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D D Koblin

Publications and source records attributed to D D Koblin.

At least 73 records · Page 4Linked to original sources
PubMed1983

Age-dependent alterations in nitrous oxide requirement of mice.

To determine the relationship of nitrous oxide requirement to age in mice, the authors repeatedly tested the righting-reflex response in stock CD-1 mice at 50 to 703 days of age. Over this age range, nitrous oxide requirement (+/- SE) progressively decreased from 1.48 +/- 0.02 atm to 1.09 +/- 0.06 atm. A second set of experiments measured changes in nitrous oxide requirement with age in mice selectively bred for resistance (HI mice) and susceptibility (LO mice) to nitrous oxide anesthesia. When tested at two months of age, selected HI and LO mice had nitrous oxide ED50 values of approximately 2.0 and 1.1 atm, respectively. At 11 to 14 months, the nitrous oxide ED50 of the HI mice had decreased to approximately 1.5 atm. In contrast, the nitrous oxide ED50 of the LO mice showed a much smaller decrease over this age range. Thus, the separation in nitrous oxide requirement between the HI and LO lines tended to disappear with age. By correlating the difference in anesthetic requirement between the HI and LO mice with biochemical and biophysical alterations in the central nervous system, studies on aging that use selectively bred lines may be helpful in investigating the mechanism of anesthetic action and the mechanism by which aging affects anesthetic action.

Aging↗
PubMed1982

Potencies of inhaled anesthetics and alcohol in mice selectively bred for resistance and susceptibility to nitrous oxide anesthesia.

A selective breeding process designed to produce mice resistant (HI mice) and susceptible (LO mice) to nitrous oxide anesthesia was continued through 10 generations. At the tenth, generation, the nitrous oxide requirements of the HI and LO mice (as measured by the partial pressure of nitrous oxide required to abolish the righting reflex) were separated by more than 0.7 atm. The HI mice also had a higher anesthetic requirement for cyclopropane, enflurane, isoflurane, halothane, and methoxyflurane, as measured by response to a tail-clamp stimulus. HI mice given an intraperitoneal injection of ethanol (4 g/kg) had 44 per cent shorter sleep times and 12 per cent higher blood alcohol levels upon awakening than did LO mice. For nitrogen, argon, cyclopropane, isoflurane, enflurane halothane, and methoxyflurane, we determined the doses at which the righting reflex was abolished in HI and LO mice. The separation in righting-reflex ED-50s between these two lines was inversely related to the lipid solubility of the anesthetic. For the most lipid-soluble anesthetic, methoxyflurane, no significant differences in potency, as measured by the righting-reflux ED50, could be detected between the HI and LO mice. In contrast, the separation in anesthetic requirements, as measured by the tail-clamp ED50, was approximately the same for each of the anesthetics tested.

Anesthesia, Inhalation↗
PubMed1982

Potencies of convulsant drugs in mice selectively bred for resistance and susceptibility to nitrous oxide anesthesia.

To test the possibility that mice selectively bred for resistance (HI mice) and susceptibility (LO mice) to nitrous oxide anesthesia have general differences in central nervous system excitability, we examined the effects of six convulsant agents in these two lines in mice. Using high-pressure helium, flurothyl, pentylenetetrazol, strychnine, (+)-bicuculline, and picrotoxin, we induced convulsions in HI and LO mice. For all of the agents tested, HI mice were significantly more susceptible to convulsions than LO mice. LO mice convulsed at a 13 to 25 per cent higher dose of convulsant agent than did HI mice. In contrast, nitrous oxide requirements (as measured by the partial pressure of nitrous oxide required to abolish the righting reflex), were 49 to 65 per cent higher in HI mice. Therefore, the higher nitrous oxide requirement in HI mice is probably due, at least in part to a generalized increase in central nervous system excitability.

Animals↗
PubMed1982

Nitrous oxide inactivates methionine synthetase in human liver.

Activity of methionine synthetase was measured in liver biopsies of seven patients who had received 50% to 70% nitrous oxide supplemented by a combination of a narcotic and/or barbiturate with or without a volatile anesthetic, and from seven patients who were anesthetized without nitrous oxide (control group). Methionine synthetase activity (+/- SE) averaged 219 +/- 28 nmol of methionine per hour per gran of liver in patients given nitrous oxide, and 414 +/- 29 in control patients. Inactivation of methionine synthetase progressively increased as the product of the concentration of nitrous oxide and the exposure time increased. These results in humans are similar to those in animals and suggest that inactivation of methionine synthetase may play a role in the development of the pathologic effects seen in patients and medical personnel after exposure to nitrous oxide.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1981

Chronic exposure to inhaled anesthetics increases cholesterol content in Acholeplasma laidlawii.

