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

The activity and the isozyme B and C levels of red cell carbonic anhydrase was examined before and during CO2 inhalation in 18 patients with chronic respiratory failure. Carbonic anhydrase B and C levels did not change during 5 min breathing of high (8-9%) and low (3-5%) CO2 mixture. Carbonic anhydrase activity decreased in patients with combined hypercarbia (Paco2 greater than or equal to 45 mmHg) and hypoxemia (Pao2 less than or equal to 60 mmHg). This was accompanied by an increase in red cell K+ content, 2, 3-DPG and Hct/Hb. The activity did not change in patients with only hypoxemia. Carbonic anhydrase activity and plasma HCO-3 concentration were positively correlated (r = 0.4, P less than 0.05). A significant inverse correlation was also found between changes in red cell K+ content and those in carbonic anhydrase activity (r = - 0.42, P less than 0.05). These results indicate that 1), there is a dissociation between activity and isozyme levels in red cell carbonic anhydrase during the initial 5 min of CO2 breathing in patients with combined hypercarbia and hypoxemia, and 2), there seems a linkage exists between K+ movement across the red cell membrane and carbonic anhydrase activity.
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PMID:Effect of CO2 on carbonic anhydrase activity and isozyme levels in respiratory failure. 41 57

Asphyxia can cause neurologic damage in the fetus, but there are few data relating severity or duration of asphyxia to the degree of cerebral damage. We report cerebral histologic and electrophysiologic changes after asphyxia in chronically instrumented late-gestation fetal sheep. We reduced uterine blood flow to produce an ascending aortic blood oxygen content less than 1.5 mM for either 30 or 60 min (n = 13). In a subsequent protocol (n = 6), if full occlusion of the common uterine artery for 15 min did not reduce the EEG voltage to less than 20% of baseline, supplementary maternal hypoxia was added for a maximum of 120 min. Histologic outcome was assessed 3 d postinsult. Uterine artery occlusion resulted in severe hypoxemia, hypercarbia, acidosis, and an initial hypertension and bradycardia. Eight of 14 surviving fetuses showed neuronal damage, with greatest loss in the parasagittal cortex, striatum, and the CA1/2 region of the hippocampus. Neuronal damage was strongly associated with the percentage of decrease in blood pressure during the insult (r = 0.75, p less than 0.005) but not with the degree of hypoxia. No other factor was independently predictive, but, when considered separately, pH (r = 0.54; p less than 0.05) and loss of intensity of the EEG (r = 0.61, p less than 0.02) at the end of asphyxia were also correlated with outcome. The pH fell to less than 7.0 in six of eight fetuses with damage, whereas it remained greater than 7.0 in five of six without damage (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebral histologic and electrocorticographic changes after asphyxia in fetal sheep. 160 25

1. Interstitial pH (pHo) was measured with ion-selective microelectrodes in the fascia dentata of rats anaesthetized with urethane, while CO2 levels were controlled by varying pulmonary ventilation and CO2 content of inspired air. In the CA1 sector of hippocampal tissue slices in vitro pHo was similarly measured and altered by varying CO2 in the gas phase, or by adding HCl or NaOH to the artificial cerebrospinal fluid (ACSF) of the bath, or by changing the concentration of HCO3-. 2. Orthodromically evoked compound action potentials ('population spikes') were depressed in hypercapnia and increased in hypocapnia. In the fascia dentata of intact brains the population spike of the granule cells varied on average by more than 40% of control amplitude for each 0.1 change of pHo. In the CA1 zone of tissue slices in vitro, the change of population spike amplitude was approximately 30% per pH change of 0.1 caused by altered CO2 or HCO3- concentration, but only about 15% per pH change of 0.1 when HCl or NaOH were administered. 3. In anaesthetized rats the focal synaptic potential (FEPSP) evoked by a given stimulus intensity was weakly influenced by varying [CO2]; in tissue slices weak effects on FEPSP were inconsistent. In hippocampus both in situ and in vitro the population spike triggered by a given magnitude of FEPSP increased in hypocapnia and decreased in hypercapnia. This suggests that the main effect of CO2 is on the electric excitability of postsynaptic cells, with minor or no effect on transmitter release and on the interaction of the transmitter with its receptors. 4. Hypercapnia of anaesthetized rats was usually associated with a slight increase of [K+]o in the fascia dentata. Tissue [Ca2+]o changed little and not consistently. Neither of these two ions, nor concomitant changes of blood pressure or tissue partial pressure of oxygen, (Pt, O2), could account for the effects of pH on neuronal excitability. 5. The results show that increasing the extracellular concentration of H+ ions has a moderately depressant effect on the firing threshold of hippocampal neurones. The more powerful effects of elevated [CO2] and of lowered [HCO3-] may probably be explained by a direct effect on the neuronal membrane. The brain, by regulating breathing, controls its own excitability.
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PMID:Concentration of carbon dioxide, interstitial pH and synaptic transmission in hippocampal formation of the rat. 284 90

