Acute Carbon Monoxide Exposure Research Articles

Causes of Mortality From Acute Carbon Monoxide Exposure: A Step Towards Preventative Long-Term Care?*

Causes of Mortality From Acute Carbon Monoxide Exposure: A Step Towards Preventative Long-Term Care?*

Association between risk of preterm birth and long-term and short-term exposure to ambient carbon monoxide during pregnancy in chongqing, China: a study from 2016-2020

BackgroundPreterm birth (PTB) is an important predictor of perinatal morbidity and mortality. Previous researches have reported a correlation between air pollution and an increased risk of preterm birth. However, the specific relationship between short-term and long-term exposure to carbon monoxide (CO) and preterm birth remains less explored.MethodsA population-based study was conducted among 515,498 pregnant women in Chongqing, China, to assess short-term and long-term effects of CO on preterm and very preterm births. Generalized additive models (GAM) were applied to evaluate short-term effects, and exposure-response correlation curves were plotted after adjusting for confounding factors. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using COX proportional hazard models to estimate the long-term effect.ResultsThe daily incidence of preterm and very preterm birth was 5.99% and 0.41%, respectively. A positive association between a 100 µg/m³ increase in CO and PTB was observed at lag 0–3 days and 12–21 days, with a maximum relative risk (RR) of 1.021(95%CI: 1.001–1.043). The exposure-response curves (lag 0 day) revealed a rapid increase in PTB due to CO. Regarding long-term exposure, positive associations were found between a 100 µg/m3 CO increase for each trimester(Model 2 for trimester 1: HR = 1.054, 95%CI: 1.048–1.060; Model 2 for trimester 2: HR = 1.066, 95%CI: 1.060–1.073; Model 2 for trimester 3: HR = 1.007, 95%CI: 1.001–1.013; Model 2 for entire pregnancy: HR = 1.080, 95%CI: 1.073–1.088) and higher HRs of very preterm birth. Multiplicative interactions between air pollution and CO on the risk of preterm and very preterm birth were detected (P- interaction<0.05).ConclusionsOur findings suggest that short-term exposure to low levels of CO may have protective effects against preterm birth, while long-term exposure to low concentrations of CO may reduce the risk of both preterm and very preterm birth. Moreover, our study indicated that very preterm birth is more susceptible to the influence of long-term exposure to CO during pregnancy, with acute CO exposure exhibiting a greater impact on preterm birth. It is imperative for pregnant women to minimize exposure to ambient air pollutants.

Evaluation of cardiac autonomic function using heart rate variability in children with acute carbon monoxide poisoning.

The present study included 40 children aged 1-17 years who were admitted to the Pediatric Intensive Care Unit with acute carbon monoxide poisoning and 40 healthy age- and sex-matched controls. Carboxyhaemoglobin and cardiac enzymes were measured at admission. Electrocardiography was performed on admission and discharge, and 24-hour Holter electrocardiography was digitally recorded. Heart rate variability was analysed at both time points - 24-hour recordings - and frequency domains - from the first 5 minutes of intensive care unit admission. Time domain and frequency indices such as high-frequency spectral power and low-frequency spectral power were similar between patient and control groups (p>0.05). The ratio of low-frequency spectral power to high-frequency spectral power was significantly lower in the carbon monoxide poisoning group (p<0.001) and was negatively correlated with carboxyhaemoglobin levels (r=-0.351, p<0.05). The mean heart rate, QT dispersion, corrected QT dispersion, and P dispersion values were higher in the carbon monoxide poisoning group (p<0.05) on admission. The QT dispersion and corrected QT dispersion remained longer in the carbon monoxide poisoning group compared with controls on discharge (p<0.05). The frequency domain indices, especially the ratio of low-frequency spectral power to high-frequency spectral power, are useful for the evaluation of the cardiac autonomic function. The decreased low-frequency spectral power-to-high-frequency spectral power ratio reflects a balance of the autonomic nervous system, which shifted to parasympathetic components.

Effects of hyperbaric oxygen on hippocampal neuronal apoptosis in rats with acute carbon monoxide poisoning.

