance of transmitting and recording optical fibers. We designed an LDF probe using two wavelengths of laser light (543 nm and 780 nm), and three separation distances of optical fibers to measure CBF in four layers of the cerebral cortex at the same time. In vitro comparison with electromagnetic flow measurements showed linear relationship between LDF and blood flow velocity at four depths within the range relevant to physiologic measurements. Using artificial brain tissue slices we showed that the signal for each channel decreased in a theoretically predictable fashion as a function of slice thickness. Application of adenosine at various depths in neocortex of halothane-anesthetized rats showed a predominant CBF increase at the level of application. Electrical stimulation at the surface of the cerebellar cortex demonstrated superficial predominance of increased CBF as predicted from the distribution of neuronal activity. In the cerebellum, hypercapnia increased CBF in a heterogeneous fashion, the major increase being at apparent depths of approximately 300 and 600 microns, whereas in the cerebral cortex, hypercapnia induced a uniform increase. In contrast, the CBF response to cortical spreading depression in the cerebral cortex was markedly heterogeneous. Thus, real-time laminar analysis of CBF with spatial resolution of 200 to 300 microns may be achieved by LDF. The real-time in depth resolution may give insight into the functional organization of the cortical microcirculation and adaptive features of CBF regulation in response to physiologic and pathophysiologic stimuli.
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PMID:Laminar analysis of cerebral blood flow in cortex of rats by laser-Doppler flowmetry: a pilot study. 939 32

The influence of hyperglycemic ischemia on tissue damage and cerebral blood flow was studied in rats subjected to short-lasting transient middle cerebral artery (MCA) occlusion. Rats were made hyperglycemic by intravenous infusion of glucose to a blood glucose level of about 20 mmol/L, and MCA occlusion was performed with the intraluminar filament technique for 15, 30, or 60 minutes, followed by 7 days of recovery. Normoglycemic animals received saline infusion. Perfusion-fixed brains were examined microscopically, and the volumes of selective neuronal necrosis and infarctions were calculated. Cerebral blood flow was measured autoradiographically at the end of 30 minutes of MCA occlusion and after 1 hour of recirculation in normoglycemic and hyperglycemic animals. In two additional groups with 30 minutes of MCA occlusion, CO2 was added to the inhaled gases to create a similar tissue acidosis as in hyperglycemic animals. In one group CBF was measured, and the second group was examined for tissue damage after 7 days. Fifteen and 30 minutes of MCA occlusion in combination with hyperglycemia produced larger infarcts and smaller amounts of selective neuronal necrosis than in rats with normal blood glucose levels, a significant difference in the total volume of ischemic damage being found after 30 minutes of MCA occlusion. After 60 minutes of occlusion, when the volume of infarction was larger, only minor differences between normoglycemic and hyperglycemic animals were found. Hypercapnic animals showed volumes of both selective neuronal necrosis and infarction that were almost identical with those observed in normoglycemic, normocapnic animals. When local CBF was measured in the ischemic core after 30 minutes of occlusion, neither the hyperglycemic nor the hypercapnic animals were found to be significantly different from the normoglycemic group. Brief focal cerebral ischemia combined with hyperglycemia leads to larger and more severe tissue damage. Our results do not support the hypothesis that the aggravated injury is caused by any disturbances in CBF.
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PMID:Hyperglycemia and focal brain ischemia. 1007 81

