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PubMed2000

Multiple measures of axonal excitability: a new approach in clinical testing.

From measurements of nerve excitability and the changes in excitability produced by nerve impulses and conditioning currents, it is possible to infer information about the membrane potential and biophysical properties of peripheral axons. Such information cannot be obtained from conventional nerve conduction studies. This article describes a new method that enables several such measurements to be made on a motor nerve quickly and reproducibly, with minimal operator intervention. The protocol measures stimulus-response behavior using two stimulus durations (from which the distribution of strength-duration time constants can be estimated), threshold electrotonus to 100-ms polarizing currents, a current-threshold relationship (indicating inward and outward rectification), and the recovery of excitability following supramaximal activation. The method was tested on 30 healthy volunteers, stimulating the median nerve at the wrist and recording from the abductor pollicis brevis. The results were comparable with previously published normal data, but the recordings took less than 10 min. The convenience and brevity of the new method make it appropriate for routine clinical use.

Action Potentials↗
PubMed2000

Effect of maturation on nerve excitability in an experimental model of threshold electrotonus.

Threshold electrotonus (TE) is a new tool for investigating axonal function noninvasively in vivo. To increase its potential clinical value, we developed a rat model of TE, and examined the effects of maturation and pharmacological intervention. We recorded TE in 92 male rats (body weight 90-650 g) by stimulating the motor nerve in the tail, and applying 100-ms conditioning currents. Motor conduction velocities increased up to a body weight of 330 g, and remained constant thereafter. TE in mature rats was similar to that in humans, and two parameters were analyzed: TEd(10-20) or the mean threshold reduction 10-20 ms after the onset of the depolarizing conditioning current at 40% of threshold intensity; and TEh(10-20) or the corresponding threshold decrease on hyperpolarization. Like latency, the absolute value of TEh(10-20) decreased up to 330 g, and then stabilized thereafter, probably reflecting the progressive increase in the axonal diameter and relative reduction in internodal impedance. In contrast, TEd(10-20) gradually decreased up to 330 g, and then jumped to a higher level, which was maintained for animals of >400 g. 4-Aminopyridine, a blocker of fast potassium channels, selectively increased TEd(10-20) only in the immature or young (<330 g) rats. This suggests that, in the mature animals, fast potassium channels become sequestrated from the nodal membrane and not activated in response to nodal depolarization. These findings indicate that mature rats (>400 g) may provide a useful experimental model for interpreting abnormal TE responses in humans, and provide evidence for nonlinear maturation of potassium channel function in myelinated axons.

4-Aminopyridine↗
PubMed1999

Studies on the mode of action of the essential oil of lavender (Lavandula angustifolia P. Miller).

Lavender (Lavandula angustifolia, P. Miller) is used in aromatherapy as a holistic relaxant and is said to have carminative, antiflatulence and anticolic properties. Its sedative nature, on inhalation, has been shown both in animals and man. Lavender has a spasmolytic activity on guineapig ileum and rat uterus in vitro and it also decreases the tone in the skeletal muscle preparation of the phrenic nerve-diaphragm of rats. As the mechanism of action has not been studied previously, the spasmolytic activity was studied in vitro using a guinea-pig ileum smooth muscle preparation. The mechanism of action was postsynaptic and not atropine-like. The spasmolytic effect of lavender oil was most likely to be mediated through cAMP, and not through cGMP. The mode of action of linalool, one of lavender's major components, reflected that of the whole oil. The mode of action of lavender oil resembled that of geranium and peppermint oils.

Animals↗
PubMed1981

Muscle fatigue due to changes beyond the neuromuscular junction.

A number of changes in function occur beyond the neuromuscular junction during activity; three main types are described. (a) During high frequency stimulation there is a rapid loss of force accompanied by a slowing of the action potential waveform and an increase in the excitation threshold of the muscle. It is suggested that accumulation of K+ in the extracellular spaces of the muscle may be responsible for these changes. (b) Slowing of relaxation is a feature of fatigued muscle. The slowing allows a reduction in activation frequency (minimizing high frequency fatigue) without resulting in an appreciable loss of force. (c) Changes in shape and amplitude of the twitch have considerable effects on the force generated by low frequencies of stimulation. After a brief tetanus there is a reduction in the width of the twitch which increases the fusion frequency of the muscle and may account for the "sag' seen at the start of low frequency contractions. After a prolonged series of contractions the twitch amplitude is reduced and remains so for several hours. This may be the result of some structural damage to the sarcoplasmic reticulum or transverse tubular system.

Action Potentials↗
PubMed1981

Effect of metabolic changes on force generation in skeletal muscle during maximal exercise.

