Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic tolerance of low intracellular pH (pH(i)) was studied in well-oxygenated, perfused, neonatal, rat cerebrocortical brain slices (350 microns thick) by inducing severe hypercapnia. In each of 17 separate experiments 80 brain slices (approximately 3.2 g wet weight) were suspended in an NMR tube, perfused with artificial CSF (ACSF), and studied at 4.7 T with 31P and 1H NMR spectroscopy. Spectra obtained every 5 min monitored relative concentrations of lactate or high-energy phosphate metabolites, from which pH(i) and extracellular pH were determined. Unperturbed slice preparations were metabolically stable for > 10 h, with no significant changes occurring in pHi, ATP, phosphocreatine (PCr), inorganic phosphate, or lactate. Different levels of hypercapnia were produced by sequentially perfusing slices with the following different ACSF batches, each having previously been equilibrated with a specific mixture of CO2 in oxygen: (a) 10% CO2, 15 min of perfusion; (b) 30% CO2, 15 min of perfusion; (c) 50% CO2, 15 min of perfusion; (d) 70% CO2, 30 min of perfusion; (e) 50% CO2, 15 min of perfusion; (f) 30% CO2, 15 min of perfusion; and (g) 10% CO2, 15 min of perfusion. At the completion of this protocol slices were again perfused with fresh ACSF that was equilibrated with a 95% O2/5% CO2 gas mixture. In each of five separate 1H and 31P experiments, brain slices were recovered within 2 h after termination of exposure to high CO2. The pHi was determined from measurements of the chemical shift difference between phosphoethanolamine and PCr, using a calibration curve obtained for our preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tolerance of low intracellular pH during hypercapnia by rat cortical brain slices: A 31P/1H NMR study. 140 24

The contributions of central and peripheral chemoreceptors to respiratory control in lightly anesthetized Bufo marinus, were assessed by measuring the ventilatory responses to unidirectional ventilation (UDV) of the lungs at several concentrations of CO2 or O2, during intracranial perfusion (ICP) with hypercapnic acidic (5% CO2, pH 7.2) or hypocapnic alkaline (0% CO2, pH 8.3) mock CSF solutions. Peripheral chemoreceptor stimulation alone (hypoxia or hypercapnia during ICP with hypocapnic alkaline CSF) significantly increased breathing frequency and amplitude. ICP with hypercapnic acidic CSF further stimulated ventilation, primarily by significantly increasing the number of breaths/bout of breathing and decreasing the non-ventilatory time at all levels of peripheral ventilatory drive. When peripheral and central chemoreceptor stimulation was low toads were apneic. Stimulation of either central or peripheral chemoreceptors was sufficient to reinitiate breathing. Responses to ICP were greatest when perfusion was directed to the ventral medullary surface (VMS). These results suggest that the initiation of breathing and overall levels of breathing are functions of the combined afferent input from peripheral chemoreceptors and central CO2/pH sensitive chemoreceptors, located near the VMS. Stimulation of central chemoreceptors, however, produced longer duration bouts of rhythmic breathing than did peripheral chemoreceptor stimulation.
 ...
PMID:Effects of central and peripheral chemoreceptor stimulation on ventilation in the marine toad, Bufo marinus. 190 95

The chemosensitive area on the ventral surface of the brain stem responds to local acidosis by eliciting hyperventilation and to local alkalosis by hypoventilation. The stimulus is conventionally thought to be the hydrogen ion concentration in the area's extracellular fluid. It is pointed out, however, that the elegant studies by Loeschcke & Ahmad have demonstrated that [pH]e and [pH]i are normally tightly and rapidly coupled (Loeschcke & Ahmad, 1980). For this reason, the stimulus might just as well be the intracellular hydrogen ion concentration in the chemoreceptor area. The administration of acetazolamide allows the dissociation of [pH]e from [pH]i. With acetazolamide a sharp acid shift of CSF pH [( pH]c) is measured and in two consonance with this shift a marked increase in CBF is seen. Comparing these two reactions to that obtained with CO2 breathing, it is apparent that 7% CO2 causes about the same decrease in [pH]e and the same increase in CBF. In other words CBF acidosis can quantitatively account for the CBF increase induced by acetazolamide. But CO2 and acetazolamide influence [pH]i quite differently, as CO2 drops [pH]i to almost the same extent as [pH]c, while two recent studies by MR spectroscopy have shown that acetazolamide does not drop [pH]i measurably, if tissue hypercapnia is prevented in artificially ventilated rabbits or by the mild spontaneous hyperventilation caused by acetazolamide in normal man.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Is central chemoreceptor sensitive to intracellular rather than extracellular pH? 211 40

