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[Lesions in cross-breed pregnant cows, experimentally infected with Sarcocystis cruzi (Hasselmann, 1923) Wenyon, 1926 (Apicomplexa: Sarcocytidae)].

To identify pathologic alterations, sixteen cows, in the last 3 months of gestation, all cross-breed, Holstein x Zebu, serum positive for Sarcocystis, were selected and divided into four groups of four animals each. The first group was considered as control and the other three groups were experimentally infected with 1x10(4) (2nd group), 5x10(4) (3rd group) and 1x10(5) (4th group) sporocysts obtained from dog's feces. The gross lesions in the cows were consisted of pale mucous membranes, paleness of the skeletal striated muscle and enlargement of lymph nodes, heart, liver, spleen and lungs. In the aborted fetus, the most prominent gross lesion were excess of fluid in peritoneal and thoracic cavities, and petecheas in the surface of intercostal muscles, thymus and spleen. On histological sections, no parasitic form was found in the tissues of the fetus, placenta or uterine tissue of the exposed cows. However, meronts, young and mature cysts of S. cruzi were observed in striated muscle. In the aborted fetus, hemorrhage, was the main histological lesion observed in brain, cerebellum and kidneys.

Abortion, Veterinary↗

Evaluation of the antimyotonic activity of mexiletine and some new analogs on sodium currents of single muscle fibers and on the abnormal excitability of the myotonic ADR mouse.

To search for use-dependent sodium channel blockers to selectively solve skeletal muscle hyperexcitability in hereditary myotonias, mexiletine (MEX; compound I) and its newly synthetized analogs, 2-(4-chloro-2-methylphenoxy)-benzenethanamine (compound II) and (-)-S-3-(2,6-dimethylphenoxy)-2-methylpropanamine (compound III), were tested on intercostal muscle fibers from the myotonic ADR mouse through use of the standard current-clamp microelectrode technique. In parallel, the effects of these compounds on the sodium channels were measured on frog muscle fibers under voltage-clamp conditions. The tonic and use-dependent blocks of peak sodium currents (I(Namax)) produced by each compound were evaluated by using a single depolarizing pulse and a pulse train at 10 Hz frequency, respectively. At 10 and 50 microM, MEX decreased the occurrence of spontaneous excitability in myotonic muscle fibers; 100 microM was required to decrease the amplitude of the action potential and the stimulus-induced firing of the membrane as well as to increase the threshold for generation of action potential. At 300 microM, MEX decreased the latency of the action potential and increased the threshold current to elicit a single action potential. MEX produced a tonic block of I(Namax) with an half-maximal concentration (IC50) of 83 microM, but the IC50 value for use-dependent block was 3-fold lower. Compound III, which differs from MEX in that it has a longer alkyl chain, similarly blocked first the spontaneous and then the stimulus-evoked excitability of myotonic muscle fibers but at 2-fold lower concentrations than MEX. Compound III was less potent than MEX in producing a tonic block of I(Namax) (IC50 = 108 microM) but was a strong use-dependent blocker with an IC50 close to 15 microM. The more lipophylic compound II irreversibly blocked both spontaneous and stimulus-evoked membrane excitability at concentrations as low as 10 microM and shortened the latency of the action potential in a concentration-dependent fashion. Compound II produced a potent tonic block of I(Namax) (IC50 = 30 microM), and its potency increased 2-fold during high-frequency stimulation. Both of the new analogs (compound II in particular), but not MEX, were less effective on the excitability parameters of striated fibers of healthy vs. ADR mice, a characteristic that increases their interest as potential antimyotonic agents.

Animals↗

Dietary protein-induced changes in porcine muscle respiration, protein synthesis and adipose tissue metabolism.

