Creatine kinase in developing skeletal and cardiac muscle of the rat

This paper reports the changes in specific activity and isoenzyme pattern of creatine kinase in skeletal and cardiac muscle of Holtzman rats during development. There is a rapid accumulation of enzyme after day 17 of gestation and, starting at a slightly earlier time, a transition from “brain” to “heart” and then to predominantly “muscle” isoenzyme takes place. Although the changes are similar in the two types of muscle, important differences are found. The specific activity of creatine kinase is much lower in developing and mature cardiac muscle, but adult levels of the enzyme are approximated sooner in cardiac than in skeletal muscle tissue. The changes in isoenzymes are more gradual and less profound in cardiac muscle than in skeletal muscle. The factors which may relate to these striking changes in creatine kinase are discussed.     

Measurements of muscle stiffness, the electromyogram and activity in single muscle spindles of human flexor muscles following conditioning by passive stretch or contraction

In experiments on adult human subjects we examined the effect on passive mechanical properties of a muscle by conditioning it with either an isometric contraction or passive muscle extension. The test measurement was the amount of muscle displacement (stiffness) and the accompanying EMG in response to a brief torque pulse. Two muscles were tested, flexor digitorum profundus (FDP) and brachialis. In FDP the discharge of single muscle spindles was recorded as well. After muscle extension and return to the initial length, passive stiffness was less than after an isometric contraction. The changes in stiffness were accompanied by changes in pattern of EMG and in the responses of muscle spindles. It is suggested that in resting muscle there are stable cross bridges between actin and myosin filaments of muscle fibres which largely determine the passive stiffness. Muscle extension leads to detachment of these cross bridges which then re-form at the longer length. Return of the muscle to its starting length leads to development of slack in muscle fibres because, stiffened by the presence of the stable cross bridges, they are unable to shorten. Slack in muscle fibres lowers their measured stiffness. Muscle contraction, on the other hand, will result in any preexisting slack being taken up by the actively shortening muscle fibres, thereby raising muscle stiffness. Stiffness in intrafusal fibres is likely to follow a similar pattern to that in extrafusal fibres, leading to changes in stretch responsiveness of muscle spindles and consequently in the reflex EMG. It is concluded that the changes in stiffness and accompanying reflexes observed in this study are likely to be seen, at least under some conditions, in normal movements.     

Dystrophia myotonica: A model of combined neural and myopathic muscle atrophy

Reports on clinical, electrophysiological and histological studies in dystrophia myotonica have shown that the peripheral nerves are usually not intact. In a few patients the neuropathy exceeds the myopathy. On the basis of these findings some authors believe that muscle changes in dystrophia myotonica are entirely due to the nerve lesions. However, despite the commonly found evidence of neuropathy, electromyographic and muscle biopsy findings are reported usually as “myopathic”. Furthermore, clinical and laboratory findings indicate that the degree of muscle atrophy and peripheral nerve changes are unrelated. This report attempts to explain the discrepancies by suggesting that the “myopathic” and “neuropathic” changes in the muscle fibres in dystrophia myotonica are independent processes.     

Skeletal muscle response to tenotomy

Tenotomy is a commonly encountered clinical entity, whether traumatic or iatrogenic. This article reviews the response of skeletal muscle to tenotomy. The changes are subdivided into molecular, architectural, and functional categories. Architectural disruption of the muscle includes myofiber disorganization, central core necrosis, Z-line streaming, fibrosis of fibers and Golgi tendon organs, changes in sarcomere number, and alterations in the number of membrane particles. Molecular changes include transient changes in myosin heavy chain composition and expression of neural cell adhesion molecule (NCAM). Functionally, tenotomized muscle produces decreased maximum tetanic and twitch tension. Alterations in normal skeletal muscle structure and function are clinically applicable to the understanding of pathological states that follow tendon rupture and iatrogenic tenotomy.     

Studies on skeletal muscle biopsies in endemic skeletal fluorosis

Neurological manifestations of skeletal fluorosis have been attributed to compressive radiculomyelopathy. Experimental fluorosis has shown evidence of myopathic changes. Data on human muscle pathology is very scanty. This study included 22 patients with established osteofluorosis. 16 of them showed only EMG changes of neurogenic muscle disease. Histochemistry and histopathology of muscle biopsies showed features of muscle atrophy, evidenced by 'type I' atrophy and 'type I' grouping. No myopathic changes were observed. It may be concluded that the primary changes are related to the nerve, with muscle being affected secondarily. There was no evidence of any primary muscle pathology due to fluorosis.     

