Role of nitric oxide-derived oxidants in vascular injury from carbon monoxide in the rat. (1/461)

Studies were conducted with rats to investigate whether exposure to CO at concentrations frequently found in the environment caused nitric oxide (NO)-mediated vessel wall changes. Exposure to CO at concentrations of 50 parts per million or higher for 1 h increased the concentration of nitrotyrosine in the aorta. Immunologically reactive nitrotyrosine was localized in a discrete fashion along the endothelial lining, and this was inhibited by pretreatment with the NO synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). The CO-induced elevations of aortic nitrotyrosine were not altered by neutropenia or thrombocytopenia, and CO caused no change in the concentration of endothelial NOS. Consequences from NO-derived stress on the vasculature included an enhanced transcapillary efflux of albumin within the first 3 h after CO exposure and leukocyte sequestration that became apparent 18 h after CO exposure. Oxidized plasma low-density lipoprotein was found immediately after CO exposure, but this was not inhibited by L-NAME pretreatment. We conclude that exposure to relatively low CO concentrations can alter vascular status by several mechanisms and that many changes are linked to NO-derived oxidants.  (+info)

High predictive value of red cell volume measurement using carboxy-haemoglobin in a rabbit model of haemorrhage. (2/461)

We have studied the accuracy of blood volume measurements using carbon monoxide (CO)-labelled haemoglobin (COHb) injection and dilution (CO method) by comparing changes in red cell volume (RCV) measured using the CO method and 51Cr-labelled erythrocyte dilution (51Cr method) in a haemorrhage and infusion model in rabbits. RCV was measured repeatedly using the CO method at four different blood volume stages (stages I-IV). At stages I and IV, RCV was measured simultaneously using the 51Cr method. In comparing the sum of the circulating RCV and extracted RCV (SUM RCV) using the CO method, the values were almost equal and there were no significant differences between the values at the four stages. In comparing circulating RCV measured using the CO method and the 51Cr method, mean difference between the two methods was 0.80 (SD 0.76) ml kg-1 or 4.7 (4.6)%, and a positive correlation was observed (r = 0.91). We conclude that the CO method can be used to measure blood volume during perioperative periods in infants because it avoids use of a radioactive tracer, is simple and repeated measurements are possible.  (+info)

A physiological model for predicting carboxyhemoglobin formation from exposure to carbon monoxide in rats. (3/461)

A time-dependent simulation model, based on the Coburn-Forster-Kane equation, was written in Advanced Continuous Simulation Language to predict carboxyhemoglobin (HbCO) formation and dissociation in F-344 rats during and after exposure to 500 parts/million CO for 1 h. Blood-gas analysis and CO-oximetry were performed on samples collected during exposure and off-gassing of CO. Volume displacement plethysmography was used to measure minute ventilation (VE) during exposure. CO diffusing capacity in the lung (DLCO) was also measured. Other model parameters measured in the animals included blood pH, total blood volume, and Hb concentration. Comparisons between model predictions using values for VE, DLCO, and the Haldane coefficient cited in the literature and predictions using measured VE, DLCO, and calculated Haldane coefficient for individual animals were made. General model predictions using values for model parameters derived from the literature agreed with published HbCO values by a factor of 0.987 but failed to simulate experimental data. On average, the general model overpredicted measured HbCO level by nearly 9%. A specific model using the means of measured variables predicted HbCO concentration within a factor of 0.993. When experimentally observed parameter fluctuations were included, the specific model predictions reflected experimental effects on HbCO formation.  (+info)

Neonatal bilirubin production, reflected by carboxyhaemoglobin concentrations, in Down's syndrome. (4/461)

