Role of endogenous carbon monoxide in central regulation of arterial pressure

We investigated the contribution of neural mechanisms to the arterial pressure increase produced by zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG), an inhibitor of endogenous carbon monoxide synthesis. The arterial baroreceptor reflex control of heart rate was examined in rats with and without ZnDPBG pretreatment (45 micromol/kg IP) by analysis of the arterial pressure-heart rate relationship during infusions of phenylephrine or sodium nitroprusside to vary arterial pressure. ZnDPBG increased arterial pressure from 110 +/- 3 to 126 +/- 2 mm Hg without eliciting bradycardia. The maximum gain of the heart rate response to changes in arterial pressure was attenuated by ZnDPBG treatment (-1.9 +/- 0.3 versus -4.8 +/- 1.0 bpm/mm Hg). The possibility that ZnDPBG elevates arterial pressure by attenuating baroreceptor reflex function was addressed by comparing the pressor response to ZnDPBG (45 micromol/kg IP) in rats with and without sinoaortic denervation. The pressor effect of ZnDPBG was similar in rats with and without arterial baroreceptor deafferentation, implying that the increase in pressure is not simply the consequence of attenuated baroreceptor reflex function per se. The possibility that ZnDPBG increases arterial pressure via an effect on the nucleus tractus solitarii (NTS) also was investigated. ZnDPBG (1 nmol in 100 nL) injected into the NTS of rats increased arterial pressure from 111 +/- 4 to 126 +/- 5 mm Hg, and this effect was reversed by an ipsilateral microinjection of carbon monoxide into the NTS. Accordingly, the pressor effect of ZnDPBG may rely on inhibition of carbon monoxide production in the NTS. This implies that carbon monoxide formed by brain heme oxygenase plays a role in the central regulation of arterial pressure.     

The effect of intermittent carbon monoxide exposure on experimental atherosclerosis in the rabbit

(1) Twenty-four female New Zealand White rabbits were fed commercial diet plus 2% cholesterol. Twelve of these animals were exposed to carbon monoxide for 4 hours per day, seven days per week for 10 weeks. The carbon monoxide exposure was such that the mean blood carboxy-haemoglobin was raised to approximately 20% during each exposure period. Twelve control animals breathed atmospheric air under the same conditions of confinement as the carbon monoxide-exposed group. (2) No significant differences in the plasma levels of cholesterol, triglycerides or glutamate oxalacetate transaminase were observed between the two groups during the experiment. (3) When the animals were sacrificed at the end of the experiment no significant differences were observed between the two groups in the aortic content of triglycerides, cholesterol or phospholipids. (4) The extent of coronary artery atherosclerosis was statistically significantly higher in the carbon monoxide group than in the control group. (5) Ultracentrifugal analysis of plasma lipoproteins revealed that there was significantly more cholesterol in the d less than l.006 fraction from the CO-exposed rabbits. (6) These findings, are discussed with particular reference to the claim that the causal agent in tobacco smoke associated arterial disease is carbon monoxide.     

Screening for carbon monoxide in children

We present the use of risperidone as a potentiation strategy of the serotonergic antidepressants in four patients suffering from refractory obsessive-compulsive disorder. There were an important improvement in three patients. Adding risperidone to serotonergic antidepressants causes complex interactions between serotonergic, dopaminergic and noradrenergic systems, that could lay to the clinical improvement. These and other similar cases make necessary controlled studies. Adding risperidone to serotonergic antidepressants in patients suffering from refractory obsessive-compulsive disorder might be an effective strategy with low risk for secondary effects and without the presence of tics or psychotic symptoms.     