The objective of the study was to explore whether hypoglycemic brain damage is affected by super-imposed acidosis. To that end, animals with insulin-induced hypoglycemic coma, defined in terms of a negative DC potential shift, massive release of K+, or cellular uptake of Ca2+, were exposed to excessive hypercapnia (PaCO2 approximately 200 or approximately 300 mm Hg) during the last 25 min of the 30-min coma period. Animals were allowed to survive for 7 days before their brains were fixed by perfusion, and the cell damage was assessed by light microscopy. Other animals were analyzed with respect to changes in extracellular pH (pHe) or extracellular K+ or Ca2+ concentrations (K+e and Ca2+e, respectively). The total CO2 content (TCO2) was also measured to allow derivation of intracellular pH (pHi). The increase in PaCO2 to 190 +/- 15 and 312 +/- 23 mm Hg (means +/- SD) reduced the pHe from a predepolarization value of approximately 7.4 and a postdepolarization value (after the first 5 min of coma) of approximately 7.3 to 6.8 and 6.7, respectively. The corresponding mean pHi values were 6.7 and 6.5. The hypercapnia did not alter the K+e, which rose to 50-60 mM at the onset of hypoglycemic coma, but it increased the Ca2+e from approximately 0.05 to 0.10-0.16 mM. Normocapnic animals with induced hypoglycemic coma of 30-min duration showed the expected neuronal lesions in the neocortex, hippocampus, and caudoputamen. Hypercapnia clearly aggravated this damage, particularly in the caudoputamen, subiculum, and CA1 region of the hippocampus, and caused additional damage to cells in the CA3 region and piriform cortex. A rise in CO2 tension from approximately 200 to 300 mm Hg did not further aggravate the damage. The results thus demonstrate that relative moderate acidosis aggravates damage that is believed to be mostly neuronal, sparing glia cells and vascular tissue.
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PMID:The influence of acidosis on hypoglycemic brain damage. 779 41

The effects of hypercapnia, which has been reported to impair consciousness, on the long-term potentiation of the population spike in the CA1 pyramidal cell of the hippocampus in anesthetized rats were studied. Experimental hypercapnemia was induced by inspired 13% CO2 with 21% O2. Arterial blood gas analysis after 80 min inspired 13% CO2 showed pH 7.08+/-0.05, PCO2 = 104.09+/-12.86 mmHg, PO2 = 90.71+/-18.89 mmHg, BE -4.64+/-2.97 (mean +/- SD, n = 18). Inspired 13% CO2 reduced the amplitude of the population spike to 50% of the baseline. After delivery of tetanic stimulation (400 Hz, five bursts of eight pulses, inter-burst interval 1 s) population spike height was enhanced to pre-tetanic levels. Withdrawal of inspired CO2 unmasked an increase in population spike amplitude. These findings suggest that acute retention of carbon dioxide, which is designated as pure hypercapnemia without hypoxemia, may suppress hippocampal synaptic transmission but not its plasticity.
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PMID:Effects of experimental hypercapnia on hippocampal long-term potentiation in anesthetized rats. 1007 2

