A photochemical method for rapid and precise determination of carbon monoxide levels in blood.

A simple and inexpensive flash photolysis apparatus for determination of the level of carbon monoxide saturation of blood samples is described. Saturation with CO is determined by observing the change in light transmission at 432 nm produced on photolysis of bound CO with a light flash. The procedure is highly specific for carbon monoxide, requires less than 5 μl of blood (obtainable from a finger prick), and has a resolution better than 0.1% in saturation. In addition the apparatus does not require frequent calibration.     

Circulatory effects and kinetics following acute administration of carbon monoxide in a porcine model

Carbon monoxide is produced in the endothelial cells and has possible vasodilator activity through three different pathways. The aim of this study was to demonstrate circulatory effects after administration of saturated carbon monoxide blood and to describe the pharmacokinetics of carbon monoxide. Six pigs were anesthetized and 150 ml blood was removed. This blood was bubbled with carbon monoxide until the carboxyhemoglobin (COHb) levels were 90-99%. A specific amount of this blood was then injected back to the animal. At predetermined times; arterial and mixed venous blood was drawn and analyzed for carbon monoxide. Systemic and pulmonary vascular resistance index (SVRi and PVRi) were measured and exhaled air was sampled and measured for carbon monoxide. Blood samples were gathered over 300 minutes along with measurements of invasive pressures, heart rate, cardiac output, oxygen saturation (SpO2), Hb, temperature and blood gases. We conclude that this type of exposure to carbon monoxide appears to have little or no effect on general vasomotor tone and, after correcting for basal levels of carbon monoxide, elimination occurs through the lungs as predicted by a single compartment model. The half-life of carbon monoxide was determined to be 60.5 minutes (SEM 4.7).     

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.     

Carbon monoxide protects against hyperoxia-induced endothelial cell apoptosis by inhibiting reactive oxygen species formation

Hyperoxia causes cell injury and death associated with reactive oxygen species formation and inflammatory responses. Recent studies show that hyperoxia-induced cell death involves apoptosis, necrosis, or mixed phenotypes depending on cell type, although the underlying mechanisms remain unclear. Using murine lung endothelial cells, we found that hyperoxia caused cell death by apoptosis involving both extrinsic (Fas-dependent) and intrinsic (mitochondria-dependent) pathways. Hyperoxia-dependent activation of the extrinsic apoptosis pathway and formation of the death-inducing signaling complex required NADPH oxidase-dependent reactive oxygen species production, because this process was attenuated by chemical inhibition, as well as by genetic deletion of the p47(phox) subunit, of the oxidase. Overexpression of heme oxygenase-1 prevented hyperoxia-induced cell death and cytochrome c release. Likewise, carbon monoxide, at low concentrations, markedly inhibited hyperoxia-induced endothelial cell death by inhibiting cytochrome c release and caspase-9/3 activation. Carbon monoxide, by attenuating hyperoxia-induced reactive oxygen species production, inhibited extrinsic apoptosis signaling initiated by death-inducing signal complex trafficking from the Golgi apparatus to the plasma membrane and downstream activation of caspase-8. We also found that carbon monoxide inhibited the hyperoxia-induced activation of Bcl-2-related proteins involved in both intrinsic and extrinsic apoptotic signaling. Carbon monoxide inhibited the activation of Bid and the expression and mitochondrial translocation of Bax, whereas promoted Bcl-X(L)/Bax interaction and increased Bad phosphorylation. We also show that carbon monoxide promoted an interaction of heme oxygenase-1 with Bax. These results define novel mechanisms underlying the antiapoptotic effects of carbon monoxide during hyperoxic stress.     

Use of a One-man,Mobile Pressure Chamber in the Treatment of Carbon Monoxide Poisoning

For the past five years a mobile pressure chamber has been used to treat patients suffering from severe carbon monoxide poisoning with oxygen at 2 atmospheres pressure. Of the 25 patients treated, 20 recovered completely and only three died. This apparatus could also be used for hyperbaric oxygen therapy in other conditions for which it is indicated.     

