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PubMed1989

Adynamia episodica hereditaria: what causes the weakness?

The cause of weakness was investigated in a patient with adynamia episodica hereditaria without myotonia. A pattern of exercise and rest produced episodes of hyperkalemic periodic paralysis. In addition, local muscle weakness was induced by forearm cooling. Investigations on isolated intercostal muscle demonstrated that a high potassium concentration in the bathing solution triggered a noninactivating membrane current causing depolarization of the muscle fibers. This current was carried by sodium as it could be inhibited by tetrodotoxin. The abnormal sodium conductance led to an increase of sodium within the fibers. This was demonstrated directly by intracellular recordings. Weakness induced by rest after exercise and cold-induced weakness appeared to have different pathomechanisms. In the cold, the muscle fibers retained a normal resting potential, but their excitability was reduced and their mechanical threshold was increased. These findings also provide evidence that the mechanism of cold-induced weakness in adynamia episodica is distinctly different from the cold-induced weakness that occurs in paramyotonia congenita.

Adult↗
PubMed1986

How is ventilation maintained in the presence of the muscle relaxant, dantrolene sodium? A study in the anaesthetized rat.

The effects of intravenous injection of the muscle relaxant dantrolene sodium on ventilation, integrated EMG of external intercostal muscles and motor unit discharge in these muscles were measured in anaesthetized rats. Dantrolene sodium was administered in a carrier solution at pH 10. The carrier was not responsible for the effects seen on dantrolene sodium infusion. Dantrolene sodium (5 mg kg-1 body weight) reduced inspired ventilation (VI) on average from 308 +/- 106 ml min-1 (s.d., n = 8) in the control period to 247 +/- 118 ml min-1 (n = 8) after dantrolene sodium. Expired ventilation was reduced likewise from 274 +/- 132 ml min-1 (n = 8) to 229 +/- 109 ml min-1 (n = 8). These changes are significant at P less than 0.05. The integrated EMG was increased by 40.0 +/- 29.3% (n = 9), a change significant at P less than 0.001. Dantrolene sodium not only decreased the mean interspike interval of individual motor units by 16.2 +/- 11.1% (n = 13), a change significant at P less than 0.001, but also increased the duration of the burst of activity of each individual motor unit on average by 36.2 +/- 52.4% (n = 13), a change significant at P less than 0.05. The recruitment of additional motor units was also effected by dantrolene sodium. These units did not behave in any noticeably different manner from units previously active. It is concluded that the nervous system compensates for the effect of dantrolene sodium only to a limited extent by increasing the frequency of discharge of active motor units. Recruitment ofadditional motor units and increased burst duration play at least as important a role.

Anesthesia↗
PubMed1993

Disseminated malignant histiocytosis in a golden retriever: clinicopathologic, ultrastructural, and immunohistochemical findings.

Diagnosis of malignant histiocytosis (MH), a disorder characterized by systemic proliferation of morphologically atypical histiocytes and their precursors, in an 8-year-old neutered female Golden Retriever was based on light and electron microscopic and immunohistochemical findings. Clinically, the dog presented with unilateral forelimb lameness. Eight days after surgical exploration of a swollen brachium, the dog developed sudden onset of posterior paresis, fecal and urinary incontinence, and a flaccid tail. Necropsy revealed infiltrative and nodular lesions in the right forelimb and regional lymph nodes, thoracic and abdominal cavities, and lumbar epidural space. Gross lesions were not found in the lungs or integument. Histopathologic examination showed infiltrates of atypical histiocytes in skeletal muscle, joint, and regional lymph nodes of the right forelimb; intercostal muscle; lung; liver; spleen; pancreas; kidneys; and spinal dura. Most tumor infiltrates were nodular and composed of loosely aggregated cells that were 10-30 microns in diameter with abundant eosinophilic to foamy cytoplasm, had central or eccentric nuclei, and were periodic acid-Schiff negative. Many binucleated cells, multinucleated giant cells, and mitotic figures were seen. Tumor cells contained phagocytosed erythrocytes, mononuclear cells, and some leukocytes. Ultrastructural features of tumor cells included cytoplasmic lipid droplets, lysosomes, and phagolysosomes. Immunohistochemical studies on paraffin-embedded sections showed positive reactivity to human T-cell Ag (clone UCHL-1) and for lysozyme, alpha-1-antitrypsin, and cathespin B. Polyclonal intracellular immunoglobulin reactivity and lectin binding (peanut, soybean, and wheat germ agglutinins and concanavalin A) were also demonstrated. Criteria for diagnosis of malignant histiocytic tumors and differential diagnosis are discussed.

