Consequences of Brief Exposure to High Concentrations of Carbon Monoxide in Conscious Rats

Exposure to high-concentration carbon monoxide (CO) is of concern in military operations. Experimentally, the physiologic manifestations of a brief exposure to elevated levels of CO have not been fully described. This study investigated the development of acute CO poisoning in conscious male Sprague-Dawley rats (220–380 g). Animals were randomly grouped (n = 6) and exposed to either air or 1 of 6 CO concentrations (1000, 3000, 6000, 10,000, 12,000, or 24,000 ppm) in a continuous air/CO dynamic exposure chamber for 5 min. Respiration was recorded prior to and during exposures. Mixed blood carboxyhemoglobin (COHb) and pH were measured before and immediately after exposure. Before exposure the mean baselines of respiratory minute volumes (RMVs) were 312.6 ± 43.9, 275.2 ± 40.8, and 302.3 ± 39.1 ml/min for the 10,000, 12,000 and 24,000 ppm groups, respectively. In the last minute of exposure RMVs were 118.9 ± 23.7, 62.1 ± 10.4, and 22.0 ± 15.1% (p < .05) of their mean baselines in these 3 groups, respectively. Immediately after exposure, blood COHb saturations were elevated to 60.16, 63.42, and 69.37%, and blood pH levels were reduced to 7.43 ± 0.09, 7.25 ± 0.05, and 7.13 ± 0.04 in the 3 groups, respectively. Mortality during exposure was 1/12 in the 12,000 ppm group and 4/12 in the 24,000 ppm group. Deaths occurred close to the end of 5 min exposure. In each animal that died by exposure, pH was <6.87 and COHb saturation was >82%. Blood pH was unaltered and no death occurred in rats exposed to CO at concentrations <6000 ppm, although COHb saturations were elevated to 14.52, 29.94, and 57.24% in the 1000, 3000, and 6000 ppm groups, respectively. These results suggest that brief exposure to CO at concentrations <10,000 ppm may produce some significant physiological changes. However, exposure to CO at concentrations >10,000 ppm for brief periods as short as 5 min may change RMV, resulting in acute respiratory failure, acidemia, and even death.

[1]  J. E. Peterson,et al.  Experimental human exposure to high concentrations of carbon monoxide. , 1973, Archives of environmental health.

[2]  D. Ecobichon,et al.  Carbon monoxide and water vapor contamination of compressed breathing air for firefighters and divers. , 1997, Journal of toxicology and environmental health.

[3]  R E Forster,et al.  Considerations of the physiological variables that determine the blood carboxyhemoglobin concentration in man. , 1965, The Journal of clinical investigation.

[4]  J. Neubauer,et al.  Role of brain lactic acidosis in hypoxic depression of respiration. , 1988, Journal of applied physiology.

[5]  H J Clewell,et al.  Physiologically based pharmacokinetic modeling with dichloromethane, its metabolite, carbon monoxide, and blood carboxyhemoglobin in rats and humans. , 1991, Toxicology and applied pharmacology.

[6]  Gary R Ripple,et al.  Medical Evaluation of Nonfragment Injury Effects in Armored Vehicle Live Fire Tests: Instrumentation Requirements and Injury Criteria , 1989 .

[7]  H. L. Kaplan Effects Of Combustion Gases On Excape Performance Of The Baboon And The Rat , 1986 .

[8]  V A Benignus,et al.  Prediction of carboxyhemoglobin formation due to transient exposure to carbon monoxide. , 1994, Journal of applied physiology.

[9]  D. C. Sanders,et al.  Exposures to carbon monoxide, hydrogen cyanide and their mixtures: Interrelationship between gas exposure concentration, time to incapacitation, carboxyhemoglobin and blood cyanide in rats , 1995, Journal of applied toxicology : JAT.

[10]  K. Kohshi [Diagnosis and treatment for carbon monoxide poisoning]. , 2007, Chudoku kenkyu : Chudoku Kenkyukai jun kikanshi = The Japanese journal of toxicology.

[11]  S. Omaye,et al.  Cardiovascular disease hospitalization and ambient levels of carbon monoxide. , 1998, Journal of toxicology and environmental health. Part A.

[12]  P Tikuisis,et al.  Percent carboxyhemoglobin in resting humans exposed repeatedly to 1,500 and 7,500 ppm CO. , 1987, Journal of applied physiology.

[13]  J. Carroll,et al.  Response of newborn lambs to CO-induced hypoxia. , 1988, Journal of applied physiology.

[14]  S. Horvath,et al.  Effect of acute carbon monoxide exposure on cardiopulmonary function of the awake rat. , 1982, Toxicology and applied pharmacology.

[15]  R E Fromm,et al.  Carbon monoxide poisoning: a review for clinicians. , 1999, The Journal of emergency medicine.

[16]  E. Conway,et al.  Relationship between arterial, mixed venous, and internal jugular carboxyhemoglobin concentrations at low, medium, and high concentrations in a piglet model of carbon monoxide toxicity , 2000, Critical care medicine.

