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

Hypoglycemia increases the vulnerability of the perinatal brain to asphyxia, but it is not known if hypoglycemia-induced changes in cerebral hemodynamics and vascular reactivity underlie this vulnerability. This study tested the hypothesis that hypoglycemia exacerbates postischemic hypoperfusion, and impairs postischemic CO2 reactivity. The authors also examined the hypothesis that postischemic hypoperfusion is associated with a reduction in the interstitial concentration of the vasodilator metabolite adenosine. Global cerebral ischemia of 10 minutes duration was induced in newborn pigs anesthetized with isoflurane by occlusion of subclavian and brachiocephalic arteries; cortical cerebral blood flow (CBF) and interstitial adenosine concentration were evaluated simultaneously using the combined hydrogen clearance/microdialysis technique. Hypoglycemia (blood glucose < 25 mg/dl) was induced by regular insulin (25 IU/kg) administered intravenously 2 hours prior to induction of ischemia. In the eight normoglycemic animals, baseline CBF was 38 +/- 4 ml/min/100 gm and baseline adenosine concentration was 1.2 +/- 0.1 microM; in the eight hypoglycemic animals, these values were 39% (p < 0.05) and 62% (p < 0.05) greater, respectively, under baseline conditions. At 1 hour of postischemic reperfusion in normoglycemic animals, CBF was reduced 39% relative to the preischemic baseline (p < 0.01), concomitant with a 27% reduction (p < 0.05) in adenosine concentration, suggesting that this lowered concentration may underlie delayed hypoperfusion. These postischemic reductions in CBF and interstitial adenosine concentration were significantly greater in hypoglycemic animals, with CBF and adenosine concentration reduced 70% (p < 0.001) and 71% (p < 0.01), respectively, relative to baseline. In nine animals preischemic reactivity to hypercapnia was unaffected by hypoglycemia. Postischemic hypercapnic reactivity was retained in the eight normoglycemic animals, but was attenuated 73% (p < 0.05) in hypoglycemic animals. Thus, in the newborn pig, hypoglycemia exacerbates postischemic cortical hypoperfusion and impairs postischemic cerebrovascular reactivity to hypercapnia.
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PMID:Effect of hypoglycemia on postischemic cortical blood flow, hypercapnic reactivity, and interstitial adenosine concentration. 796 18

This study examined the effect of hypercarbia on cerebral agonal glycolytic rates and brain lactate accumulation after complete ischemia induced by cardiac arrest. Before cardiac arrest, the blood plasma glucose concentration in seven newborn (113 d postconception; normal gestation, 115 d) and seven 1-mo-old (144 d postconception) piglets was adjusted to a specific value (range, 1 to 64 mM), and then inspired ventilation gases were changed to 10:50:40 CO2:O2:N2 for 20 min. The agonal glycolytic rate was measured by monitoring the rate of cerebral lactate formation in vivo using proton nuclear magnetic resonance spectroscopy, and postmortem brain lactate concentrations were measured biochemically in tissue extracts obtained 40 to 45 min after cardiac arrest. These data were compared with 21 normocarbic piglets of similar age, nine examined as part of the present study and 12 examined previously (Corbett RJT, Laptook AR, Ruley JI, Garcia D: Pediatr Res 30:579-586, 1991). There was a nonlinear relationship between the final postmortem brain lactate concentration and preischemia blood plasma glucose concentration that was most prominent in newborn piglets and previously had gone unnoticed. When analyzed using a steady-state model for glucose transport, this relationship revealed that normocarbic newborns had a lower preischemia affinity constant for the transport mechanism for glucose (2.8 +/- 1.5 mM) and lower cerebral glucose utilization rate relative to transport rate (0.12 +/- 0.04), compared with 1-mo-olds (4.5 +/- 1.4 mM and 0.30 +/- 0.03, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of hypercarbia on age-related changes in cerebral glucose transport and glucose-modulated agonal glycolytic rates. 813 81