Stop-flow studies of solute uptake in rat lungs

Stop-flow studies were used to characterize solute uptake in isolated rat lungs. These lungs were perfused at 8 or 34 ml/min for 10-28 s with solutions containing 125I-albumin and two or more of the following diffusible indicators: [3H]mannitol, [14C]urea, 3HOH, 201Tl+, or 86Rb+. After this loading period, flow was stopped for 10-300 s and then resumed to flush out the perfusate that remained in the pulmonary vasculature during the stop interval. Concentrations of 201Tl+ and 86Rb+ in the venous outflow decreased after the stop interval, indicating uptake from exchange vessels during the stop interval. The amount of these K+ analogs lost from the circulation during the stop interval was greater when the intervals were longer. However, losses of 201T1+ at 90 s approached those at 300 s. Because extraction continued after the vasculature had been flushed, vascular levels had presumably fallen to negligible levels during the stop interval. By 90 s of stop flow the vascular volume that was cleared of 201T1+ averaged 0.657 +/- 0.034 (SE) ml in the experiments perfused at 8 ml/min and 0.629 +/- 0.108 ml in those perfused at 34 ml/min. Increases in perfusate K+ decreased the cleared volumes of 201T1+ and 86Rb+. Uptake of [3H]mannitol, [14C]urea, and 3HOH during the stop intervals was observed only when the lungs were loaded at high flow for short intervals. Decreases in 201T1+ and 86Rb+ concentrations in the pulmonary outflow can be used to identify the fraction of the collected samples that were within exchange vessels of the lung during the stop interval and may help determine the distribution of solute and water exchange along the pulmonary vasculature.     

Endogenous carbon monoxide in control of respiration

CASE REPORT: A patient with recurrent breast cancer was reirradiated twice on adjacent fields with a time interval of 9 months. The first time she was treated with reirradiation alone, the second time with reirradiation plus hyperthermia. The reirradiation schedule for both fields was 8 x 4 Gy in 4 weeks. Both fields overlapped partly with the field of postoperative radiotherapy, which was applied 57 and 66 months earlier to a total dose of 40.5 Gy. RESULTS: During the 52 to 61 months follow-up, a remarkable difference in telangiectasia development, between the parts of the reirradiation fields overlapping with the primary radiotherapy field, became apparent. Telangiectasia was observed 9 months after treatment with reirradiation alone and progressed to confluent in 47 months after treatment. In the reirradiation plus hyperthermia area, the maximum observed telangiectasia was slight until 52 months after treatment. DISCUSSION: The difference in the development of telangiectasia between these fields cannot be explained by differences in any of the known radiation treatment related prognostic factors. A protective effect by hyperthermia has been suggested by Haveman and coworkers, who have shown experimentally that heat treatment leads to enhanced proliferation of endothelial cells, thereby inducing a fast repopulation and replacement of X-ray damaged cells. CONCLUSION: This difference in telangiectasia formation is an interesting observation. Whether such a protective effect of hyperthermia is of general relevance has to become clear from more extensive clinical studies.     

Functional heterogeneity of the alpha and beta subunits in the association reaction between hemoglobin and carbon monoxide

A technique is described for the rapid inactivation and removal of excess ferricyanide used for the non-cryogenic oxidation of the unliganded subunits of the intermediates in the association reaction between hemoglobin and carbon monoxide. Under these conditions the asymmetric oxidized intermediates, which dissociate into non-identical dimers, disproportionate into their parent tetramers and four species, Hb+, HbCO, alpha 2+ beta 2CO, alpha 2CO beta 2+, are isolated by non-cryogenic isoelectric focusing. The relative concentrations of species alpha 2CO beta 2+ and alpha 2+ beta 2CO measure the overall distribution of the ligand between the alpha and beta subunits in the association reaction. At 20 degrees C in 0.1 M KCl, pH 7, preferential CO binding to the beta subunits was observed, in agreement with observations made by the cryogenic technique for the isolation of the intermediates [M. Perrella, N. Davids and L. Rossi-Bernardi, J. Biol. Chem. 267 (1992) 8744].     

Pulse oximetry in severe carbon monoxide poisoning

STUDY OBJECTIVES: To evaluate the accuracy and quantitate the error of pulse oximetry measurements of arterial oxygenation in patients with severe carbon monoxide (CO) poisoning. DESIGN: Retrospective review of patient clinical records. SETTING: Regional referral center for hyperbaric oxygen therapy. PATIENTS: Thirty patients referred for treatment of acute severe CO poisoning who demonstrated carboxyhemoglobin (COHb) levels >25%, with simultaneous determinations of arterial hemoglobin oxygen saturation by pulse oximetry (SpO2) and arterial blood gas (ABG) techniques. MEASUREMENTS AND RESULTS: COHb levels and measurements of arterial oxygenation from pulse oximetry, ABG analysis, and laboratory CO oximetry were compared. SpO2 did not correlate with COHb levels. SpO2 consistently overestimated the fractional arterial oxygen saturation. The difference between arterial hemoglobin oxygen saturation (SaO2) calculated from ABG analysis and SpO2 increased with increasing COHb level. CONCLUSIONS: Presently available pulse oximeters overestimate arterial oxygenation in patients with severe CO poisoning. An elevated COHb level falsely elevates the SaO2 measurements from pulse oximetry, usually by an amount less than the COHb level, confirming a prior observation in an animal model. Accurate assessment of arterial oxygen content in patients with CO poisoning can currently be performed only by analysis of arterial blood with a laboratory CO-oximetry.     

