losartan-potassium and Carbon-Monoxide-Poisoning

Carbon monoxide poisoning is both an ancient and current cause of inadvertent (accidental) death and more recently has emerged as a cause of suicide worldwide. This article describes the pathophysiology and epidemiology of this most toxic and frequently occult poison.

Topics: Accidents; Carbon Monoxide Poisoning; Carboxyhemoglobin; Erythropoietin; Hematinics; Hemoglobins; Humans; Hyperbaric Oxygenation; Suicide, Attempted; United Kingdom

The purpose of this study was to evaluate the efficacy of erythropoietin (EPO) for treating patients with carbon monoxide (CO) poisoning. We conducted a randomized, prospective study of 103 patients with CO poisoning in two groups: an EPO group (n = 54; patients received EPO) and a placebo group (n = 49; patients received normal saline). The study endpoints were the functional outcome at day 30 (the Barthel index and neurologic sequelae), National Institutes of Health Stroke Scale (NIHSS) score, and the levels of S-100β. At 18 days, the NIHSS score improved significantly and S-100β levels significantly decreased in patients in the EPO group. At 30 days, patients in the EPO group had a superior Barthel index and fewer patients had delayed neurologic sequelae (DNS). This study demonstrated that early administration of EPO to patients with CO poisoning improved neurological outcomes and reduced the incidence of DNS.

Topics: Adult; Biomarkers; Carbon Monoxide Poisoning; Carboxyhemoglobin; Data Collection; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Nerve Growth Factors; Neuroprotective Agents; Recombinant Proteins; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Treatment Outcome

Inflammatory responses play critical roles in carbon monoxide (CO) poisoning-induced cerebral injury. The present study investigated whether erythropoietin (EPO) modulates the toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) inflammatory signaling pathways in brain injury after acute CO poisoning. EPO (2500 and 5000 U/kg) was injected subcutaneously twice a day after acute CO poisoning for 2 days. At 48 h after treatment, the expression levels of TLR4 and NF-κB as well as the levels of inflammatory cytokines in the hippocampal tissues were measured. Our results showed that CO poisoning induced a significant upregulation of TLR4, NF-κB, and inflammatory cytokines in the injured rat hippocampal tissues. Treatment with EPO remarkably suppressed the gene and protein expression levels of TLR4 and NF-κB, as well as the concentrations of TNF-α, IL-1β, and IL-6 in the hippocampal tissues. EPO treatment ameliorated CO poisoning-induced histological edema and neuronal necrosis. These results suggested that EPO protected against CO poisoning-induced brain damage by inhibiting the TLR4-NF-κB inflammatory signaling pathway.

Topics: Animals; Brain Injuries; Carbon Monoxide; Carbon Monoxide Poisoning; Edema; Erythropoietin; Hippocampus; Inflammation; Interleukin-1beta; Interleukin-6; Male; Maze Learning; Necrosis; NF-kappa B; Rats; Rats, Sprague-Dawley; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Erythropoietin (EPO) plays a critical role in the development of the nervous system. In this study, the effects of EPO in carbon monoxide (CO) neurotoxicity were examined. Rats were exposed to 3000 ppm CO for 1 h and then different doses of EPO were administrated intraperitoneally. After 24 h, glial fibrillary acidic protein (GFAP) levels in the serum were determined and water content of brain and the extravasation of a tracer (Evans blue) were measured. Brain lipid peroxidation, myeloperoxidase activity Myelin basic protein (MBP) and BAX/BcL2 protein relative expressions were determined. Cation exchange chromatography was used to evaluate MBP alterations. Seven days after exposure, pathological assessment was performed after Klüver-Barrera staining. EPO reduced malondialdehyde levels at all doses (2500, 5000 and 10,000 u/kg). Lower doses of EPO (625, 1250, 2500 u/kg) significantly decreased the elevated serum levels of GFAP. EPO could not reduce the water content of the edematous poisoned brains. However, at 5000 and 10,000 u/kg it protected the blood brain barrier against integrity loss as a result of CO. EPO could significantly decrease the MPO activity. CO-mediated oxidative stress caused chemical alterations in MBP and EPO could partially prevent these biochemical changes. Fewer vacuoles and demyelinated fibers were found in the EPO-treated animals. EPO (5000 u/kg) could restore the MBP density. CO increased brain BAX/Bcl-2 ratio 38.78%. EPO reduced it 38.86%. These results reveal that EPO could relatively prevent different pathways of neurotoxicity by CO poisoning and thus has the potential to be used as a novel approach to manage this poisoning.

