PubMed Health⌕ Search

Biomedical subjects

S A Raymond

Publications and source records attributed to S A Raymond.

29 records · Page 2Linked to original sources

Effects of halothane and enflurane on firing threshold of frog myelinated axons.

1. Firing thresholds and conduction latencies of single myelinated axons in frog sciatic nerves were monitored during impulse activity in vitro. Resting threshold and the activity dependence of threshold were studied as a function of the concentration of two inhalational anaesthetic agents, halothane and enflurane. 2. At concentrations comparable to those obtained during general anaesthesia both agents produced biphasic effects on the resting threshold. A step increase in the partial pressure of anaesthetic was followed first by a transient lowering of threshold, then by a slow rise to a steady-state level above the original baseline. Step decreases in anaesthetic were followed by transient rises before threshold dropped. Transients lasted 20-30 min. During these threshold transients, the average latency of impulse conduction changed monotonically. The prolongation of latency following an increase in anaesthetic was progressive, reaching steady state concurrently with threshold (20 min to greater than 1 h). 3. The anaesthetics reduced the long-lasting increased threshold ('depression') which normally follows repetitive impulse activity in axon membrane. 4. These actions of halothane at concentrations of 0.25-2.7% (0.14-1.54 mM) and enflurane at concentrations of 0.62-3.08% (0.35-1.73 mM) on resting threshold and on the activity-dependent increase in threshold increased monotonically with anaesthetic concentration. 5. The effects on excitability at steady state are consistent with block of voltage-dependent Na+ and K+ channels by these inhalational agents. Reduced depression may occur because the anaesthetics reduce the net ion transfer per impulse, slowing the substrate-driven Na+-K+-ATPase and thereby reducing electrogenic hyper-polarization. 6. The finding that general anaesthetics inhibit depression at clinically relevant concentrations supports the possibility that general anaesthesia is produced by inhibition of processes that modulate excitability of nerve membrane. We suggest that general anaesthetics produce unconsciousness and amnesia because they disrupt activity-dependent processes, which may thus remove temporal 'context' essential for interpreting nerve impulse patterns.

Action Potentials↗

The role of length of nerve exposed to local anesthetics in impulse blocking action.

The quantitative relation between the concentration of local anesthetic (LA), the length of nerve exposed, and severity of conduction blockade was studied with use of a chamber where exposure length was varied as the concentration of lidocaine was held constant. Recordings of the compound action potential and of single axons established that small variations in the length of nerve exposed to LA strongly modulate conduction block even at exposure lengths in excess of 2 cm. Therefore, exposure length is a significant factor in determining blocking potency, and only at very high concentrations of LA, where voltage-dependent Na conductance is almost completely blocked, is the critical exposure length less than three nodes of Ranvier. The concentration required for 50% block of impulses in single fibers (that is, where 50% of the impulses would fail to propagate through the exposed region of the nerve) diminished as the exposed length of nerve increased, approximately halving as exposure length was changed from 6 mm to 15-25 mm. Conduction latency increased with the exposure length becoming sharply more variable as the critical exposure length for conduction block was approached. The results are consistent with the hypothesis of decremental conduction, where a partial active response in nodes exposed to marginal blocking concentrations extends the decay of the action potential along the axon, and do not support the interpretation that lengths of several centimeters affect blocking concentration because such distances increase the probability that three nodes will be blocked in succession. This study contradicts the broader common assumption that beyond three nodes, the length of nerve exposed is not a factor in nerve block with local anesthetics.

Action Potentials↗

Comparison of the after-effects of impulse conduction on threshold at nodes of Ranvier along single frog sciatic axons.