AIM: To determine whether increased bilirubin production, reflected by blood carboxyhaemoglobin (COHb) values, is responsible for hyperbilirubinaemia in cases of Down's syndrome with no obvious cause for excessive jaundice. METHODS: Blood was sampled on the third day of life for COHb, total haemoglobin (tHb), and serum total bilirubin, from 19 consecutively born neonates with Down's syndrome (a subset of 34 term babies), who had developed hyperbilirubinaemia (serum bilirubin >/= 256 micromol), and from 32 term controls. COHb, measured by gas chromatography, was corrected for inspired CO (COHbc) and expressed as a percentage of tHb. RESULTS: Significantly more of the Down's syndrome subset developed hyperbilirubinaemia than the controls (10/19 (52%) vs 7/32 (22%), relative risk 2.4, 95% confidence intervals (CI) 1.10 to 5.26). Third day serum bilirubin values (mean (SD)) were higher in the Down's syndrome neonates than in controls (214 +- 63 micromol/l vs 172 +- 54 micromol/l, respectively, p=0.015). Mean (SD) COHbc values were significantly higher in the Down's syndrome neonates than in controls (0.92 +- 0. 24% vs 0.63 +- 0.17%; p<0.0001). However, Down's syndrome neonates who became hyperbilirubinaemic had similar COHbc values to those who did not (0.87 +- 0.26% and 0.95 +- 0.23%, respectively). These values contrast with those of the controls, in whom a significant increase in COHbc was associated with hyperbilirubinaemia (0.74 +- 0. 15% vs 0.60 +- 0.16%, respectively; p<0.05). tHb values were similar in both groups. CONCLUSIONS: Down's syndrome neonates had a greater risk of hyperbilirubinaemia, and higher COHbc values, than controls. However, excessive bilirubin production could not be exclusively responsible for the hyperbilirubinaemia. By inference, decreased bilirubin elimination probably plays a greater part in its pathogenesis than in controls. Down's syndrome neonates may have abnormal erythropoiesis, leading to increased haem turnover.  (+info)

Validation of the end-expired method for measuring carboxyhaemoglobin levels for the use in occupational and environmental exposure studies. (5/461)

Carbon monoxide is one of the most common toxins encountered in work settings, the gas being emitted in situations where there is incomplete combustion of carbon-containing substances. Its acute and chronic health effects have been well-documented. While identification of dangerous situations and evaluation of control measures are conducted by environmental monitoring, the body burden due to inhalation of carbon monoxide is measured by an individual's blood carboxyhaemoglobin level. Carboxyhaemoglobin level can be measured directly from a blood sample or, indirectly, by measuring the end-expired carbon monoxide level and using the charts provided to read the corresponding carboxyhaemoglobin level. As the end-expired method is not an intervention method, and is therefore easy to conduct, it is being used widely in epidemiological studies and it could also be used for individual measurements. This study presents a better statistical method for validating the end-expired method than the correlation method used and described in previous studies.  (+info)

Methylene chloride poisoning in a cabinet worker. (6/461)

More than a million workers are at risk for methylene chloride exposure. Aerosol sprays and paint stripping may also cause significant nonoccupational exposures. After methylene chloride inhalation, significant amounts of carbon monoxide are formed in vivo as a metabolic by-product. Poisoning predominantly affects the central nervous system and results from both carboxyhemoglobin formation and direct solvent-related narcosis. In this report, we describe a case of methylene chloride intoxication probably complicated by exogenous carbon monoxide exposure. The worker's presentation of intermittent headaches was consistent with both methylene chloride intoxication and carbon monoxide poisoning. The exposures and symptoms were corroborated by elevated carboxyhemoglobin saturations and a workplace inspection that documented significant exposures to both methylene chloride and carbon monoxide. When both carbon monoxide and methylene chloride are inhaled, additional carboxyhemoglobin formation is expected. Preventive efforts should include education, air monitoring, and periodic carboxyhemoglobin determinations. Methylene chloride should never be used in enclosed or poorly ventilated areas because of the well-documented dangers of loss of consciousness and death.  (+info)

Effects of exposure to low concentrations of carbon monoxide on exercise performance and myocardial perfusion in young healthy men. (7/461)