1. At present, CO2 is considered to be the most important factor in regulating cerebral blood flow by modification of the interstitial fluid and extracellular pH, but the mechanism by which hypercapnia produces vasodilation is still controversial. In the present paper we investigated the effect of hypercapnia on carbonic anhydrase (CA) activity. We also studied the combined effects of CO2 with either indomethacin or an L-arginine analogue on CA activity. 2. Nine groups of 12 rabbits each were established. Groups 1-4 were ventilated with a mixture of 10% CO2, 21% O2 and 69% N2 for 20, 60, 120 and 180 min. Group 5 rabbits received 15 mg/kg bodyweight, i.v., indomethacin and, after 1 h, were ventilated with a mixture of 10% CO2, 21% O2 and 69% N2 for 2 h. Group 6 animals were ventilated with a mixture of 10% CO2, 21% O2 and 69% N2 for 2 h and then received indomethacin. Group 7 rabbits received 100 mg/kg bodyweight, i.v., NG-monomethyl-L-arginine (L-NMMA) and, after 1 h, were ventilated with a mixture of 10% CO2, 21% O2 and 69% N2 for 2 h. Group 8 rabbits were ventilated for 2 h with a mixture of 10% CO2, 21% O2 and 69% N2 and were then administered L-NMMA. Group 9 rabbits received L-NMMA treatment concomitant with ventilation for 2 h with a mixture of 10% CO2, 21% O2 and 69% N2. In all groups, the erythrocyte CA activity was measured, as well as PaCO2 before and after ventilation or treatment. 3. The present study shows that CO2 reduces CA I activity down to complete inhibition and antagonizes the activating effects of indomethacin and L-NMMA on this isozyme. Our data prove that nitric oxide- and prostaglandin-induced CA I inhibition is involved in the vasodilation produced by hypercapnia. These results suggest that, due to subsequent pH changes, CA I is directly implicated in the modulation of vascular processes in the organism.
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PMID:Carbonic anhydrase I inhibition by nitric oxide: implications for mediation of the hypercapnia-induced vasodilator response. 1069 35

It recently has been shown that whole cell calcium and sodium currents are modulated by CO(2)/HCO(3)(-)-buffered saline. While the bicarbonate ion, but not CO(2), has been proven to modulate calcium currents, this information is lacking for sodium currents. Furthermore, it is not known whether the strength of modulation dependents on the bicarbonate concentration or whether it is an all-or-nothing phenomenon. To answer these questions, we used the whole cell voltage-clamp technique on freshly isolated hippocampal CA1 neurons from the rat. A voltage step from -130 to -20 mV elicited a sodium current with an amplitude of -5.1 +/- 0.5 nA (mean +/- SE, n = 17) when cells were superfused with HEPES-buffered saline. The amplitude of this current increased during a subsequent superfusion with solutions containing increasing amounts of bicarbonate and CO(2) (%CO(2)/mM HCO(3)(-): 2.5/5.6; 5.0/18; 10/37), with a maximal increment in 10% CO(2)/37 mM HCO(3)(-) of -6.9 +/- 0.8 nA. The increase in amplitude was associated with a linear negative shift (slope: -0.7 mV/mM HCO(3)(-)) of the potential of half-maximal activation (DeltaV(h,a): -19.4 +/- 1.8 mV in 10% CO(2)) but not with an alteration in the maximal conductance (g(max): HEPES: 203.1 +/- 21.0 nS and 10% CO(2)/37 mM HCO(3)(-): 207.3 +/- 21.3 nS). In addition, the potential of half-maximal inactivation (V(h,i)) shifted to more negative potentials (slope: -0.6 mV/mM HCO(3)(-)) with increasing amounts of bicarbonate and CO(2) (HEPES: -53.6 +/- 11.8 mV; 10% CO(2)/37 mM HCO(3)(-): -69.8 +/- 2.1 mV), making the amplitude of the current highly sensitive for small potential changes at resting membrane potential. The same negative shift in voltage dependence arose when cells were exposed to solutions with different amounts of bicarbonate (5.6; 18; 26 mM) but constant CO(2) (5%) with slope rates of -0.5 mV/mM HCO(3)(-) for V(h,a) and -0.5 mV/mM HCO(3)(-) for V(h,i). Again, there was no correlation between bicarbonate concentration and the size of g(max). When currents were evoked in solutions containing a constant concentration (18 mM) of bicarbonate but different amounts of CO(2) (2.5; 5.0 10%), no significant changes have been observed. The present data demonstrate that bicarbonate ions, and not CO(2), modulate voltage-gated sodium currents in a concentration-dependent manner. Because the amplitude of the sodium current becomes highly sensitive to membrane potential changes concomitant with increased bicarbonate amounts, this may be critical for the excitability of the neuronal network in situations (like metabolic acidosis, respiratoric alkalosis and hypercapnia) in which the concentration of this ion can alter.
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PMID:Relation between bicarbonate concentration and voltage dependence of sodium currents in freshly isolated CA1 neurons of the rat. 1261 66