Generation of high-purity hydrogen from cellulose by its mechanochemical treatment

Cellulose was mixed with the hydroxides of lithium and nickel and the mixture was milled, followed by heating to produce hydrogen. Several analytical methods of X-ray diffraction (XRD), thermogravimetry/mass spectrometry (TG/MS) and gas chromatography (GC) were used to characterize the samples. Hydrogen was emitted when heating the milled sample around 400 °C together with low concentrations of methane, carbon monoxide and carbon dioxide. It is understood that an interaction occurs between cellulose and lithium hydroxide to convert the carbon of cellulose into lithium carbonate and to emit hydrogen correspondingly. It is also found that nickel catalyst is required to facilitate the interaction and the behaviours of three different nickel compounds were compared. When high yield of hydrogen emission is available, the prepared samples can also serve the purpose of hydrogen storage.     

Effects of emissions from different type of residential heating upon cyclic guanosine monophosphate (cGMP) in blood platelets of residents

We hypothesized that different types of residential heating would be associated with different levels of indoor carbon monoxide (CO) and further that this might result in a differential in the concentration of cyclic 3′:5′ guanosine monophosphate (cGMP) in blood platelets in exposed residents. Individuals, who were recruited from homes using different fuel for heating, donated a venous blood sample in the winter and in the summer. In the winter the median blood platelet cGMP value for the group using liquid propane gas (LPG) was 65% higher than for the group using piped natural gas for heating (p <0.001). Also in the group using LPG, the median concentration of cGMP in the winter was 39% higher than the summer median (p?<?0.003). The mean indoor concentrations of CO were measured over a period of 1 week during the winter and were <1 ppm. We conclude that observed differences were associated with emissions from different types of heating but that CO exposure alone is too low to explain these.     

Metabolism of haloforms to carbon monoxide. IV. Studies on the reaction mechanism in vivo

In vivo studies have been carried out in order to understand more fully the mechanism of haloform oxidation to carbon monoxide. A deuterium isotope effect on carbon monoxide production from chloroform was observed in both control and phenobarbital-treated rats. Diethyl maleate treatment decreased blood carbon monoxide concentrations produced from bromoform and chloroform and attenuated the effect of deuterium substitution on the metabolism of both compounds to carbon monoxide. Cysteine also decreased blood carbon monoxide concentrations seen after giving chloroform. A reaction mechanism similar to that proposed on the basis of in vitro data, which included a central role for dihalocarbonyl compounds in the formation of 2-oxothiazolidine-4-carboxylic acid, carbon monoxide, and carbon dioxide, is suggested for the in vivo metabolism of haloforms to carbon monoxide. These data indicate that carbon monoxide production may be a detoxification pathway for haloforms and that both the inhibition of carbon monoxide production from haloforms and the potentiation of haloform-hepatotoxicity by diethyl maleate are due to the depletion of glutathione.     

The formation of carbon monoxide during peroxidation of microsomal lipids

The evolution of carbon monoxide during lipid peroxidation has been demonstrated in microsomal membranes. The formation of carbon monoxide was dependent on the peroxidation process, but independent of the initiators (NADPH-ADP x Fe(+3) or Ascorbate-Fe(+3)) used. Contrary to published results, the carbon monoxide does not result from heme catabolism. Carbon monoxide was generated during the peroxidation of isolated phospholipids, indicating that carbon monoxide may form directly during the peroxidative degradation of unsaturated fatty acids.     

代谢组学在一氧化碳中毒研究的应用和展望

一氧化碳中毒是常见的以中枢神经系统损害为主的全身性疾病。一氧化碳作为一个脂溶性分子,进入细胞内造成组织缺氧。一氧化碳是否可以诱导产生其他特定的生物学效应,还需要我们去研究。代谢组学是继基因组学、转录组学、蛋白质组学后的又一新兴学科,在肿瘤、糖尿病、冠心病、肥胖症、脑卒中等多种临床疾病的相关研究中显示出巨大的潜力。将代谢组学技术应用到一氧化碳中毒研究中,可以加深对一氧化碳中毒发病机制的认识,丰富早期诊断方法,改善治疗效果的监测手段。但代谢组学技术在一氧化碳中毒研究中的应用仍是凤毛麟角,我们在此对代谢组学在一氧化碳中毒研究中应用及前景作一展望。     