The authors investigated the role of the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) in the mechanisms of focal cerebral ischemia and its interaction with inducible nitric oxide synthase (iNOS). Focal cerebral ischemia was produced by permanent occlusion of the middle cerebral artery (MCA) in mice. Infarct volume was measured 96 hours later by computer-assisted planimetry in thionin-stained brain sections. The highly selective COX-2 inhibitor NS398 (20 mg/kg; intraperitoneally), administered twice a day starting 6 hours after MCA occlusion, reduced total infarct volume in C57BL/6 (-23%) and 129/SVeV mice (-21%), and ameliorated the motor deficits produced by MCA occlusion (P < .05). However, NS398 did not influence infarct volume in mice with deletion of the iNOS gene (P > .05). In contrast, the neuronal NOS inhibitor 7-NI (50 mg/kg; intraperitoneally), administered once 5 minutes after MCA occlusion, reduced neocortical infarct volume by 20% in iNOS -/- mice (P < .05). NS398 did not affect arterial pressure, resting CBF or the CBF reactivity to hypercapnia in anesthetized iNOS null mice (P > .05). The data suggest that COX-2 reaction products, in mouse as in rat, contribute to ischemic brain injury. However, the failure of NS398 to reduce infarct volume in iNOS null mice suggests that iNOS-derived NO is required for the deleterious effects of COX-2 to occur. Thus, COX-2 reaction products may be another mechanism by which iNOS-derived NO contributes to ischemic brain injury.
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PMID:The cyclooxygenase-2 inhibitor NS-398 ameliorates ischemic brain injury in wild-type mice but not in mice with deletion of the inducible nitric oxide synthase gene. 1056 67

It has recently been reported in alpha-chloralose anesthetized rats that the hemodynamic response to somatosensory stimulation almost doubled following transient hypercapnia (THC). In principle, this effect could be employed to enhance the sensitivity of perfusion-based fMRI experiments. To investigate whether a comparable effect was detectable in awake normal humans, changes in cerebral blood flow (DeltaCBF) and the effective transverse relaxation time (DeltaT(2)*) induced by a visual search task were measured in 10 healthy volunteers before and after THC. Concerning DeltaT(2)* no significant differences were found, whereas in four subjects DeltaCBF was significantly decreased (p < 0.01) following THC. These results demonstrate no increase in the CBF response following THC for awake humans. We conclude that the most likely explanation for this discrepancy with the earlier results obtained with animals is an as yet unknown mechanism of modulation of the cholinergic system by the anesthesia.
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PMID:The effect of transient hypercapnia on task-related changes in cerebral blood flow and blood oxygenation in awake normal humans: a functional magnetic resonance imaging study. 1111 65

Measurement of cerebral arterial and venous blood volumes during increased cerebral blood flow can provide important information regarding hemodynamic regulation under normal, pathological, and neuronally active conditions. In particular, the change in venous blood volume induced by neural activity is one critical component of the blood oxygenation level-dependent (BOLD) signal because BOLD contrast is dependent only on venous blood, not arterial blood. Thus, relative venous and arterial blood volume (rCBV) and cerebral blood flow (rCBF) in alpha-chlorolase-anesthetized rats under hypercapnia were measured by novel diffusion-weighted (19)F NMR following an i.v. administration of intravascular tracer, perfluorocarbons, and continuous arterial spin labeling methods, respectively. The relationship between rCBF and total rCBV during hypercapnia was rCBV(total) = rCBF(0.40), which is consistent with previous PET measurement in monkeys. This relationship can be linearized in a CBF range of 50-130 ml/100 g/min as DeltarCBV(total)/ DeltarCBF = 0.31 where DeltarCBV and DeltarCBF represent rCBV and rCBF changes. The average arterial volume fraction was 0.25 at a basal condition with CBF of approximately 60 ml/100 g/min and increased up to 0.4 during hypercapnia. The change in venous rCBV was 2-fold smaller than that of total rCBV (DeltarCBV(vein)/DeltarCBF = 0.15), while the arterial rCBV change was 2.5 times larger than that of total rCBV (DeltarCBV(artery)/DeltarCBF = 0.79). These NMR results were confirmed by vessel diameter measurements with in vivo videomicroscopy. The absolute venous blood volume change contributes up to 36% of the total blood volume change during hypercapnia. Our findings provide a quantitative physiological model of BOLD contrast.
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PMID:Relative changes of cerebral arterial and venous blood volumes during increased cerebral blood flow: implications for BOLD fMRI. 1132 5


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