Effect of repeated carbon monoxide exposure to rats on cytochrome P-450 concentration and activities of monooxygenases in the liver

To determine the possible role of cytochrome P-450 in the adaptation response of an organism to chronic carbon monoxide exposure, rats received 4, 15 or 30 subcutaneous CO injections (7.2 mmol/kg body mass; maximal COHb concentration about 56%). The concentration of cytochrome P-450 is significantly reduced after 4 injections. This effect is no longer evident following 15 or 30 CO injections, which produced distinct increases of the total hemoglobin concentration. Ethylmorphine N-demethylation is distinctly inhibited after 4, 15 and 30 CO injections, whereas the initial inhibition of ethoxycoumarin O-deethylation disappears after 30 CO administrations. Ethoxyresorufin O-deethylation is only slightly influenced by CO.     

Effect of work load on the content of carboxymyoglobin in the heart and skeletal muscles of rats exposed to carbon monoxide

Female albino rats were exposed to carbon monoxide in concentrations ranging from 130 to 1030 mg/m3 for a period of 40 minutes. During the last 20 minutes of exposure, the rats were subject to forced run on a flat treadmill moving at a rate of 400 m/hour. Immediately after termination of exposure, the concentration of carboxyhemoglobin and lactic acid in blood, as also the concentration of carboxymyoglobin in the heart and skeletal muscles were determined. Work load did not influence the level of carboxyhemoglobin in blood, though inducing an increase in the concentration of carboxymyoglobin in both the heart muscle and the skeletal muscle. The increase in the concentration of lactic acid in the blood was observed only in rats exposed to carbon monoxide in an average concentration of 1030 mg/m3 and simultaneous work load. Results of the observations demonstrate that simultaneous effect of carbon monoxide and work load can induce more severe tissue hypoxia than could be expected on the basis of carboxyhemoglobin concentration in the blood.     

Analysis of factors that influence rates of carbon monoxide uptake, distribution, and washout from blood and extravascular tissues using a multicompartment model.

To better understand factors that influence carbon monoxide (CO) washout rates, we utilized a multicompartment mathematical model to predict rates of CO uptake, distribution in vascular and extravascular (muscle vs. other soft tissue) compartments, and washout over a range of exposure and washout conditions with varied subject-specific parameters. We fitted this model to experimental data from 15 human subjects, for whom subject-specific parameters were known, multiple washout carboxyhemoglobin (COHb) levels were available, and CO exposure conditions were identical, to investigate the contributions of exposure conditions and individual variability to CO washout from blood. We found that CO washout from venous blood was biphasic and that postexposure times at which COHb samples were obtained significantly influenced the calculated CO half times (P < 0.0001). The first, more rapid, phase of CO washout from the blood reflected the loss of CO to the expired air and to a slow uptake by the muscle compartment, whereas the second, slower washout phase was attributable to CO flow from the muscle compartment back to the blood and removal from blood via the expired air. When the model was used to predict the effects of varying exposure conditions for these subjects, the CO exposure duration, concentration, peak COHb levels, and subject-specific parameters each influenced washout half times. Blood volume divided by ventilation correlated better with half-time predictions than did cardiac output, muscle mass, or ventilation, but it explained only approximately 50% of half-time variability. Thus exposure conditions, COHb sampling times, and individual parameters should be considered when estimating CO washout rates for poisoning victims.     

Carbon monoxide effects on calcium levels in vascular smooth muscle

Previously we showed that carbon monoxide (CO) relaxes vascular smooth muscle in the working heart and thoracic aorta preparations perfused with hemoglobin-free, Krebs-Henseleit (KH) solution. The CO-induced relaxation was not caused by hypoxia, nor was it mediated by adrenergic influences, adenosine, or prostaglandins. In these studies the effect of CO on calcium (Ca++) concentrations in vascular smooth muscle was determined using 45Ca as a tracer. Isolated rat thoracic aorta segments were incubated with 45Ca and gassed with O2, N2, or CO for 60 min. Verapamil was used to verify the effectiveness of the test system. Ca++ concentrations were 488 +/- 35 and 515 +/- 26 mM/g tissue (X +/- SE) in aortic rings gassed with O2 and N2, respectively. CO reduced Ca++ concentrations significantly (P less than 0.01) by 29% to 369 +/- 18 mM/g tissue. Verapamil treatment reduced Ca++ concentrations by 40% to 314 +/- 23 mM/g tissue. These results suggest that CO relaxes vascular smooth muscle and dilates blood vessels by decreasing Ca++ concentrations in vascular smooth muscle.     