The rat carotid body was immunohistochemically stained for carbonic anhydrase I, II and III (CA-I, CA-II and CA-III). Immunoreactivity for CA-I was distributed in type I cells, type II cells and nerve bundles. Smooth muscle cells and endothelial cells of blood vessels were also strongly stained for CA-I. CA-II immunoreactivity was distinctly positive in type I cells and nerve bundles. Vascular smooth muscle cells were weakly positive, and type II cells were negative for CA-II. CA-III immunoreactivity was identified in type I cells and vascular smooth muscle cells. Our results suggest that carbonic anhydrase isozymes in type I cells play an important role in chemoreception for hypercapnia. Immunoreactivities for CA-I and CA-II in the nerve fibres may participate in the synergic action of carotid sinus nerve between hypoxic and hypercapnic stimuli.
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PMID:Immunohistochemical localization of carbonic anhydrase isozymes in the rat carotid body. 1284 78

The conditions of the protein-synthesizing system in neurons of the hippocampus (areas CA1 and C A3) and of the cortex (sensomotor region) in rats subjected to y-irradiation at a dose of 8 Gy under hypothermia (16 - 18 degrees C) and hypoxia-hypercapnia were investigated by fluorescent and electron microscopy. Under hypothermia, the protein-synthesizing system was shown to be damaged to a lesser degree and to be restored faster in comparison with similar neurons in rats irradiated at room temperature. In rats irradiated under hypothermia, the rRNA biogenesis and the protein-synthesizing activity of polyribosomes were restored in two days. The protective influence of hypothermia did not spread to changes in membrane structures (endoplasmic reticulum and Golgy apparatus); i.e., a partial loss of integrity and possible transformation of their structure caused by the irradiation and the restoration of these structures occurred at a lower rate.
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PMID:[Protective effect of hypothermia on brain neurons of rats exposed to ionizing radiation]. 1763 50

Nicotine in cigarette smoke has been linked to several deleterious side effects on the offspring of smoking mothers, including impaired development of the sympathoadrenal system, abnormal arousal reflexes, and sudden infant death syndrome. Catecholamine (CA) release from adrenomedullary chromaffin cells (AMCs) in response to asphyxial stressors, e.g., low O(2) (hypoxia) and elevated CO(2) (hypercapnia), is critical for adaptation to extrauterine life and occurs before splanchnic innervation. Here, we investigated the effects of prenatal nicotine bitartrate exposure on the ability of neonatal (P0) rat AMCs to respond appropriately to asphyxial stressors. Control AMCs isolated from pups born to saline-treated dams displayed typical responses to hypoxia and hypercapnia, including inhibition of outward K(+) current, membrane depolarization, increased cytosolic calcium, and CA secretion. In contrast, P0 AMCs from pups born to nicotine-treated dams showed a marked suppression or loss of hypoxic sensitivity, although hypercapnic sensitivity and the expression of CO(2) markers (i.e., carbonic anhydrase I and II) appeared normal. Moreover, isolated saline-treated P0 AMCs lost their hypoxic sensitivity when grown in culture for approximately 1 wk in the presence of a subsaturating concentration of nicotine base (50 microM), and this effect was abolished by the nicotinic acetylcholine receptor (nAChR) blocker mecamylamine (100 microM). Taken together, these data suggest that the adverse effects of maternal smoking on sympathoadrenal function in the offspring are due in part to a loss or suppression of acute hypoxic sensitivity in adrenal chromaffin cells, triggered by the direct action of nicotine on endogenous nicotinic acetylcholine receptors.
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PMID:Chronic nicotine in utero selectively suppresses hypoxic sensitivity in neonatal rat adrenal chromaffin cells. 1807 Aug 22


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