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

Diabetes has been reported to impair vasodilatory responses in the peripheral vascular tissue. However, little is known about vasodilatory function in the diabetic brain. We therefore studied, in the N2O-sedated, paralyzed, and artificially ventilated rat, the effects of chronic hyperglycemic diabetes on the cerebral blood flow (CBF) responses to 3 acutely imposed vasodilatory stimuli: hypoglycemia (HG) (plasma glucose = 1.6-1.9 mumol ml-1), hypoxia (HX) (PaO2 = 35-38 mm Hg), or hypercarbia HC) (PaCO2 = 75-78 mm Hg). In addition, we evaluated the somatosensory evoked potential (SSEP) and plasma catecholamine changes in rats exposed to acute glycemic reductions. Diabetes was induced via streptozotocin (STZ, 60 mg kg-1 i.p.). All results in diabetic rats were compared to those obtained in age-matched nondiabetic controls. The animals were studied at 6-8 weeks (HG experiments) or 4-6 months (HG, HX, and HC experiments) post-STZ. Values for CBF were obtained for the cortex (CX), subcortex (SC), brainstem (BS), and cerebellum (CE) employing radiolabeled microspheres. Up to three CBF determinations were made in each animal. In 6-8 week diabetics vs. controls, CBF increased to a lesser value in the CX, SC, and BS (p less than 0.05). Thus, in the diabetics, going from chronic hyperglycemia to acute hypoglycemia, CBF values (in ml 100 g-1 min-1 +/- SD) increased (p less than 0.05) from 89 +/- 22 to 221 +/- 57 in the CX, from 82 +/- 21 to 160 +/- 52 in the SC, and from 79 +/- 34 to 237 +/- 125 in the BS. In controls, going from normoglycemia to acute hypoglycemia, the CBF changes (p less than 0.05) were 128 +/- 27 to 350 +/- 219 (CX), 117 +/- 11 to 358 +/- 206 (SC), and 130 +/- 29 to 452 +/- 254 (BS). CBF changes and absolute values in the CE were similar in the two groups. At 4-6 months post-STZ, a complete loss of the hypoglycemic CBF response was found in the CX, SC, and CE. In the BS, a CBF response to hypoglycemia was seen in the diabetic rats, with the CBF increasing from 114 +/- 28 (hyperglycemia) to 270 +/- 204 ml 100 g-1 min-1 (p less than 0.05), compared to a change from 147 +/- 36 (normoglycemia) to 455 +/- 299 ml 100 g-1 min-1 (p less than 0.05) in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1991 Jul
PMID:Chronic hyperglycemic diabetes in the rat is associated with a selective impairment of cerebral vasodilatory responses. 205 Jul 55

The tolerance of low intracellular pH (pHi) was examined in vivo in rats by imposing severe, prolonged respiratory acidosis. Rats were intubated and ventilated for 10 min with 20% CO2, for 75 min with 50% CO2, and for 10 min with 20% CO2. The maximum PaCO2 was 320 mm Hg. Cerebral intracellular lactate, pHi, and high-energy phosphate metabolites were monitored in vivo with 31P and 1H nuclear magnetic resonance (NMR) spectroscopy, using a 4.7-T horizontal instrument. Within 6 min after the administration of 50% CO2, pHi fell by 0.57 +/- 0.03 unit, phosphocreatine decreased by approximately 20%, and Pi increased by approximately 100%. These values were stable throughout the remainder of the hypercapnic period. Cerebral intracellular lactate, visible with 1H NMR spectroscopy in the hyperoxic state, decreased during hypercapnia, suggesting either a favorable change in oxygen availability (decreased lactate production) or an increase in lactate clearance or both. All hypercapnic animals awakened and behaved normally after CO2 was discontinued. Histological examination of cortical and hippocampal areas, prepared using a hematoxylin and eosin stain, showed no areas of necrosis and no glial infiltrates. However, isolated, scattered, dark-staining, shrunken neurons were detected both in control animals (no exposure to hypercapnia) and in animals that had been hypercapnic. This subtle histological change could represent an artifact resulting from imperfect perfusion-fixation, or it could represent subtle neurologic injury during the hypercapnia protocol. In summary, extreme hypercapnia and low pHi (approximately 6.5) are well tolerated in rats for periods up to 75 min if adequate oxygenation is maintained.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1990 Mar
PMID:Stability of brain intracellular lactate and 31P-metabolite levels at reduced intracellular pH during prolonged hypercapnia in rats. 230 43

