Biomedical subjects

R B Stein

Publications and source records attributed to R B Stein.

At least 109 records · Page 6Linked to original sources

PubMed1991

H-reflex modulation during walking in spastic paretic subjects.

Hoffman (H) reflexes were elicited from the soleus muscle during treadmill walking in 21 spastic paretic patients. The soleus and tibialis anterior muscles were reciprocally activated during walking in most patients, much like that observed in healthy individuals. The pattern of H-reflex modulation varied considerably between patients, from being relatively normal in some patients to a complete absence of modulation in others. The most common pattern observed was a lack of H-reflex modulation through the stance phase and slight depression of the reflex in the swing phase, considerably less modulation than that of normal subjects under comparable walking conditions. The high reflex amplitudes during periods of the step cycle such as early stance seems to be related to the stretch-induced large electromyogram bursts in the soleus in some subjects. The abnormally active reflexes appear to contribute to the clonus encountered during walking in these patients. In three patients who were able to walk for extended periods, the effect of stimulus intensity was examined. Two of these patients showed a greater degree of reflex modulation at lower stimulus intensities, suggesting that the lack of modulation observed at higher stimulus intensities is a result of saturation of the reflex loop. In six other patients, however, no reflex modulation could be demonstrated even at very low stimulus intensities.

Adult↗

PubMed1991

Myocardial contractile behavior of a new sotalol derivative.

The effects of E4031, a new class III antiarrhythmic agent similar to sotalol, were tested in isometrically contracting rabbit papillary muscles and in anesthetized, open-chest dogs. In papillary muscles, E4031 caused a modest dose-dependent increase of 26 +/- 8% in developed tension and 38 +/- 8% in its maximal rate of rise. Since there was no significant change in the maximal rate of relaxation, the ratio between both maximal velocities increased from 0.92 +/- 0.03 to 1.19 +/- 0.10. Time to peak tension did not change significantly, whereas time to half relaxation increased from 72 +/- 3 to 85 +/- 4 ms. The effective refractory period in the rabbit papillary muscles increased from 179 +/- 10 to 414 +/- 45 ms. In the open-chest dog, the i.v. administration of E4031 did not induce significant changes in heart rate, mean arterial pressure, or left ventricular end diastolic pressure. +dP/dt increased from 1,839 +/- 162 to 2,470 +/- 247 mm Hg/s with no significant change in -dP/dt after 100 micrograms/kg of E4031. Consequently, (+dP/dt)/(-dP/dt) increased from 0.97 +/- 0.07 to 1.18 +/- 0.08. To further evaluate the effects of E4031 on myocardial relaxation, the time constant of isovolumic left ventricular pressure decay was measured by two different methods (tau 1 and tau 2) before and after administering 10 micrograms/kg E4031. Tau 1 increased from 27 +/- 1.8 to 33 +/- 1.6 ms and tau 2 increased from 30 +/- 2.3 to 41 +/- 3.3 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Comparison of force and EMG measures in normal and reinnervated tibialis anterior muscles of the rat.

The relationship between motor unit force and the recorded voltage produced by activated muscle unit fibres (electromyogram, EMG) was examined in normal and reinnervated rat tibialis anterior muscles. The number, cross-sectional area, and radial distance from the recording electrode of muscle fibres in a given unit, obtained directly from a sample of glycogen-depleted motor units, were analysed in relation to the magnitude of the EMG signal produced by that unit. EMG peak to peak amplitude and area varied as approximately the square root of twitch force in both normal and reinnervated units. Furthermore, the EMG amplitude increased approximately as the total cross-sectional area of the motor unit (number of muscle fibres x the average cross-sectional area of the fibres) and inversely with approximately the square root of the distance of fibres from the recording electrodes on the surface of the muscle.

Animals↗

PubMed1991

Factors that determine the magnitude and time course of human H-reflexes in locomotion.