OBJECTIVE: To assess the effects of exposure to low concentrations of carbon monoxide (CO), as commonly measured in atmospheric urban air pollution and certain occupational environments, on exercise performance and myocardial perfusion in young healthy men, and the possible need for tighter restrictions on ambient concentrations of CO. METHODS: 15 young, healthy non-smoking men, 18-35 years old, were exposed blindly and randomly to air or to a mixture of CO and air, followed by an exercise treadmill test with thallium heart scintigraphy. Blood was drawn for determination of carboxyhaemoglobin before and at the end of the exposure, and for lactic and pyruvic acid at the beginning and the end of the exercise test. The main outcome measures include the duration of the exercise test, the maximal effort expressed in metabolic equivalent units (METs), the mean plasma lactic to pyruvic acid ratio at the end of the ergometry, ECG changes in the exercise test, and perfusion deficits in thallium heart scintigraphy. RESULTS: At the end of exposure to CO, the mean (SD) blood carboxyhaemoglobin concentration rose from 0.59% (0.08%) to 5.12% (0.65%) (p < 0.0001). At the end of the exercise period, the mean (SD) plasma lactate/pyruvate ratio, which reflects the level of anaerobic metabolism (69.9 (5.9) after air and 75.9 (7.0) after CO), was not significantly different between the two experimental groups. Exercise induced electrocardiographic changes were noted in only one subject after exposure to CO. No arrhythmias were detected in any of the subjects. Significant differences were found in the mean duration of the exercise test (p = 0.0012) and the METs (p = 0.0001). The mean adjusted difference of exercise duration between exposure to air and CO was 1.52 minutes 95% confidence interval (95% CI) 0.73 to 2.32 minutes. The mean adjusted difference of METs between exposure to air and CO was 2.04 95% CI 1.33 to 2.76. The models for duration of exercise and METs showed no significant sequence and period effects. Thallium myocardial perfusion imaging disclosed normal perfusion in all regions of the heart, with no significant differences in perfusion between the two exercise tests (after air or CO). CONCLUSION: Acute exposure to a low concentration of CO which produces blood carboxyhaemoglobin concentrations of 4%-6% significantly decreases exercise performance in young healthy men. No ischaemic electrocardiographic changes or disturbances in myocardial perfusion were found by graded exercise with thallium scintigraphy. Our findings suggest that pollution of atmospheric air by CO at concentrations which are commonly found in urban and industrial environments may exert an adverse effect on skeletal muscles, manifesting as decreased exercise performance.  (+info)

UV resonance raman spectra of ligand binding intermediates of sol-gel encapsulated hemoglobin. (8/461)

We report for the first time specific conformational changes for a homogeneous population of ligand-bound adult deoxy human hemoglobin A (HbA) generated by introducing CO into a sample of deoxy-HbA with the effector, inositol hexaphosphate, encapsulated in a porous sol-gel. The preparation of ligand-bound deoxy-HbA results from the speed of ligand diffusion relative to globin conformational dynamics within the sol-gel (1). The ultraviolet resonance Raman (UVRR) difference spectra obtained reveal that E helix motion is initiated upon ligand binding, as signaled by the appearance of an alpha14beta15 Trp W3 band difference at 1559 cm(-1). The subsequent appearance of Tyr (Y8a and Y9a) and W3 (1549 cm(-1)) UVRR difference bands suggest conformational shifts for the penultimate Tyralpha140 on the F helix, the "switch" region Tyralpha42, and the "hinge" region Trpbeta37. The UVRR results expose a sequence of conformational steps leading up to the ligation-induced T to R quaternary structure transition as opposed to a single, concerted switch. More generally, this report demonstrates that sol-gel encapsulation of proteins can be used to study a sequence of specific conformational events triggered by substrate binding because the traditional limitation of substrate diffusion times is overcome.  (+info)