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Biomedical subjects

E N Cohen

Publications and source records attributed to E N Cohen.

At least 37 records · Page 2Linked to original sources
PubMed1979

Nerve membrane lipid fluidity: opposing effects of high pressure and ethanol.

Studies on model phospholipid membranes have shown that general anesthetics and pressure exert opposing effects--anesthetics increase and high pressure decreases membrane fluidity. The present study extends these investigations to intact nerve membranes. The fluidity of the membranes of spin-labeled crayfish claw nerves was measured with electron paramagnetic resonance spectroscopy. Nerves exposed to 5- or 10% ethanol showed a linear increase in membrane fluidity. In contrast, 100 ATA of helium pressure decreased nerve fluidity. Successive application of ethanol and pressure to the nerve produced opposing effects. The similarity of effects between model and nerve membranes supports the relevance of studies with model systems.

Animals↗
PubMed1978

Pressure, temperature, and repetitive impulse generation in crustacean axons.

Increases in nerve axon excitability, including repetitive activity, have from time to time been reported in nerves subjected to high hydrostatic pressure. With the description of the high-pressure nervous syndrome (HPNS) in human divers and experimental animals, this phenomenon is of interest as a possible basis for the hyperexcitability associated with HPNS. The present study was designed to define the relationships between temperature, pressure, and repetitive activity in isolated crayfish axons. Crayfish claw nerves were exposed to helium pressures between 1 and 200 atmospheres absolute (ATA) in a temperature-controlled recording chamber. Repetitive and spontaneous impulses were reliably evoked on compression. The probability of repetitive response was increased by low temperature and high pressure; the frequency of the repetitive activity was increased by high temperature and pressure. Repetitive activity appeared spontaneously in the unstimulated preparation but could be entrained by the stimulus. The results are consistent with a mechanism involving changes in nerve membrane lipid fluidity and in the time course of membrane ionic channel state changes, including those involved in repolarization and accommodation.

Action Potentials↗
PubMed1978

Anesthetics inhibit pressure-induced repetitive impulse generation.

Repetitive and spontaneous impulse generation appears in nerve axons exposed to high pressure. This phenomenon is a possible basis for high-pressure nervous syndrome (HPNS) or pressure reversal of anesthesia, two examples of an antagonistic interaction between anesthetic drugs and high pressure. In the present study, the interactions between three classes of anesthetic drug (ethyl alcohol, the volatile inhalation agent halothane, and phenobarbital) and repetitive activity were explored. Ethyl alcohol (5% in solution) and halothane (1.3 and 3.4% in oxygen) inhibited pressure-induced repetitive activity. Phenobarbital at 0.25 mM in solution, the maximum concentration obtainable at low temperature, was partially effective. The three drugs produce an unconscious state that is "reversed" at hyperbaric pressure. Halothane and phenobarbital inhibit HPNS, but ethyl alcohol has not been tested for this property. The results thus support a relevance of repetitive activity to HPNS, to pressure reversal of anesthesia, or to both.

Action Potentials↗
PubMed1978

The rates of interaction of local anesthetics with sodium channels in nerve.

Voltage clamp experiments were carried out on Rana catesbiana nodes of Ranvier in order to test predictions regarding the relationship between local anesthetic lipid solubility and the rate of development of and recovery from frequency-dependent increments of sodium channel block. Contrary to expectations, the drugs of greater lipid solubility than lidocaine showed slower rates of development of frequency-dependent block and, in addition, induced longer rather than shorter memories for recent frequency-depent increments in channel block. Relaxation time constants for bupivacaine (50 micrometer), etidocaine (15 micrometer) and tetracaine (0.7 micrometer) measured 50, 8 and 8 sec, respectively, compared to shorter time constant of 2 sec for lidocaine (250 micrometer). Rate constants were calculated for binding to channels in both open and closed states. Open channels displayed a 130- to 6000-fold greater affinity for the local anesthetics than did closed channels, verifying an important feature of the "modulated receptor" hypothesis. In addition, binding to closed channels was enhanced by holding the membrane at more depolarizing potentials, which favored the development of inactive channel states. The exceptionally large binding constants of lidocaine for interactions with both closed and open channels cannot be attributed to its lipid solubility characteristics alone.