The soleus H-reflex amplitude is deeply modulated during locomotion in humans (Capaday and Stein, 1986). Moreover, at a constant stimulus intensity, the slope of the relationship between the amplitude of the soleus H-reflex and the background electromyogram (EMG) changes with different locomotor tasks (Capaday and Stein, 1987a). Two further aspects are studied here. First, we recorded the reflex during overlapping speeds of walking (2.0-7.5 km/hr) and running (5-9 km/hr) to determine whether the speed, the motor output, or the form of locomotion was most important in setting the slope of this relationship between H-reflex and background EMG. Second, we determined the time course of change in the H-reflex amplitude and the possible site of action for the reflex depression during the transition from standing to walking. The primary determinant of the slope was found to be the form of locomotion. The differences between running and walking could not be explained entirely by either movement speed or motor output. For walking, the slope varied inversely with the speed and the motor output of locomotion. This compensation in slope as a function of motor output may prevent saturation of the motoneuron pool. The appropriate reflex amplitudes for a particular locomotor pattern are activated rapidly and completely within a reaction time, and simultaneously with the activation of muscle activity for the initiation of walking. Mechanisms for the rapid change seen during the initiation of locomotion most likely act presynaptically on the muscle spindle afferents. The time course and magnitude of this change are correlated with the activity of the tibialis anterior muscle.

Electromyography↗

PubMed1990

Methods for estimating the number of motor units in human muscles.

The number of motor units in the thenar muscle group was calculated by dividing the surface electromyogram and twitch force, in maximal stimulation of the median nerve, by estimates of the average electromyogram and twitch force from single units. The following three techniques were used to estimate the average electromyogram from single units: spike-triggered averaging from units recorded with a needle electrode, intramuscular microstimulation of motor nerve branches, and graded whole nerve stimulation at the wrist. The first two techniques also provided independent estimates of motor unit numbers based on the average force generated by single units. The five estimates (three based on the electromyogram and two on force) ranged from 116 to 170 motor units in the thenar group. Correcting for cancellation when unit responses sum to form the compound action potential or twitch increased the estimated number of units, which ranged from 130 to 179. The estimates were not statistically different from one another but were substantially lower than some previous electrophysiological estimates based on graded whole nerve stimulation. The recruitment pattern of single units during whole nerve stimulation was recorded and simulated mathematically. The most likely reason for the higher estimates in previous studies using graded whole nerve stimulation is shown to be alternation of motor units. Potential errors in all the techniques are discussed and compared.

Electric Stimulation↗

PubMed1990

Motor unit numbers and contractile properties after spinal cord injury.

The number of motor units in the thenar muscle group was estimated in 11 patients with cervical spinal cord injuries. The surface electromyogram and twitch force, in response to maximal stimulation of the median nerve was divided by the average surface electromyogram and twitch of single units. The average single unit size was obtained by intramuscular microstimulation of motor nerve branches and by graded whole nerve stimulation, which provided three independent estimates, two based on the electromyogram and one based on force. The motor unit estimates from the patients covered a wide range. Some had essentially normal motor units both in numbers and contractile properties, while others had varying reductions in numbers of units. Those patients who showed a large reduction in motor unit numbers also had greatly enlarged units, which produced an average of up to sixfold the normal force. These enlarged units summed to produce maximal compound action potentials and twitches that were sometimes indistinguishable from normal. Magnetic resonance imaging scans of the cervical spine obtained from some patients provided independent evidence that patients with low motor unit counts had sustained direct injury to the anterior aspect of the spinal cord at the relevant segmental levels. Some patients showed a normal number of motor units long after the injury. No evidence of transneuronal degeneration could be demonstrated in the thenar group in these patients with the current techniques.

Adult↗

PubMed1990

Optimal task performance of antagonistic muscles.

Movements against a variety of loads are relatively invariant in form. These movements are controlled in general by antagonistic groups of muscles. In this paper optimal control strategies are computed for coupling antagonistic muscles so as to minimize deviations from a desired trajectory. Simulations are presented for linear and nonlinear "decision functions" linking control of the two muscles for a variety of movements in a way that may be compared with experimental observations.