The present study investigates the question of whether increases in CBF induced by hypercapnia in awake rats are accompanied by increases in the number of perfused capillaries. For the detection of perfused capillaries, gamma-globulin-coupled fluorescein isothiocyanate was injected intravenously. In 10 brain structures the density of perfused capillaries per square millimeter was determined from coronal sections using a highly sensitive fluorescent microscopical method that, in contrast to others, avoided air drying of the frozen brain sections. The results showed an inhomogeneous local distribution of the density of perfused capillaries during normo- and hypercapnia. The density of perfused capillaries was unchanged during hypercapnia compared with normocapnia, although blood flow was markedly increased. It is concluded that a capillary recruitment does not exist in the brain during the high-flow situation of hypercapnia.
J Cereb Blood Flow Metab 1989 Aug
PMID:Lack of capillary recruitment in the brains of awake rats during hypercapnia. 210 67

The influence of lactic acidosis and of extreme hypercapnia on free radical generation and lipid peroxidation in brain tissues was studied. Cortical homogenates were prepared from the rat brain in a bicarbonate buffer and incubated for 60 min. Lipid peroxidation was evaluated by measurements of thiobarbituric acid reactive (TBAR) material and alpha-tocopherol analysis. The pH during incubations were decreased to 6.10-6.20 by either lactic acid administration or equilibration with 60% CO2 gas in paired experiments. In homogenates treated with lactic acid there was a 20-fold increase in TBAR material and the alpha-tocopherol concentration decreased to approximately 60% of control. There was only a 10-fold increase in TBAR material and no change in alpha-tocopherol concentration if acidosis was induced by CO2. These differences between lactic acidosis and hypercapnic acidosis were statistically highly significant. The results indicate that lactic acidosis has a more pronounced effect in augmenting free radical generation in brain tissues than acidosis due to an increase in CO2 tension. It is suggested that this effect of lactic acid is mediated by increased dissociation of catalytic iron from proteins of the transferrin type.
J Cereb Blood Flow Metab 1989 Feb
PMID:Enhancement of iron-catalyzed free radical formation by acidosis in brain homogenates: differences in effect by lactic acid and CO2. 249 27

CBF, as measured by the clearance of 133Xe or 85Kr in the pentobarbital-anesthetized cat, displays a monotonic increase as the PaCO2 is elevated over a range of 20-60 mm Hg (slope Xe, 1.65 +/- 0.14 ml/100g/min/mm Hg; slope Kr, 1.40 +/- 0.11 ml/100 g/min/mm Hg). Clonidine (20 micrograms/kg i.v.), a centrally acting, alpha 2-preferring agonist, reduced the slope of the PaCO2-CBF response functions for Xe and Kr by 70 and 64%, respectively. Clonidine reduced normocarbic CBF-Xe by 36%, but had no effect on normocarbic CBF-Kr. ST-91, a polar structural analog of clonidine that does not cross the blood-brain barrier, did not reproduce the effects of clonidine when administered at an equivalent dose. This indicates that the effects of clonidine observed were secondary to its action on central rather than peripheral sites. In addition to the effects on the clearance of CBF markers, clonidine reduced the increased MABP otherwise evoked by elevated PaCO2. Reduction in the MABP response to PaCO2 did not account for the lowering of CBF during hypercarbia. In separate experiments where MABP was elevated to correspond with the PaCO2-MABP response observed in the absence of clonidine, a comparable reduction in the slope of the PaCO2 response was also observed. In addition, the pressure autoregulatory response was unaltered after clonidine treatment. These observations suggest that the central action of alpha 2-receptors on the CBF-CO2 response cannot be attributed to an altered perfusion pressure.
J Cereb Blood Flow Metab 1986 Jun
PMID:Effects of clonidine on cerebral blood flow and the response to arterial CO2. 301 28