[17]  J. Mccammon,et al.  Carbon monoxide poisonings resulting from open air exposures to operating motorboats--Lake Havasu City, Arizona, 2003. , 2004, MMWR. Morbidity and mortality weekly report.

[18]  S KAYE,et al.  Carbon monoxide poisoning. , 1957, Virginia medical monthly.

[19]  A. Hayes,et al.  Nose-Only Exposure of Rats to Carbon Monoxide , 1989 .

[20]  M. Stupfel,et al.  Animal models and acute and long-term carbon monoxide intoxication. , 1979, Preventive medicine.

[21]  E Braun,et al.  Toxicological interactions between carbon monoxide and carbon dioxide. , 1987, Toxicology.

[22]  G. Turino Effect of carbon monoxide on the cardiorespiratory system. Carbon monoxide toxicity: physiology and biochemistry. , 1981, Circulation.

[23]  K. Imaizumi,et al.  Prediction of the carbonmonoxyhemoglobin levels during and after carbon monoxide exposures in various animal species. , 1981, The Japanese journal of physiology.

[24]  Yang Ms,et al.  Determination of endogenous trace metal contents in various mouse brain regions after prolonged oral administration of aluminum chloride , 1998 .

[25]  G E Hartzell,et al.  Overview of combustion toxicology. , 1996, Toxicology.

[26]  T. V. Santiago,et al.  Mechanism of the ventilatory response to carbon monoxide. , 1976, The Journal of clinical investigation.

[27]  S. Helps,et al.  Acute Carbon Monoxide Exposure and Cerebral Blood Flow in Rabbits , 1991, Anaesthesia and intensive care.

[28]  P. Tikuisis,et al.  Rate of formation of carboxyhemoglobin in exercising humans exposed to carbon monoxide. , 1992, Journal of applied physiology.

[29]  N H Edelman,et al.  Correlation between ventilatory and cerebrovascular responses to inhalation of CO. , 1977, Journal of applied physiology: respiratory, environmental and exercise physiology.

[30]  Arthur F. Grand,et al.  Effects of Combustion Gases On Escape Performance of the Baboon and the Rat , 1985 .

[31]  H. Gautier,et al.  Ventilatory response of intact cats to carbon monoxide hypoxia. , 1983, Journal of applied physiology: respiratory, environmental and exercise physiology.

[32]  N B Hampson,et al.  Carbon monoxide poisoning--a public health perspective. , 2000, Toxicology.

[33]  S. S. Gammon Respiratory acidosis. , 1982, Nursing.

[34]  Playing in the back seat , 2000, Journal of accident & emergency medicine.

[35]  B C Levin,et al.  New research avenues in toxicology: 7-gas N-Gas Model, toxicant suppressants, and genetic toxicology. , 1996, Toxicology.

[36]  J. E. Peterson,et al.  Effect of carbon monoxide on time perception. , 1973, Archives of environmental health.

[37]  J. E. Peterson,et al.  Predicting the carboxyhemoglobin levels resulting from carbon monoxide exposures. , 1975, Journal of applied physiology.

[38]  V. Benignus,et al.  Carbon monoxide and the nervous system , 2002, Neuroscience & Biobehavioral Reviews.

[39]  R. L. Carpenter,et al.  A physiological model for predicting carboxyhemoglobin formation from exposure to carbon monoxide in rats. , 1999, Journal of applied physiology.

[40]  J. Stuhmiller,et al.  Evaluation of lethality estimates for combustion gases in military scenarios. , 1996, Toxicology.

[41]  J. Haldane The Action of Carbonic Oxide on Man , 1895, The Journal of physiology.

[42]  P. Obert,et al.  CARDIAC MORPHOLOGY AND FUNCTION FOLLOWING LONG-TERM EXPOSURE TO CARBON MONOXIDE AT HIGH ALTITUDE IN RATS , 2002, Journal of toxicology and environmental health. Part A.

[43]  CARBON MONOXIDECO,et al.  Carbon Monoxide , 2020, Definitions.

[44]  S. Horvath,et al.  Maximal aerobic capacity at different levels of carboxyhemoglobin. , 1975, Journal of applied physiology.

[45]  L. Fechter Promotion of Noise-Induced Hearing Loss by Chemical Contaminants , 2004, Journal of toxicology and environmental health. Part A.

[46]  D. Penney Acute carbon monoxide poisoning: animal models: a review. , 1990, Toxicology.

[47]  T. Amis,et al.  Respiratory failure , 2018, ERS Handbook Respiratory Medicine.

[48]  M. Turner,et al.  Carbon monoxide poisoning treated with hyperbaric oxygen: metabolic acidosis as a predictor of treatment requirements. , 1999, Journal of accident & emergency medicine.

[49]  Z. Annau,et al.  Carboxyhemoglobin formation due to carbon monoxide exposure in rats. , 1994, Toxicology and applied pharmacology.

[50]  Gordon E. Hartzell,et al.  Modeling of Toxicological Effects of Fire Gases: V. Mathematical Modeling of Intoxication of Rats By Combined Carbon Monoxide and Hydrogen Cyanide Atmospheres , 1985 .