Acholeplasma laidlawii cells were grown in cholesterol-enriched medium and exposed continuously to either air (control), 4.0 vol.% halothane in air at 1 atm pressure (4% atm halothane), or 80% cyclopropane in oxygen for 24 h at 37 degrees C. Cells grown in the presence of 4% atm halothane or 80% cyclopropane had approximately twice as much membrane cholesterol content/mg protein as the control cells. Cells grown in an anesthetic environment also tended to have a higher membrane cholesterol/phospholipid molar ratio compared to control cells. Membranes isolated from halothane-exposed cells grown in a cholesterol-enriched medium were more ordered at 37 degrees C (measurements were made with no anesthetic present) than membranes from control cells grown in an identically enriched medium. This difference in membrane physical state between control and anesthetic-exposed cells decreased as the temperature decreased, and disappeared at approx. 23 degrees C. Continuous exposure of A. laidlawii to 4% atm halothane or 80% cyclopropane for 24 h did not markedly affect membrane fatty acid composition, either in cells grown on an unsupplemented medium or in cells grown in a medium enriched in myristic, palmitic or stearic acids. These results further support the hypothesis that an increased membrane cholesterol content may play a role in the tolerance or dependence that develops after chronic exposure to anesthetic agents.

Acholeplasma laidlawii↗
PubMed1981

Anaesthetic requirement in mice selectively bred for differences in ethanol sensitivity.

Anaesthetic requirements for nitrous oxide, enflurane and isoflurane were determined in mice selectively bred for their susceptibility ("long-sleep" mice) or resistance ("short-sleep" mice) to alcohol. Nitrous oxide and enflurane requirements, measured by the rolling-response test, were 34 and 20% greater, respectively, in short-sleep mice than in long-sleep mice. Although isoflurane requirement was 39% greater when measured by the tail-clamp test, it was not significantly different when measured by the rolling-response test. The greater anaesthetic requirement for short-sleep mice was not associated with a different synaptic membrane phospholipid, fatty acid or cholesterol composition.

Anesthesia, Inhalation↗
PubMed1981

Anesthetic requirement in the quaking mouse.

Anesthetic requirements for nitrous oxide, cyclopropane, enflurane, and isoflurane were determined in quaking mice (autosomal recessive mutants with a deficiency in central nervous system myelin) and their littermate (non-quaking) controls. Although quaking mice had significantly (15 to 23 per cent) lower nitrous oxide and cyclopropane rolling-response ED50S than did littermate controls, enflurane and isoflurane rolling-response ED50S were not significantly different. Tail-clamp ED50S for cyclopropane, enflurane, and isoflurane in quaking and control mice were not significantly different. Myelin from quaking mice showed higher levels of palmitic, stearic, and docosahexaenoic acids, lower levels of oleic, eicosenoic, and docosatetraenoic (and/or nervonic) acids, and a lower cholesterol/phospholipid ratio. In contrast, the phospholipid, fatty acid, and cholesterol compositions of synaptic plasma membranes isolated from quaking and control mice were essentially identical. It is concluded that gross alterations in the lipid composition of central nervous system myelin have little or no influence on anesthetic requirement.

Anesthetics↗
PubMed1981

Minimum alveolar concentrations and oil/gas partition coefficients of four anesthetic isomers.

We determined the minimum alveolar concentration (MAC) of four structural isomers having the empirical formula C3H2F5CIO in dogs. MAC for three of the four isomers (including isoflurane and enflurane) ranged from 1.41 to 2.67 (volumes per cent at one atmosphere pressure). The olive oil/gas partition coefficients at 37 degrees C for these isomers ranged from 90.8 to 96.6. In contrast, MAC for the fourth isomer, compound 485, was 12.53 per cent atm. However, the oil/gas partition coefficient for that compound was 25.8. These results suggest that isomer 485, despite its high MAC, does not deviate strikingly from the established correlation between anesthetic potency and lipid solubility.

Anesthetics↗
PubMed1981

Inactivation of methionine synthetase by nitrous oxide in mice.