Growth rate, physically separable tissues of the ham and loin, heat production, skeletal muscle respiration and protein synthesis, and lipogenesis and lipolysis in s.c. adipose tissue were measured in a single experiment in which pigs were offered a 13 (n = 8), or 21% (n = 6) protein diet from 20 to 100 kg live weight. Pigs that were fed the 13% protein diet gained body weight slower, ate less, converted feed less efficiently and took 31 d longer to reach 100 kg live weight. Fat depth (cm) was greater (P less than .05) and loin eye area (cm2) was less (P less than .01) in pigs fed the 13% protein diet (2.6 vs 2.3 and 29.8 vs 35.3). Pigs that were fed the 13% protein diet had lower (P less than .05) ham and loin separable muscle and greater (P less than .05) ham and loin separable fat. The mean heat production was less (P less than .05) in pigs offered the 13% (22.49) vs 21% (24.63 MJ/d) protein diets. In the intercostal muscle preparation, total and Na+,K+-ATPase-dependent respiration (microliter O2.mg-1.h-1) were lower (P less than .05) in pigs offered the 13% (2.39 and .41) vs the 21% (3.89 and .68) protein diets. The energy used for the support of Na+ transport across membrane accounted for approximately 17% of muscle respiration. Absolute rates of protein synthesis in the muscle preparations were lower (P less than .01) at 13 than at 21% dietary protein. Lipogenesis in s.c. adipose tissue was not affected by dietary protein level. There was no difference in basal and norepinephrine-stimulated lipolysis between the two dietary protein levels.

Adipose Tissue↗

Transversalis, endoabdominal, endothoracic fascia: who's who?

In Terminologia Anatomica of 1998, the fasciae of the trunk are listed as parietal, extraserosal, and visceral. Parietal fascia is defined as the fascia located outside the parietal layer of a serosa (e.g., pleura, peritoneum) lining a body wall cavity. The parietal fascia of the thorax is endothoracic fascia, and that of the abdomen is endoabdominal fascia. According to Terminologia Anatomica, endoabdominal fascia comprises: 1) transversalis fascia and 2) investing abdominal fascia: deep, intermediate and superficial. Thus, transversalis fascia is the innermost layer of endoabdominal fascia and, consequently, not synonymous with it. We assert that transversalis fascia is the inner epimysium of transversus abdominis muscle; no separate deep investing fascia exists. Embryologically, deep, intermediate and superficial layers of investing fascia are produced as muscular primordia--originating from somites invading somatopleura--penetrate somatic wall connective tissue, and thus obtain epimysium on either side, which give layers of investing fascia. In the thoracic wall, muscle layers are not separated and no distinct investing fasciae are found on them. Furthermore, in the thorax extraserosal fascia does not exist. Therefore, only endothoracic fascia is found on the inner side of the innermost intercostal muscle, which is deprived of investing fascia, to separate this muscle from pleura.

Abdomen↗

Pulmonary and chest wall mechanics in the control of respiration in the newborn.

Although the respiratory system is not fully developed at birth, the human newborn infant has flexible strategies to sustain breathing and defend blood gas homeostasis in both health and disease conditions. Initially the thresholds for chemoreceptor response to PO2 and PCO2 closely mimic those of the fetus, but the threshold resets to sustain ventilation adequate for blood gas homeostasis appropriate to the extrauterine milieu. The muscles of respiration have been "trained" in utero and effectively assume the function of the respiratory pump, despite their marginal reserve against fatigue. The pliable chest wall is functionally stabilized by the tonic activity of the intercostal muscles, thereby allowing effective ventilation. Finally, expiration is prolonged by the postinspiratory activity of the diaphragm and laryngeal braking as a means of maintaining an elevated lung volume and augmenting FRC. The ventilatory response of the newborn to respiratory disease is limited. The magnitude of the VE response is smaller than that of the adult, and is characterized by an increase in the respiratory rate and a limited increase in the VT. The poor effort reserve of the muscles, especially the diaphragm, predisposes the newborn to muscle fatigue and ventilatory failure. To avoid fatigue, recruitment of accessory muscles occurs, along with laryngeal braking of expiration, thereby decreasing the work of the diaphragm, recruiting new alveoli by an auto-PEEP effect, increasing the FRC volume, and improving gas exchange by an increase in the pulmonary surface area. These mechanisms help to avoid muscle exhaustion and facilitate adequate gas exchange in the presence of lung disease. We do not know precisely the postconceptual age at which the newborn is sufficiently developed to adopt these various defensive strategies of breathing, but the presence of tachypnea and grunting in 28-week-old premature infants suggests that long before term the human infant is capable of remarkable variation in the defense of breathing.

Biomechanical Phenomena↗

[Rib cross thoracotomy for a huge thoracic lesion].