Animals↗
PubMed2003

Melanocortin-4 receptor messenger ribonucleic acid expression in rat cardiorespiratory, musculoskeletal, and integumentary systems.

We determined melanocortin-4 receptor (MC4-R) mRNA ontogeny in the rat using in situ hybridization and a rat MC4-R riboprobe and showed numerous peripheral sites of expression for MC4-R. The developing heart showed MC4-R mRNA expression as early as embryonic day (E) 14. In the lungs of E16-E20 fetuses, the cells surrounding developing bronchi expressed relatively strong in situ signal. Muscles associated with the respiratory system such as diaphragm and intercostal muscle expressed MC4-R mRNA as early as E14. Occipital and tongue muscles, in particular the genioglossus, showed diffuse signal at E15-E20. In the eye, a discrete signal was detected in an outer neuroblastic layer which may correspond to retina or extraocular muscle. Developing limb buds expressed relatively strong signal at E14, whereas skull bone and joint capsules of the paw of the forelimb showed signal at E18-E20. Using RT-PCR and ribonuclease protection assays, we determined that MC4-R mRNA is also expressed in adult rat heart, lung, kidney, and testis. The expression of the MC4-R in cardiorespiratory, musculoskeletal, and integumentary systems supports functional roles for the MC4-R in addition to its roles in appetite, weight control, and regulation of linear growth.

Animals↗
PubMedDate not supplied

[Evaluation of the pharmacological properties of a new steroid curarelike agent, RGH 1106].

Tests on cats showed the compound RGH 1106 to possess an antidepolarizing mechanism of action. The sequence of myorelaxation, arising under the effect of this agent, is characterized by relaxation in the first place of the musculus masseter, muscles of limbs, then of abdominal muscles and those of the diaphragm and, finally, of the intercostal muscles. RGH 1106 doses not possess cardiotropic m-cholinolytic action, does not exert a ganglion blocking effect, nor affects the central nervous system. It neither changes the blood supply of the myocardium and the uptake of oxygen by the latter, nor inhibits the acetylcholinesterase.

Animals↗
PubMed2001

Discharge frequencies of single motor units in human diaphragm and parasternal muscles in lying and standing.

Single motor unit discharge was measured directly in diaphragm and parasternal intercostal muscles to determine whether neural drive to human inspiratory muscles changes between lying and standing. The final discharge frequency of diaphragmatic motor units increased slightly, by 1 Hz (12%; P < 0.01), when subjects were standing [182 units, median 9.1 Hz (interquartile range 7.6-11.3 Hz)] compared with lying supine [159 units, 8.1 Hz (6.6-10.3 Hz)]. However, this increase with standing occurred in only two of six subjects, in one of whom tidal volume increased significantly during standing. Parasternal intercostal motor unit final discharge frequencies did not differ between standing [116 units, 8.0 Hz (6.6-9.6 Hz)] and lying [124 units, 8.4 Hz (7.0-10.3 Hz)]. The discharge frequencies at the onset of inspiration did not differ between lying and standing for either muscle. A larger proportion of motor units in both inspiratory muscles had postinspiratory or tonic expiratory activity for lying compared with standing (15 vs. 4%; P < 0.05). We conclude that there is no major difference in the phasic inspiratory drive to the diaphragm with the change in posture.

Diaphragm↗
PubMed1999

Pattern of expiratory muscle activation during lower thoracic spinal cord stimulation.

Large positive airway pressures (Paws) can be generated by lower thoracic spinal cord stimulation (SCS), which may be a useful method of restoring cough in spinal cord-injured patients. Optimal electrode placement, however, requires an assessment of the pattern of current spread during SCS. Studies were performed in anesthetized dogs to assess the pattern of expiratory muscle recruitment during SCS applied at different spinal cord levels. A multicontact stimulating electrode was positioned over the surface of the lower thoracic and upper lumbar spinal cord. Recording electromyographic electrodes were placed at several locations in the abdominal and internal intercostal muscles. SCS was applied at each lead, in separate trials, with single shocks of 0.2-ms duration. The intensity of stimulation was adjusted to determine the threshold for development of the compound action potential at each electrode lead. The values of current threshold for activation of each muscle formed parabolas with minimum values at specific spinal root levels. The slopes of the parabolas were relatively steep, indicating that the threshold for muscle activation increases rapidly at more cephalad and caudal sites. These results were compared with the effectiveness of SCS (50 Hz; train duration, 1-2 s) at different spinal cord levels to produce changes in Paw. Stimulation at the T9 and T10 spinal cord level resulted in the largest positive Paws with a single lead. At these sites, threshold values for activation of the internal intercostal (7-11th interspaces) upper portions of external oblique, rectus abdominis, and transversus abdominis were near their minimum. Threshold values for activation of the caudal portions of the abdominal muscles were high (>50 mA). Our results indicate that 1) activation of the more cephalad portions of the abdominal muscles is more important than activation of caudal regions in the generation of positive Paws and 2) it is not possible to achieve complete activation of the expiratory muscles with a single electrode lead by using modest current levels. In support of this latter conclusion, a two-electrode lead system results in more uniform expiratory muscle activation and significantly greater changes in Paw.