During vigorous, strong contractions there is a rapid decline in the mechanical output or tension development in skeletal muscle. Several studies have indicated that this rapid decline in force development (often referred to as fatigue), is caused by metabolic changes in the muscles. During brief intense exercise there is a rapid breakdown of phosphocreatine and glycogen and a concomitant increase in the lactate and hydrogen ion concentration. The muscle lactate concentration is increased from about 1-2 mmol kg-1 wet weight at rest before exercise to approximately 25-30 mmol kg-1 wet weight immediately after intensive brief exercise to exhaustion. The muscle pH (i.e. the pH of muscle homogenates) falls from about 7.0 at rest to approximately 6.4 at exhaustion. The changes in the concentrations of ATP, ADP, and AMP are small. It is suggested that the changes in intracellular pH might affect the force generation of skeletal muscle by two different mechanisms: (1) The fall in intracellular pH reduces the activity of key enzymes in glycolysis, thus reducing the rate of ATP resynthesis, and (2) the increased hydrogen ion concentration has a direct effect on the contractile processes, thus reducing the rate of ATP utilization. It is suggested that the increased hydrogen ion concentration might be the common regulator for the maximal rate at which ATP is being utilized and the maximal rate at which it is being resynthesized.

Acidosis↗
PubMed1988

Nascent muscle fiber appearance in overloaded chicken slow-tonic muscle.

The application of a weight overload to the humerus of chickens induces a hypertrophy of anterior latissimus dorsi (ALD) muscle fibers. This growth is accompanied by a rapid and almost complete replacement of one slow-tonic myosin isoform, SM-1, by another slow-tonic isoform, SM-2. In addition, a population of small fibers appears mainly in extrafascicular spaces and, concurrently, three additional myosin bands are detected by gel electrophoresis. Five antibodies against myosin heavy chain (MHC) isoforms were selected as immunocytochemical probes to determine the cellular location and nature of these myosins. The antibodies react with ventricular, fast skeletal muscle and either SM-1 or SM-2, or both the slow-tonic MHCs. The antifast and antiventricular antibodies react with myosin present in the 10-day embryonic ALD muscle but do not react with myosin in posthatch ALD muscle. The small fibers in overloaded muscle contain a myosin isoform characteristically expressed during the embryonic stage of ALD muscle development and therefore are named nascent myofibers. Some of the nascent myofibers do not react with the antibody to both slow-tonic MHCs, indicating the lack of the normal adult slow-tonic myosins which are expressed in 10-day embryos. In order to explore the origin of the nascent fibers, an electron microscopic study was performed. Stereological analysis of the existing fibers shows a stimulation of numbers and sizes of satellite cells. In addition, the volume occupied by nonmuscle and undifferentiated cells increases dramatically. Myotube formation with incipient myofibrils is seen in extrafascicular spaces. These data suggest that new muscle fiber formation accompanies hypertrophy in overloaded chicken ALD muscle and the process may involve satellite cell migration.

Animals↗
PubMed2005

Static magnetic fields alter arteriolar tone in vivo.

This study was designed to directly quantify the effect of localized static magnetic field (SMF) exposure on the diameter of microvessels in adult rat skeletal muscle in vivo. Microvascular networks in the exteriorized rat spinotrapezius microvasculature were exposed to a localized, uniform 70 mT SMF for 15 min. Arteriolar vessel diameters were measured; and the extent of vessel contraction, microvascular tone, was calculated before exposure, immediately after exposure, and 15 and 30 min after removal of the field. A calculated value of high tone corresponds to vessels that are vasoconstricted and a calculated value of low tone refers to vessels that are vasodilated. Vessels with initial tone <15% showed an increasing trend in tone and, conversely, vessels with initial tone >15% showed a significant (P < 0.05) decrease in tone 15 and 30 min following application, respectively. Further classification of the data with regards to the initial vessel diameter demonstrated that vessels with initial diameters <30 microm and initial tone <15%, smaller diameter vessels that are initially vasodilated, showed significant (P < 0.05) increase in tone immediately, 15 and 30 min following SMF exposure. Additionally, <30 microm vessels with >15% initial tone, smaller diameter vessels that are initially vasoconstricted, demonstrated a significant (P < 0.05) decrease in tone 30 min after SMF exposure. Vessels with initial diameters >30 microm had no significant response to the SMF. These results imply that SMF exposure influences arteriolar diameters, and therefore microvascular tone, in a restorative fashion acting to normalize the tone to the median tone value of 15% following exposure. Because this response occurs primarily in the resistance arterioles, which significantly influence tissue perfusion, SMF application could be efficacious for the treatment of both ischemic and edematous tissue disorders involving compromised microvascular function.

Adaptation, Physiological↗
PubMed2005

Comparison of the effects of nitric oxide donors and calcium channel blockers on the intrinsic myogenic tone of sheep isolated internal anal sphincter.