Topics: Animals; bcl-2-Associated X Protein; Blood-Brain Barrier; Brain; Carbon Monoxide; Carbon Monoxide Poisoning; Central Nervous System Diseases; Dose-Response Relationship, Drug; Erythropoietin; Gene Expression Regulation; Lipid Peroxidation; Male; Myelin Basic Protein; Proto-Oncogene Proteins c-bcl-2; Random Allocation; Rats; Rats, Wistar

Topics: Adult; Aged; Carbon Monoxide Poisoning; Erythropoietin; Female; Humans; Magnetic Resonance Imaging; Male; Neurotoxicity Syndromes; Recombinant Proteins

Topics: Animals; Carbon Monoxide Poisoning; Erythropoiesis; Erythropoietin; Female; Hypoxia; Mice

Plasma erythropoietin titers (Ep) were compared in rats subjected to different kinds of systemic hypoxia. Ep increased exponentially, when hypoxia was induced by exposure to simulated altitude (from less than 0.025 IU Ep/ml plasma at sea-level up to 3.65 IU Ep/ml at 7000 m). An acute increase in the O2 affinity of blood augmented Ep production in normal rats but not in rats exposed to hypobaria. Ep also rose exponentially when isovolemic anemia was induced (e.g., 0.5 IU Ep/ml plasma were found at 7 g Hb/dl blood). When the same reduction in blood O2 carrying capacity was produced by CO-inhalation (0.1% CO in air), Ep increased to 5.57 IU/ml plasma. This very high value was considered to be partly due to the very high O2 affinity of carboxyhemoglobin. These results indicate that a left shift in the hemoglobin-O2 dissociation curve produces a stimulation of Ep production, particularly, when the O2-carrying capacity of blood is lowered.

Topics: Anemia; Animals; Atmospheric Pressure; Carbon Monoxide Poisoning; Erythropoietin; Hemoglobins; Hypoxia; Male; Oxygen; Rats; Rats, Inbred Strains

Topics: Animals; Carbon Monoxide Poisoning; Erythropoiesis; Erythropoietin; Heart Rate; Mice; Oxygen Consumption; Temperature

The effects of the beta-adrenergic blocking agent (propranolol) on erythropoietin production in carbon monoxide intoxicated mice were studied. The raise in plasma erythropoietin after a 4 hour intoxication with carbon monoxide was 47% less in the propranolol treated group. A decrease of 65% in the endogenous erythropoietic response after 75 minutes of carbon monoxide intoxication was found in policithemic treated mice, as against the untreated ones. The tissue oxygen tension was reduced in the propranolol treated group. No changes was found in the hemoglobin oxygen affinity.

Topics: Animals; Carbon Monoxide Poisoning; Erythropoiesis; Erythropoietin; Iron Radioisotopes; Mice; Mice, Inbred C3H; Oxygen Consumption; Partial Pressure; Propranolol

Various stimuli (hypoxic hypoxia, bleeding, carbon monoxide hypoxia and cobalt administration), well known to increase erythropoietin plasma level in many species including man, failed to increase the erythropoietin activity in plasma of guinea pigs when measured in the polycythaemic mice assay. Nevertheless, the plasma of these guinea pigs stimulated the erythropoiesis in polycythaemic guinea pigs which, however, failed to respond to rat erythropoietin. From this it was concluded that not only the erythropoietin, but also the erythropoietin responsive cells in the bone marrow of guinea pigs are species specific. Bilateral nephrectomy in guinea pigs exposed to hypoxia prevented the increase in the erythropoietin plasma level, thus suggesting that, similarly as in other species, also in guinea pigs the kidney is the main organ of erythropoietin elaboration. The species specificity of guinea pig erythropoietin - erythropoiesis system is an interesting exception among mammals, since the erythropoietin of a large number of species belonging to this class was demonstrated to lack species specificity.

Topics: Animals; Bloodletting; Carbon Monoxide Poisoning; Cobalt; Erythropoietin; Female; Guinea Pigs; Hypoxia; Kidney; Mice; Nephrectomy; Rats; Species Specificity

The effects of hypoxemia caused by hypoxia (H-H) and CO (H-CO) on the production of erythropoietin (ESF) in mice were investigated. When mice breathed for 6 hr mixtures of air containing 0.1% of CO or a mixture of air and nitrogen with a pO2 of 52 mm Hg, the tissue pO2 as measured by the gas pocket technique was 16.9 +/- 1.1 and 17.1 +/- 1.4 (mean +/- S.D.), respectively. Plasma ESF content in H-CO mice, however, was twice higher than in the H-H mice. The greater ESF production in H-CO was associated to a significantly less hyperventilatory response as measured by acid-base balance changes and to a lower O2 consumption and was interpreted as the result of displacement of the OHb curve in opposite directions. The ESF organ appears thus to be sensitive to variations in the amount of O2 delivered to the tissues but independent of the arterial pO2.

Topics: Acid-Base Equilibrium; Animals; Carbon Monoxide Poisoning; Erythropoiesis; Erythropoietin; Female; Hyperventilation; Hypoxia; Mice; Nitrogen; Oxygen; Oxygen Consumption; Partial Pressure

Carbon monoxide injected subcutaneously in mice produces a profound intoxication during a six hour-period. From 2 to 4 hr after the start of carbon monoxide (CO)-hypoxemia large amounts of erythropoietin (ESF) are released in the plasma. Renal extracts obtained at the same time showed higher specific activity than that found in the plasma extracts. No activity was recovered from liver and spleen extracts. Removal of the kidney abolishes totally the production of ESF.

Topics: Animals; Carbon Monoxide Poisoning; Erythropoietin; Female; Kidney; Mice; Spleen; Time Factors

Topics: Animals; Biological Assay; Bone Marrow; Bone Marrow Cells; Bone Marrow Examination; Carbon Monoxide Poisoning; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Hemoglobins; Hypoxia; Injections, Intraperitoneal; Iron; Iron Isotopes; Mice; Polycythemia; Reticulocytes