We have developed an automated method [Short Pulse Response (SPR)] of measuring craniospinal compliance using an electronic square wave pressure generator to produce a small (0.05 ml) and reproducible transient volume increase in the CSF space (pulse duration 100 msec). In experimental models of intracranial hypertension, arterial hypertension, arterial hypotension and arterial hypercarbia in cats, the new method accurately followed physiological changes in compliance when compared to the manual volume-pressure injection method. The VPR overestimated compliance compared to the new SPR method (by 20% to 162%, mean = 77%). The SPR method was less variable between sequential measurements with a coefficient of variation (CV) ranging from 0.6% to 9.6% (mean CV = 2.6%), compared with a CV ranging from 5.6% to 48% (mean CV = 17%) for the VPR method. Repeated compliance measurements by the new method over a 12 hour period, produced no neuropathological evidence of either blood brain barrier breakdown or tissue damage resulting from the repeated volume injections.
 ...
PMID:Automated time-averaged analysis of craniospinal compliance (short pulse response). 212 80

A modification of the closed cranial window technique for small laboratory animals is presented. The method facilitates investigation of blood-brain barrier permeability in association with studies of the cerebrovascular response under normal and pathological conditions. Following trephination and preparation of the pia-arachnoid surface, the skull defect is closed again by sealing a cover glass onto a wall of dental cement surrounding the cranial window. The intracranial pressure can then be studied and experimentally manipulated. Care is taken to maintain normal blood-brain barrier function to a small barrier indicator (Na(+)-fluorescein, MW: 376). This is accomplished by opening the skull and dura mater under a column of paraffin oil to avoid exposure of brain tissue to atmospheric pressure. Reactivity of the cerebral surface vessels was assessed during hypercapnia at an arterial PaCO2 of 50.8 +/- 1.1 mm Hg. It was found that small arterioles of 20-50 microns phi had a significantly larger CO2-response than large arterioles of 50-100 microns phi. Pial venules did not respond at all. Superfusion of the cranial window preparation at a rate of 5 ml/h with buffered artificial CSF was tolerated for hours. No alterations of arteriolar or venular diameters nor opening of the blood-brain barrier to Na(+)-fluorescein was observed. These technical modifications enable us to employ a closed cranial window model in small laboratory animals for studies of cerebral microcirculation and blood-brain barrier function under normal as well as under pathological conditions related to brain damage.
 ...
PMID:An improved closed cranial window technique for investigation of blood-brain barrier function and cerebral vasomotor control in the rat. 227 56

Magnetic resonance imaging was used to measure the effect of inhalation of 7% CO2 and hyperventilation with 60% O2 on human cranial cerebrospinal fluid volume. During CO2 inhalation there was a reduction in the cranial CSF volume ranging from 0.7-23.7 ml (mean 9.36 ml). The degree of reduction in cranial CSF volume was independent of the individual subject's increase in end-expiratory pCO2 or mean arterial blood pressure, in response to hypercapnia. During hyperventilation with high concentration oxygen the cranial CSF volume increased in all subjects (range 0.7-26.7 ml, mean 12.7 ml). The mean changes in cranial CSF volume, induced by hypercapnia and hypocapnia, were very similar to the expected reciprocal changes in cerebral blood volume.
 ...
PMID:Changes in cranial CSF volume during hypercapnia and hypocapnia. 249 39

The CSF pressure was measured continuously at the lumbar level during nocturnal sleep in 3 patients with sleep apnea hypersomnia syndrome. Nocturnal sleep was very unstable with frequent episodes of obstructive sleep apnea. When the patients were awake and relaxed in the supine position, their CSF pressure was stable and within the normal range. Episodic marked elevations of CSF pressure occurred frequently during sleep, and each elevation was preceded and accompanied by an episode of sleep apnea or hypopnea. Significant correlations were found between the duration of apneic episodes and increase of CSF pressure, and between decrease of SaO2 or TcPO2 and increase of CSF pressure. The duration of sleep apnea was longer, increase of CSF pressure was greater, and decreases of SaO2 and TcPO2 were more marked during REM sleep than during NREM sleep. It is suggested that the frequent marked episodic elevations of CSF pressure are caused by an increase in the intracranial vascular volume occurring mainly in response to transient hypercapnia and hypoxia, which are induced by pulmonary hypoventilation during the episodes of sleep apnea.
 ...
PMID:Marked episodic elevation of cerebrospinal fluid pressure during nocturnal sleep in patients with sleep apnea hypersomnia syndrome. 257 29