We have previously demonstrated that topical cortical application of nitro-L-arginine (L-NA), a potent inhibitor of nitric oxide (NO) synthesis, attenuates resting cerebral blood flow (CBF) and the cerebrovasodilation elicited by hypercapnia. In this study, we sought to determine whether these cerebrovascular effects of L-NA are secondary to a depression in cerebral metabolism. Rats were anesthetized (chloralose, 80 mg/kg) and artificially ventilated. Arterial pressure and blood gases were monitored. The frontal cortex was exposed and superfused with normal Ringer (pH 7.3-7.4; 37 degrees C) or with Ringer containing L- or D-NA. CBF or cerebral glucose utilization (CGU) was measured autoradiographically using the [14C]iodoantipyrine or 2-[14C]deoxy-D-glucose method, respectively. Application of normal Ringer did not affect CBF at the site of superfusion (n = 5; P > 0.05, paired t test). Application of L-NA (1 mM; n = 5), but not D-NA (1 mM; n = 6), attenuated resting CBF by 33 +/- 5% (P < 0.05; analysis of variance). During hypercapnia (partial pressure of CO2 = 55-60 mmHg), L-NA attenuated the CBF increase by 78 +/- 6% (n = 5/group; P < 0.05 from Ringer), whereas D-NA had no effect (P > 0.05). Resting CBF and the CBF response to hypercapnia were largely unaffected in brain regions outside the field of superfusion. In contrast to hypercapnia, L-NA (1 mM) did not attenuate the increases in CBF elicited by topical application of papaverine (10-1,000 microM; n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitro-L-arginine attenuates hypercapnic cerebrovasodilation without affecting cerebral metabolism. 814 11

Sympathoexcitatory neurons of the rostral ventrolateral medulla are tonically active and required for maintenance of resting levels of arterial pressure. They are also selectively excited by hypoxia and responsible for the associated sympathoexcitation. Since electrical or chemical stimulation of RVL will increase regional cerebral blood flow (rCBF) independently of changes in regional cerebral glucose utilization (rCGU) we investigated whether the RVL was also required to maintain resting levels of rCBF and also participated in the cerebrovascular vasodilation elicited by hypoxia. Rats were anesthetized (chloralose; 40 mg/kg, s.c.), paralyzed (tubocurarine) and ventilated (100% O2). rCBF was measured in 10 dissected brain regions using [14C]iodoantipyrine; rCGU was measured by 2-deoxy-D-[14C]glucose. In controls (n = 6) rCBF ranged from 56 +/- 5 in corpus callosum to 101 +/- 6 ml/min x 100 g in inferior colliculus. Hypoxic-hypoxia (PaO2 = 36 +/- 1 mmHg, n = 6) increased rCBF in all structures maximally, at 204% of control, in occipital cortex. Hypercapnia (PaCO2 = 63.5 +/- 0.9, n = 5) also increased rCBF (P < 0.01) maximally to 299% of control in superior colliculus. Spinal cord transection with maintenance of arterial pressure did not affect resting rCBF and increased the vasodilation to hypoxia (PaO2 = 39 +/- 1 mmHg, n = 5) from 2- to 3-fold in all structures (P < 0.01). Bilateral lesions within the RVL had no effect on resting rCBF or rCGU. However, they significantly reduced, in all areas by 50-69% (P < 0.01, n = 5), the cerebrovascular dilation elicited by hypoxia but not hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lesions of the rostral ventrolateral medulla reduce the cerebrovascular response to hypoxia. 817 58

We studied the effect of halothane anesthesia on the increases in cerebral blood flow (CBF) and arterial pressure (AP) elicited by electrical stimulation of the cerebellar fastigial nucleus (FN). Rats were anesthetized (0.75-2% halothane), instrumented for continuous recording of AP, and ventilated. The FN was stimulated through stereotaxically implanted microelectrodes. In CBF experiments the elevations in AP resulting from FN stimulation were eliminated by spinal cord transection at C1. After cord transection AP was maintained by intravenous phenylephrine. CBF or cerebral glucose utilization (CGU) was measured by laser-Doppler flowmetry or the 2-deoxyglucose method, respectively. FN stimulation produced increases in CBF that were graded with the intensity (10-150 microA) or frequency (10-150 Hz) of stimulation. At 1% halothane, FN stimulation (100 microA; 75 Hz; n = 8) increased CBF by 123 +/- 16%. The elevations in CBF were attenuated by increasing levels of halothane anesthesia in a dose-dependent manner. At halothane concentrations of 1.5 and 2% the CBF response to FN stimulation (100 microA; 75 Hz) was reduced by 58 +/- 6 and 77 +/- 4%, respectively (p < 0.05 from 0.75% halothane; analysis of variance and Tukey's test). In contrast, the increases in CBF elicited by hypercapnia were not attenuated (P > 0.05 from 0.75% halothane). At 1% halothane, FN stimulation did not change CGU in neocortex (frontal cortex: unstimulated 48 +/- 6, mumol.100 g-1.min-1, FN stimulation: 47 +/- 11; P > 0.05; n = 5/group). In the group of rats in which the pressor response was studied (n = 7), halothane produced a dose-dependent attenuation of the elevations in AP. The degree of attenuation of the AP response was comparable to that of the CBF response (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebrovasodilation elicited by fastigial stimulation is preserved under deep halothane anesthesia. 834 86