Changes in fusimotor outflow during vibration-induced contraction of triceps surae muscles in decerebrate cats

Changes in fusimotor outflow in medial gastrocnemius and lateral gastrocnemius plus soleus nerves were investigated during vibration-induced contraction of triceps surae muscles in decerebrate cats. A sustained increase in spike occurrence appeared in 33 of 58 investigated neurons, and a decrease in 13. Transient changes of an opposite sign occurred in 19 excited and 6 inhibited fusimotor neurons during the rising phase of reflex muscle contraction. The later changes appeared coincidently with silence in the electromyogram. Thus the discharge of one-third of the examined fusimotor population directed to the triceps surae muscles was modulated parallelly with that of the skeletomotor neurons. It is supposed that the changes in fusimotor spike occurrence during the rising phase of reflex muscle tension are induced mainly by changes in afferent input from muscle spindle primary endings and/or Golgi tendon organs. We could not ascertain whether the different responses (excitation vs inhibition) are related to fusimotor type or to changes in transmission through the reflex pathways. The possible influence of the changes in fusimotor outflow on muscle spindle pause and the silent period in skeletomotor discharge at the beginning of reflex muscle contraction induced by vibration is considered.     

AAEM case report #22: polymyositis

Polymyositis usually presents with progressive proximal muscle weakness, increased serum levels of muscle enzymes, inflammatory changes on muscle biopsy, and characteristic electromyographic (EMG) abnormalities. Motor unit action potential (MUAP) changes of configuration, duration, and amplitude are the most frequently observed EMG abnormality. Fibrillation potentials are commonly seen and tend to reflect active disease, diminishing after successful medical management or disease regression. Other muscle diseases can present with similar electromyographic abnormalities, thereby necessitating muscle biopsy for definitive diagnosis.     

Degenerative changes at the neuromuscular junctions of red, white and intermediate muscle fibers. Part 1. Response to short stump nerve section

Degeneration at the neuromuscular function following cutting the phrenic nerve at the 9th intercostal space differs in red, white and intermediate skeletal muscle fibers. The ultrastructure of the nerve terminal and the muscle fiber between 12 hours and 21 days following denervation suggests that lack of neurotrophic influences results in responses specific for each fiber type. Degeneration of axon ends is rapid and by 2 days axon terminals are missing from the end-plate areas of all 3 fiber types. Schwann cells "engulf" degenerating axon terminals and eventually replace them in the primary clefts. Schwann cells display specific morphological changes directly related to axonal degeneration. In all instances axon terminal degeneration precedes muscle fiber degeneration. Synaptic cleft changes are similar for all types of muscle fibers. Primary cleft structure appears to be dependent upon neurotrophic influence, whereas secondary cleft structure is relatively unaffected by denervation. Initial changes in subsynpatic regions of muscle fibers include focal loss of sarcomere alignment and skewing of the Z lines. By 21 days myofibrillar disorganization appears most severe in white fibers and least in red muscle fibers. The rate and degree of degeneration of the axon terminal and subjacent muscle fiber are different for each of the 3 muscle fiber types.     

Mast cells in neuromuscular diseases

The lectin Dolichos biflorus agglutinin has been used to identify mast cells in normal skeletal muscle and to investigate changes in their number in a wide range of human neuromuscular diseases and in rat muscle damaged by the local anaesthetic bupivacaine. Few mast cells were found in the perimysium of normal skeletal muscle but numbers were increased in human muscle biopsies which showed necrosis and regeneration of fibrosis. In bupivacaine-induced muscle damage, increased mast cell counts occurred during the necrotic phase and particularly during the phase of active regeneration. In addition, increased numbers of mast cells were observed in the underlying histologically normal muscle. These results show that mast cells are influenced by pathological changes in skeletal muscle and, in view of the known functions of mast cells in other tissues, it is possible that they are capable of modulating disease processes in muscle.