A study of vibrational relaxation of B-state carbon monoxide in the heme pocket of photolyzed carboxymyoglobin.

The vibrational energy relaxation of dissociated carbon monoxide in the heme pocket of sperm whale myoglobin has been studied using equilibrium molecular dynamics simulation and normal mode analysis methods. Molecular dynamics trajectories of solvated myoglobin were run at 300 K for both the delta- and epsilon-tautomers of the distal histidine, His64. Vibrational population relaxation times were estimated using the Landau-Teller model. For carbon monoxide (CO) in the myoglobin epsilon-tautomer, for a frequency of omega0 = 2131 cm-1 corresponding to the B1 state, T1epsilon(B1) = 640 +/- 185 ps, and for a frequency of omega0 = 2119 cm-1 corresponding to the B2 state, T1epsilon(B2) = 590 +/- 175 ps. Although the CO relaxation rates in both the epsilon- and delta-tautomers are similar in magnitude, the simulations predict that the vibrational relaxation of the CO is faster in the delta-tautomer. For CO in the myoglobin delta-tautomer, it was found that the relaxation times were identical within error for the two CO substate frequencies, T1delta(B1) = 335 +/- 115 ps and T1delta(B2) = 330 +/- 145 ps. These simulation results are in reasonable agreement with experimental results of Anfinrud and coworkers (unpublished results). Normal mode calculations were used to identify the dominant coupling between the protein and CO molecules. The calculations suggest that the residues of the myoglobin pocket, acting as a first solvation shell to the CO molecule, contribute the primary "doorway" modes in the vibrational relaxation of the oscillator.     

Effect of potassium deficiency on carbon dioxide,cation, and phosphate content of muscle,with a note on the carbon dioxide content of human muscle

Albino rats weighing 160 to 175 gm. were fed a complete synthetic diet containing 0.003 per cent potassium and 0.7 per cent sodium for 40 days. Controls were given the same diet plus adequate added potassium. 1. Data from analyses of serum and skeletal muscle showed (a) a fall in serum chloride concentration and an increase in serum carbon dioxide concentration and pH in the potassium-deficient rats; (b) increases of sodium, magnesium, and calcium and a decrease of potassium in the muscle of the potassium-deficient rats; (c) no change of muscle chloride or carbon dioxide concentrations in the potassium-deficient rats. (2) Application of the Wallace-Hastings calculations to these data revealed (a) intracellular pH of the skeletal muscle of the normal rat to be 6.98 +/- 0.08; (b) an increase in serum partial pressure of carbon dioxide (pCO(2)) in potassium deficiency, together with increases in concentrations of [H(2)CO(2)] and [HCO(3) (-)] per kg. extracellular water and [H(2)CO(3)] per kg. cell water; (c) a decrease in values for [CO(2)] and [HCO(3) (-)] per kg. intracellular water; (d) a fall of intracellular pH in potassium deficiency to 6.42 +/- 0.05. (3) Analyses of sacrospinalis muscle from five men undergoing operation for ruptured intervertebral disc showed a mean value of 9.46 +/- 1.31 mM carbon dioxide per kg. blood-free tissue. Some problems of interpretation of data are briefly discussed.     

Identification of the rhaA, rhaB and rhaD gene products from Escherichia coli K-12

Washed cells of Peptostreptococcus products (strain Marburg), which were incubated in the presence of CO/CO2/N2 (50%/17%/33%; 200 kPa) catalyzed the synthesis of acetate from carbon monoxide. The rate of acetate formation from CO was stimulated more than threefold by the addition of sodium (10 mM); potassium did not effect acetate synthesis. The degree of stimulation was dependent on the sodium concentration; the dependence followed simple Michaelis-Menten kinetics. The apparent Km for sodium was determined to be about 2 mmol/l. Sodium also stimulated acetate synthesis from H2 plus CO2. In the absence of added sodium the formation of formate as an intermediate in methyl group synthesis was stimulated. It is suggested that the sodium dependent reaction(s) is one (or more) of the reactions involved in methyl group synthesis from CO2.     