In the present study on nine cats, repeated tests were made of the effects of superfusion of the ventral surface of the medulla oblongata with acid or alkaline CSF. Only two animals showed slight hyperventilation, tachycardia, mesenteric vasoconstriction and variable changes in hindlimb vascular conductance when the ventral surface was superfused with acid CSF; alkaline CSF produced opposite effects. These changes are qualitatively similar to, but much smaller than, published results which support the idea that the central chemoreceptor areas for CO2 are near the surface of the ventral medulla. But, in accord with those who have disputed this idea, the remaining 7 animals showed no response to superfusion with acid or alkaline CSF. Yet, all 9 animals showed marked hyperventilation in response to inhalation of 5% or 8% CO2. These findings accord with the view that chemosensitive structures on the ventral medulla represent part, but not all of the central chemosensitive mechanism for CO2. Inhalation of CO2 also induced bradycardia, mesenteric vasodilatation and either vasodilatation or vasoconstriction in hindlimb, attributable to a predominance of the direct myocardial depressant and local vasodilator effects of CO2, over the increase in sympathetic activity produced by central hypercapnia. But, despite the different effects of acid CSF and inhaled CO2 on baselines, they produced comparable effects on the visceral altering/defence response evoked by electrical stimulation in the ventral amygdalo-hypothalamic pathway viz, the magnitude of the characteristic hindlimb dilatation was reduced while that of the mesenteric constriction was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Modulation of the centrally-evoked visceral alerting/defence response by changes in CSF pH at the ventral surface of the medulla oblongata and by systemic hypercapnia. 373 81

In this study we examined the reactions of cerebral vessels to hypercapnia and hypoxia during the recovery period following cerebral ischemia. We used ventilated, lightly anesthetized rats and induced complete ischemia by CSF compression, incomplete ischemia by bilateral carotid occlusion combined with hypotension. After 15 min of ischemia and 60 min of recirculation the animals were rendered hypercapnic or hypoxic for 2-3 min and local CBF was then measured autoradiographically with 14C-iodoantipyrine. Following complete ischemia vascular CO2 responsiveness was abolished or attenuated in most structures analysed. However, there was a considerable interstructural heterogeneity. For example, in the cerebellum and the red nucleus flow rates were observed which approached values obtained in hypercapnic control animals, whereas CO2 responsiveness was abolished in several cortical areas and hippocampus. The response to CO2 following incomplete ("forebrain") ischemia varied considerably. In the cerebral cortices areas with low flow rates were often mixed with hyperemic zones, and in most structures that had very low flow rates during ischemia, CO2 responsiveness was lost or grossly attenuated. Structures that had suffered moderate or only mild ischemia had better retained or completely preserved CO2 response. The cerebrovascular reaction to hypoxia was found to be attenuated in most, but not abolished in any of the structures examined. In general, the vascular response to hypoxia was better preserved than that to hypercapnia. Reactivity was similar following complete and incomplete ischemia. As observed during hypercapnia, there were pronounced interstructural variations with considerable increases in flow rates e.g. in the substantia nigra and the cerebellum.
 ...
PMID:Cerebral circulatory responses to hypercapnia and hypoxia in the recovery period following complete and incomplete cerebral ischemia in the rat. 641 51

The effect of intracarotid prostacyclin (PGI2) on cerebral blood flow (CBF) was measured by the 133xenon intracarotid injection technique in 8 baboons. Intracarotid prostacyclin increased CBF by 22% at 10(-7) g/kg/min and by 71% at 5 x 10(-6) g/kg/min, accompanied by systemic hypotension and tachycardia. The effects of PGI2 (10(-7) g/kg/min) were not potentiated by transient opening of the blood-brain barrier with the intracarotid hypertonic urea technique. At hypercapnia, the vasoconstrictor effect of indomethacin on the cerebral circulation was reversed by PGI2. These results support our suggestion that a prostaglandin, in particular PGI2, is required for hypercapnia to produce full cerebral vasodilatation. In separate experiments, following craniectomy in 5 cats, PGI2, but not its stable metabolite 6-keto-PGF1 alpha, dilated pial arterioles when locally injected into the mock CSF overlying the arteriole.
 ...
PMID:Prostacyclin, indomethacin and the cerebral circulation. 677 15


<< Previous 1 2 3 4 5 Next >>