Role of nitric oxide and carbon monoxide in modulating the ACTH response to immune and nonimmune signals

The role played by nitric oxide (NO) and carbon monoxide (CO) was explored in the adult male rat by determining whether antagonizing the activity of the enzymes responsible for the formation of these gases altered the response of the hypothalamic-pituitary-adrenal (HPA) axis to immune (cytokines) or nonimmune (mild electroshocks) signals. The arginine derivative Nomeganitro-L-arginine-methylester (L-NAME), which inhibits all three NO synthase (NOS) isoforms [inducible (i), endothelial (e) and neuronal (n)] significantly augments the ACTH response to blood-borne cytokines, but decreases it in rats exposed to shocks or other physico-emotional stresses. The effect of L-NAME in both models is mimicked by L-nitroarginine (L-NNA) and L-nitromethylarginine (L-NMMA), which block constitutive (e and n) forms of NOS, but not by aminoguanidine (which blocks iNOS) or 7-nitroindazole (which specifically blocks nNOS). Despite the ability of L-NAME to markedly augment the stimulatory effect of vasopressin on ACTH secretion, removal of this peptide does not interfere with the interaction between L-NAME and systemically administered interleukin-1beta (IL-1beta). In contrast, blockade of prostaglandin formation prevents both the stimulatory effect of IL-1beta on ACTH release, and its potentiation by L-NAME. In contrast to the investigation of the importance of endogenous NO, studies focused on the role of CO remain scarce. Our preliminary results suggest that while blockade of the formation of this gas decreases the ACTH response to various stimuli, it also significantly interferes with the effect of L-NAME in rats systemically administered cytokines, and further decreases the ACTH response to shocks in animals also injected with arginine analogs. These results indicate the possible presence of functional interactions between NO and CO in regulating the activity of the HPA axis. Our present working hypothesis is that in the presence of elevated circulating cytokine levels, endogenous NO acts presynaptically to inhibit the release of ACTH secretagogues from nerve terminals in the infundibulum. As the acute ACTH response to these immune proteins is believed to primarily depend on events taking place within the median eminence, blockade of NO formation results in exaggerated ACTH release. During exposure to shocks and other nonimmune stresses, on the other hand, increased ACTH secretion is primarily due to activation of hypothalamic neurons. In this case, because of the stimulatory influence of endogenous NO on hypothalamic perikarya that manufacture corticotropin-releasing factor (CRF) and/or of the afferents to these neurons, blockade of NOS activity blunts CRF production, and consequently ACTH release. What remains undetermined is the net effect of the opposite influences of NO during long-term exposure to immune or nonimmune stress. Finally, it is possible that the conflicting results reported by investigators who study the role of NO and CO in isolated cell preparations may reflect, at least in part, these opposite effects of NO on different elements of the HPA axis.     

The use of exhaled carbon monoxide for the diagnosis of carbon monoxide poisoning. A case report

Antigliadin antibodies (AGA) mark celiac disease, but AGA are also encountered in IgA-nephritis, psoriasis, sickle-cell anemia, hepatic disorders, juvenile rheumatoid arthritis, autoimmune thyroidism and in persons who occupationally contact great amounts of wheat. AGA IgA and/or IgG were registered in 19 of 60 subjects (51 adults and 9 children) with various immunomediated diseases without symptoms of celiac disease: in 4 cases of chronic active hepatitis, in 2 of 4 cases of chronic persistent hepatitis, in 4 of 16 cases of rheumatoid arthritis, in 3 of 19 cases of IgA-deficiency, in 1 of 8 cases of SLE, in 2 cases of postvaccine reaction, in all the single cases of juvenile rheumatoid arthritis, focal scleroderma, macroglobulinemia. IgA only occurred in in 6 patients, IgG- in 6 patients, both IgA and IgG in 7 patients. The most pronounced positive reaction to AGA was recorded in 8-year-old girl with juvenile rheumatoid arthritis. The emergence of AGA in immunomediated diseases may be attributed to the response to food protein in pathological conditions and is often unrelated closely with celiac disease.     