Biohydrogen production from CO-rich syngas via a locally isolated Rhodopseudomonas palustris PT

Biohydrogen production through water–gas shift (WGS) reaction by a biocatalyst was conducted in batch fermentation. The isolated photosynthetic bacterium Rhodopseudomonas palustris PT was able to utilize carbon monoxide and simultaneously produce hydrogen. Light exposure was provided as an indispensable requirement for the first stage of bacterial growth, but throughout the hydrogen production stage, the energy requirement was met through the WGS reaction. At ambient pressure and temperature, the effect of various sodium acetate concentrations in presence of CO-rich syngas on cell growth, carbon monoxide consumption, and biohydrogen production was also investigated. Maximal efficiency of hydrogen production in response to carbon monoxide consumption was recorded at 86 % and the highest concentration of hydrogen at 33.5 mmol/l was achieved with sodium acetate concentration of 1.5 g/l. The obtained results proved that the local isolate; R. palustris PT, was able to utilize CO-rich syngas and generate biohydrogen via WGS reaction.     

1953-2011年小兴安岭森林火灾含碳气体排放的估算

根据1953-2011年小兴安岭森林调查数据和森林火灾统计资料,结合野外火烧迹地调查与室内控制试验数据,估算了小兴安岭1953-2011年森林火灾的碳排放量和含碳气体排放量.结果表明: 1953-2011年小兴安岭森林火灾的总碳排放量为1.12×10⁷ t,年均排放量为1.90×10⁵ t,约占全国年均森林火灾碳排放量的1.7%;其中,含碳气体CO₂、CO、CH₄和非甲烷烃(NMHC)的排放量分别为3.39×10⁷、1.94×10₅、1.09×10⁵和7.46×10⁴ t,相应年均排放量5.74×10⁵、3.29×10⁴、1.85×10³、1.27×10³ t分别占全国年均森林火灾含碳气体排放量的1.4%、1.2%、1.7%和1.1%.不同林型的燃烧效率和单位过火面积的碳排放量均为针叶林＞阔叶林＞针阔混交林.最后提出了合理的林火管理措施.     

Prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 and carbon monoxide reduces extracellular glutamate levels in primary rat cerebral cortex cell cultures

The effects of prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 (0.5 mg/kg s.c.), alone or in combination with carbon monoxide, on extracellular glutamate levels in primary rat cerebral cortical neuronal cultures, were investigated. Dam weight gain, pregnancy length and litter size at birth were not affected by prenatal treatment with WIN 55,212-2 and carbon monoxide alone or in combination. Basal and K(+)-evoked extracellular glutamate levels were reduced in cortical cultures from pups born to mothers exposed to WIN 55,212-2 and carbon monoxide alone or in combination compared to cultures from rats born to vehicle-treated mothers. In cultures obtained from rats exposed to vehicle or carbon monoxide alone during gestation, WIN 55,212-2 (0.01-100 nM) increased extracellular glutamate levels, displaying a bell-shaped concentration-response curve. In cultures from rats born to mothers exposed to WIN 55,212-2 alone or in combination with carbon monoxide the WIN 55,212-2 ( 1 nM)-induced increase in extracellular glutamate levels was lower than that observed in cultures from rats born to vehicle-treated mothers and similar at those observed at 10 and 100 nM concentrations. The selective CB1 receptor antagonist SR141716A (10 nM) counteracted the WIN 55,212-2-induced increase in extracellular glutamate levels in cultures exposed to vehicle or carbon monoxide during gestation, but failed to antagonise it in cultures from rats born to mothers exposed to WIN 55,212-2 alone or in combination with carbon monoxide. These findings provide evidence that prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 and carbon monoxide, alone or in combination, is associated with an impairment in cortical glutamatergic transmission. It could be speculated that such detrimental effects might be involved in the reported deficit in learning and memory associated with prenatal marijuana exposure.     

