Effects of Carbon Dioxide on Brain Excitability and Electrolytes

Woodbury, Dixon M.; Rollins, Lawrence T.; Gardner, Morris D.; Hirschi, Wayne L.; Hogan, John R.; Rallison, Marvin L.; Tanner, George S.

doi:10.1152/ajplegacy.1957.192.1.79

Cited by 108 publications

(50 citation statements)

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“…The inhalation of 5 per cent carbon dioxide in oxygen has been reported to result in an increase in the rate of entry of radio-sodium into the CSF in human subjects (33). Inhalation of 50 per cent carbon dioxide has also been reported to result in an increase in brain intracellular sodium concentration in rats (34). In the present study, however, carbon dioxide inhalation did not affect the sodium exchange time.…”

Section: Discussioncontrasting

confidence: 53%

Factors Influencing the Exchange of Sodium Between Plasma and Cerebrospinal Fluid*†

Fishman¹

1959

J. Clin. Invest.

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This study is concerned with the mechanism of exchange of sodium between plasma and cerebrospinal fluid (CSF). Several workers (1, 2) have reported that there is no significant difference between the concentration of sodium in plasma and CSF. reported that the average concentration of sodium in CSF, in man, exceeded the plasma concentration by about four mEq. Davson (4) has determined the distribution ratio of sodium between CSF and plasma as 0.975 in the dog, correcting for the difference in water content of these fluids. Despite the similarity in sodium concentration of these fluids and the superficial resemblance of CSF to a protein-free filtrate of plasma, intravenously administered radio-sodium reaches equilibrium in the CSF far more slowly than in the extracellular fluid (5, 6). The delay in exchange between plasma and CSF has been attributed to the existence of a blood-CSF barrier for sodium (5-7). The present experiments have been devised to note the effect of a variety of physiological and pharmacological alterations on the exchange of sodium between these fluid compartments. intervals. The time necessary for the activity of the cisternal fluid to reach 50 per cent of the serum activity was obtained by graphic analysis of the CSF/serum ratios at these time intervals. As the serum radioactivity was not maintained at a constant level, a time constant was not calculated but the half-time as determined was used as the measure of the rate of sodium exchange. This half-time is referred to as the sodium exchange time. A typical experiment is illustrated in Figure 1. Radioactivity was measured in duplicate with a welltype scintillation counter and sodium content with a flame photometer. Each animal had at least one control study in addition to one or more experimental studies. Each animal was given at least a seven day recovery period between experiments. Cisternal fluid pressure, when required, was measured with a spinal water manometer. Blood pressure was recorded in some experiments with a strain-gage manometer. METHODS RESULTSI. Concentration of sodium in serum and cerebrospinal fluid of normal dogs The serum and CSF sodium concentrations were determined in 27 normal dogs. The average serum sodium concentration was 155 ± 6 mEq. per L. The average CSF sodium concentration was 158 + 6 mEq. per L. Statistical analysis using Student's "t" test (8)

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Section: Discussioncontrasting

confidence: 53%

Factors Influencing the Exchange of Sodium Between Plasma and Cerebrospinal Fluid*†

Fishman¹

1959

J. Clin. Invest.

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“…Animals experienced asphyxia (as evidenced by gasping with mouth open (Woodbury et al 1958, Coenen et al 1995; the present authors calculated these times when they were not specified directly by the authors of the original papers. NS = not specified (Woodbury et al 1958, Coenen et al 1995; the present authors calculated these times when they were not specified directly by the authors of the original papers. NS ¼ not specified and head turned up and backward) in some conditions and those in the 100% CO 2 group showed most evidence of this behaviour.…”

Section: Laboratory Animals (2005) 39mentioning

confidence: 99%

Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats

et al. 2005

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SummaryCarbon dioxide (CO 2 ) is the most commonly used agent for euthanasia of laboratory rodents, used on an estimated tens of millions of laboratory rodents per year worldwide, yet there is a growing body of evidence indicating that exposure to CO 2 causes more than momentary pain and distress in these and other animals. We reviewed the available literature on the use of CO 2 for euthanasia (as well as anaesthesia) and also informally canvassed laboratory animal personnel for their opinions regarding this topic. Our review addresses key issues such as CO 2 flow rate and final concentration, presence of oxygen, and prefilled chambers (the animal is added to the chamber once a predetermined concentration and flow rate have been reached) versus gradual induction (the animal is put into an empty chamber and the gas agent(s) is gradually introduced at a fixed rate). Internationally, animal research standards specify that any procedure that would cause pain or distress in humans should be assumed to do so in non-human animals as well (Public Health Service 1986, US Department of Agriculture 1997, Organization for Economic Cooperation and Development 2000). European Union guidelines, however, specify a certain threshold of pain or distress, such as 'skilled insertion of a hypodermic needle', as the starting point at which regulation of the use of animals in experimental or other scientific procedures begins (Biotechnology Regulatory Atlas n.d.). There is clear evidence in the human literature that CO 2 exposure is painful and distressful, while the non-human literature is equivocal. However, the fact that a number of studies do conclude that CO 2 causes pain and distress in animals indicates a need for careful reconsideration of its use. Finally, this review offers recommendations for alternatives to the use of CO 2 as a euthanasia agent.Keywords Carbon dioxide; euthanasia; pain; distress; anaesthesia; welfare; rodents Carbon dioxide (CO 2 ) is commonly used for euthanasia and anaesthesia of laboratory rodents, largely because of its ease of use, relative safety, and low cost, as well as its capacity to euthanize large numbers of animals in a short time span (Ambrose et al. 2000). In large institutions and those with significant rodent-breeding programmes, large numbers of rodents are often euthanized in a short time (Kline et al. 1963) and an appropriate gas agent is often the best way to approach such a challenge. However, CO 2 is not physiologically inert and the published evidence on whether or not CO 2 administration causes pain or distress in animals raises questions about its routine use. This paper reviews this published evidence and includes information on the effects of CO 2 in both humans and nonhumans. Methodological details are included when possible in order to provide a clear