A 4-AP-sensitive current is enhanced by chronic carbon monoxide exposure in coronary artery myocytes

A physiological role of carbon monoxide has been suggested for coronary myocytes; however, direct evidence is lacking. The objective of this study was to test the effect of chronic carbon monoxide exposure on the K(+) currents of the coronary myocytes. The effect of 3-wk chronic exposure to carbon monoxide was assessed on K(+) currents in isolated rat left coronary myocytes by the use of the patch-clamp technique in the whole cell configuration. Moreover, membrane potential studies were performed on coronary artery rings using intracellular microelectrodes, and coronary blood flow in isolated heart preparation was recorded. Carbon monoxide did not change the amplitude of global whole cell K(+) current, but it did increase the component sensitive to 1 mM 4-aminopyridine. Carbon monoxide exposure hyperpolarized coronary artery segments by approximately 10 mV and, therefore, increased their sensitivity to 4-aminopyridine. This effect was associated with an enhancement of coronary blood flow. We conclude that chronic carbon monoxide increases a 4-aminopyridine-sensitive current in isolated coronary myocytes. This mechanism could, in part, contribute to hyperpolarization and to increased coronary blood flow observed with carbon monoxide.     

A Resting-State Functional Magnetic Resonance Imaging Study of Acute Carbon Monoxide Poisoning in Humans

The objective of this study was to evaluate the brain function characteristics of carbon monoxide poisoning patients using resting-state functional magnetic resonance imaging (fMRI) method. For this purpose, 12 carbon monoxide poisoning patients and healthy controls were subjected to resting-state fMRI scans separately. A regional homogeneity (ReHo) approach was used to analyze the brain function in carbon monoxide poisoning patients. Compared with control group, the value of ReHo in carbon monoxide poisoning group showed distinct decrease in bilateral superior frontal gyrus, middle frontal gyrus, right cuneus, left middle temporal gyrus, right insula, and cerebellum. Therefore, it was concluded that the brain functions in carbon monoxide poisoning patients were abnormal under the resting-state. The cuneate lobe function may indicate the degree of brain hypoxia and strengthening the cerebellar function training may promote the rehabilitation process.     

Production of trace levels of carbon monoxide during methanogenesis on acetate and methanol

Summary Production of trace levels of carbon monoxide was consistently observed in the off-gas of a laboratory anaerobic digester fed Waste Activated Sludge. Inocula from this digester was enriched for acetate and methanol utilizing methanogenic populations. These enriched inocula were then monitored in batch assays for carbon monoxide and hydrogen production. Results demonstrated that carbon monoxide is produced during methanogenesis on both substrates. Subsequent utilization of CO was observed to occur after methane production was essentially complete for the assays conducted with methanol. Carbon monoxide evolution during methanogenesis on acetate displayed a markedly different trend from that observed from methanol.     

Alteration in the Postnatal Ontogeny of Cerebellar Norepinephrine Content Following Chronic Prenatal Carbon Monoxide

The postnatal ontogeny of norepinephrine content in the cortex and cerebellum was determined in rats exposed prenatally to a chronic low level of carbon monoxide (150 parts per million). In the cerebellum, norepinephrine concentration and total norepinephrine content among carbon monoxide-exposed rats were consistently elevated over that of control rats from the second through the sixth postnatal weeks. In the cortex, norepinephrine concentration and total norepinephrine content among carbon monoxide-exposed rats did not differ from that of control rats over the same period. These results identify the cerebellum as a region whose postnatal development is altered by prenatal exposure to low levels of carbon monoxide-induced hypoxia.     

Would a medium-nicotine,low-tar cigarette be less hazardous to health?