Acute carbon monoxide (CO) poisoning causes serious health problems such as neuropsychological sequelae. This study aimed to investigate neuronal apoptosis and the effects of hyperbaric oxygen (HBO₂) on different regions of the rat hippocampus after CO poisoning. 90 mature male Sprague Dawley rats were randomly divided into three groups: the normal control group (NC group), the acute carbon monoxide-poisoned group (CO group) and the hyperbaric oxygen treatment group (HBO₂ group). CO exposure included 0, 1, 3, 7, 14 and 21 treatment days, one exposure on the first day, and sacrifice on each of the following days. HBO₂ exposure included treatment for 0, 1, 3, 7, 14 and 21 days, daily treatment after CO exposure, and sacrifice after the last HBO₂ treatment on each of those days. Hematoxylin-eosin staining, immunohistochemical staining, immunofluorescence staining, and western blot analysis were performed to detect apoptosis in brain tissue samples. MMP-9 and caspase-3 were prominently increased by CO exposure and inhibited by HBO₂ in the CA3 region in the hippocampus at one, three and seven days (immunohistochemical staining [IHC]: P ⟨ 0.05). Neu N and the ratio of Bcl-2/ BAX were prominently decreased by CO exposure and rescued by HBO₂ in the CA3 region after seven days of treatment (IHC: P ⟨ 0.05). These findings indicated that neuronal apoptosis in the rat hippocampus could be induced by acute CO exposure, especially in the CA3 region. HBO₂ could effectively inhibit neuronal apoptosis, especially in the CA3 region after seven days of treatment. The application of HBO₂ to inhibit MMP-9 and apoptosis may contribute to brain recovery after acute CO poisoning.

Reversible Changes of Brain Perfusion SPECT for Carbon Monoxide Poisoning-Induced Severe Akinetic Mutism.

This study aimed to characterize changes in regional cerebral blood flow (rCBF) in patients who experienced carbon monoxide (CO) poisoning and subsequently developed severe delayed neuropsychiatric sequelae (DNS) with akinetic mutism. We determined whether these changes were reversible in parallel with improvements in neuropsychological function in response to treatment, including hyperbaric oxygen therapy. Patients who developed severe DNS with akinetic mutism after acute CO intoxication between 2007 and 2011 were enrolled. Tc-ECD brain SPECT findings were compared between the patients with severe akinetic mutism and age-matched control subjects to characterize the pattern of rCBF. Perfusion SPECT was correlated with clinical outcomes after treatment with statistical parametric mapping (SPM8); the height threshold was P < 0.01 at peak level, and the corrected false discovery rate was P < 0.05 at the cluster level. Seven patients with akinetic mutism were analyzed. All patients had neurological symptoms caused by acute CO exposure, and all recovered to nearly normal daily function after initial treatments. In all cases, after a "lucid interval," DNS progressed to akinetic mutism. The SPECT images acquired at the onset of akinetic mutism demonstrated variable hypoperfusion in frontal-temporal-parietal regions, with the greatest severity in the left temporal-parietal regions. In parallel, we performed functional neuropsychiatric tests. After treatment, the brain SPECT showed significantly fewer hypoperfusion regions, and neuropsychiatric tests showed dramatically improved function. Our findings demonstrated both cerebral cortical and subcortical injuries in patients with CO-induced akinetic mutism. Improvement in rCBF correlated well with functional recovery after treatment.

Salvianolic acids attenuate rat hippocampal injury after acute CO poisoning by improving blood flow properties.

Carbon monoxide (CO) poisoning causes the major injury and death due to poisoning worldwide. The most severe damage via CO poisoning is brain injury and mortality. Delayed encephalopathy after acute CO poisoning (DEACMP) occurs in forty percent of the survivors of acute CO exposure. But the pathological cause for DEACMP is not well understood. And the corresponding therapy is not well developed. In order to investigate the effects of salvianolic acid (SA) on brain injury caused by CO exposure from the view point of hemorheology, we employed a rat model and studied the dynamic of blood changes in the hemorheological and coagulative properties over acute CO exposure. Compared with the groups of CO and 20% mannitol + CO treatments, the severe hippocampal injury caused by acute CO exposure was prevented by SA treatment. These protective effects were associated with the retaining level of hematocrit (Hct), plasma viscosity, fibrinogen, whole blood viscosities and malondialdehyde (MDA) levels in red blood cells (RBCs). These results indicated that SA treatment could significantly improve the deformation of erythrocytes and prevent the damage caused by CO poisoning. Meanwhile, hemorheological indexes are good indicators for monitoring the pathological dynamic after acute CO poisoning.