Action Potentials↗
PubMed1999

Determinants of rib motion in flail chest.

We have previously developed a canine model of isolated flail chest to assess the effects of this condition on the mechanics of breathing, and these studies have led to the conclusion that the respiratory displacement of the fractured ribs is primarily determined by the fall in pleural pressure (Delta Ppl) and the action of the parasternal intercostal muscles. The present studies were designed to test the validity of this conclusion. A flail was induced in six supine anesthetized animals by fracturing both dorsally and ventrally the second to fifth ribs on the right side of the chest, after which the phrenic nerve roots were bilaterally sectioned in the neck. Sectioning the phrenic nerves caused a 34% decrease in Delta Ppl, associated with a 39% increase in parasternal intercostal inspiratory EMG activity (p < 0.05), and resulted in a marked reduction in the inspiratory inward displacement of the ribs. In three animals, the inward rib displacement was even reversed into a small outward displacement. When the airway was then occluded at end-expiration to increase Delta Ppl during the subsequent inspiration, all animals again showed a clear-cut inward rib displacement. These observations therefore confirm that in dogs with flail chest, the inspiratory displacement of the fractured ribs is set by the balance between the force related to pleural pressure and that generated by the parasternal intercostals. These observations also point to the critical importance of the pattern of inspiratory muscle activation in determining the magnitude of rib cage paradox in such patients.

Animals↗
PubMed1981

Tonic inspiratory muscle activity as a cause of hyperinflation in asthma.

We studied tonic activity of the inspiratory muscles during exacerbation of asthma in five female and two male patients. Exacerbation was provoked by withholding bronchodilatory medication for 12 h prior to the study. Thoracic gas volume (TGV) at the end of resting expiration was determined before and after albuterol (salbutamol) inhalation with a body plethysmograph. Intercostal muscle electromyogram (EMG) was recorded with surface electrodes and diaphragmatic EMG with esophageal electrodes. Tonic activity was defined as electrical activity in the EMG present throughout expiration. After salbutamol the TGV decreased 13.4 +/- 2.9% (mean +/- SE) (P less than 0.01). This decrease in TGV was accompanied by a proportional reduction in tonic intercostal (r = 0.78, P less than 0.05) and diaphragmatic activity (r = 0.84, P less than 0.05). These findings suggest that the hyperinflation present during exacerbation of asthma is at least in part due to active inspiratory muscle activity present throughout expiration.

Adult↗
PubMed1995

Thoracic spinal nerve and root conduction: a magnetic stimulation study.

We describe a technique of magnetic coil (MC) stimulation of the thoracic spinal nerves and roots in 12 normal subjects and a patient with diabetes mellitus. We kept the MC flat against the vertebral column in the midline over T-7, T-8, and T-9 spinous processes and obtained compound muscle action potentials from the upper rectus abdominis, external oblique, and intercostal muscles. We obtained mean latencies to these muscles after stimulation in the posterior axillary line. We noted that the onset latencies remained fixed despite increasing the intensity of stimulation from 30% to 100% and on moving the coil up to 3 cm lateral to the spinous processes suggesting that the stimulation of the fastest conducting fibers was occurring at a fixed site, most likely at the intervertebral foramina. Prolonged latencies in the diabetic patient confirmed the diagnosis of radiculoneuropathy.

Adult↗
PubMed2003

Effects of inflation on the coupling between the ribs and the lung in dogs.