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“…Petty and Sulkowski (1971b) observed cardiac arrythmias, particularly when the concentration of CO 2 exceeded 700/0,decreases in heart rate which were inversely proportional to the concentration of CO2, and increases in serum potassium concentration. Woodbury et al (1958) found that the inhalation of 50% CO 2 decreased brain intracellular sodium and potassium concentrations. Roth and Barlow (1961) recorded marked increases in brain penetration by urea, phenobarbital and salicylic acid during hypercapnic acidosis.…”

Section: Abstract: Anaesthesia; Rats; Carbon Dioxide; Restraintmentioning

confidence: 96%

“…The advantages of CO 2 are that it is odourless and colourless, and appears to have no insidious effects on laboratory staff. Studies of electroencephalographs (EEGs) and cortical somatosensory evoked responses (Forslid et al, 1986), electroshock seizure threshold (Woodbury et al, 1958),and behaviour during induction (Blackshaw et al, 1988) all indicate that CO2, at anaesthetic concentrations, has a sedative effect and depresses the central nervous system. Physiologically, CO 2 inhalation can produce changes which may affect the results of certain types of research.…”

Section: Abstract: Anaesthesia; Rats; Carbon Dioxide; Restraintmentioning

confidence: 99%

Carbon dioxide as a short-term restraint anaesthetic in rats with subclinical respiratory disease

Fenwick

Blackshaw

1989

Lab Anim

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SummaryThe use of carbon dioxide (C0 2 ) with, and without, oxygen (0 2 ) as a short-term restraint anaesthetic for Wistar rats in which subclinical respiratory disease was endemic, was assessed in 3 separate experiments. In the first, rats were placed in a CO 2 atmosphere generated from solid CO 2 chips in a 70 Iplastic bin, and removed at time intervals ranging from 0 to 120 s after disappearance of the pedal reflex. Eight of 25 rats died, including 2 which were removed immediately the pedal reflex disappeared; it was concluded that CO 2 without O 2 was not a suitable short-term anaesthetic for rats. In a second study, rats were anaesthetized in atmospheres of 50 : 50 and 80 : 20 (C0 2 : O 2 ) provided from commercially available cylinders, in 2 different environments -a 3, 41 glass jar and a 171 plastic bin. Rats became excited in the plastic bin but not the glass jar. Rats in the glass jar displayed visible depression and cessation of whiskers movement significantly more quickly in the 80: 20 (C0 2 : O 2 ) than in the SO: 50 mixture (4'2±0'98s, n=6, and 66·0±4·9s, n=6 vs 13·8±2·77s, n=5 and 152·0±20·8s, n=5, respectively). Rats in the 171 plastic bin lost their pedal reflexes in a mean 41· 5 ± 4· 55 s (n = 11) in the SO : SO mixture and in a mean 30·9 ± 6·38 s (n = 11) in the 80: 20 (C02: O 2 ) group. Those left in the 50 : 50 mixture for 60 sand 180 s after disappearance of their pedal reflexes, recovered these reflexes in 20· 2 ± 0,44 sand 21·5 ± 7· 23 s respectively after removal from the gas. Respiration and heart beat ceased in one rat remaining in the SO : 50 mixture after 13 min 10 s. Received 12 March 1987. Accepted 25 November 1988 No untoward effects occurred in rats left in the 50 : 50 mixture for 180 s after disappearance of the pedal reflex, but 2 died when left for an equivalent period in the 80: 20 mixture. In the third study, examples of the practical use of a 50 : 50 mixture as a short term restraint anaesthetic are described. It was concluded that this mixture was a cheap, safe, and effective means of short-term restraint for rats with subclinical respiratory disease, when the minimal time of exposure to the gases was employed.

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Effects of Carbon Dioxide on Brain Excitability and Electrolytes

Cited by 108 publications

References 0 publications

Factors Influencing the Exchange of Sodium Between Plasma and Cerebrospinal Fluid*†

Factors Influencing the Exchange of Sodium Between Plasma and Cerebrospinal Fluid*†

Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats

Carbon dioxide as a short-term restraint anaesthetic in rats with subclinical respiratory disease

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