Resonance Raman studies of CO and O2 binding to elephant myoglobin (distal His(E7)----Gln)

Carbon monoxide and dioxygen were employed as resonance Raman-visible ligands for probing the nature of the heme-binding site in elephant myoglobin, which has glutamine in the distal position (E7) instead of the usual histidine. The distal histidine (E7) residue has been thought to be responsible for weakening carbon monoxide binding to hemoproteins. It is of interest to see how the His(E7)----Gln replacement affects such parameters as nu(Fe-N epsilon), nu(Fe-CO), delta(Fe-C-O), nu(C-O), delta(Fe-O-O), and nu(O-O) vibrational frequencies and relative intensities. Elephant myoglobin has a CO affinity approximately 6 times higher than that for human/sperm whale myoglobin (Mb). If this enhanced affinity were solely due to the removal of some of the steric hindrance that normally tilts the CO off the heme axis, one would expect the nu(Fe-CO) frequency to decrease and the nu(C-O) frequency to increase relative to the corresponding values in sperm whale Mb. However, the opposite was found. In addition, strong enhancement of the Fe-C-O bending mode was observed. These results suggest that the Fe-C-O linkage remains distorted. In elephant Mb, new interactions resulting from the conformational change accompanying ligand binding may be responsible for the increased CO binding. Similar spectra were obtained for elephant and sperm whale oxymyoglobin. This suggests that the interactions of bound O2 are not markedly affected by the glutamine replacement.     

The role of alpha-adrenergic receptors in carbon monoxide hypoxia

The importance of alpha-adrenergic receptors in the cardiac output and peripheral circulatory responses to carbon monoxide (CO) hypoxia was studied in anesthetized dogs. Phenoxybenzamine (3 mg/kg i.v.) was injected to block alpha-receptor activity and the data obtained were then compared with those from a previous study of CO hypoxia in unblocked animals. Values for cardiac output, hindlimb blood flow, vascular resistance, and oxygen uptake were obtained prior to and at 30 and 60 min of CO hypoxia which reduced arterial oxygen content by approximately 50%. alpha-Adrenergic blockade resulted in a lower (p less than 0.05) control value for cardiac output than observed in unblocked animals, but no differences were present between the two groups at 30 or 60 min of CO hypoxia. Similarly, limb blood flow was lower (p less than 0.05) during the control period in the alpha-blocked group but rose to the same level as that in the unblocked animals at 60 min of COH. No change in limb blood flow occurred during CO hypoxia in the unblocked group. These findings demonstrated that during CO hypoxia alpha-receptor mediated venoconstriction does not contribute to the cardiac output response and alpha-receptor mediated vasoconstriction probably does prevent a rise in hindlimb skeletal muscle blood flow.     

Lactate as substrate for glycogen resynthesis after exercise

Muscle glycogen levels in the perfused rat hemicorpus preparation were reduced two-thirds by electrical stimulation plus exposure to epinephrine (10(-7) M) for 30 min. During the contraction period muscle lactate concentrations increased from a control level of 3.6 +/- 0.6 to a final value of 24.1 +/- 1.6 mumol/g muscle. To determine whether the lactate that had accumulated in muscle during contraction could be used to resynthesize glycogen, glycogen levels were determined after 1-3 h of recovery from the contraction period during which time the perfusion medium (flow-through system) contained low (1.3 mmol/l) or high (10.5 or 18 mmol/l) lactate concentrations but no glucose. With the low perfusate lactate concentration, muscle lactate levels declined to 7.2 +/- 0.8 mumol/g muscle by 3 h after the contraction period and muscle glycogen levels did not increase (1.28 +/- 0.07 at 3 h vs. 1.35 +/- 0.09 mg glucosyl U/g at end of exercise). Lactate disappearance from muscle was accounted for entirely by output into the venous effluent. With the high perfusate lactate concentrations, muscle lactate levels remained high (13.7 +/- 1.7 and 19.3 +/- 2.0 mumol/g) and glycogen levels increased by 1.11 and 0.86 mg glucosyl U/g, respectively, after 1 h of recovery from exercise. No more glycogen was synthesized when the recovery period was extended. Therefore, it appears that limited resynthesis of glycogen from lactate can occur after the contraction period but only when arterial lactate concentrations are high; otherwise the lactate that builds up in muscle during contraction will diffuse into the bloodstream.     