To characterize the nitrous oxide-induced inhibition of the enzyme, methionine synthetase, we measured enzyme inactivation as a function of nitrous oxide concentration and exposure time. Mice exposed to 0.8 atm nitrous oxide exhibited more than a 50 per cent decrease in liver methionine synthetase activity within 30 min, and activity dropped to 5--25 per cent of the original value after a 4-hour exposure. Although 4-hour exposures to low nitrous oxide partial pressures (less than 0.05 atm) did not significantly alter methionine synthetase activity, higher concentrations of nitrous oxide caused a progressive inhibition over this time period. Continuous exposure to trace levels of nitrous oxide (approximately 1100 ppm) for eight to 22 days produced a small but significant reduction in liver and brain methionine synthetase activity. Methionine synthetase activity returned to control levels two to four days following inactivation. Other anesthetics (xenon, halothane, isoflurane, enflurane) did not produce inactivation.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1981

Mice tolerant to nitrous oxide are not tolerant to barbiturates.

Mice continuously exposed to 50% nitrous oxide for 2 weeks or more become tolerant to nitrous oxide, as measured by an 8% to 19% increase in their nitrous oxide ED50 (the dose required to abolish the righting reflex in 50% of the animals). Control mice tolerant to nitrous oxide were given intraperitoneal injections of secobarbital (50 mg/kg), phenobarbital (120 mg/kg), or pentobarbital (55 or 65 mg/kg). Sleep onset times, sleep times, and serum levels of barbiturates upon awakening did not differ between the two groups. These results suggest that nitrous oxide and barbiturates do not share a common mechanism of action.

Anesthesia, Inhalation↗
PubMed1981

Dioxychlorane: a challenge to the correlation of anesthetic potency and lipid solubility.

Dioxychlorane is a five-membered cyclic halogenated diether which has been reported to be anesthetic at an inspired concentration of 0.3% atm and to have an oil/gas partition coefficient to 260 to 275. These values suggested that dioxychlorane might represent a significant deviation from the correlation of anesthetic potency with lipid solubility. However, the results of this study did not confirm the above data: MAC in four dogs was 0.11 +/- 0.02 (SE) % atm, and the oil/gas partition coefficient was 1,286 +/- 44. Dioxychlorane appears not to be an exception to the correlation of anesthetic potency with lipid solubility.

Anesthetics↗
PubMed1981

Anesthetic potencies and the unitary theory of narcosis.

Anesthetic potencies of nitrous oxide, isoflurane, enflurane, halothane, cyclopropane, or chloroform were measured in male (CD-1) mice using three end points: (a) the ability to maintain an upright position (the righting-response ED50, RR ED50); (b) the response to a tail-clamp stimulus (MAC); and (c) the response to heat applied to the tail (tail-flick ED50, TF ED50). The ratio of RR ED50 to MAC ranged from mean values of 0.475 for isoflurane, 0.507 for cyclopropane, 0.524 for enflurane, and less than 0.55 for N2O, to 0.600 for halothane and 0.621 for chloroform. The ratios of RR EDS50 to MAC for halothane differed significantly from the ratios for isoflurane and enflurane. The mean values for TF ED50/MAC and RR ED50/TG ED50 ranged from 0.688 to 1.01 and 0.664 to 0.682, respectively, for isoflurane, enflurane, and halothane. The nitrous oxide RR ED50/TF ED50, however, was 1.34. The ratios of TF ED50 to MAC were significantly different for halothane and isoflurane. The different end points were measured in an attempt to determine whether the response in mice anesthetized with a particular agent was the same with varying stimuli. The differences found suggest that a unitary mechanism of anesthetic action cannot completely explain the depression defined by these three end points.

Anesthesia, Inhalation↗
PubMed1981

Are convulsant gases also anesthetics?

