The Inspired Median Effective Dose, Brain Concentration at Anesthesia, and Cardiovascular Index for Halothane in Young Rats

Cook, David; Brandom, Barbara W.; Shiu, Gerald K.; Wolfson, Bernard

doi:10.1213/00000539-198104000-00002

Cited by 23 publications

(8 citation statements)

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“…The activation curve was steep, and the current reached a maximum amplitude over a 5-to 10-mV range (n ϭ 17). As in another report of thalamic slices (Crunelli et al 1989), the delayed all-or-none manner of activation contrasted with reports of graded recordings from dissociated neurons (cf. Huguenard 1996) and presumably reflected a compromised voltage control as well as the rapid response from a large dendritic T-channel population.…”

Section: Ifl Shunted T-current Generationsupporting

confidence: 40%

“…Age and temperature require consideration when determining IFL concentrations that are equivalent to (not "relevant to") concentrations used for in vivo anesthesia. The minimum alveolar concentration (MAC), the concentration that prevents movement in response to a noxious stimulus in 50% of subjects, is 30% higher in juvenile rats than in adults (Cook et al 1981). Hence the adult MAC for IFL in rats of 1.46% (Mazze et al 1985) corresponds to a juvenile rat MAC of Ͼ1.9%.…”

Section: Experimental Considerations Of Anesthetic Potencymentioning

confidence: 99%

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Mechanism of Anesthesia Revealed by Shunting Actions of Isoflurane on Thalamocortical Neurons

Ries

Puil

1999

Journal of Neurophysiology

129

105

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By using thalamic brain slices from juvenile rats and the whole cell recording technique, we determined the effects of aqueous applications of the anesthetic isoflurane (IFL) on tonic and burst firing activities of ventrobasal relay neurons. At concentrations equivalent to those used for in vivo anesthesia, IFL induced a hyperpolarization and increased membrane conductance in a reversible and concentration-dependent manner (ionic mechanism detailed in companion paper). The increased conductance short-circuited the effectiveness of depolarizing pulses and was the main cause for inhibition of tonic firing of action potentials. Despite the IFL-induced hyperpolarization, which theoretically should have promoted bursting, the shunt blocked the low-threshold Ca2+ spike (LTS) and associated burst firing of action potentials as well as the high-threshold Ca2+ spike (HTS). Increasing the amplitude of either the depolarizing test pulse or hyperpolarizing prepulse or increasing the duration of the hyperpolarizing prepulse partially reversed the blockade of the LTS burst. In voltage-clamp experiments on the T-type Ca2+ current, which produces the LTS, IFL decreased the spatial distribution of imposed voltages and hence impaired the activation of spatially distant T channels. Although IFL may have increased a dendritic leak conductance or decreased dendritic Ca2+ currents, the somatic shunt appeared to block initiation of the LTS and HTS as well as their electrotonic propogation to the axon hillock. In summary, IFL hyperpolarized thalamocortical neurons and shunted voltage-dependent Na+ and Ca2+ currents. Considering the importance of the thalamus in relaying different sensory modalities (i.e., somatosensation, audition, and vision) and motor information as well as the corticothalamocortical loops in mediating consciousness, the shunted firing activities of thalamocortical neurons would be instrumental for the production of anesthesia in vivo.

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Section: Ifl Shunted T-current Generationsupporting

confidence: 40%

Section: Experimental Considerations Of Anesthetic Potencymentioning

confidence: 99%

Mechanism of Anesthesia Revealed by Shunting Actions of Isoflurane on Thalamocortical Neurons

Ries

Puil

1999

Journal of Neurophysiology

129

105

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“…However, iso¯urane and other volatile anaesthetics lipophilicities (i.e. brain/gas and brain/ blood partition coecients) do not change with the advancement of age after sexual maturity in man and experimental animals (Cook et al, 1981;Webb & Weaver 1981;Lerman et al, 1985;1986). There is also no evidence, to date, that ageing induces alteration in grey matter brain lipid content.…”

Section: Ageing Potentiation Of Anaesthetic Actionsmentioning

confidence: 98%

Enhanced isoflurane suppression of excitatory synaptic transmission in the aged rat hippocampus

Ouanounou

Carlen

El‐Beheiry

1998

British J Pharmacology

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2S81 The e ects of the volatile anaesthetic, iso¯urane, were investigated on evoked dendritic ®eld excitatory postsynaptic potentials (f.e.p.s.p.) and antidromic and orthodromic population spikes recorded extracellularly in the CA1 cell layer region in the in vitro hippocampal slice taken from young mature (2 ± 3 months) and old (24 ± 27 months) Fisher 344 rats. 2 Iso¯urane depressed the f.e.p.s.ps and the orthodromically-evoked population spikes in both old and young hippocampi. However, the magnitude of the anaesthetic-induced depression was greater in slices taken from old rats compared to those taken from young rats during the application of di erent iso¯urane concentrations (0.5 ± 5%). 3 In the presence of the GABA A antagonist, bicuculline methiodide (15 mM), iso¯urane suppressed the f.e.p.s.ps to the same extent as was observed in the absence of the GABA A antagonist. 4 Orthodromically evoked population spikes were suppressed by iso¯urane in a manner quantitatively similar to the suppression of the f.e.p.s.ps. However, antidromic population spikes and presynaptic volleys evoked in young and old slices were resistant to anaesthetic action. In addition, paired pulse facilitation ratio of the evoked dendritic f.e.p.s.ps was not a ected in both young and old slices during the application of iso¯urane. 5 When slices were exposed to low Ca 2+ /high Mg 2+ solution, iso¯urane (1 and 3%) depressed the f.e.p.s.ps in aged slices to the same extent as in young slices. 6 The augmented anaesthetic depression of f.e.p.s.ps in old compared to young hippocampi in the absence and presence of bicuculline, and the lack of anaesthetic e ects on antidromic population spikes and presynaptic volleys in old and young slices, suggest that the increased sensitivity of anaesthetic actions in old hippocampi is due to age-induced attenuation of synaptic excitation rather than potentiation of synaptic inhibition. Furthermore, elimination of the increased sensitivity of old slices to anaesthetic actions when the slices were perfused with low Ca 2+ /high Mg 2+ medium, which presumably would decrease intracellular [Ca 2+ ], suggests that the enhanced anaesthetic e ects in aged neurones might be related to increased intraneuronal [Ca 2+ ] in the synaptic terminal.

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“…4'5 This further limits the safety of potent anaesthetics in infants. Moreover, Cook et al 6 have demonstrated that the cardiovascular index for halothane is smaller in younger animals than in older animals. The cardiovascular index is a reflection of the therapeutic index (i.e., the ratio between the anaesthetic concentration at cardiovascular collapse to that of anaesthesia).…”

mentioning

confidence: 99%

Newborn anaesthesia: Pharmacological considerations

Cook

1986

Can Anaesth Soc J

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The Inspired Median Effective Dose, Brain Concentration at Anesthesia, and Cardiovascular Index for Halothane in Young Rats

Cited by 23 publications

References 0 publications

Mechanism of Anesthesia Revealed by Shunting Actions of Isoflurane on Thalamocortical Neurons

Mechanism of Anesthesia Revealed by Shunting Actions of Isoflurane on Thalamocortical Neurons

Enhanced isoflurane suppression of excitatory synaptic transmission in the aged rat hippocampus

Newborn anaesthesia: Pharmacological considerations

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