Biomedical subjects

D A Finn

Publications and source records attributed to D A Finn.

46 records · Page 3Linked to original sources

PubMed1987

Rectal and brain temperatures in ethanol intoxicated mice.

The present study tested the assumption that deep rectal temperature reflects brain temperature in ethanol-intoxicated mice exposed to a range of ambient temperatures. Adult C57BL/6J mice were injected IP with one of three hypnotic doses of ethanol (3.2, 3.6, or 4.0 g/kg, 20% w/v) or with normal saline and were exposed to ambient temperatures of 15, 22, 32, or 34 degrees C. Thirty minutes post-injection, the mice were killed by cervical dislocation, decapitated and their rectal and brain temperatures were recorded simultaneously. Rectal and brain temperatures in the intoxicated mice increased significantly as the ambient temperature increased and were highly correlated and linearly related with each other. Although correlated, brain and rectal temperatures in these mice did not change in parallel, with brain temperatures increasing less rapidly than rectal temperatures. Additional studies indicated that similar relationships (correlated, but non-parallel) exist between the brain and rectal temperatures at 60, 120, and 180 min after injection of 3.6 g/kg ethanol. These findings suggest that rectal temperature can be used to quantify brain temperature in intoxicated mice, and extend to intoxicated animals evidence that brain temperature is controlled independently from rectal temperature.

Animals↗

PubMed1987

Hyperbaric exposure acts as an ethanol antagonist: evidence from chronic ethanol studies.

Hyperbaric exposure has been shown to antagonize the acute depressant effect of ethanol on behavior. The present studies extended the investigation to animals chronically treated with ethanol. The results indicate that exposure to 12 atmospheres absolute (ATA) helium-oxygen (HEOX) precipitated and exacerbated withdrawal signs in ethanol dependent C57BL/6 mice compared to dependent animals exposed to 1 ATA air or HEOX. A second study found that hyperbaric exposure during acquisition significantly reduced the development of chronic, functional ethanol tolerance measured by sleep-times and wake-up ethanol concentrations. Further investigations suggest that hyperbaric exposure during dependence acquisition also attenuates the development of ethanol dependence. These results support the hypothesis that hyperbaric exposure directly antagonizes molecular actions of ethanol leading to acute intoxication, tolerance and physical dependence.

Air Pressure↗

PubMed1986

Temperature dependence of ethanol depression in rats.

The relationship between ambient temperature, body temperature, and brain sensitivity to ethanol was investigated in rats. Drug naive male Long Evans rats were injected IP with a hypnotic dose of ethanol (2.75 g/kg, 20% w/v). Immediately after injection, separate groups were exposed to one of five ambient temperatures from 12 to 34 degrees C. Ambient temperature significantly affected wake-up rectal temperature, sleep-time, and wake-up brain ethanol concentration. Sleep-times in individual rats increased 387% (from 24.0 min at 12 degrees C to 116.8 min at 34 degrees C) and wake-up brain ethanol concentrations decreased 79% (from 3.6 mg/g at 12 degrees C to 2.3 mg/g at 34 degrees C) as body temperatures increased from 35 to 41 degrees C. In addition, wake-up rectal temperatures were significantly, positively correlated with sleep-times (r = 0.32, P less than 0.05) and significantly, negatively correlated with wake-up brain ethanol concentrations (r = -0.49, P less than 0.01), further suggesting that brain sensitivity to ethanol increases as body temperature increases. These results are consistent with previous findings in mice, fit membrane perturbation theories of anesthesia, and indicate that temperature dependence of ethanol sensitivity is a general phenomenon extending across species. In conjunction with previous findings, the results also suggest that body temperature during intoxication may participate in mediating species differences in ethanol sensitivity.

Animals↗

PubMed1985

Ethanol withdrawal in mice precipitated and exacerbated by hyperbaric exposure.

Mice were fed an ethanol-containing liquid diet for 9 days. On removal of the diet, exposure to 12 atmospheres absolute of a mixture of helium and oxygen precipitated earlier withdrawal, increased withdrawal scores for the first 6 hours, and increased the peak withdrawal intensity compared to dependent animals exposed to control conditions. The enhanced withdrawal did not appear to reflect alterations in ethanol elimination, oxygen or helium partial pressures, body temperature, or general excitability. These results extend to chronically treated animals the evidence that hyperbaric exposure antagonizes the membrane actions of ethanol.

Animals↗

PubMed1985

Reduced lethality from ethanol or ethanol plus pentobarbital in mice exposed to 1 or 12 atmospheres absolute helium-oxygen.

The present experiments investigated the effects of 1 and 12 atmospheres absolute (ATA) helium-oxygen on potentially lethal doses of ethanol given alone or in combination with pentobarbital. Drug-naive, male C57BL/6J mice were injected IP with 5.4-6.5 g/kg ethanol, 4.5-6.9 g/kg ethanol plus 20 mg/kg pentobarbital, or 50-110 mg/kg pentobarbital plus 2.5 g/kg ethanol. Following injection, the mice were placed into chambers and exposed to environments of 1 ATA air, 1 ATA helium-oxygen, or 12 ATA helium-oxygen. Exposure to 1 or 12 ATA helium-oxygen significantly reduced the lethal effect (percent mortality at given doses and LD50) of ethanol given alone or with 20 mg/kg pentobarbital when compared to animals exposed to 1 ATA air. The pattern and degree of reduction in lethality for the 1 and 12 ATA helium-oxygen treatments were similar, suggesting that the antagonism resulted from increased helium or decreased nitrogen and not from increased atmospheric pressure. Exposure to these environments did not reduce lethality in mice given 2.5 g/kg ethanol in combination with relatively high doses (50-110 mg/kg) of pentobarbital. These findings suggest that helium-oxygen breathing mixtures may be useful in the treatment of some overdose patients.