The coupling between the ribs and the lung in dogs increases with increasing rib number in the cranial part of the rib cage and then decreases markedly in the caudal part. The hypothesis was raised that this non-uniformity is primarily related to differences between the areas of the lung subtended by the different ribs, and in the current study we tested this idea by assessing the effects of passive lung inflation. Thus, by causing a descent of the diaphragm, inflation would expand the area of the lung subtended by the caudal ribs and improve the coupling between these ribs and the lung. The axial displacements of the ribs and the changes in airway opening pressure (DeltaP(ao)) were measured in anaesthetized, pancuronium-treated, supine dogs while loads were applied in the cranial direction to individual rib pairs at functional residual capacity (FRC) and after passive inflation to 10 and 20 cm H(2)O transrespiratory pressure. In agreement with the hypothesis, inflation caused an increase in DeltaP(ao) for ribs 9 and 10. The most prominent alteration, however, was a marked decrease in DeltaP(ao) for ribs 2-8; at 20 cm H(2)O, DeltaP(ao) for these ribs was only 30% of the value at FRC. Additional measurements indicated that this decrease in DeltaP(ao) results partly from the increase in diaphragmatic compliance but mostly from the reduction in outward rib displacement. This alteration in the pattern of rib motion should add to the decrease in muscle length to reduce the lung expanding action of the external intercostal muscles at high lung volumes.

Abdomen↗
PubMed1989

Congenital paucity of secondary synaptic clefts (CPSC) syndrome in 2 adult sibs.

We studied 2 elderly sibs with a congenital form of myasthenia who had ptosis since early childhood. The extraocular muscles were weak and the proximal limb muscles became slowly weaker throughout life. Laboratory investigations of biopsies of intercostal muscle from these patients showed the following abnormalities: the amplitude of miniature end-plate potentials was small and the binding of 125I-alpha-bungarotoxin at the end-plate area was reduced, suggesting a considerable reduction of acetylcholine receptors (AChRs). Secondary synaptic clefts were scarce, whereas the number of end-plates per muscle fiber was increased. There was no indication of impaired transmitter release as the quantal content was within the range of controls. We conclude that these patients suffered from the congenital paucity of secondary synaptic clefts (CPSC) syndrome, described recently in 2 cases of myasthenic children, and suggest that the CPSC syndrome is a developmental disorder in which a deficiency of AChRs may be caused by a decreased clustering or insertion of AChRs. The increased number of end-plates per muscle fiber in both patients could serve as a compensatory mechanism.

Bungarotoxins↗
PubMed2001

[Skeletal muscle pathology of chronic graft versus host disease accompanied with myositis, affecting predominantly respiratory and distal muscles, and hemosiderosis].

We report the muscle pathology in a 43-year-old woman who died of chronic graft versus host disease (GVHD) complicated by myositis and systemic transfusional hemosiderosis, after an allogeneic bone marrow transplantation and a donor leukocyte transfusion for acute myelogenous leukemia. Despite cyclosporin A treatment, fatal ventilatory failure progressed while she was still ambulant. Autopsy revealed the presence of chronic GVHD mildly involving the liver, skin, pericardium, pancreas, and salivary glands, in addition to skeletal muscles. Myopathic changes with mild inflammation and prominent iron deposition were found in the tibialis anterior muscle and, to a lesser degree, in the diaphragm and the intercostal muscle. There were iron deposits in both macrophages and sarcoplasm in the tibialis anterior. The iliopsoas and pectoralis major muscles showed prominent type 2 fiber atrophy; inflammation and iron deposition were minimal in the iliopsoas, but none in the pectoralis. Although we ascribed respiratory failure largely to GVHD myositis, weakness of the lower leg appeared to be aggravated by iron deposition superimposing the underlying GVHD myositis.

Adult↗
PubMed1990

[Control mechanism of the respiratory muscle during forced expiration].

Control mechanism of the respiratory muscle during forced expiration was analyzed. Respiratory flow. EMG of the intercostal muscle (IC), external oblique (EO) and internal oblique (IO) abdominal muscle were analyzed in eleven healthy volunteers. The pattern of EMG activity during forced expiration could be classified according to its shape i.e., taper- or hill-shaped. The taper shape was found in 7 of 9 subjects for IC and in 8 of 11 subjects for EO. The hill shape was found in 4 of 6 subjects for 10. Twelve consecutive trials without intervals did not alter the pattern of flow-volume curve, activity of respiratory muscle and frequency component (i.e., H/L ratio). When the expiratory circuit was obstructed for a short interval during forced expiration, the rise in pleural pressure was slight but that in oral pressure was large, and the activity of respiratory muscle decreased for a short period. The latencies from the onset of expiratory circuit obstruction to the reduction in EMG activity were 61.5-100 msec. In IC, 61.5-106.5 msec in EO. and 58.0-92.3 msec in 10. These values did not differ significantly any given subject. Airway anesthesia with xylocaine did not alter latency. In conclusion, the pattern of respiratory muscle activity for forced expiration is predetermined and is specific for each muscle. Negative feedback from receptors in airway or in respiratory muscle was strongly suggested. Repetitive trials up to twenty times did not cause respiratory muscle fatigue.