Chronic carbon monoxide enhanced IbTx-sensitive currents in rat resistance pulmonary artery smooth muscle cells

Exogenous carbon monoxide (CO) can induce pulmonary vasodilation by acting directly on pulmonary artery (PA) smooth muscle cells. We investigated the contribution of K+ channels to the regulation of resistance PA resting membrane potential on control (PAC) rats and rats exposed to CO for 3 wk at 530 parts/million, labeled as PACO rats. Whole cell patch-clamp experiments revealed that the resting membrane potential of PACO cells was more negative than that of PAC cells. This was associated with a decrease of membrane resistance in PACO cells. Additional analysis showed that outward current density in PACO cells was higher (50% at +60 mV) than in PAC cells. This was linked to an increase of iberiotoxin (IbTx)-sensitive current. Chronic CO hyperpolarized membrane of pressurized PA from -46.9 +/- 1.2 to -56.4 +/- 2.6 mV. Additionally, IbTx significantly depolarized membrane of smooth muscle cells from PACO arteries but not from PAC arteries. The present study provides initial evidence of an increase of Ca2+-activated K+ current in smooth muscle cells from PA of rats exposed to chronic CO.     

Weedy adaptation in Setaria spp. V. Effects of gaseous environment on giant foxtail (Setaria faberii) (Poaceae) seed germination

The effects that naturally occurring gases (oxygen, nitrogen, carbon monoxide) may cause in dormant giant foxtail (Setaria faberii) seed germination under favorable temperature and moisture conditions were investigated. The germination responses to gas mixtures supported the hypothesis that S. faberii germination behavior is regulated by the amount of oxygen taken into hydrated seed over time. Setaria faberii seed germination was markedly affected by O(2) concentration (in N(2)) above and below that of air (20% O(2)): the largest increase in germination (from 37 to 60%) occurred between 20-25% O(2); between 0-10% O(2), germination increased from 0-30%; and surprisingly germination at 10 and 20% O(2) was similar. These observations reveal an asymmetrical response to incremental changes in O(2) above and below that typically found in agricultural soils. Carbon monoxide had opposite effects on S. faberii germination in air depending on concentration, stimulation, and inhibition: germination increased from 37 to 56% with the addition of 1% CO, but decreased from 37 to 14% with 75% added CO. An explanation may be that there are two separate effects of CO, each occurring in different physiological systems of dormant seeds at the same time. At high concentrations (75%) in air CO inhibited seed germination, probably by inhibiting mitochondrial respiration. But low CO concentrations (0.1 or 1%) in air stimulated seed germination. It was not apparent which physiological system(s) CO and O(2) affected. It seems unlikely that CO-stimulated germination arises from effects on the respiratory apparatus, but may be a consequence of CO interactions with an as yet unknown physiological factor in the seed. We provide a model of Setaria spp. dormancy consistent with its seed morphology, the gas-germination data, and the hypothesized second physiological factor that may be involved in CO stimulated germination.     

Reactivity of ferrous myoglobin at low pH.

The rates of reaction of myoglobin with carbon monoxide at low pH are reported. The pH versus rate profile of these kinetics resembles that found for heme model compounds, revealing an increase in combination rate at low pH. These facts suggest that CO binding by myoglobin changes from a mechanism of "direct ligant association" at pH 5 to a mechanism, similar to that proposed for heme model compounds, which assumes a tetracoordinated intermediate as a result of the protonation of the proximal imidazole.     

Growth of Seliberia carboxydohydrogena carboxy bacteria with an altered composition of the gas mixture

The growth and gas exchange of Seliberia carboxydohydrogena Z-1062 were studied in the regime of turbidostat when the conditions of gaseous nutrition were changed: a decrease in hydrogen concentration and an increase in carbon monoxide concentration, growth on two carbon sources (CO+CO2) and on two energy sources (H2+CO). The inhibition of the bacterial growth by CO was expressed in a decrease of the specific growth rate and in the reduced effectiveness of using a gaseous substrate. When the concentration of carbon monoxide was elevated from 0 to 40% and that of hydrogen was reduced from 80 to 40%, the specific growth rate of the cells was decreased from 0.4 to 0.04 h-1; here, the economic coefficient in terms of hydrogen fell from 3.6 to 0.62 g/g. The CO-oxidizing system of the bacterium was shown to be resistant. The rate of CO oxidation by the culture was from 0.6 to 0.8 L/h per 1 g of the synthesized biomass at the following concentration of gases in the medium (%); H2, 80-40; CO2, 5; O2, 15; CO, 10-40. The rate of CO oxidation by the culture rose when hydrogen concentration was decreased and CO concentration was increased.     