Rhabdomyolysis Complicating Acute CO Poisoning: A Case Study and a Review

Introduction: Carbon Monoxide (CO) is a colourless, odourless, tasteless gas. Mild poisoning by CO can be Mistaken for a non-specific headache or a viral illness headache or viral illness. Moderate to severe CO poisoning produces significant morbidity and mortality that provokes treatment controversy. Rhabdomyolysis, compartment syndrome, renal failure and peripheral neuropathy are unusual complications of CO That can be faced during practice and should be considered by physicians. Case presentation: A 34-years old Egyptian male was referred to the Toxicology Unit from the ED for evaluation of his lower limb weakness. Initial examination revealed a fully conscious patient with stable vital signs and arterial blood gases. However, the patient cannot stand steadily or walk. Neurologic examination revealed hypotonia and diminished reflexes in both lower limbs. No history of toxin exposure but a condition of sudden acute illness affecting him and his parents and upon which his old-age parents, were transferred to ICUin coma. Investigations revealed increased serum alanine transaminase and serum creatinine. A work-up that involved appropriate imaging and serum creatinekinase (CK) measurement revealed extremely elevated serum CK, normal appearance of liver and increased echogenicity of both kidneys with preserved cortico-medullary differentiation. Based on the above-mentioned data, a diagnosis of rhabdomyolysis complicating acute CO exposure with secondary renal insult was made. The patient begins haemodialysis with follow up of his serum K+, creatinine and CK. After one month, levels of serum creatinine and alanine transaminase became normal. The patient underwent rehabilitation therapy to improve his neuromuscular state. Conclusion: Carbon monoxide poisoning should be suspected in patients presented with acute illness without prior medical or surgical cause, and rare complications of CO poisoning like rhabdomyolysis should be suspected particularly in patients with delayed seek of medical care. Timely prompt medical care involving team therapy is necessary to prevent further complications like RF and muscle wasting.

Can MRI Findings in Carbon Monoxide Poisoning Predict Carbon Monoxide Encephalopathy?

Carbon monoxide (CO) is a tasteless, odorless, non-irritating, but highly toxic gas. CO encephalopathy (COE) may occur from 3 days up to 240 days after acute CO exposure, and has poor prognosis. Brain magnetic resonance imaging (MRI) changes after CO poisoning are variable and well reflect the neuropathological lesions. The areas of the brain that are the most sensitive to the effects of CO poisoning include the globus pallidus and other basal ganglia, the white matter, and the cerebral cortex. This study was conducted to investigate the role of MRI in predicting COE in patients with CO poisoning.

Dynamic Changes of Heme Oxygenase-1 in the Hippocampus of Rats After Acute Carbon Monoxide Poisoning

Heme oxygenase-1 (HO-1), an inducible enzyme, degrades heme to carbon monoxide (CO), iron, and bilirubin. We have investigated the relationship among HO-1 protein expression, HO activity, and CO concentrations in the hippocampus of CO-exposed rats. Western blotting and immunohistochemistry revealed that the enzyme is predominantly localized in hippocampal CA1 and CA3 pyramidal cells and in granule cells of the dentate gyrus. HO enzyme activity was reduced immediately following CO exposure, while expression of HO-1 protein was consistently upregulated in a time-dependent manner. Local CO concentrations in hippocampus rose immediately following exposure, but the elevation was maintained for ~20 h despite the decline in blood carboxyhemoglobin levels toward baseline. We suggest that CO initially inhibits HO enzyme activity, whereas at later time points the inhibition is released and local CO generation is maintained by the activity of the endogenous HO enzyme. And the noninducible form of heme oxygenase, HO-2, was not altered following CO administration. Together these results indicate that the HO/CO pathway in the rat hippocampus is induced by acute CO exposure; local CO production may play a regulatory role in brain injury following CO poisoning.

Induction of heme oxygenase-1 with hemin attenuates hippocampal injury in rats after acute carbon monoxide poisoning

Carbon monoxide (CO) poisoning is a major cause of brain injury and mortality; delayed neurological syndrome (DNS) is encountered in survivors of acute CO exposure. The toxic effects of CO have been attributed to oxidative stress induced by hypoxia. Heme oxygenase-1 (HO-1) is the inducible heme oxygenase isoform, and its induction acts as an important cellular defense mechanism against oxidative stress, cellular injury and disease. In this study, we examined the functional roles of HO-1 induction in a rat model of CO-exposured hippocampal injury. We report that acute CO exposure produces severe hippocampal injury in rats. However, hemin pretreatment reduced both the CO-induced rise in hippocampal water content and levels of neuronal damage in the hippocampus; survival rates at 24 h were significantly improved. Upregulation of HO-1 by hemin pretreatment resulted in a significant decrease in hippocampal levels of malondialdehyde (MDA), a marker of oxidative stress; levels of pro-apoptotic caspase-3 were also reduced. In contrast, inhibition of HO activity by administration of tin protoporphyrin IX (SnPP, a specific inhibitor of HO) abolished the neuroprotective effects of HO-1 induction. These data suggested that the upregulation of endogenous HO-1 expression therefore plays a pivotal protective role in CO neurotoxicity. Though the precise mechanisms underlying hemin-mediated HO-1 induction and neuroprotection are not known, these may involve the anti-oxidant and anti-apoptotic effects of HO-1 enzyme activity.