Pial artery pressure was measured in anesthetized control cats and in animals subjected to 1 h of global ischemia and 6 h of recirculation. Cerebral blood flow (CBF) was measured with the intraarterial 133Xe technique before and after ischemia, and lumped segmental resistances upstream and downstream to the pial artery were calculated. In the control brain, upstream resistance was 1.30 +/- 0.28 and downstream resistance 0.94 +/- 0.1 mm Hg ml-1 100 g min. During the postischemic hypoperfusion period, both resistances significantly increased, indicating that hypoperfusion constitutes a dysregulation of both large extracerebral and small intracerebral vessels. Hypercapnia induced an increase of CBF in the control brain and was accompanied by a fall in downstream resistance, demonstrating intracortical vasodilation. By contrast, hypercapnia did not provoke changes in either CBF or segmental resistances in the hypoperfusion period. In conclusion, during the postischemic hypoperfusion period, both extra- and intracortical resistances are increased and vascular reactivity to CO2 is abolished.
J Cereb Blood Flow Metab 1987 Feb
PMID:Pial artery pressure after one hour of global ischemia. 310 May 44

In chloralose-urethanized cats, vasoactive intestinal peptide (VIP), applied by superfusion in steady-state concentration (10(-10)-10(-6) M) onto cortical vessels in situ resulted in a rapid concentration-dependent vasodilatation in vessels that were mildly constricted by prostaglandin F2 alpha (PGF2 alpha) (5 X 10(-5) M) or hypocarbia (PaCO2 = 26). The maximum dilatation produced by VIP (10(-6) M) was about 60% over baseline in pial arteries and 40% in pial veins. Blockade of local neuronal activity with tetrodotoxin (TTX) (10(-5) M) had no effect on the VIP-evoked dilation of pial vessels. Activation of the cortex by either direct electrical stimulation or indirectly by stimulation of the mesencephalic reticular formation (MRF) resulted in a rapid dilatation of pial arterioles and venules. The vasodilatory effects of VIP and of cortical activation via direct cortical stimulation were not blocked by phentolamine (10(-4) M), propranolol (10(-4) M), atropine (10(-4) M), or naloxone (10(-4) M), indicating that the stimulated vasodilatation was not mediated by adrenergic, cholinergic, or opiate receptors. The dilatory effects of MRF, but not direct cortical stimulation, were not blocked by TTX. VIP antiserum (1:25) preincubated in cortical cups had no effect on resting vessel diameter, but resulted in a significant, though subtotal, reduction in the vasodilatation elicited by direct cortical and MRF stimulation. Normal rabbit sera or VIP antiserum preincubated with saturating amounts of VIP were ineffective. In similar experiments, pial arteriolar and venular dilation evoked by hypercarbia was not attenuated by cortically applied VIP antisera. These observations suggest that pial dilation evoked by local increases in neuronal activity may be mediated in part by the local release of VIP from intrinsic neurons. Such a substrate would define a close obligatory coupling between local neuronal activation and local perfusion, such that nutritive flow could be enhanced prior to the onset of any metabolic deficit.
J Cereb Blood Flow Metab 1987 Jun
PMID:Cortical vasodilatation produced by vasoactive intestinal polypeptide (VIP) and by physiological stimuli in the cat. 310 70

