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Biomedical subjects

J A Faulkner

Publications and source records attributed to J A Faulkner.

At least 109 records · Page 6Linked to original sources

Temperature-dependent physiological stability of rat skeletal muscle in vitro.

Stability of rat skeletal muscle contractile properties with time in vitro as a function of incubation temperature was characterized. Female Sprague-Dawley rats (8 wk, 148 g) were anesthetized with pentobarbital sodium (40 mg/kg, ip). Intact soleus (SOL) and extensor digitorum longus (EDL) muscles of 70- to 90-mg mass were removed and studied at incubation temperatures of 20, 25, 30, 35, and 40 degrees C. The average muscle thickness was 2.0 mm. Each muscle was studied at one temperature only. At 5, 15, 30, 45, and 60 min following immersion in an oxygenated Krebs-Ringer bicarbonate solution, isometric contractile properties were measured. Peak twitch tension, maximum tetanic tension, and rate of tension development of both SOL and EDL muscles were stable with time at 20 and 25 degrees C but decreased with time as a function of bath temperature above 25 degrees C. The calculated critical radius for O2 diffusion declined from 1.19 mm at 20 degrees C to 0.51 mm at 40 degrees C. For SOL and EDL muscles incubated at 25 degrees C, the histochemical demonstration of glycogen content was similar to that of fresh muscles, whereas muscles incubated at 40 degrees C showed staining for glycogen only in peripheral fibers. Observed and calculated results both infer a progressively larger hypoxic core at incubation temperatures above 25 degrees C.

Animals↗

Single motor unit and fiber action potentials during fatigue.

Muscle fatigue is defined as a loss of tension development during constant stimulation. Although the relationship is not well documented, muscle fatigue has been inferred from electromyogram (EMG) signals. The purpose of this study was to determine the relationship between the amplitude and duration of single motor unit action potentials (MUAPs) and the loss of tension development (fatigue) in the medial gastrocnemius muscles of cats. Single motor units were fatigued by continuous stimulation at 10 or 80 Hz or with trains of 40-Hz stimuli. When motor units were stimulated at 10 Hz and with trains at 40 Hz (low frequency), tension declined and remained depressed during recovery. The changes in the MUAP correlated poorly with changes in tension. During and after stimulation at 80 Hz (high frequency), changes in the amplitude and duration of MUAPs correlated highly with changes in tension development. Since the EMG signal is dependent on a summation and cancellation of individual MUAPs, the EMG provides a reasonable estimate of high-frequency fatigue but an unreliable measure of low-frequency fatigue.

Action Potentials↗

Injury to skeletal muscle fibers of mice following lengthening contractions.

We tested the hypothesis that lengthening contractions result in greater injury to skeletal muscle fibers than isometric or shortening contractions. Mice were anesthetized with pentobarbital sodium and secured to a platform maintained at 37 degrees C. The distal tendon of the extensor digitorum longus muscle was attached to a servomotor. A protocol consisting of isometric, shortening, or lengthening contractions was performed. After the contraction protocol the distal tendon was reattached, incisions were closed, and the mice were allowed to recover. The muscles were removed after 1-30 days, and maximum isometric force (Po) was measured in vitro at 37 degrees C. Three days after isometric and shortening contractions and sham operations, histological appearance was not different from control and Po was 80% of the control value. Three days after lengthening contractions, histological sections showed that 37 +/- 4% of muscle fibers degenerated and Po was 22 +/- 3% of the control value. Muscle regeneration, first seen at 4 days, was nearly complete by 30 days, when Po was 84 +/- 3% of the control value. We conclude that, with the protocol used, lengthening, but not isometric or shortening contractions, caused significant injury to muscle fibers.

Animals↗

Chronic electrical stimulation of nongrafted and grafted skeletal muscles in rats.