Animals↗

PubMed1990

Mechanisms relating force and high-frequency stiffness in skeletal muscle.

Muscle stiffness increases faster than muscle force during the rising phase of a tetanic contraction, and decreases more slowly during the falling phase. Different models of the stiffness arising from series, parallels, and crossbridge elasticity were compared to determine whether they could account quantitatively for the observed time course of force and stiffness. Data for slow and fast twitch mouse muscles at temperatures from 6 to 37 degrees C (Stein and Gordon, Can. J. Physiol. Pharmacol. 64, 1236-1244, 1986) and for single frog muscle fibers (Cecchi et al., Contractile Mechanisms in Muscle, pp. 641-655. Plenum, New York, 1984) were compared. The results showed that a good fit to the data for mouse muscles could be obtained with a model in which: (1) a nonlinear series elasticity contributed significantly to stiffness; (2) the attached crossbridges went from a stiff, force-generating state to a stiff, non-force-generating state; and (3) the rate of transition between these two states increased abruptly at the onset of relaxation. The increased transition rate probably arises from the internal rearrangement in which some sarcomeres shorten at the expense of other sarcomeres, once the muscle begins to relax. A significant series elasticity was not required for the frog data, but a pre-tension state was then needed to obtain a good fit.

Animals↗

PubMed1990

Negative lusitropic effect of DPI 201-106 and E4031. Possible role of prolonging action potential duration.

In open-chest anesthetized dogs, the time constant of isovolumic left ventricular pressure decay increased following the intravenous administration of either E4031, a class III antiarrhythmic agent which acts by K+ channel blockade, or DPI 201-106 (DPI), a cardiotonic agent which acts by delaying Na+ channel inactivation. In addition to prolonging cardiac refractoriness, both E4031 and DPI increased left ventricular +dP/dt but without significantly altering -dP/dt. Consequently, the value of the ratio (+dP/dt)/(-dP/dt) increased. There were no significant changes in heart rate, mean arterial pressure, or left ventricular end diastolic pressure. Since both E4031 and DPI prolonged the action potential duration (APD) and the refractory period, and slowed relaxation in vivo, the possibility of a causal link between these effects was further investigated under in vitro conditions. In isometrically contracting rabbit papillary muscles, E4031 and DPI increased peak developed tension (DT) and its maximal rate of rise (+T). Since the maximal rate of fall of DT (-T) did not increase by the same factor that +T increased, the value of the ratio +T/-T increased. Time to half relaxation increased, whereas time to peak tension was not significantly changed by either E4031 or DPI. These negative lusitropic effects produced by E4031 or DPI were not observed when equivalent increases in contractility were produced by increasing the extracellular Ca2+ concentration. The effective refractory period measured in the papillary muscles increased following superfusion with either of the two drugs, consistent with their known ability to increase APD. A causal link between the prolongation of APD and the negative lusitropic effects of E4031 and DPI is postulated as the possible mechanism.

Action Potentials↗

PubMed1990

Cloning and expression of the delayed-rectifier IsK channel from neonatal rat heart and diethylstilbestrol-primed rat uterus.

cDNAs encoding a delayed-rectifier-type K+ channel were cloned from both neonatal rat heart and ovariectomized, diethylstilbestrol-primed rat uterus by using the polymerase chain reaction. Both clones have nucleotide sequences identical to that encoding the rat kidney IsK channel [Takumi, T., Ohkubo, H. & Nakanishi, S. (1988) Science 242, 1042-1045] and encode a putative protein of 130 amino acids. Injection of RNA transcripts of the cDNAs into Xenopus oocytes resulted in the expression of a slowly activating, voltage-dependent K+ current. An antisense oligonucleotide, derived from the sequence of the clone, specifically inhibited the expression of the slow, outward current observed in cells injected with mRNAs isolated from the parent tissues (i.e., kidney, heart, and uterus), indicating that the cloned gene underlies the major K+ current expressed from RNA isolated from these tissues.