Intracellular pH and ammonium ion concentration are potent modulators of cerebral amino acid metabolism. Furthermore, intracellular acidosis and hyperammonemia accompany conditions such as ischemic encephalopathy and seizures and may contribute to the pathological sequelae observed. In vivo NMR spectroscopy permits multiple, non-destructive measurements of important cerebral metabolic intermediates in the same animal. We describe here the use of 1H, and 31P NMR spectroscopy to investigate the effects of acute changes in intracellular pH and ammonium ions on cerebral glutamate, glutamine, and lactate levels in vivo. We then show how 1H NMR can be used to indirectly follow the flow of 13C label from [1-13C] glucose into the cerebral glutamate pool, allowing us to measure cerebral TCA activity in normal and chronically hyperammonemic rats. Male Sprague-Dawley rats (160-210 gm), fasted 24-hours, were tracheotomized, paralyzed and ventilated on 30% O2/70% N2O. NMR spectroscopy was performed at a field strength of 8.4 Tesla using a Bruker AM-360 wide bore spectrometer. An elliptical surface-coil (8 x 12 mm) was double-tuned to either the 1H and 31P or 1H and 13C frequencies. After retraction of extracranial tissues, the coil was positioned over the skull 2 mm posterior to the bregma. Tail arteries and veins were cannulated allowing periodic measurements of PO2, pCO2, pH and glucose in arterial blood and intravenous infusions. Respiratory acidosis was induced in rats by the addition of CO2 to the ventilation gas mixture. Arterial pCO2 increased within 5 min from a pre-hypercarbic value of 36.4 +/- 6.1 mm Hg to 200-220 mm Hg and was maintained at this level for over 1 hour. Hypercarbia led to rapid cerebral acidification. Intracellular pH decreased from 7.18 +/- 0.08 (pre-hypercarbic period) to 6.68 +/- 0.06 (n = 4) at 10 min and remained stable throughout the NMR observation period. Glutamate decreased to 53 +/- 4% of control after 60 min of hypercarbia, while glutamine increased to 126 +/- 7% of control. Acute hyperammonemia was produced by a programmed intravenous infusion of 250 mM ammonium acetate, which rapidly raised and maintained the concentration of ammonium ions in the blood at approximately 500 microM. Shortly after the start of the infusion (10-20 min), the levels of glutamine and lactate rose continuously throughout the experiment, reaching levels of 170 +/- 25% and 260 +/- 60% of control, respectively (n = 12) after 50 min. Glutamate decreased during the same time interval to 80 +/- 4% of control (n = 12).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cerebral metabolic studies in vivo by combined 1H/31P and 1H/13C NMR spectroscopic methods. 842 59

The effect of diabetes mellitus on the cerebrovascular response to CO2 is unclear. We examined the effects of diabetes on cerebral blood flow (CBF) and cerebral oxygen uptake (CMRO2) during CO2 alterations. Four groups of dogs were studied: nondiabetic, normoglycemic controls; non-diabetic acute hyperglycemia; diabetic (pancreatectomy) with high-dose insulin treatment to maintain blood glucose between 4.0 and 6.0 mM; and diabetic with low-dose insulin treatment to maintain blood glucose at 13.2 +/- 0.4 mM. Six weeks after either sham surgery or pancreatectomy, dogs were anesthetized with fentanyl (50 micrograms/kg) plus pentobarbital (10 mg/kg), and microsphere determinations of CBF were made during normo-, hypo-, and hypercapnia. On the day of the study, arterial glucose levels in the control, acute hyperglycemia, and high- and low-dose insulin diabetic groups were 4.0 +/- 0.3, 14.9 +/- 2.5, 3.3 +/- 0.8, and 13.3 +/- 0.7 mM, respectively, at control. The corresponding baseline CMRO2 levels were 2.8 +/- 0.2, 3.0 +/- 0.2, 4.1 +/- 0.4, and 4.0 +/- 0.3 ml O2.100 g-1 x min,1, and the values in both diabetic groups were higher than control. Normocapnic CBF in the acute hyperglycemia, high-dose insulin, and low-dose insulin groups was elevated from control (54 +/- 3, 50 +/- 3, 51 +/- 3 vs. 36 +/- 1 ml x 100 g-1 x min-1) and cerebrovascular resistance was lower (2.24 +/- 0.15, 2.51 +/- 0.14, 2.38 +/- 0.21 vs. 3.35 +/- 0.18 mmHg.ml-1 x 100 g.min). CBF responses to both hypercapnia and hypocapnia were similar among groups. Thus both acute hyperglycemia and diabetes decrease cerebrovascular resistance and increase CBF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebral blood flow responsivity to CO2 in anesthetized chronically diabetic dogs. 847 84