Our purpose was to determine the effects of chronic electrical stimulation on the structure and function of neve-intact grafts in rats. Fourteen days after grafting, extensor digitorum longus (EDL) grafts (n = 6) and nongrafted EDL muscles (n = 4) were stimulated 8 h/day at 10 Hz for 26 days. Measurements were made subsequently of cytochrome c concentration, capillary density, contraction and relaxation times, developed tension, and the resistance to fatigue. Compared with contralateral nonstimulated grafts, chronically stimulated grafts demonstrated a 65% greater cytochrome c concentration, 45% greater number of capillaries per millimeter squared, 30% greater resistance to fatigue, 35% longer contraction time, 30% longer relaxation time, and 30% lower maximum tetanic tension. The differences that resulted from the stimulation of nongrafted EDL muscles were significant but of less magnitude. Chronic stimulation of 8 h/day provided a mixed stimulus for adaptation that enhanced the metabolic and endurance characteristics of fibers in muscles and grafts, but decreased the total fiber cross-sectional area and development of force.

Adaptation, Physiological↗

Abnormal neuromuscular transmission in an infantile myasthenic syndrome.

A term infant required intubation for respiratory depression. Examination revealed hypotonia and areflexia with intact extraocular movements. Electrodiagnostic studies demonstrated defective neuromuscular transmission characterized by borderline low motor evoked amplitudes, profound decremental responses at all stimulation rates, and moderate facilitation (50 to 740%) 15 seconds after 5 seconds of 50 Hz stimulation. Repetitive muscle action potential responses were not recorded following stimulation of nerves by single shocks. Sensory evoked responses and needle electromyographic findings were normal, as were acetylcholine receptor antibody levels. Results of muscle histochemical analyses, including acetylcholinesterase stains, were normal. End-plate histometric analyses demonstrated only a slight reduction in mean synaptic vesicle diameter compared with that in an adult control subject. In vitro muscle contractile properties, stimulating the muscle directly, were normal. Anticholinesterase medications were ineffective. Guanidine produced clinical deterioration. The amplitude of motor evoked responses progressively declined, whereas the percentage of decrement and amount of post-tetanic facilitation increased. Although the nature of the transmission defect was not identified, the data are consistent with abnormal acetylcholine resynthesis, mobilization, or storage without abnormality of release or receptors.

Acetylcholinesterase↗

Growth of regenerating skeletal muscle fibers in cats.

Extensor digitorum longus (EDL) muscles of cats were grafted heterotopically or orthotopically, and either with or without prior denervation. The autografted muscles were studied at times from 4 to 518 days after grafting. Muscle weight, fiber cross-sectional area, and ultrastructural, histochemical, and biochemical characteristics of regenerating muscle fibers were determined. Prior denervation reduced the mass of muscle at the time of grafting, but had no significant effect on the characteristics of the regenerating muscles. Orthotopic and heterotopic autografts achieved similar recovery of structure. Mean fiber area reached control values. Differentiation into fiber types occurred, but compared to control muscles, autografts had fewer Type I and Type IIA fibers. Electron microscopic analysis of regenerating muscle fibers revealed centrally located nuclei, but otherwise normal ultrastructure. The bimodal distribution of Z-band width was consistent with differentiation into fiber types. Mean data of some morphological variables did not stabilize.

Animals↗

Motor unit function in skeletal muscle autografts of rats.

Standard and nerve-intact grafts of the extensor digitorum longus (EDL) muscles of rats do not fully recover control values for maximum tetanic tension (Po). We compared the physiologic properties of motor units from standard and nerve-intact EDL grafts of rats with those of control EDL muscles. Standard grafts were completely removed and replaced in their original site. For nerve-intact grafts all physical connections were severed except for the nerve. Isometric contractile properties of whole muscles and single motor units were measured in situ 75 and 50 days after surgery for standard and nerve-intact grafts, respectively. Motor units from both types of grafts showed a mean and distribution for time-to-peak twitch tension (TPT) not different from control motor units. The absolute Po of nerve-intact grafts showed a greater recovery than the standard grafts, but was still significantly lower than the control value. The average decrease in the Po of motor units from nerve-intact grafts of 16% was not different from the decrease in the Po of the total EDL graft which suggests no loss of motor units in nerve-intact grafts. In standard grafts, the 57% decrease in Po for the whole muscle was attributable to a 20% decrease in the average tension development per motor unit and a 45% decrease in the number of motor units. These differences suggest a more complete reinnervation of the nerve-intact grafts than standard grafts.