Reversible delayed neuropsychiatric syndrome following acute carbon monoxide exposure

A 40-year-old male presented with acutely oncoming neuropsychiatric symptoms in the form of extrapyramidal disturbances, personality change, behavior changes and urinary incontinence. One month prior to this symptomatology, he had been found unconscious in his closed room where a coal fire was burning overnight. He recovered completely in two days with supportive therapy. Magnetic resonance imaging during this presentation showed bilateral white matter changes suggestive of demyelination. Tc99m-ECD SPECT study revealed hypoperfusion in bilateral frontal region. He was managed conservatively and eventually made a nearly complete recovery. Repeat SPECT study revealed marked improvement in tracer uptake correlating with his improvement. Delayed neuropsychiatric syndrome after acute carbonmonoxide poisoning is a rare and distinct entity. This case report discusses the various aspects of this disease entity.

Study of physiological responses to acute carbon monoxide exposure with a human patient simulator

Human patient simulators are widely used to train health professionals and students in a clinical setting, but they also can be used to enhance physiology education in a laboratory setting. Our course incorporates the human patient simulator for experiential learning in which undergraduate university juniors and seniors are instructed to design, conduct, and present (orally and in written form) their project testing physiological adaptation to an extreme environment. This article is a student report on the physiological response to acute carbon monoxide exposure in a simulated healthy adult male and a coal miner and represents how 1) human patient simulators can be used in a nonclinical way for experiential hypothesis testing; 2) students can transition from traditional textbook learning to practical application of their knowledge; and 3) student-initiated group investigation drives critical thought. While the course instructors remain available for consultation throughout the project, the relatively unstructured framework of the assignment drives the students to create an experiment independently, troubleshoot problems, and interpret the results. The only stipulation of the project is that the students must generate an experiment that is physiologically realistic and that requires them to search out and incorporate appropriate data from primary scientific literature. In this context, the human patient simulator is a viable educational tool for teaching integrative physiology in a laboratory environment by bridging textual information with experiential investigation.

Acute carbon monoxide exposure

Acute carbon monoxide exposure

In vivo exposure to carbon monoxide causes delayed impairment of activation of soluble guanylate cyclase by nitric oxide in rat brain cortex and cerebellum.

Carbon monoxide induces delayed neurological and neuropathological alterations, including memory loss and cognitive impairment. The bases for the delay remain unknown. Activation of soluble guanylate cyclase by nitric oxide modulates some forms of learning and memory. Carbon monoxide binds to soluble guanylate cyclase, activating it but interfering with its activation by nitric oxide. The aim of this work was to assess whether exposure of rats to carbon monoxide alters the activity of soluble guanylate cyclase or its modulation by nitric oxide in cerebellum or cerebral cortex. Rats exposed chronically or acutely to carbon monoxide were killed 24 h or 7 days later. Acute carbon monoxide exposure decreased cyclic guanosine monophosphate (cGMP) content and reduced activation of soluble guanylate cyclase by nitric oxide. Cortex was more sensitive than cerebellum to chronic exposure, which reduced activation of soluble guanylate cyclase by nitric oxide in cortex. In cerebellum, chronic exposure induced delayed impairment of soluble guanylate cyclase activation by nitric oxide. Acute exposure effects were also stronger at 7 days than at 24 h after exposure. This delayed impaired modulation of soluble guanylate cyclase by nitric oxide may contribute to delayed memory loss and cognitive impairment in humans exposed to carbon monoxide.

