Scientific Foundations of Anesthesia

Scurr, C. F.; Feldman, Sid

doi:10.1097/00000542-197609000-00029

Cited by 5 publications

(4 citation statements)

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“…The cytotoxic effects of hyperthermia as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method (13) were enhanced by subtoxic levels of anesthetics, and the potency of these effects was related to their respective lipophilicity (13,25). Fluidization of the hydrophobic core of the membrane may contribute to anesthetic potentiation of heatinduced cell death (13).…”

Section: Discussionmentioning

confidence: 99%

“…The apparent enhancement of hyperthermia-induced DNA fragmentation by LAs was observed at concentrations of more than 0.5 mM. The order of concentration of LAs for the maximum DNA fragmentation was prilocaine Ͼ lidocaine Ͼ bupivacaine, and this was the reverse order of lipophilicity and potency as anesthetic agents (25). When the cells were treated with LAs at 37°C no DNA fragmentation induced by prilocaine was observed.…”

Section: Effects Of Las On Hyperthermia-induced Apoptosis-mentioning

confidence: 94%

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Enhancement of Hyperthermia-induced Apoptosis by Local Anesthetics on Human Histiocytic Lymphoma U937 Cells

Arai¹,

Kondo²,

Toko³

et al. 2002

Journal of Biological Chemistry

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The combined effects of hyperthermia at 44°C and local anesthetics on apoptosis in human histiocytic lymphoma U937 cells were investigated. When the cells were exposed to hyperthermia for l0 min marginal DNA fragmentation and nuclear fragmentation were observed. In the presence of amide-type local anesthetics further enhancement was found depending on concentration. The order of the concentration required for maximum induction was the reverse order of the lipophilicity (prilocaine > lidocaine > bupivacaine). Western blotting revealed that in hyperthermia there was initial release of Ca 2؉ from the intracellular store site as indicated by increased expression of the type 1 inositol-1,4,5-trisphosphate receptor. The effectiveness of hyperthermia combined with radiotherapy in the treatment of various solid tumors has been demonstrated (1). Furthermore, recent clinical randomized trials of patients with brain tumors, recurrent or metastatic malignant melanoma, advanced breast carcinoma, locally advanced pelvic tumors, and malignant germ cell tumors clearly have indicated the advantages for patients treated with hyperthermia combined with radiotherapy (2-6) or chemotherapy (7) compared with radiotherapy alone. However, the uniform and precise delivery of heat to tumors still remains a challenge. In many circumstances the tumor cell killing is insufficient. Drugs that have been discussed as overcoming this difficulty are heat sensitizers. An ideal sensitizer would be nontoxic at normothermia but could become cytotoxic at hyperthermic temperatures.Local anesthetics belong to a class of clinically useful compounds that exert a pharmacological effect by blocking nerve impulse propagation. The involvement of cell membranes as the site for these drug actions has been widely accepted, and many reports showing modification of cell killing due to hyperthermia by LAs 1 have been published (e.g. potentiation by procaine in murine L5178Y lymphoma cells (8) and by lidocaine in murine FM3A mammary carcinoma cells (9), potentiation of survival of tumor-bearing mice after hyperthermia combined with lidocaine (10), enhancement of hyperthermia-induced tumor regression by lidocaine in murine tumor models (11, 12), and enhancement of cytotoxic effects of hyperthermia by dibucaine, tetracaine, and procaine in hepatoma tissue culture cells (13)). However, little is known about the modification and mechanism of apoptosis when hyperthermia is combined with LAs.Here we will present our recent findings that subtoxic levels of LAs enhanced hyperthermia-induced apoptosis via the Ca 2ϩ -and mitochondria-dependent pathways in human lymphoma U937 cells. Evidence for the cardinal roles of initial release of Ca 2ϩ from intracellular store sites due to hyperthermia and the subsequent increase of [Ca 2ϩ ] i and the additional activation of the mitochondrial caspase-dependent pathway in enhancement of apoptosis induced by the combination of hyperthermia and lidocaine will also be presented. In addition the potential usefulness of LAs as sensitizers o...

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Section: Discussionmentioning

confidence: 99%

Section: Effects Of Las On Hyperthermia-induced Apoptosis-mentioning

confidence: 94%

Enhancement of Hyperthermia-induced Apoptosis by Local Anesthetics on Human Histiocytic Lymphoma U937 Cells

Arai¹,

Kondo²,

Toko³

et al. 2002

Journal of Biological Chemistry

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“…On bubbling with 95% O 2 -5% CO 2 , the solution had a pH of 7.32 at 22°C. Gas dispersion tubes were not used because their high resistance reduced gas flow to Ͻ500 ml/min, which is insufficient for proper function of the anesthetic vaporizers (Scurr and Feldman 1982). In some experiments, Mg 2ϩ was substituted for Ca 2ϩ .…”

Section: E T H O D Smentioning

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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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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“…In making calculations for their proper regulation, the anaesthetist requires a simple formula for the expression of vapour pressure as a function of temperature. The vapour pressure of an ideal substance can be related to temperature by the Clausius-Clapeyron relationship (Glasstone, 1940;Scurr and Feldman, 1974): AH/1 4.571 (i) where AH = latent heat of vaporization (cal mol" 1 ) and temperature is in K.…”

mentioning

confidence: 99%

Equations for Vapour Pressure Versus Temperature: Derivation and Use of the Antoine Equation on a Hand-Held Programmable Calculator

Rodgers

Hill

1978

British Journal of Anaesthesia

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The Antoine equation is a semi-empirical equation which expresses vapour pressure as a function of temperature. A new, rapid and highly accurate method for obtaining its three constants from experimental data is presented and applied to ethanol, water and 14 anaesthetic substances. Alternative vapour pressure equations are discussed and references for original temperature--vapour pressure data are summarized. A series of equations utilizing vapour pressure is detailed: these formulas are of use in both the practice and teaching of anaesthesia.

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Scientific Foundations of Anesthesia

Cited by 5 publications

References 0 publications

Enhancement of Hyperthermia-induced Apoptosis by Local Anesthetics on Human Histiocytic Lymphoma U937 Cells

Enhancement of Hyperthermia-induced Apoptosis by Local Anesthetics on Human Histiocytic Lymphoma U937 Cells

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

Equations for Vapour Pressure Versus Temperature: Derivation and Use of the Antoine Equation on a Hand-Held Programmable Calculator

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