Amino Acid Sequence↗

PubMed1990

Suppression of lethal ischemic ventricular arrhythmias by the class III agent E4031 in a canine model of previous myocardial infarction.

The antiarrhythmic efficacy of a new and potent class III agent E4031 [1-[2-(6-methyl-2-pyridyl)-ethyl]-4-(4- methylsulfonylaminobenzoyl)piperidine] was evaluated in several canine models of recent myocardial infarction. In anesthetized dogs with baseline inducible ventricular arrhythmias studied 4-10 days after anterior myocardial infarction, 30-300 micrograms/kg i.v. E4031 suppressed induction of ventricular tachyarrhythmias by programmed ventricular stimulation in 7 of 10 animals tested, while significantly prolonging refractoriness in both noninfarcted and infarcted ventricular myocardium. The incidence of lethal ischemic ventricular arrhythmias developing in response to acute posterolateral myocardial ischemia in the presence of previous anterior infarction was reduced from 10 of 10 (100%) in a vehicle pretreatment group to 3 of 10 (30%, p less than 0.01) in an E4031 (300 micrograms/kg intravenously, i.v.) pretreatment group. Neither the sizes of the underlying anterior myocardial infarctions (26.9 +/- 3.7 vs. 33.2 +/- 2.1% of left ventricle) nor the times to development of acute posterolateral myocardial ischemia (43 +/- 11 vs. 40 +/- 8 min) differed significantly between the vehicle and E4031 pretreatment groups, respectively, suggesting that the reduction in the incidence of lethal ischemic arrhythmias in the E4031 pretreatment group was not due to smaller underlying, electrically unstable myocardial substrates nor to a delay in onset of the acute ischemic insult. In conscious dogs with spontaneous ventricular ectopy at 48 h after myocardial infarction and in anesthetized dogs with no baseline inducible arrhythmias at 4-10 days after myocardial infarction, E4031 (30-3,000 micrograms/kg i.v.) produced no facilitation or aggravation of spontaneous or inducible ventricular arrhythmias. These findings suggest that pharmacologic agents such as E4031 that increase ventricular refractoriness (class III electrophysiologic activity) may provide significant protection against development of malignant ischemic ventricular arrhythmias in the setting of previous myocardial infarction.

Anesthesia↗

PubMed1990

Failure of lidocaine to suppress lethal ischemic ventricular arrhythmias in a canine model of previous myocardial infarction.

The antiarrhythmic actions of high-dose intravenous (i.v.) lidocaine infusions were assessed in conscious dogs with spontaneous ventricular ectopy subacutely (48 h) after anterior myocardial infarction and in anesthetized dogs with ventricular tachyarrhythmias inducible by programmed ventricular stimulation at 4-11 days after anterior myocardial infarction. In conscious dogs administered cumulative doses of lidocaine at 48 h after myocardial infarction, a significant reduction in the frequency of spontaneous ventricular ectopic complexes (from 61 +/- 12 to 11 +/- 9% of total complexes) occurred only after administration of 10 mg/kg i.v. lidocaine. In anesthetized postinfarction dogs responding to baseline programmed stimulation with ventricular tachyarrhythmias, lidocaine administration (6 mg/kg i.v. loading dose + 100 micrograms/kg/min i.v. maintenance infusion) resulted in a selective increase in infarct zone conduction time (53.0 +/- 5.6 to 60.5 +/- 6.2 msec; p less than 0.05), increases in infarct zone relative refractory periods (RRPs 182 +/- 5 to 193 +/- 5 ms; p less than 0.05), and effective refractory periods (ERPs 156 +/- 4 to 165 +/- 3 ms; p less than 0.05), and an increase in noninfarct zone ERP (154 +/- 5 to 166 +/- 8 ms; p less than 0.05). The induction of ventricular arrhythmias by programmed stimulation was suppressed by lidocaine (6 mg/kg + 100 micrograms/kg/min i.v.) in 5 of 10 postinfarction animals tested, with an additional 3 animals displaying favorable stabilizations of induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1990

Fusimotor control of muscle spindle sensitivity during respiration in the cat.