Hyperbaric Oxygen Therapy for Acute Carbon Monoxide Exposure

Source: Weaver LK, Hopkins RO, Chan KJ, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med. 2002;347:1057–1067.The authors from Salt Lake City, Utah, randomized 152 patients (>16 years of age) who had documented exposure to carbon monoxide (CO) and any of the following symptoms: loss of consciousness, confusion, headache, malaise, fatigue, dizziness, forgetfulness, visual disturbances, vomiting, heart ischemia, or a metabolic acidosis to either hyperbaric-oxygen (HBO) or normobaric-oxygen. HBO was administered 3 times at 6–12 hour intervals in a monoplace chamber. The first exposure to HBO occurred within 24 hours of exposure to CO and used 100% inspired oxygen (FiO2) at 3 atm for 1 hour followed by 2 atm for an additional 2 hours. The 2 remaining HBO sessions used 100% FiO2 at 2 atm for the entire 3 hours. Patients who received normobaric oxygen received 100% FiO2 at 1 atm for 3 hours each session.A battery of neuropsychological tests were administered immediately after the first and third oxygen session and then after 2 weeks, 6 weeks, 6 months, and 12 months. The patients in each group had similar ages and symptoms of headache, vomiting, and confusion. Thirteen percent were admitted to the hospital and 8 percent were mechanically ventilated. The carboxyhemoglobin level (COHb) at time of the first treatment session was 4.3% in the HBO group and 4.6% in the normobaric group.The first HBO session was stopped in 9 patients (7 because of anxiety, 1 due to tympanic membrane rupture, and 1 due to cough). The second or third session was omitted in 4 patients due to middle ear pressure. Data were analyzed using the intent to treat principle. Testing at 6 weeks showed that 25% of the HBO patients had cognitive sequelae compared to 46% of the normobaric group (P=.007). Patients in the HBO group continued to have lower rates of impairment at 6 months (21% versus 38%, P=.02) and 12 months (18% versus 33%, P=.04). The frequency of cognitive sequelae did not differ between patients who completed 3 sessions (24%) from those who did not (28%). The authors concluded that 3 sessions of HBO within the first 24 hours after carbon monoxide poisoning reduced cognitive deficits at both 6 weeks and 12 months after injury.In this study, patients were transported over a 3-state region and several hours had typically elapsed prior to treatment. Treatment with HBO occurred after COHb levels were reduced by treatment with conventional oxygen administration. The half-life of COHb is approximately 5 hours and 20 minutes at room air. This is reduced to 90 minutes with FiO2 of 1.0 at 1 atmosphere, and to 23 minutes at 3 atm.1 Toxic symptoms typically occur when COHb levels are 15–20%.In addition to causing tissue hypoxia, carbon monoxide reacts with reduced metallic ions and forms weak associations with proteins. HBO therapy has been shown to decrease lipid peroxidation, neutrophil adherence, and CO binding to cytochromes resulting in improved brain metabolism.2 Hypoxia is not the sole mechanism by which carbon monoxide causes brain injury and HbCO levels correlate poorly with neurologic injury. Carbon monoxide toxicity has 2 patterns. Patients can present with acute brain and heart injuries and/or with a delayed neurological syndrome that manifests itself in approximately 15–50% of severely poisoned patients between 2 to 28 days after exposure. Age and loss of consciousness have been identified as risk factors for delayed injury.3Complications of HBO therapy include bronchospasm, seizures, progression of untreated pneumothorax, pain and/ or rupture of tympanic membranes, anxiety, and need for patient transport to centers that can offer HBO.4 Delivery of HBO to critically ill patients is difficult. Chambers are monoplace or multi-place. Care providers are pressurized with a patient in a multi-place chamber but the monitoring devices are located outside the chamber with cables that penetrate the chamber hull. Providers are not immediately available to patients in a monoplace chamber. Critically ill patients with COHb and shock from burns may require frequent interventions and be too unstable for HBO.Although children were not included in the above study, children exposed to carbon monoxide may also benefit from HBO treatment; infants may require placement of myringotomy tubes.4 Primary care providers need to be aware of the signs and symptoms of CO poisoning and of the nearest HBO facilities in their region.5It is interesting to note that although patients had near normal carboxyhemoglobin concentrations prior to getting HBO therapy, cognitive impairment occurred nonetheless —suggesting a mechanism other than hypoxia for the cause of this impairment.

Mouse model for thoracic congenital scoliosis.