1. Single axons were teased from the distal end of whole frog sciatic nerve and impulses were recorded with a suction electrode. The whole nerve trunk was stimulated using a gross electrode that was slowly moved for several centimetres along the length of the nerve. The threshold for initiation of an action potential showed periodic minima which were interpreted as the location of nodes of Ranvier. 2. Internodal distances were uniform along individual fibres but differed among fibres having matching conduction velocities, suggesting that other individuating characteristics are also important in determining the spacing of nodes. 3. A standard protocol was used to measure the activity dependence of threshold. Nodes along any given fibre were found to be alike in the dependence of threshold on impulse activity. Both the superexcitable phase and the depressed phase of the after-effects of impulse activity were similar for successive nodes. This suggests that the activity dependence of an unbranched length of axon can be well characterized by looking at any one of its nodes. 4. Comparison of nodes from different axons showed large variations in activity dependence. Depressibility, denoting the relative tendency of an axon to show depression, was quantified either as the initial rate of rise in threshold (percentage increase/min) following the onset of repetitive stimulation or as the total rise in threshold (percentage increase) after 5 min of exposure to a standardized rate of repetitive stimulation. By either measure depressibility differed among axons more than it differed among nodes from a single axon. 5. Superexcitability following single impulses was measured in the absence of depression. Axons exhibiting a larger decrease in threshold during the superexcitable phase also tended to show larger depressions relative to other axons when stimulated at a given rate. 6. There was little correlation between conduction velocity and the magnitude of either the depressed phase or the superexcitable phase within the population of fibres studied. This suggests that axon diameter alone (as indicated by conduction velocity) cannot be responsible for the wide variations in the amplitude of the depressed phase or the superexcitable phase. 7. The results suggest that some process exists to constrain the nodes along a fibre to have a uniform activity dependence.

Action Potentials↗

Dependence of lidocaine potency on pH and PCO2.

Lidocaine solutions with different concentrations of CO2, NaOH, and HCl in two buffering systems were applied to frog sciatic nerves. The peak of the compound action potential (APc) and the firing threshold for single axons were measured. The amount of lidocaine required at steady state to double the firing threshold of single fibers or to reduce the peak of the APc by 40% was used as the index of potency. Acidification with CO2 increased potency (less lidocaine was needed to achieve either criterion), whereas acidification with HCl diminished potency, as compared with alkaline conditions. These results were true whether or not the perineurium was present. Frequency-dependent block (Bf) increased in acid conditions produced by CO2, whereas Bf was less under acid conditions produced with HCl (P less than 0.02). The experiments indicate that CO2 potentiates conduction block with lidocaine either by a direct effect on the membrane or by its indirect action on intracellular pH, but not from effects on the extracellular pH.

Action Potentials↗

Differential spread of blockade of touch, cold, and pinprick during spinal anesthesia.

The differential levels of sensory blockade of pinprick, cold, and touch were monitored throughout the course of spinal anesthesia administered to 50 patients to determine variations in the degree of spread during onset, plateau, and regression, and to establish the effects of epinephrine and the effect of posture during injection. A significant difference was observed between the dermatomal level of sensory loss of touch and the dermatomal level of loss of either pinprick or cold during onset, at 5 min in patients given tetracaine with epinephrine, at time of maximum spread in patients given tetracaine with epinephrine or in the sitting position, and in all groups during regression. Loss of touch began later, never extended as far cephalad, and regressed sooner. The extent of this difference was greatest during regression, when the anesthetic was given to patients in the sitting position, after epinephrine. The level at which the sense of touch was lost seemed to mark the limits of the zone of solid spinal anesthesia; these limits could not be assessed effectively using pinprick. We propose that loss of touch sensation be used to assess whether anesthesia is adequate to avoid tourniquet pain. If there is loss of touch sensation above the L1 dermatome, it is unlikely that tourniquet pain will occur.

Adult↗

Threshold measurement: applications to excitable membranes of nerve and muscle.

Tracking the firing threshold of membranes is best accomplished with threshold hunters, automatic devices that adjust stimulus strength so as to hold constant the probability of an all-or-none response. We present a formalism for analyzing the performance of threshold hunters. An index for error is defined between the threshold of the membrane and the output of the threshold hunter. Errors are separated into tracking error, quantization error, and a fluctuation error that reflects the probabilistic nature of responses to liminal stimuli. The engineering trade-offs between these errors are quantified for conditions where the threshold undergoes rapid transients (e.g. after conditioning impulses) and where it changes more gradually (e.g. during exposure to anesthetics or recovery from tetanus). Several methods for decreasing the total error of the threshold hunter by using the outcomes from previous test stimuli are analyzed quantitatively to provide criteria for the design of hunters to extract a maximum of information concerning threshold with a minimum of interference with the preparation. In nerve axon the distribution of the firing threshold depends on impulse activity patterns, and a strategy for measuring this effect is presented.