1. The two types of fusimotor neurones, dynamic and static, can be differentiated by their effects on muscle spindle afferents. We have recorded the activity of muscle spindle primary afferents from the intercostal nerves of anaesthetized or decerebrate cats. A 4 Hz sinusoidal stretch was applied to the muscle containing the spindles of interest before and after crushing the nerve proximal to the recording site to eliminate fusimotor effects. The relative activity of the dynamic and static fusimotor neurones was inferred from the change in the spindle afferents' response. 2. Some areas of intercostal muscle normally showed phasic activity linked to respiration, where as other areas of intercostal muscle showed no EMG activity under our experimental conditions. In areas of intercostal muscle lacking EMG activity, the afferents' mean rate was higher and the modulation around the mean was lower at all phases of the breathing cycle when the efferent supply was intact. This result suggests the muscle spindles were receiving a steady level of static fusimotor activity. 3. Spindle primary afferents from regions of intercostal muscle that were typically recruited during respiration had an additional increase in mean rate and modulation around the mean rate in phase with the EMG activity. This is suggestive of phasic activation of dynamic fusimotor neurones in addition to static fusimotor discharge. 4. Thus, the two types of fusimotor neurones can be activated separately by the CNS to control the sensitivity of muscle spindles. The regional differences in the recruitment patterns of fusimotor neurones parallels the functional specializations of different areas of the intercostal muscles. The temporal modifications of fusimotor activity during each respiratory cycle means that the segmental reflex gain will vary in those intercostal muscles that are active during respiration. 5. These findings regarding the CNS recruitment of the two types of fusimotor neurones during respiration are similar to those reported for the hindlimb extensors during locomotion, but differ from those reported for jaw muscles during chewing. This may reflect differing control strategies being used by the CNS to meet the unique demands of the various rhythmical movements.

Action Potentials↗

PubMed1990

Motor units in incomplete spinal cord injury: electrical activity, contractile properties and the effects of biofeedback.

The electrical and contractile properties of hand muscles in a selected population of quadriplegic subjects were studied intensively before and after EMG biofeedback. Spontaneously active motor units and units that could only be slowly and weakly activated were observed in these subjects, in addition to units that were voluntarily activated normally. This suggests a considerable overlap of surviving motor neurons to a single muscle that are below, near or above the level of a lesion. Despite the common occurrence of polyphasic potentials and other signs of neuromuscular reinnervation, the average twitch tension of single motor units in hand muscles of quadriplegic subjects was not significantly different from that in control subjects. Nor did it increase after biofeedback training that typically increased the peak surface EMG by a factor of 2-5 times. The percentage of spontaneously active units was also constant. The surface EMG may be increased during biofeedback by using higher firing rates in motor units that can already be activated, rather than by recruiting previously unavailable motor units.

Adult↗

PubMed1990

Phase-dependent reflex reversal in human leg muscles during walking.

1. Reflex responses during walking were elicited in humans by stimulation of the tibial nerve at the ankle. The stimulus intensity was controlled by monitoring the M-wave from an intrinsic foot muscle. Responses were observed in the ipsilateral tibialis anterior (TA), soleus (SO), and rectus femoris (RF) muscles. The most reproducible responses were observed at a middle latency between 50 and 90 ms. The responses were most likely of cutaneous origin, because they closely resembled the responses to stimulation of a purely cutaneous nerve, the sural nerve. 2. A reversal in the direction of the middle latency response from excitation to inhibition was observed for the first time within single muscles during walking. Evidence for a reversal was seen in all three muscles examined and in all seven subjects. 3. The reflex reversal could not be elicited in standing. An inhibition whose amplitude varied in a linear fashion with stimulus intensity and background activation level was always observed at middle latency. The responses elicited during standing resembled those during the stance phase of walking. The two tasks shared some common movement goals and appeared to make use of similar reflex pathways.