Anesthetics, Local↗
PubMed1977

Occupational hazards for operating room-based physicians. Analysis of data from the United States and the United Kingdom.

Comparative analysis of data from three large retrospective surveys in the United States and the United Kingdom reaffirms an increased incidence of spontaneous abortion among female physicians working in the operating room. The live-born children of female physicians exposed in the operating room also had substantially more congenital abnormalities. Male anesthetists, compared with nonanesthetist physicians, had an increased incidence of hepatic disease; there was also an increased frequency of congenital abnormality in their children. The incidence of spontaneous abortion in wives of male anesthetists and in the rate of cancer among exposed male anesthetists was similar to control. Despite differences in survey methods and analysis, there was remarkable agreement in conclusions to be drawn from the independent studies.

Abnormalities, Drug-Induced↗
PubMed1977

The actions of neuromuscular relaxants at hyperbaric pressures.

Previous studies have shown that high pressures increase the twitch tension of directly or indirectly stimulated mammalian muscle, while depressing transmission at the neuromuscular junction. The present paper explores the interaction between high pressures and muscle relaxants on the indirectly stimulated rat phrenic nerve--diaphragm preparation. Two muscle relaxants, d-tubocurarine and succinylcholine, were studied. Measurements of the electromyogram and twitch tension amplitudes were made before and after application of the muscle relaxants and compared with results of measurements of those two variables under hyperbaric conditions. High pressures tended to enhance neuromuscular blockade by d-tubocurarine more than that by succinylcholine, as indicated by electromyographic suppression, and high pressures tended to antagonize the succinylcholine effect on twitch tension more than that of d-tubocurarine. The findings are in agreement with previous observations that high pressures increase muscular twitch tension and depress excitatory synapses. They further demonstrate a complex interaction between hyperbaric pressures and neuromuscular blocking drugs.

Animals↗
PubMed1976

Neuromuscular function at hyperbaric pressures: pressure-anesthetic interactions.

Hydrostatic pressure and anesthetic agents exert mutually antagonistic effects, including pressure reversal of anesthesia and anesthetic amelioration of the high-pressure nervous syndrome. To clarify the cellular basis for these phenomena, twitch tension and electromyogram (EMG) were monitored in the indirectly stimulated isolated rat diaphragm. Compression to 137 atm increased twitch tension without changing EMG amplitude. Partial phrenic nerve block accompanied EMG depression induced by methoxyflurane and chloroform; pressure antagonized these effects. To examine subthreshold pressure effects, calcium concentration was decreased from 2.5 to 0.5 mM. Compression to 137 atm then reversibly decreased EMG amplitude, while enhancing twitch tension. In 0.5 mM calcium, methoxyflurane and chloroform depressed EMG amplitude before blocking phrenic nerve conduction; pressure to 137 atm produced additional depression. These results suggest that pressure enhances twitch tension by acting on excitation-contraction coupling or on the contractile mechanism. They also indicate that pressure may inhibit transmission at the neuromuscular junction, and they do not support synaptic transmission as a site of pressure-anesthetic antagonism.

Action Potentials↗
PubMed1975

The antagonistic effect of an inhalation anesthetic and high pressure on the phase diagram of mixed dipalmitoyl-dimyristoylphosphatidylcholine bilayers.

Several workers have shown that phase transition-related changes in membrane lipids have a profound effect on membrane-solvated protein function. This phase transition temperature dependence has been explained as resulting from the formation of lateral phase separations within the membrane bilayer. The present study demonstrates that a clinical concentration of an inhalation anesthetic produces changes in both the phase transition temperature of pure lipid bilayers and the lateral phase separation temperature of mixed dipalmitoyl- and dimyristoylphosphatidylcholine bilayers of a magnitude sufficient to influence protein function. It is further shown that pressure is able to antagonize the effect of the anesthetic on these transition temperatures. It is proposed that anesthetic action within nerve membranes may be the result of changes in the lateral phase separation-controlled environment of the membrane-solvated proteins essential to nerve function.

Anesthesia, Inhalation↗