Adult↗
PubMedDate not supplied

Effect of nicardipine on the isolated uterus and other smooth muscles of the rat.

Increasing concentrations of nicardipine were found to inhibit various types of muscular activation (electrical stimulation, acetylcholine, oxytocin, potassium chloride), as well as the spontaneous rhythmic activity of the isolated rat uterus. The degree of the inhibitory effect of nicardipine depends on the type of activation. Nicardipine showed an exceptionally high efficacy in inhibiting contractions induced by electrical stimulation and of spontaneous rhythmic activity. For inhibition of these contractions, even femtomolar concentrations of nicardipine were sufficient. The relaxant effect of nicardipine depends on the concentration of extracellular calcium and the temperature of the medium. Nicardipine shows high selectivity for the uterine smooth muscle because even in very high concentrations it exerts an insignificant relaxation of the other isolated smooth muscles (oesophagus, bladder, colon descendens) as well as of the isolated intercostal muscle of the rat. Our experiments indicate that nicardipine might have a role in the therapy of premature delivery and abortion because of its great selectivity for the uterine smooth muscle. Nicardipine causes a stronger inhibition of the tonic than of the phasic component of contraction induced by potassium chloride and oxytocin. These findings suggest that potassium chloride and oxytocin act through various populations of calcium channels.

Animals↗
PubMed1971

Miniature end-plate potentials in neuromuscular disease: an electrophysiological investigation of motor-point muscle biopsies.

A technique is described for the electrophysiological investigation of motor-point muscle biopsies and the data from 13 biopsies are reported. It was not possible to demonstrate any influence of disease upon the resting potentials of individual biopsies, but resting potentials were in general lower than those reported for limb muscle in vivo. Miniature end-plate potentials (MEPPs) in clinically normal limb muscle were smaller and more frequent than those previously described in isolated intercostal muscle. In two biopsies from myasthenic patients very small amplitude MEPPs were recorded and, in one of these, MEPPs were also of very low frequency, possibly associated with the severity of the disease. The frequency and amplitude of MEPPs in muscular dystrophy and neurogenic disease have been reported and the possible significance of these findings is discussed.

Adolescent↗
PubMed1992

Electrical activation of expiratory muscles increases with time in pentobarbital-anesthetized dogs.

Although the pentobarbital-anesthetized dog is often used as a model in studies of respiratory muscle activity during spontaneous breathing, there is no information regarding the stability of the pattern of breathing of this model over time. The electromyograms of several inspiratory and expiratory muscle groups were measured in six dogs over a 4-h period by use of chronically implanted electrodes. Anesthesia was induced with pentobarbital sodium (25 mg/kg iv), with supplemental doses to maintain constant plasma pentobarbital concentrations. Phasic electrical activity increased over time in the triangularis sterni, transversus abdominis, and external oblique muscles (expiratory muscles). The electrical activity of the costal diaphragm, crural diaphragm, and parasternal intercostal muscles (inspiratory muscles) was unchanged. These changes in electrical activity occurred despite stable plasma levels of pentobarbital and arterial PCO2. They were associated with changes in chest wall motion and an increased tidal volume with unchanged breathing frequency. We conclude that expiratory muscle groups are selectively activated with time in pentobarbital-anesthetized dogs lying supine. Therefore the duration of anesthesia is an important variable in studies using this model.

Anesthesia↗
PubMed2005

Extended resection of lung cancer invading the left subclavian artery by using cardiopulmonary bypass.

We treated a 54-year-old man with large cell carcinoma of the left upper lobe invading the esophagus and the left subclavian artery (SCA) from its origin. The tumor was completely resected by lobectomy under cardiopulmonary bypass. The left SCA was dissected at the aortic arch and reconstructed with a graft. The muscle layer of the esophagus was resected, followed by patching with an intercostal muscle flap. The pathological tumor stage was T4N0M0. The tumor recurred at two months after surgery in the neck lymph nodes and brain. Both sites were treated with radiation therapy and the patient is now alive without recurrence at 26 months after surgery. Lung cancer invading the great vessels and other mediastinal structures can be cured or long survival can be obtained by extended resection and postoperative adjuvant therapy.

Brain Neoplasms↗