Animals↗

PubMed1985

Temperature dependence of ethanol depression: linear models in male and female mice.

The relationship between body temperature and ethanol sensitivity was studied in male and female mice. Age-matched drug-naive mice of both sexes were injected with 3.6 g/kg ethanol (20% w/v) and placed into a chamber kept at one of 8 designated temperatures from 13 to 36 degrees C. In both sexes, wake-up rectal temperatures were significantly, positively correlated with chamber temperatures and sleep-times and were significantly, negatively correlated with wake-up brain and blood ethanol concentrations. Linear regression analyses indicated that wake-up temperature accounted for up to 71% of the variability in sleep-times and wake-up ethanol concentrations in these mice. Similar relationships were found when the change in body temperature from baseline (delta T) was substituted for wake-up rectal temperature. Adding body weights and baseline temperatures did not improve the predictive ability of linear models based on wake-up rectal temperature alone. The results support the contention that body temperature represents an important determinant of ethanol sensitivity in both sexes. These findings provide additional evidence that ethanol sensitivity varies with body temperature in accordance with membrane perturbation theories of anesthesia.

Animals↗

PubMed1983

The importance of experience in the development of tolerance to ethanol hypothermia.

Studies were conducted to determine if an animal has to experience a reduction in body temperature during the acquisition period in order to develop tolerance to the hypothermic effect of ethanol. Adult, drug-naive C57BL/6J mice were injected with 2.6 or 3.6 g/kg ethanol or normal saline once daily for 6 days. During the tolerance acquisition period, days 1-5, mice were placed into warmed chambers (36 +/- 2(0)C) which offset ethanol hypothermia or into chambers at room temperature (24 +/- 1(0)C). On day 6, all mice were injected with ethanol and placed into chambers at room temperature. Tolerance to ethanol's hypothermic effect did not develop in the ethanol-warm acquisition group. These mice had a significantly greater degree of hypothermia on test day than the ethanol-room temperature acquisition group, which showed tolerance, and their degree of hypothermic response was similar to that of mice injected with saline during acquisition. The differences between groups cannot be attributed to pharmacokinetic alterations or to conditioned responses since there were no differences between groups in blood or brain ethanol concentrations on test day and all groups were exposed to the same acquisition and test situations. These results extend previous work to suggest that the development of tolerance to the physiological, as well as behavioral, aspects of ethanol intoxication requires more than simple exposure to ethanol.

Animals↗

PubMedDate not supplied

Temperature modulates ethanol sensitivity in mice: generality across strain and sex.

Findings in our laboratory indicate that body temperature alters ethanol potency as measured by sleep-time, wake-up brain ethanol concentration and mortality in male C57BL/6J mice. The current studies tested the generality of these results. Experiment one tested age-matched, drug-naive, male C57BL/6S and BALB/cS mice. Experiment two tested age-matched, drug-naive, male and female C57BL/6J mice. Each mouse was injected IP with 3.6 g/kg ethanol (20% w/v). After losing its righting reflex, the mouse was placed into a v-shaped sleep tray within a chamber kept at a designated temperature from 12 to 36 degrees C. Upon awakening, rectal temperature was measured and blood and brain samples were taken for gas chromatographic analysis. As in previous studies, ambient temperature modulated the body temperatures and sleep-times of intoxicated animals. More important, wake-up rectal temperatures were positively correlated with sleep-times and negatively correlated with wake-up ethanol concentrations in all animals tested. These results support the hypothesis that brain sensitivity to ethanol depression varies with body temperature in accordance with membrane perturbation theories of anesthesia.

Anesthetics↗

PubMedDate not supplied

Body temperature and ethanol pharmacokinetics in temperature-challenged mice.

The relationships between ambient temperature, body temperature, ethanol pharmacokinetics and behavioral sensitivity to ethanol were examined in C57BL/6 mice. Mice were injected intraperitoneally with 3.6 or 2.0 g/kg ethanol. Exposure to increasing ambient temperatures of 4-34 degrees C immediately after ethanol injection resulted in a significant increase in body temperature, ethanol elimination rate and brain:blood ethanol concentration ratios in 3.6 g/kg ethanol-injected mice, but not in mice injected with 2.0 g/kg ethanol. As the mean body temperature increased from 26.0 to 38.2 degrees C in the 3.6 g/kg mice, there was a 50% increase in ethanol elimination rate. Delayed (30 min) exposure to increasing ambient temperatures following injection of 3.6 g/kg ethanol resulted in a significant increase in ethanol elimination rate, a marked increase in the duration of loss of righting reflex and a decrease in ethanol concentration at the regain of righting reflex. The results indicate that temperature-induced changes in the absorption, distribution and elimination of ethanol do not appear to mediate the effects of temperature on behavioral sensitivity to ethanol in C57 mice.

Animals↗

PubMedDate not supplied

Body temperature influences ethanol and ethanol/pentobarbital lethality in mice.

The effect of body temperature on ethanol (ETOH) or ethanol plus pentobarbital (ETOH/PB) lethality was investigated in C57BL/6J mice. Decreasing ambient temperatures from 35-20 degrees C, decreased rectal temperatures from 38-20 degrees C and increased 8-hour survival from 0-93% for ETOH-treated and from 0-100% for ETOH/PB-treated mice. ETOH and ETOH/PB animals with no hypothermia (body temperatures = 38 degrees C) had the highest lethality. Those with body temperatures between 30-32 degrees C had the highest 24-hour survival. These results suggest that controlled hypothermia may be useful in reducing lethality from ethanol or ethanol/combination overdoses.

Animals↗