Smoking behaviour and exposure to carbon monoxide, nicotine, and tar were studied in 19 middle-tar smokers. All smoked their own brands for three weeks and then switched to either a conventional low-nicotine, low-tar brand (control) or a medium-nicotine, low-tar cigarette for a further three weeks, the order then being reversed. The medium-nicotine, low-tar brand also had a low delivery of carbon monoxide. With the medium-nicotine, low-tar cigarette mouth-level delivery and intake of nicotine was similar to that with the smokers'' usual brands, and significantly greater than with the control low-tar cigarette. Intake of carbon monoxide from the medium-nicotine, low-tar cigarette was significantly less than with either own or control brands. With both low-tar brands mouth-level exposure to tar was reduced relative to smokers'' usual cigarettes. There was no evidence, however, that the reduction in tar exposure was greater with the medium-nicotine brand than with the control low-tar cigarette. Both low tar brands were "''oversmoked" relative to subjects'' usual middle-tar cigarettes. The medium-nicotine, low-tar cigarette was marginally more acceptable than the control brand, and the particular design used in the study resulted in a lower intake of carbon monoxide. In terms of reducing mouth-level exposure to tar, however, the medium-nicotine, low-tar cigarette had no advantage over the control low-tar product. In part this was because of the ratio of tar to nicotine delivery obtained by human smokers was not the same as that obtained by smoking machine.     

A role for nickel-iron cofactors in biological carbon monoxide and carbon dioxide utilization

Ni-Fe containing enzymes are involved in the biological utilization of carbon monoxide, carbon dioxide, and hydrogen. Interest in these enzymes has increased in recent years due to hydrogen fuel initiatives and concerns over development of new methods for CO2 sequestration. One Ni-Fe enzyme called carbon monoxide dehydrogenase (CODH) is a key player in the global carbon cycle and carries out the interconversion of the environmental pollutant CO and the greenhouse gas CO2. The Ni-Fe center responsible for this important chemistry, the C-cluster, has been the source of much controversy, but several recent structural studies have helped to direct the field toward a unifying mechanism. Here we summarize the current state of understanding of this fascinating metallocluster.     

一氧化碳在心血管系统中的调控作用

一氧化碳作为众所周知的毒性气体,其毒性机制早已阐明。然而,在机体内一氧化碳可以被内源合成,并在心血管系统中发挥了重要生理调节功能。这些生理调节功能机制的初步阐明提示我们一氧化碳可能可以作为多种心血管疾病的治疗靶点,这值得未来更多开创性的研究。     

Binding of exogenously added carbon monoxide at the active site of the iron-only hydrogenase (CpI) from Clostridium pasteurianum.

A site for the binding of exogenously added carbon monoxide has been identified at the active site of the Fe-only hydrogenase (CpI) from Clostridium pasteurianum. The binding and inhibition of carbon monoxide have been exploited in biochemical and spectroscopic studies to gain mechanistic insights. In the present study, we have taken advantage of the ability to generate an irreversibly carbon monoxide bound state of CpI. The crystallization and structural characterization of CpI inhibited in the presence of carbon monoxide indicates the addition of a single molecule of carbon monoxide. The ability to generate crystals of the carbon monoxide bound state of the hydrogenase that are isomorphous to those of the native enzyme has allowed for a direct comparison of the crystallographic data and an unambiguous identification of the site of carbon monoxide binding at the active site of CpI. Carbon monoxide binds to an Fe atom of the 2Fe subcluster at the site of a terminally bound water molecule in the as crystallized native state of CpI that has been previously suggested to be a potential site of reversible hydrogen oxidation. Binding of carbon monoxide at this site results in an active site that is coordinately saturated with strong ligands (S, CO, and CN), providing a rational potential mechanism for inhibition of reversible hydrogen oxidation at the active site of CpI.     

Is the oxygen atom of carbon monoxide coordinated to the copper of hemocyanin?

The carbon monoxide binding site of hemocyanins was studied by comparing the isotope shift of the CO-stretching frequencies in CO-hemocyanins with that of carbon monoxide diethylenetriaminecopper(I)tetraphenylboron in which the carbon atom of CO is coordinated to the copper. Coordination by the carbon atom of CO in CO-hemocyanin is suggested.     

Binding of carbon monoxide to alpha-hemocyanin and beta-hemocyanin from Helix pomatia.

The binding of carbon monoxide to alpha and beta-hemocyanin from the snail Helix pomatia was studied under equilibrium conditions. Homotropic interactions upon carbon monoxide binding were much weaker than upon the binding of oxygen. Heterotropic interactions (Bohr effect and calcium-ion effect), however, were just as strong as in the case of the binding of oxygen. For alpha-hemocyanin a linkage has been observed between the binding of carbon monoxide and a change in quaternary structure of the protein.