Animals↗

Clinical conference in pulmonary disease. Factors influencing upper airway closure.

The factors which produce closure of the upper airway (UAW) in patients with the sleep apnea syndrome are still poorly understood. A distinction should be made between the factors which induce closure and those which reopen the UAW. Neurologic factors include arousal phenomena, the magnitude and timing of various motor outputs, and postsynaptic inhibition. Mechanical factors include the anatomy of the UAW, especially that above the tongue, the position of the neck and jaw, and mucosal adherence once occlusion has occurred. Muscle factors include the type of myosin isozyme, the forces generated by the large number of UAW muscles and the diaphragm, and the possibility of high-frequency fatigue occurring during occlusion. Hypoxia and acidosis probably play a critical role in making the UAW less stable. Currently, the best method to prevent UAW closure is by nasal CPAP. Patients with life-threatening arrhythmias due to sleep apnea should have a tracheostomy. The role of drugs is controversial. Respiratory or muscle stimulants should probably be avoided; oxygen, medroxyprogesterone, and protriptyline may be useful adjuncts.

Humans↗

Characteristics of cat skeletal muscles grafted with intact nerves or with anastomosed nerves.

Grafting of 3-g extensor digitorum longus (EDL) muscles of cats may be made with (i) severence of the nerve with spontaneous reinnervation, termed standard grafts (ii) severence of the nerve with reinnervation facilitated by anastomosis of the nerve, termed nerve-anastomosed grafts; and (iii) preservation of the nerve, termed nerve-intact grafts. In previous studies, standard grafts developed a maximum isometric tetanic tension (P0) that was 22% of the value for control EDL muscles. We hypothesized that the low values of P0 resulted from incomplete reinnervation of muscle fibers. To test this hypothesis, EDL muscles were grafted in cats with nerves intact and with nerves anastomosed. In standard grafts differences were observed in both structure and function at 120 compared with 240 days after grafting. Characteristics of the nerve-intact and nerve-anastomosed grafts did not change significantly between 120 and 240 days and the data were pooled for comparisons with control EDL muscles. Nerve-anastomosed and nerve-intact grafts developed P0 values that were 34 and 64% of the control values, respectively. Nerve-intact grafts had a mass and fiber cross-sectional area not different from control EDL muscles. Compared with control values, all grafts had fewer fibers, more connective tissue, lower absolute and normalized P0, reduced capillary density, and increased fatigability. The greater P0 of nerve-intact compared with standard and nerve-anastomosed grafts supported our hypothesis that the degree of reinnervation is a factor that limits graft development. The presence of a necrotic core and the low tension development of even the nerve-intact grafts suggested that revascularization is a significant limitation as well.

Animals↗

Revascularization of skeletal muscle transplanted into the hamster cheek pouch: intravital and light microscopy.

Small fiber bundles from the extensor digitorum longus (EDL) muscle were transplanted into the hamster cheek pouch to observe the process of revascularization. We tested the hypothesis that blood vessels of a graft degenerate and that revascularization results from the ingrowth of blood vessels from the cheek pouch into the graft. Degeneration and regeneration of muscle fibers followed a pattern similar to that reported for autografts of whole muscles in rats. Blood vessels in the graft that were adjacent to vascularized host tissue survived. At 1 day, surviving blood vessels in the graft had normal structure but erythrocytes were packed tightly in the lumen. At 2 days, sprouts from surviving graft vessels had grown into the cheek pouch. Between 2 and 2.5 days, anastomoses of blood vessels from the graft with those of the cheek pouch reestablished circulation. After circulation was established, the blood vessels contained well-spaced erythrocytes. By 3 days, blood vessels which increased in number and diameter throughout the graft occupied 40-60% of the graft. Over the next 24 hr, blood vessels in the graft regressed toward the control value. We conclude that blood vessels in muscle grafts in the cheek pouch survive transplantation, and that circulation in grafts is reestablished by the anastomoses of blood vessel sprouts from the graft with the blood vessels of the host.