Differential regulation of hepatic arterial and portal venous vascular resistance by nitric oxide and carbon monoxide in rats

Nitric oxide (NO), a gaseous mediator that accounts for the biological activity of endothelium-derived relaxing factor, has been shown to play an important role in the reduction of basal vascular tone in multiple vascular beds, including the hepatic circulation. On the other hand, recent studies have provided first evidence that endogenously generated carbon monoxide (CO) may exert vasodilatory effects in the hepatic portal vein and within sinusoids. Thus, we defined the differential role of NO and CO in the regulation of vascular resistance in the two inflows to the liver in the normal rat in vivo. Male Sprague-Dawley rats were anesthetized with pentobarbital sodium and surgically instrumented in order to study the change in hepatic arterial (Rha) and portal venous vascular resistance (Rpv) in response to intravenous bolus administration of either the NO-synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (1 mg/kg; n = 7 animals) or of tin protoporphyrin-IX (SnPP-IX) (50 micromol/kg), a specific inhibitor of the CO-generating enzyme heme oxygenase (n = 8 animals). While L-NAME caused a substantial increase in Rha, Rpv increased only slightly under these conditions. In sharp contrast, SnPP-IX did not affect Rha, but caused a profound increase in Rpv. In conclusion, Rha and Rpv are differentially regulated by NO and CO in the normal rat liver in vivo, i.e., NO serves as a potent vasodilator in the hepatic arterial circulation, but exerts only a minor vasodilatory effect in the portal venous vascular bed. In contrast, while there is no intrinsic CO-mediated vasodilation in the hepatic artery, CO acts to maintain portal venous vascular tone in a relaxed state.     

Lime-enhanced carbon monoxide reduction of cuprous sulfide

Kinetic studies were conducted on the carbon monoxide reduction of cuprous sulfide powder in the presence of lime as a function of quantity of lime in the charge, CO flowrate, temperature, and time of reduction and particle size of the sulfide. Lime was found to enhance drastically the rate of reduction as well as reduce the COS emission into the off-gas to negligible levels. Both temperature and flowrate of the reducing gas were found to influence the reduction rate, and best results were obtained at 1273 K and at a CO flowrate of 3.33 cm³ s⁻¹. The overall reaction seems to be governed by the intrinsic kinetics of the Cu₂S-CO reaction. Kinetic analysis reveals the observance of the Valensi’s equation, indicating diffusional control through the product layer formed over reacting Cu₂S particles. The calculated experimental activation energy of 169.6 kJ/mole in the termperature range of 1123 to 1273 K is in good agreement with that reported in the literature for sulfur diffusion in copper. A critical comparison has been made of the lime-scavenged reduction of Cu₂S by different reagents, namely, hydrogen, carbon monoxide, and carbon.     

HMPAO brain SPECT in acute carbon monoxide poisoning

Technetium-99m-hexamethylpropylene amine oxime (HMPAO) brain images with fanbeam SPECT, in combination with surface three-dimensional display, were used to detect basal ganglion and cerebral cortex anomalies in the acute phase of carbon monoxide (CO) poisoning. METHODS: Ten patients, aged 16-29 yr, with acute CO poisoning and no past history of neurologic disorders were enrolled in this study. After oxygen treatment, all 10 patients were investigated using 99mTc-HMPAO brain images with fanbeam SPECT and surface three-dimensional display. Meanwhile, 6 of 10 patients also received a brain CT scan. RESULTS: CT scan findings were negative in all 6 patients. Fanbeam SPECT demonstrated unilateral or bilateral hypoactivity of basal ganglia in 6 patients. Local hypoactivity anomalies were found in the brain cortex of 7 patients, using surface three-dimensional display of the brain. Only 2 of 10 patients had normal 99mTc-HMPAO brain images. CONCLUSION: This study suggests that, in comparison with traditional brain imaging techniques, 99mTc-HMPAO brain imaging with fanbeam SPECT in combination with surface three-dimensional display is a better tool for early detection of regional cerebral anomalies in acute CO poisoning.     