BACKGROUND: Chronic anal fissure is associated with considerable pain and anal hypertonia. Numerous clinical studies attest to the effectiveness of individual nitro-containing drugs and organic calcium channel blockers in this condition but there are few comparative studies. METHODS: Isolated segments of sheep internal anal sphincter were prepared for isometric tension recording. The effect of various drugs on myogenic tone was examined in the absence or presence of sodium orthovanadate (SOV), an agent used to mimic anal hypertonia by increasing myogenic tone. RESULTS: All the drugs tested produced concentration-dependent inhibition of myogenic tone, with the maximum effect ranging from 66.4 per cent (verapamil) to 100 per cent (sodium nitroprusside). Sodium nitroprusside and diltiazem were the most potent, followed by glyceryl trinitrate (GTN), nifedipine and verapamil, which had similar potency, and finally nicorandil. The potency of GTN and diltiazem was reduced threefold in the presence of 1 mmol/l SOV. The combined effect of GTN and diltiazem was greater than the effect of either agent alone, even in the presence of 3 mmol/l SOV. CONCLUSION: Nitro-containing drugs and organic calcium channel blockers are potent inhibitors of anal sphincter myogenic tone that may be used in combination to treat chronic anal fissure.

Anal Canal↗
PubMed1982

Motor asymmetries in preterm infants: effects of prematurity and illness.

Two types of motor asymmetry, postural asymmetry and lateral head turning, were assessed in 3 groups of preterm infants, one of which had experienced respiratory distress syndrome (RDS) in the postnatal period. Results reveal that maintenance of a right postural asymmetry is present as early as 34 weeks conceptional age and is not disrupted by postnatal illness. Lateral head turning after midline placement was evident as early as 36 weeks conceptional age but was disrupted by physiologic condition. Infants who had experienced RDS had poor muscle tonus and did not assume the head right position even at 39 weeks conceptional age. These data argue that lateral responding may be affected by illness and that studies of preterm populations must evaluate postnatal medical condition when assessing both the short- and long-term outcomes of lateral asymmetries.

Age Factors↗
PubMed1986

Postnatal locomotion development in a neurological mutant of rolling mouse Nagoya.

Postural control skills and quadrupedal locomotor pattern in infant rolling mice, a neurological mutant, were observed in the following situations: hindlimb support when suspended, rope descent, narrow path traverse, quadrupedal locomotion on an inclined corridor, and swimming behavior when entirely submerged. Until the second week of age, rolling mice developed primitive responses similar to, or somewhat slower than, their unaffected littermates, but failed to show mature adaptive and coordinated movements from Days 16-18 onward in hinblimb support and rope descent tests. The gait was broadbased and they frequently lurched, rolled over on the side in the narrow-path and incline situations. Also, swimming behavior was extremely clumsy with varying degrees of disturbed rhythm and inconsistent movement of hindlimb paddling. These findings might result from an immature development of hindlimb muscle tonus control system and distortion of smooth and orderly sequence of hindlimb muscular contractions which characterize skillful quadrupedal locomotion.

Animals↗
PubMed1988

Behavioral effects of developmental lead exposure in rhesus monkeys.

Postnatal lead exposure has been found to cause long-term learning and memory deficits in monkeys. Pulse-chronic exposure, consisting of acute high-level exposure followed by chronic lower-level exposure, has been particularly effective in causing these impairments. We investigated possible antecedents of lead-induced cognitive dysfunction by evaluating the behavioral effects of pulse-chronic lead exposure in rhesus monkeys during the first 6 months of postnatal life. Blood lead concentrations in the monkeys reached a peak of 55.8 +/- 7.8 ug/dl during week 5 after birth and then averaged between 33.1 and 42.9 ug/dl during the rest of the first 6 months after birth. Zinc protoporphyrin levels were increased by lead exposure, but hematocrits were unaffected. Significant lead-related effects were detected on a visual exploration test and a neonatal behavioral assessment battery. Lead-treated monkeys exhibited decreased looking behavior on the visual exploration test and decreased muscle tonus and increased arousal or agitation on the behavioral assessment battery. No effects were seen on a Piagetian object permanence task and no toxic effects on health or growth were detected. In addition to providing indices of behavioral dysfunction during postnatal lead exposure, performance on these early behavioral tests may predict later lead-induced cognitive dysfunction.

Animals↗
PubMed2004

Impaired calmodulin binding of myosin-7A causes autosomal dominant hearing loss (DFNA11).