Animals↗

Revascularization of skeletal muscle transplanted into the hamster cheek pouch: electron microscopy.

Revascularization of bundles of skeletal muscle fibers transplanted into the cheek pouch of hamsters was examined previously by intravital and light microscopy. Some blood vessels survived the ischemia of transplantation and revascularization resulted from the growth of surviving vessels. We have now examined the cellular events of graft revascularization by electron microscopy (EM). Approximately 20 skeletal muscle fibers were autografted into the hamster cheek pouch. Segments of the graft were prepared for EM from 0.5 to 5 days after transplantation. At 0.5 day, the endothelial cells of surviving blood vessels had short processes extending from them. By 1.0 day, some endothelial cells had separated. At 1.5 days, many endothelial cells were undergoing mitosis. Blood vessels at 2 to 2.5 days were of narrow diameter and most were densely packed with erythrocytes. Circulation was reestablished between 2.5 and 3 days. The fine structure of the blood vessels changed little after 3 days except for a decrease in the number of vesicles in the endothelial cell cytoplasm and the formation of normal endothelial cell injections. After 5 days, blood vessels were larger in diameter, but otherwise similar to control capillaries. We conclude that, despite the initial absence of circulation, surviving blood vessels underwent a rapid, orderly sequence of growth.

Animals↗

Length-tension relationship of mammalian diaphragm muscles.

We tested the hypothesis that the length-tension relationship of diaphragm muscle is different from that of other skeletal muscle. Isometric contractile properties of small bundles of diaphragm muscle from rats, cats, rhesus monkeys, dogs, and pigs were measured in vitro at 37 degrees C. For diaphragm muscles from all species, twitch contraction and relaxation times and histochemical myofibrillar ATPase indicated a mixture of fast and slow muscle fiber types. By use of tetanic stimulations of 400-ms duration, isometric tension was recorded from bundles of diaphragm muscle at lengths between 50 and 130% of the muscle fiber length at which active tension was maximal (Lo). At lengths below 60-70% of Lo, tetanic tension did not reach a plateau within 400 ms. With longer stimulation durations, active tension could be recorded between 30 and 40% of Lo. The length-tension curves for bundles of fibers from the diaphragm muscle were not different among species and were consistent with results reported for intact limb muscles.

Animals↗

The regeneration of skeletal muscle fibers following injury: a review.

Regeneration is a unique adaptation of skeletal muscle that occurs in response to injury. Following direct trauma or disease, regeneration results in restoration, to some degree, of the original structure and function of the muscle. Our purpose is to summarize the main features of the regeneration of skeletal muscle fibers and entire muscles with an emphasis on aspects of regeneration that may be important to the understanding and treatment of sports injuries. The regeneration of skeletal muscle is compared structurally and functionally with its embryonic development. The free muscle graft is used as a model to illustrate the integration of regenerating muscle with the rest of the body. Finally, the breakdown and regeneration of skeletal muscle fibers are discussed in relation to local anesthetics, sports injuries, and disease.

Anesthetics, Local↗

Translocation of the temporalis muscle for treatment of facial paralysis.

Our purpose was to characterize in the rhesus monkey the structure and function of vascularized temporalis muscle flaps innervated by the facial nerve after translocation into the site of the denervated zygomaticus muscle. Animals were killed at 28 to 120 days following translocation. Control data were obtained from the contralateral side. Twenty-eight days after translocation, the time to reach peak twitch tension and one-half relaxation time were 170% of control zygomaticus muscle. Contraction times decreased with time and reached control values by 100 days. Absolute isometric tetanic tension was not different between the flap (4.29 +/- 1.28 newtons; X +/- SEM) and control zygomaticus (3.95 +/- 0.80 newtons). Succinate oxidase activity of the flap decreased from 279 +/- 18 nl O2/mg protein/min to control zygomaticus values (98 +/- 18) by 110 days. The type 1 fiber cross-sectional area of the flap was 52% of control temporalis muscle and 150% of control zygomaticus muscle (P less than 0.05). The temporalis flap demonstrated viable structure and function and appeared useful in facial movements.