Regulation of carbon monoxide dehydrogenase and hydrogenase in Rhodospirillum rubrum: effects of CO and oxygen on synthesis and activity.

Exposure of the photosynthetic bacterium Rhodospirillum rubrum to carbon monoxide led to increased carbon monoxide dehydrogenase and hydrogenase activities due to de novo protein synthesis of both enzymes. Two-dimensional gels of [35S]methionine-pulse-labeled cells showed that induction of CO dehydrogenase synthesis was rapidly initiated (less than 5 min upon exposure to CO) and was inhibited by oxygen. Both CO dehydrogenase and the CO-induced hydrogenase were inactivated by oxygen in vivo and in vitro. In contrast to CO dehydrogenase, the CO-induced hydrogenase was 95% inactivated by heating at 70 degrees C for 5 min. Unlike other hydrogenases, this CO-induced hydrogenase was inhibited only 60% by a 100% CO gas phase.     

Effect of dietary protein, zinc, and carbon monoxide on fetal zinc concentration in mice

Dietary protein and zinc deficiencies known to be detrimental to the developing fetus are common in pregnant women in developing countries. Everyone in modern society is at risk of exposure to carbon monoxide (CO). This study was conducted to observe the effect of dietary protein, zinc, and exposure to CO on the fetal zinc concentrations by factorial experimentation. Pregnant mice of CD-1 strain were maintained on 17% (control) or 9% (deficient) protein diets mixed with deficient, normal (control), or supplemental zinc throughout gestation. The dams in each dietary group were exposed to air (control) or 500 ppm CO in air in environmental chambers from gestation day 8 to gestational day 18. The dams were sacrificed on d 18 and fetal zinc levels were measured by atomic absorption spectrophotometry. Carbon monoxide levels used in this study had no significant effect on fetal zinc concentration in any treatment group. When both dietary protein and zinc levels were normal, the mean fetal zinc concentrations were higher than all other dietary protein/zinc combinations (15.2±6.0 and 14.2±4.1 μg Zn/g of tissue for 0 and 500 ppm CO levels). However, when dietary protein levels were deficient, supplemental zinc increased the fetal zinc concentrations significantly (12.7±3.8 and 13.1±0.3.6 μg Zn/g of tissue, in 0 and 500 ppm CO groups) as compared to zinc-deficient groups (8.7±3.0 and 10.0±3.3 μg Zn/g of tissue in 0 and 500 ppm CO groups). The results of this study may be relevant to populations that experience both marginal zinc and protein diets during gestation.     

Effect of vacuolization on the sodium concentration in an isolated muscle fiber]

Using the Perkin Elmer flame photometer sodium and potassium concentrations have been measured in muscle fibers from the m. ileofibularis of Rana temporaria. After 30 minutes preincubation in the Ringer solution, made hypertonic by the addition of 0.22M glycerol, the muscle fibers were incubated in the normal Ringer solution for 30 min. These fibers showed a vacuolation and an increase in total fiber sodium up to 37.2 mmol/l +/- 5.9 S. E., or 45.8 mmol/kg H2O +/- 7.3 S. E. No significant changes in potassium concentration were observed. Then, the fibers were exposed again to the Ringer solution containing 0.22 M glycerol. This procedure caused the disappearance of vacuoles and decrease in fiber sodium concentration down to 17.7 mmol/l +/- 1.6 S. E., or 21.8 mmol/kg H2O +/- 2.0 S. E. The effect of vacuolation was not blocked by ouabain (1.10(-4) M). It is suggested that the vacuoles have a high NaCl concentration. A model for NaCl and water accumulation in T-tubules is presented.