Electric Stimulation↗

PubMed1990

Reciprocal inhibition of soleus motor output in humans during walking and voluntary tonic activity.

1. The extent to which an active, human motoneuron pool can be inhibited via short-latency inhibitory pathways was studied by stimulating the common peroneal nerve and recording the inhibition of on-going soleus electromyographic (EMG) activity. The responses were compared at the same EMG level during walking and tonic voluntary activity to determine whether the inhibition was task dependent. 2. In both tasks the amount of inhibition (measured as the depression in rectified, filtered, and averaged EMG activity) increased approximately linearly with the amount of motor activity, as determined from the mean EMG level before stimulation (correlation coefficient greater than or equal to 0.9). No difference in the amount of inhibition was found between the two tasks at the same stimulus and EMG levels. 3. Previously published studies based on the H-reflex method have reported that the amount of inhibition decreases with the amount of motor activity. On the contrary, single-unit studies and the present results suggest that segmental inhibitory reflexes retain their capacity to mediate a rapid reduction of motoneuronal discharge during voluntary activity. This inhibition may be important in regulating the amount of activity early in the stance phase of walking and during the transition from stance to the swing phase. 4. Analytic results are derived in an APPENDIX that should be of general interest in interpreting the inhibition of motor units from a peristimulus time histogram (PSTH). The linear correlation between inhibition and level of voluntary activity can be explained if newly recruited units are strongly inhibited by the stimulus, whereas previously active motor units are inhibited relatively less, as their firing rate increases with increasing background activity.

Adult↗

PubMed1989

Patterns of gamma-motoneuron activity in the external intercostal muscles of the cat during respiration.

Recordings of gamma-motoneurons from fine filaments of external intercostal nerves were made during spontaneous breathing in the anesthetized cat. The patterns of alpha- and gamma-motoneuron activity varied within different areas of the rib cage. Areas of muscle which were recruited during inspiration received input from both tonically and phasically active gamma-motoneurons. Those areas of the rib cage which were not recruited during inspiration received activity from tonically active gamma-motoneurons. These patterns of gamma-motoneuron activity are in agreement with those suggested from previous recordings of muscle spindle activity.

2-Amino-5-phosphonovalerate↗

PubMed1989

The effects of postsynaptic inhibition on the monosynaptic reflex of the cat at different levels of motoneuron pool activity.

The motoneurons to the Soleus muscle in the decerebrate cat were activated by the crossed extensor reflex, elicited by stimulation of the contralateral common peroneal (CP) nerve. Monosynaptic reflexes were obtained from the Soleus motoneuron pool by stimulation of the cut L7-S1 dorsal roots. The amplitude of the reflex increased approximately linearly with the recruitment level of the motoneuron pool. Tonic postsynaptic inhibition was induced in the Soleus motoneuron pool by repetitive antidromic stimulation of the Lateral Gastrocnemius (LG) and Medial Gastrocnemius (MG) nerves at a rate of 17-47 stimuli/s. This reduced the size of the monosynaptic reflex at rest by at least 40%. However, when the motoneurons were active, the amplitude of the monosynaptic reflex obtained during repetitive stimulation of the LG-MG nerve increased with the recruitment level along the same curve as the control reflexes. Thus, tonic postsynaptic inhibition of the motoneurons per se cannot control the amplitude of the monosynaptic reflex independently of the recruitment level of the motoneuron pool. These experimental results verify predictions from computer simulations and suggest by exclusion that presynaptic inhibition is needed to control the amplitude of the monosynaptic reflex independently of the recruitment level of the motor pool.

Action Potentials↗