Animals↗

Relationship among fibre type, myosin ATPase activity and contractile properties.

At least two types of skeletal muscle myosin have been described which differ in ATPase activity and stability in alkaline or acidic media. Differences in ATPase characteristics distinguish Type I and Type II fibres histochemically. In this study, ATPase activity of myosin from muscles of several species with known histochemical and contractile properties has been determined to test the hypothesis that (1) myosin ATPase activity, (2) histochemical determination of fibre types and (3) maximum shortening velocity, all provide equivalent estimates of contractile properties in muscles of mixed fibre types. Maximum shortening velocity appears to be proportional to ATPase activity as expected from previous reports by Barany. However, both myosin ATPase and the maximum shortening velocity exhibit curvilinear relationships to the fraction of cross-sectional area occupied by Type II fibres. Therefore, we reject the hypothesis and conclude that histochemically determined myofibrillar ATPase does not accurately reflect the intrinsic ATPase activity or shortening velocity in muscles of mixed fibre types. Our data are consistent with the presence of more than two myosin isozymes or with a mixture of isozymes within single muscle fibres.

Adenosine Triphosphatases↗

Contractile properties of the muscles of mastication of rhesus monkeys (Macaca mulatta) following increase in muscle length.

The hypothesis was tested that increasing the resting length of the masseter and temporalis muscles by a bite-opening appliance with or without detachment and re-attachment of the masseter would not affect the contractile properties of these muscles. Appliances opened the bite of 10 adult female monkeys 20 mm. Five received the appliance alone (Group A); five received the appliance and in addition the masseter was detached and re-attached (Group ADR). Comparisons were made 48 weeks later. Small bundles of fibres were excised from the masseter and temporalis muscles of experimental animals and from 8 control animals. Isometric and isotonic contractile properties were measured in vitro and fibre classification and fibre areas were determined histochemically. No significant differences were observed within either masseter or temporalis muscles between animals in Groups A and ADR. In both groups, the bundles of fibres from the masseter had prolonged contraction and relaxation times compared to control masseter muscles but no difference was observed in the percentage of Type II fibres. As detachment and re-attachment had no significant effect on morphological or physiological characteristics, other than those due to lengthening, this procedure may be useful in decreasing the passive tension induced when orthognathic surgery increases muscle length. The significant prolongation of the contractile response of the masseter is similar to the adaptation induced by long-term stimulation at low frequency.

Adaptation, Physiological↗

Contractile properties of bundles of fiber segments from skeletal muscles.

Our purpose was to determine whether contractile properties of bundles of skeletal muscle fiber segments were significantly different from those of bundles of intact fibers. In frog muscles, the only difference between the contractile properties of fiber segments and intact fibers was a lower maximum velocity of shortening (Vo) for the fiber segments. In mammalian muscles, the contraction time (TPT), relaxation time (RT1/2), and maximum tetanus tension (Po) of bundles of fiber segments were not different from those of intact fibers, but the rate of tension development (dP/dt), twitch-to-tetanus ratio (Pt/Po) and Vo were lower. The lower dP/dt and Pt/Po resulted from increased compliance due to damaged sarcomeres near cut ends. Within 4-9 mm of a cut end, membrane potentials were less than control values, and sarcomeres lengthened during a fixed-end contraction. after the length of fiber segments was corrected for the exact portion that was not shortening, the Vo of fiber segments was not different from that of intact fibers. We conclude that valid estimates of contractile properties can be obtained from bundles of skeletal muscle fiber segments.

Action Potentials↗