On-line laser-photometric monitoring of aerosol deposition in ventilated rabbit lungs

A photometric technique was developed for on-line measurement of aerosol deposition in isolated, ventilated, and perfused rabbit lungs. A jet nebulizer was used for aerosolization of saline (hygroscopic particles) and di(2-ethylhexyl) sebacate (nonhygroscopic particles). Aerosol concentration (laser photometer, constructed for measurements in rabbit lungs) and flow rate (commercial pneumotachograph) were continuously monitored at the inlet of the tracheal cannula. Computer-assisted data processing allowed the breath-by-breath calculation of inhaled and exhaled aerosol mass, thus providing the deposition fraction. With the use of hygroscopic particles, however, this approach was hampered by the humidity-induced particle growth in the airways, leading to an overestimation of the aerosol concentration in exhaled air. This effect was corrected by an algorithm using a "particle growth factor" derived breath by breath from the photometer signal. To test the reliability of this approach, saline particles carrying technetium-99m label were aerosolized into rabbit lungs with the use of various ventilator settings, and the aerosol deposition was assessed in parallel by photometry and by radioactivity detection over the lung and over a trap in the exhaled-air circuit. Superimposable curves of cumulative aerosol deposition, with changes in kinetics dependent on the ventilator mode, were obtained. For a given ventilator setting, absolute values of the deposition fraction were 0.32 +/- 0.04 (radiotracer quantification) and 0.36 +/- 0.04 (photometry; means +/- SD; n = 4). We conclude that the presented laser-photometric technique allows reliable on-line monitoring of the deposition of both nonhygroscopic and hygroscopic aerosol particles in ventilated lungs.     

Mechanism of the toxic action of carbon monoxide

Our studies indicate that a high concentration of carboxyhemoglobin (COHb) does not interfere with the O2--carrying capacity of the blood. In dogs, both the transfusion of erythrocytes containing 80 percent COHb and the i.p. injection of carbon monoxide (CO) gas do not produce CO toxicity even though the COHb is above 50 percent. Dogs inhaling CO (13 percent in air) for 15 minutes died within 15 minutes to 65 minutes with an average COHb level of 65 percent. The probable toxic action of CO is on the cellular respiration taking place in the mitochondria when CO competes with O2 for cytochrome a3. The presence of dissolved CO in plasma, which is necessary for CO to enter the tissue, probably occurs when the exchange takes place between alveolar air and the blood in the lungs. When air containing CO is inhaled, there will be a significant CO tension in the blood when it leaves the lungs and when it reaches the organs especially the heart and brain. While COHb level is useful as a clinical measure of CO exposure, the most important mechanism by which CO causes toxicity is its combination with cytochrome oxidase.     

The chlorination kinetics of zirconium dioxide in the presence of carbon and carbon monoxide

Chlorination of zirconium dioxide, an important step in the commercial production of reactor grade zirconium metal, has been studied using carbon and carbon monoxide as reductants. Zirconium tetrachloride was produced when the oxide was reacted with chlorine alone above 1000°C; by introducing carbon the reaction temperatures could be lowered 200°C, and when carbon monoxide was used the reaction temperatures necessary for similar rates were even lower. With carbon monoxide the chlorination of zirconium dioxide is described by two regions differentiated by temperature and the dependence of reaction rate upon chlorine and carbon monoxide pressures.     

Role of oxygen in limiting respiration in the in situ myocardium

1H NMR has now detected the proximal histidyl N delta H myoglobin (Mb) signal from the myocardium in situ. Upon ligation of the left anterior descending coronary artery in the rat myocardium, the deoxy Mb signal appears at 78 ppm During dopamine infusion at up to 80 micrograms/kg/min, the heart rate pressure product (RPP) increases by a factor of 2, the phosphocreatine (PCr) decreases by 17%, and the ratio of the change in inorganic phosphate over PCr (delta Pi/PCr) increases by 0.2. However, no deoxy myoglobin signal is detected. Oxygen availability does not appear to limit oxygen consumption nor oxidative phosphorylation under dopamine enhanced work state in myocardium.     

职业性急性一氧化碳中毒五例报告

2009年2月2日,宝鸡市某县水泥厂发生5例职业性急性一氧化碳中毒,现报告如下. 1 中毒经过 2009年2月2日上午8时30分宝鸡市某水泥厂生料车间的5名维修工人在生料车间进行焊接加固时,没有采取任何防护措施,稍后有人感觉胸闷、头晕,但未引起重视,9时10分左右,有两人晕倒.随后赶来的工人把5名工人转移到安全地带并迅速送往医院进行抢救.