This study sought to produce a dose-response curve for acute and chronic maternal carbon monoxide (CO) exposure versus vertebral anomalies in mouse offspring and to determine the critical day of exposure. In Part I, pregnant CD-1 mice were exposed to an acute dose of CO at 9 days of gestation. A positive dose-response relationship of acute maternal CO exposure and vertebral anomalies in the offspring was produced. In Part II, pregnant females were exposed to chronic CO for the first 11 days of gestation. Chronic exposure to CO did not produce significant vertebral anomalies. In Part III, pregnant females were exposed to an acute dose of 600 ppm of CO at gestation day 8, 9, or 10. Day 9 in this mouse breed is the critical day for maternal exposure to CO. The detected anomalies were predominately in the thoracic spine.

Mouse Model for Thoracic Congenital Scoliosis

This study sought to produce a dose–response curve for acute and chronic maternal carbon monoxide (CO) exposure versus vertebral anomalies in mouse offspring and to determine the critical day of exposure. In Part I, pregnant CD-1 mice were exposed to an acute dose of CO at 9 days of gestation. A positive dose–response relationship of acute maternal CO exposure and vertebral anomalies in the offspring was produced. In Part II, pregnant females were exposed to chronic CO for the first 11 days of gestation. Chronic exposure to CO did not produce significant vertebral anomalies. In Part III, pregnant females were exposed to an acute dose of 600 ppm of CO at gestation day 8, 9, or 10. Day 9 in this mouse breed is the critical day for maternal exposure to CO. The detected anomalies were predominately in the thoracic spine.

Induction of the c-fos in Rat Brain after Acute Carbon Monoxide Exposure

Induction of the c-fos in Rat Brain after Acute Carbon Monoxide Exposure

Cochlear Protection from Carbon Monoxide Exposure by Free Radical Blockers in the Guinea Pig

Acute carbon monoxide exposure produces a significant impairment in high-frequency auditory sensitivity that can be prevented using theN-methyl-d-aspartate receptor blocker MK-801. This finding suggests an excitotoxic component to carbon monoxide ototoxicity and establishes the potential for free radical formation. Free radical scavengers and inhibitors are protective in many organs, including the brain and cochlea, during hypoxic events such as ischemia/reperfusion and, in the cochlea, during noise exposure. This study evaluated the protection afforded by two such agents, phenyl-n-tert-butyl-nitrone (PBN), which acts as a general free radical scavenger, and allopurinol, which acts as a free radical inhibitor specific to the xanthine oxidase metabolic pathway. Guinea pigs were pretreated with PBN (100 mg/kg ip), allopurinol (100 mg/kg ip), or saline 1 hr prior to exposure to carbon monoxide (35 ml/kg ip) or to an equal volume of air. They were monitored at 15, 30, and 60 min after carbon monoxide exposure for alterations in compound action potential threshold and cochlear microphonic amplitude. The groups receiving carbon monoxide alone displayed characteristic compound action potential threshold elevations particularly at the higher test frequencies (16–40 kHz), consistent with earlier studies; no loss of cochlear microphonic amplitude was exhibited. Both free radical inhibitors, PBN and allopurinol, blocked loss of auditory threshold sensitivity produced by carbon monoxide. These data suggest that free radical generation may play a significant role in the impairment of highfrequency auditory sensitivity resulting from carbon monoxide.

Low-dose carbon monoxide does not reduce vasoconstriction in isolated rat lungs.

Recent studies have demonstrated that nitric oxide (NO) acts as a pulmonary vasodilator when inhaled in low concentrations. Due to the physicochemical similarities between NO and carbon monoxide (CO), it was speculated that low concentrations of CO would have similar effects in the isolated rat lung. The purpose of this study was to determine the role of CO (200 and 1000 ppm) in modulating hypoxia- and angiotensin II (AII)-induced pulmonary vasoconstriction, using isolated salt-perfused lungs of normotensive (CON) or pulmonary hypertensive male rats. Pulmonary hypertensive rats (ALT), induced by simulated altitude exposure (4572 m; 430 mm Hg for 32-48 days), were studied to determine the actions of low-dose CO in a remodeled pulmonary vascular bed. Right ventricular hypertrophy and polycythemia were evident in the ALT rats, suggesting that simulated altitude exposure induced pulmonary hypertension and consequent pulmonary vascular remodeling. CO did not significantly affect pulmonary vascular responses to acute hypoxia (6% CO2, balance N2) in either CON or ALT rats. There were also no significant differences in pulmonary pressor responses to AII injections (0.2 or 0.4 micrograms) in CON or ALT lungs either immediately following or during an acute hypoxia + CO exposure. Therefore, acute low-dose CO exposure (< 1000 ppm) does not appear to attenuate pulmonary vasoconstriction in isolated rat lungs.