This study investigated whether the convulsant gas flurothyl deviates from the correlation between anesthetic potency and lipid solubility. Flurothyl (CF3CH2OCH2CF3) produced convulsions in 50% of mice at 0.122 +/- 0.006% atm. Mice often convulsed repeatedly after exposure to flurothyl, the maximum number of convulsions occurring when the concentration was 0.24% atm. Concentrations greater than 0.6% atm produced convulsions immediately after addition of flurothyl, but rarely at later times. An ED50 value for loss of the righting reflex was obtained when the concentration was 1.22 +/- 0.19% atm. The oil/gas partition coefficient was found to be 46.9 for flurothyl at 37 C. The product of righting-reflex ED50 and oil/gas partition coefficient (0.0122 atm x 46.9 = 0.57 atm) is similar to that found for conventional anaesthetics in mice. Therefore, flurothyl does not deviate from the correlation of anesthetic potency and lipid solubility. It was also found that 0.3 to 0.8% atm flurothyl increased isoflurane MAC in dogs, but that 3 to 4% atm flurothyl decreased it. The increase of isoflurane requirement at lower concentrations of flurothyl suggests that anesthetics with a potential to cause convulsions may partly antagonize their own anesthetic effect. The decrease in isoflurane MAC in dogs at higher concentrations of flurothyl also implies that this compound has an anesthetic effect. A structural isomer of flurothyl, iso-Indoklon [(CSF3)2CHOCH3], was only anesthetic and did not have convulsant properties. Its MAC in dogs was 4.60 +/- 0.45% atm, and its righting-reflex ED50 in mice was 2.65 +/- 0.13% atm. The product of iso-Indoklon MAC in dogs and its oil/gas partition coefficient (27.0) was 1.24 atm, and the product of iso-Indoklon righting-reflex ED50 in mice and oil/gas partition coefficient was 0.72 atm. These values are close to those found for conventional anesthetic agents in dogs and mice; thus iso-Indoklon also does not deviate from the correlation between anesthetic potency and lipid solubilities.

Anesthesia, Inhalation↗
PubMed1981

Cross-mating of mice selectively bred for resistance or susceptibility to nitrous oxide anesthesia: potencies of nitrous oxide in offspring.

To investigate the genetic bases of differences in nitrous oxide requirement in mice selectively bred for resistance (HI mice) or susceptibility (LO mice) to nitrous oxide anesthesia, the potency of nitrous oxide in offspring having one HI and one LO parent was measured. Nitrous oxide ED50S (+/- SD) in offspring having HI male and LO female parents or LO male and HI female parents were 1.53 +/- 0.10 and 1.63 +/- 0.14 atm, respectively. In contrast, the nitrous oxide ED50 for offspring having two LO parents was 1.26 +/- 0.09 atm, and for offspring having two HI parents, 1.96 +/- 0.10 atm. Thus, the nitrous oxide ED50S for offspring produced by cross-mating HI and LO animals approximated the average values for their parents. We conclude that no single one gene determines dominance or recessiveness for nitrous oxide requirement in mice, and that the genetic control of resistance or susceptibility to nitrous oxide anesthesia probably involves many genes.

Anesthetics↗
PubMed1980

Selective breeding alters murine resistance to nitrous oxide without alteration in synaptic membrane lipid composition.

A normal population of mice was separated into two groups with reproducibly high (greater than 1.63 atm) or reproducibly low (less than 1.29 atm) nitrous oxide requirements. Males (n = 4) and females (n = 5) with the reproducibly high anesthetic requirements were mated, as were males (n = 4) and females (n = 3) with the reproducibly low anesthetic requirements. The first-generation offspring from parents with the high anesthetic requirements had a higher nitrous oxide ED50 (concentration of nitrous oxide required to abolish the righting reflex in half of the animals) than did offspring from parents with the low anesthetic requirements. Mice with the lowest and the highest anesthetic requirements in the first generation were bred to give the second generation. By repeating this process of breeding, nitrous oxide ED50 testing, and selection of mice with the highest and lowest anesthetic requirements through five generations, the authors were able to breed two groups of mice separated by approximately 0.5 atm in nitrous oxide requirements. This alteration in anesthetic requirement could not be explained by an altered synaptic membrane lipid composition, since no significant difference in synaptic membrane phospholipid, fatty acid, or cholesterol compositions could be detected in the two groups of mice with high and low anesthetic requirements.

Animals↗
PubMed1980

Alteration of synaptic membrane fatty acid composition and anesthetic requirement.

Mice fed a saturated, Purina chow or unsaturated fat diet from birth have different synaptic membrane fatty acid compositions. The saturated diet decreased docosahexaenoic [22:6 (n - 3)] and increased eicosatrienoic [20:3 (n - 9)], docosatrienoic [22:3 (n - 9)] and docosapentaenoic [22:5 (n - 6)] fatty acids compared to the Purina chow or unsaturated fat diet. The most notable alterations occurred in the synaptic membrane phosphatidylserine and phosphatidylethanolamine fractions. The saturated diet also caused a minor increase in oleic acid [18:1 (n - 9)i1. Animals fed the saturated diet showed a small, significant decrease in nitrous oxide ED50 (dose required to abolish the righting reflex in half the animals) but not in isoflurane ED50, compared to animals fed the Purina chow or unsaturated fat diet. Thus, large alterations in several synaptic membrane fatty acid components have little or no influence on anesthetic requirement.

Acetylcholinesterase↗