Laparoscopy has been considered a relative contraindication in pregnant patients because the CO2 pneumoperitoneum may cause maternal and/or fetal hypotension, acidosis, hypercarbia, hypoxia, changes in cardiac output, or uterine artery blood flow. These potential changes were studied in an established animal pregnancy model. Twelve gravid ewes (116-120 days gestation) underwent catheterization of maternal femoral artery and vein, fetal hindlimb artery and vein, insertion of a uterine artery flow probe, and pulmonary artery catheter. Six animals underwent creation of a CO2 pneumoperitoneum (10 mm Hg for 30 min; 15 mm Hg for 30 min). Six control animals were studied without a pneumoperitoneum. The following parameters were recorded at baseline and at preset time points: cardiac output (CO), uterine blood flow (UtBF), amniotic cavity pressure (ACP), end-tidal CO, (Et CO2), maternal and fetal heart rate (HR), blood pressure (BP), and lactate, glucose, and arterial blood gasses. Percent change at each time point compared to baseline was determined for each variable. Statistical significance was determined by repeated measures analysis of variance. No changes were found between study and control animals in maternal BP; CO; lactate, glucose, oxygenation, or fetal HR; oxygenation, lactate, or glucose. Statistically significant differences (P < 0.01) between study and control animals were noted in ACP, Et CO2, MHR, UtBF, FBP, and Maternal/fetal pH, PCO2. All ewes delivered healthy lambs at full gestation. A CO2 pneumoperitoneum up to 15 mm Hg pressure in gravid ewes causes increased intrauterine pressure, decreased UtBF, and induces maternal and fetal acidosis. Despite these intraoperative deleterious effects, long-term fetal well being was not effected.
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PMID:Effects of CO2 pneumoperitoneum in pregnant ewes. 866 Dec 22

Cerebral blood flow (CBF), oxygen metabolism (CMRO2), and glucose metabolism (CMRGlc) were measured using positron emission tomography in five patients diagnosed as having mitochondrial encephalomyopathy. The molar ratio between the oxygen and glucose consumptions was reduced diffusely, as CMRO2 was markedly decreased and CMRGlc was slightly reduced. The CBF showed less changes. The CBF increase on hypercapnia was smaller than normal, though this was not significant. CBF with hypocapnia demonstrated a significant reduction compared with the normal. These results suggest that oxidative metabolism is impaired and anaerobic glycolysis relatively stimulated, due to a primary defect of mitochondrial function, and that mild lactic acidosis occurs in brain tissue because of impaired utilisation of pyruvate in the TCA cycle. As these findings appear to indicate directly a characteristic of this disease, such measurements may be a useful tool for assessment of the pathophysiology and for diagnosis of mitochondrial encephalomyopathy.
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PMID:Cerebral oxygen and glucose metabolism and blood flow in mitochondrial encephalomyopathy: a PET study. 869 16

1. We investigated the neural mechanisms of the increases in blood flow produced by synaptic activity using the parallel fiber (PF) system of the cerebellum as a model. The midline cerebellum was exposed in anesthetized rats and the PFs were stimulated with tungsten microelectrodes. Cerebellar blood flow (BFcrb) was recorded using a laser-Doppler probe, whereas field potentials were recorded using glass micropipettes. PF stimulation produced increases in BFcrb that were related to the frequency and intensity of stimulation (+60 +/- 9%, mean +/- SE, at 100 microA and 30 Hz; n = 6). The greatest increases were confined to a band stretching along the major axis of the stimulated folium and corresponding to the beam of activated PFs. The increase in evoked by PF stimulation was associated with a corresponding increase in glucose utilization, assessed by the 2-deoxyglucose method. The increases in BFcrb and the field potentials evoked by PF stimulation were abolished by tetrodotoxin (1 microM; n = 6). Ringer solution containing 12 mM Mg2+ and 0 mM Ca2+ blocked synaptic activity in the PFs and abolished the increases in flow (P > 0.05 from baseline; n = 5). The broad-spectrum glutamate receptor antagonist kynurenate (5 mM) prevented depolarization of Purkinje cells and interneurons and abolished the increase in BFcrb evoked by PF stimulation (P > 0.05; n = 6). Treatment with tetrodotoxin, Mg2+, or kynurenate did not affect the increase in BFcrb elicited by systemic hypercapnia or by topical application of the nitric oxide donor 3-morpholino sydnonimine (P > 0.05 from Ringer solution). We conclude that the increases in flow produced by synaptic activity are linked to glutamate-induced depolarization of Purkinje cells and interneurons. These findings provide evidence that activation of glutamate receptors participates in the mechanisms of functional hyperemia, and they support the validity of the PF system as a model for study of the relationship between synaptic activity and blood flow in the CNS.
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PMID:Neural mechanisms of blood flow regulation during synaptic activity in cerebellar cortex. 871 66


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