Both myosin 7A (MYO7A) and calmodulin (CaM) are required for transduction and adaptation processes in inner ear hair cells. We identified a novel heterozygous missense mutation (c.2557C>T; p.R853C) in a family with autosomal dominant non-syndromic hearing loss that changes an evolutionarily invariant residue of the fifth IQ motif (IQ5), a putative calmodulin (CaM) binding domain, of MYO7A. Functional effects of the p.R853C mutation were investigated in a physiological cellular environment by expressing MYO7A IQ5-containing peptides in smooth muscle cells of microarteries, in which overexpression of wildtype IQ5 (with intact calmodulin binding) would be expected to compete with myosin light chain kinase (MLCK) for CaM binding. Indeed, analysis of calmodulin-dependent vasoconstriction suggests constitutive binding of CaM to the wildtype, but not the p.R853C-mutated IQ5 motif at all physiologically relevant Ca2+ concentrations. Thus our data suggest a disturbed CaM/MYO7A binding of the p.R853C mutant, this amino acid change may result in impaired adaptation to environmental stimuli and progressive deterioration of hearing transduction in heterozygotes. A defect in CaM/MYO7A interaction represents a novel pathomechanism for genetic hearing loss. It provides an attractive molecular target for therapeutic interventions aimed to delay or prevent the onset of hearing loss in families with mutations in myosin IQ domains.

Adolescent↗
PubMedDate not supplied

Antihypertensive action of nifedipine: effects on arteries and veins.

Nifedipine is a calcium-channel antagonist with effective antihypertensive activity and has been suggested for the treatment of high blood pressure as an alternative to vasodilators. The aim of this study was to define the acute effect of nifedipine and in particular the dose-effect relationship, effects on veins, influence on adrenergic reflexes, and effectiveness on hypertension according to severity and etiologic type. The effects of nifedipine on blood pressure, heart rate, forearm blood flow, peripheral vascular resistance, orthostatic and cold reflexes, and venous tone were examined in 45 patients with hypertension of different etiologies (essential, renovascular, and renal parenchymal) and different World Health Organization grades. The antihypertensive effect was dose dependent, but a dose of 20 mg has nearly maximal activity with acceptable side effects. The drug acts by lowering peripheral vascular resistance, and this lowering is directly related to baseline values; therefore, the antihypertensive effect increases with severity of the hypertension. Nifedipine had the same effect in all three etiologic groups of hypertension studied. The drug seems to increase venous tone, since it caused venoconstriction when locally injected in hand veins. Nifedipine did not alter adrenergic reflexes induced by both cold application and standing and was well tolerated. In conclusion, the calcium antagonist nifedipine for its characteristics of action, at least in acute administration, seems to be a useful alternative in the treatment of various forms of hypertension.

Adult↗
PubMed1982

Active length-tension relation and the effect of muscle pinnation on fiber lengthening.

The active length-tension relation was determined for the left digastric muscle of seven New Zealand White rabbits anesthetized with pentobarbital. Measurements of muscle length and fiber architecture were made from photographs of resting and actively contracting muscle. There was a marked difference between length-tension curves based upon resting as compared to active muscle length. The active length-tension relation had a longer descending limb than ascending limb, whereas the length-tension relation based on passive muscle length tended to be symmetrical around optimum length. On the average, muscle fibers lengthened 0.77 mm for each 1 mm of extension of the muscle belly. Since the rabbit digastric muscle is unipinnate, this suggests that pinnation serves to enhance the range of muscle excursion in this muscle.

Animals↗
PubMed1999

Stiffness and muscle function with age and reduced muscle use.

Changes in passive muscle stiffness with age and disuse were assessed in male Fischer-344 and Brown Norway rats. Three groups of rats were studied: young (approximately 7 months old), old (approximately 33 months old), and old that had undergone 2 weeks of hindlimb unweighting, a model of reduced muscle use. Four hindlimb muscles were examined: the soleus (postural), plantaris (locomotor), extensor digitorum longus (nonpostural), and peroneus longus (nonpostural). Supramaximal stimuli elicited peak tetanic tensions throughout the available range of motion (amount of muscle elongation before the maximal attainable contractile or tetanic tension is obtained) for each muscle, permitting the creation of length-tension curves. Passive tension (amount encountered at each millimeter of change in muscle length) was also recorded throughout the available range of motion and was unchanged with aging and unchanged or reduced with hindlimb unweighting; muscle stiffness remained unchanged under both conditions. Passive tension, however, accounted for a greater proportion of total tension with age and particularly with hindlimb unweighting. A significant loss in muscle range of motion, resulting in a leftward shift in the length-tension curve, occurred with aging in only the plantaris. Hindlimb unweighting resulted in a marked loss in muscle range for all four muscles studied, suggesting that the remaining muscle force was constrained to a very small arc. Significant declines in muscle mass and peak contractile tension, associated with age and hindlimb unweighting, were observed for all four muscles.

Aging↗