The time course of changes in cortical tissue pH (pHi) and blood flow during cortical seizures in halothane-anesthetized cats was examined. The clearance of the molecular form of umbelliferone (Um) was used to estimate focal cortical blood flow (CBFu), whereas the ratio of the molecular to the ionic form of the molecule was used to concurrently calculate the local pHi. Resting pHi and flow in normocarbic animals was 7.116 +/- 0.008 and 46 +/- 8 ml/100 g/min, respectively. Respiratory induced alterations of PaCO2 over a range of 20-60 torr revealed a correlated change in pHi from 7.39 +/- 0.05 to 7.01 +/- 0.03 and a monotonic increase in the rate of Um clearance (slope 0.89 +/- 0.13 ml/100 g/min/torr). Focal electrical stimulation of the cortex resulted in a rapid vasodilation (50% dilation = 1-3 s) of pial arterioles and venules and an increase in Um clearance. pHi showed no significant change until around 10 s. The maximum fall in pHi occurred by 30-60 s (6.85 +/- 0.054). Longer intervals of stimulation (10 min) resulted in no further decline in pHi, but upon cessation of stimulation. pHi remained acidotic for poststimulation periods up to 10 min, with a mild but statistically significant acidosis being observed at 20 min. The absolute decline in pH observed following stimulation appeared to be closely regulated, as comparable levels following stimulation were observed during hypocarbia and hypercarbia. These observations thus suggest that pHi regulation during intense cortical activation may be considered in three phases: following the onset of activity, an initial acute regulation of pHi at control levels; an intracellular acidosis of around 6.8, which is closely regulated and which can be readily reversed upon termination of stimulation; and during continued stimulation, a change in state where in spite of no further change in pHi, the ability of the cortex to return to control pHi appears to be significantly impaired.
J Cereb Blood Flow Metab 1987 Jun
PMID:In vivo studies on intracellular pH, focal flow, and vessel diameter in the cat cerebral cortex: effects of altered CO2 and electrical stimulation. 310 71

The oxygen extraction fraction (OEF) at maximally vasodilated tissue in patients with chronic cerebrovascular disease was evaluated using positron emission tomography. The vascular responsiveness to changes in PaCO2 was measured by the H2(15)O autoradiographic method. It was correlated with the resting-state OEF, as estimated using the 15O steady-state method. The subjects comprised 15 patients with unilateral or bilateral occlusion and stenosis of the internal carotid artery or middle cerebral artery or moyamoya disease. In hypercapnia, the scattergram between the OEF and the vascular/responsiveness to changes in PaCO2 revealed a significant negative correlation in 11 of 19 studies on these patients, and the OEF at the zero cross point of the regression line with a vascular responsiveness of 0 was 0.53 +/- 0.08 (n = 11). This OEF in the resting state corresponds to exhaustion of the capacity for vasodilation. The vasodilatory capacity is discussed in relation to the lower limit of autoregulation.
J Cereb Blood Flow Metab 1988 Apr
PMID:Oxygen extraction fraction at maximally vasodilated tissue in the ischemic brain estimated from the regional CO2 responsiveness measured by positron emission tomography. 312 86

Qualitatively different responses of ADP levels have previously been observed in the brain during hypercarbia. One investigation has found that cerebral ADP stayed constant during hypercarbia in rats that were anesthetized with halothane, while another observed that ADP decreased during supercarbia in rats that received no supplemental anesthesia. This article reports an in vivo 31P nuclear magnetic resonance study to test the hypothesis that halothane anesthesia accounts for the discrepant observations. Isoflurane anesthesia was also studied in a second group of rats to see if a different general anesthetic agent would cause the same effects that halothane causes. The two groups of five rats underwent dual episodes of hypercarbia that were separated by a 45-min recovery period. General anesthesia, either 0.5% halothane or 1.0% isoflurane, was administered during the first episode but not during the second. Hypercarbia during halothane anesthesia caused the measured phosphocreatine (PCr) to decrease by 40%, while the calculated change in ADP was 10%, in agreement with the former investigation. In contrast, hypercarbia during either isoflurane anesthesia or no anesthesia caused a decrease of only 10% in PCr, which meant that the calculated decrease in ADP was 60%, in agreement with the results of the second investigation. We conclude that during hypercarbia, clinical concentrations of halothane, unlike clinical concentrations of isoflurane, interfere with the regulation of ATP metabolism.
J Cereb Blood Flow Metab 1986 Jun
PMID:Cerebral intracellular ADP concentrations during hypercarbia: an in vivo 31P nuclear magnetic resonance study in rats. 371 Nov 64


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