Biophysical Phenomena↗

Effects of nerve impulses on threshold of frog sciatic nerve fibres.

1. The firing thresholds of single myelinated fibres of frog sciatic nerves were monitored as a function of impulse activity in the fibre. The threshold was given by the number of coulombs in current pulses that excited a particular fibre half the time when delivered to the whole nerve. Threshold was tracked by a device that incrementally decreased the number of coulombs in the current pulse whenever the fibre responded and increased the pulse if it did not respond. 2. There was a pattern to the after-oscillations of threshold following activity. The fibres were briefly refractory, transiently superexcitable for about 1-1.5 sec and then entered a phase of raised threshold or 'depression' that lasted for many minutes. 3. Activity produced little change in the threshold curve during the refractory period. Strong depressions following prolonged activity prevented the threshold from returning to the base-line level within the time associated with the refractory period for the same fibre at rest. 4. After an impulse, superexcitability reached a maximum within 7-20 msec. This peak was larger as the number of impulses in a preceding burst increased and as the intervals between the impulses became briefer. Each successive impulse of a burst contributed less to the growth of superexcitability, and after the burst had 6-10 impulses additional impulses contributed nothing. 5. The depression phase was marked by the interaction between build-up, which depended on the activity rate, and recovery, which required as long as an hour or more for the threshold to be completely restored to resting level. These two mechanisms, one causing build-up and the other recovery, led to formation of dynamic equilibria. The threshold level at equilibrium increased monotonically with the activity rate. 6. The processes associated with superexcitability interact with those producing depression. In active fibres showing raised thresholds, impulses are followed by a relative superexcitability that persists for at least as long as an absolute superexcitability (with threshold below the resting level) can be measured in the same fibre at rest. 7. The duration of the superexcitable phase interpreted as a relative change in excitability was roughly the same regardless of the level of depression. 8. The magnitude of the oscillation in threshold was give to ten times larger than the grey region (the range of stimuli for which response is probabilistic). It is concluded that at regions of low conduction safety such as axonal branches, where weak forces can influence whether an impulse will pass, such pronounced and long-lasting after-effects of firing can be expected to modulate conduction of nerve impulses.

Action Potentials↗

The NerveSeeker: a system for automated nerve localization.

BACKGROUND AND OBJECTIVES: The NerveSeeker is a new instrument for locating peripheral nerves. Like existing nerve stimulators, it is based on injecting current through the needle used for drug injection. However, the NerveSeeker was designed to automatically adjust the amplitude of the stimulating current pulses. It does this by feedback control to hold the level of response constant at a small but reliably detectable fraction of a maximal neural response. We report experimental tests of the NerveSeeker using an excised frog nerve in a transparent chamber, where we could observe the needle approach. METHODS: A control voltage proportional to the stimulus magnitude was used to indicate the proximity of the needle tip to the nerve. The proximity was validated by direct measurement of the distance from the tip of the needle to the nerve. Parameters governing the performance of the NerveSeeker in tracking needle movement were analyzed. RESULTS: The following combined strategy was found effective: As the needle approached the nerve, the stimulus was reduced in proportion to the amplitude of the recorded response; as the needle moved away, the stimulus magnitude was incremented by a constant amount (enough to increase the neural response by approximately 1% of its maximum amplitude) after each stimulus that failed to elicit a neural response exceeding the criterion value. Stimulation throughout simulated penetrations was at a frequency of 10 Hz or higher to give more immediate guidance during insertion. Optimal settings for each control parameter were determined, reflecting both engineering and physiologic tradeoffs. With these settings, the device proved successful in localizing nerves, closely tracking needle movements at velocities as high as 2 mm/second. CONCLUSION: These experimental results suggest that clinical tests of the NerveSeeker would be appropriate.

Action Potentials↗