Panpleuropneumonectomy, resection of a huge tumor in the thorax or operation of thoracic aneurysm requires good view of the entire thorax. Two separate incisions of lateral thoracotomy would not usually provide a sufficient operative field. The procedure of rib cross thoracotomy is as follows: The 6th, 7th, 8th, 9th rib with the intercostal muscle and vessels are cut at mid axillary line and removed 1 cm length at each edge of the ribs. The posterior half of the 6th ribs is removed. Thorax is entered posterioly at the 5th intercostal space and caudally to the 9th rib at the axillary line and anteriorly at the same intercostal space. Two rib expanders are needed.

Humans↗

Time to peak tidal expiratory flow and the neuromuscular control of expiration.

The ratio of the time needed to reach peak tidal expiratory flow (tPTEF) and the duration of expiration (tE) is used to detect airflow obstruction in young children. tPTEF is decreased in patients with asthma, but knowledge about the physiological determinants of this parameter is scarce. This study examined the relationship between tPTEF and postinspiratory activities of inspiratory muscles and evaluated the effects of changing sensory information from the lung. Airflow patterns and electromyographic (EMG) activity of inspiratory muscles were recorded in seven spontaneously breathing, anaesthetized cats. The trachea was cannulated and, as a result, the larynx and upper airways were bypassed. Changes in postinspiratory muscle activity were induced by changing afferent sensory nerve information (by cooling the vagus nerves, by administration of histamine and by additional application of continuous positive airway pressure (CPAP)). Durations of postinspiratory activities of the diaphragm and intercostal muscles (characterized by their time constants tau diaphr and tau interc) correlated strongly with tPTEF (r=0.85 and 0.77, respectively). Tau diaphr, tau interc and tPTEF were significantly increased during cooling of the vagus nerves (4-8 degrees C) compared with values at 22 and 37 degrees C (p<0.05). Conversely, administration of histamine and CPAP caused significant decreases in tau diaphr, tau interc and tPTEF, which were absent during cooling of the vagus nerves. In conclusion, the time needed to reach peak tidal expiratory flow is highly influenced by the activities of inspiratory muscles during the early phase of expiration which, in turn, depend on the activities of vagal receptors in the lung.

Animals↗

[The relative contribution of the muscles of the chest cavity and diaphragm to the work of breathing under inspiratory resistive loading].

The inspiratory resistive load decreases the relative contribution of the diaphragm into formation of the respiratory volume, as has been show in anesthetised cats. The phenomenon can be due to both a sharp increase in the external intercostal muscles activity and to a fatigue of the diaphragmatic muscle in the inspiratory load. The contraphasic changes of these muscles' activity seem to be an adaptive response aiding to a more efficient overcoming of the resistance against breathing.

Airway Resistance↗

Effect of posture on inspiratory muscle electromyogram response to hypercapnia.

The aim of our study was to examine the effect of posture on inspiratory muscle activity response to hypercapnia. Recent research has revealed that in normal subjects the activation of the rib cage muscles and of the diaphragm is actually greater in the upright than in the supine position during resting tidal breathing. In this study we examined whether the upright position necessarily entails a greater activation of the inspiratory muscles also under conditions of ventilatory stress. For this purpose we compared the responses to CO2-rebreathing in the supine and sitting positions in five volunteers, by simultaneously recording the electromyogram of the diaphragm (EMGdi) and the intercostal muscles (EMGint). The electromyogram was recorded by means of surface electrodes to measure the EMG amplitude. While the slopes of ventilatory (VE) response to increasing arterial CO2 tension (PaCO2) were similar in the two positions, both the EMGdi-VE and EMGint-VE relationship showed steeper slopes in the supine than in the sitting position. In each CO2 run the increases in EMGdi were linearly related to those in EMGint. This relationship was not affected by the body position. These results suggested that, in spite of similar ventilatory responses to CO2-rebreathing in the lying and sitting positions, the supine position, in humans, required a higher activation of the inspiratory muscles.

Adult↗

Newly recognized congenital myasthenic syndrome associated with high conductance and fast closure of the acetylcholine receptor channel.

We describe here a new congenital myasthenic syndrome associated with a kinetic abnormality of the acetylcholine receptor (AChR) channel. The propositus had poor suck and cry after birth. Subsequently, she had intermittent ocular symptoms and fatigued abnormally on exertion. At age 9 years, significant weakness was detected only in the frontalis, levator palpebrae, and neck flexor muscles. Electromyography showed no decrement in limb muscles but single-fiber examination of the facial muscles was consistent with a neuromuscular transmission defect. The ocular symptoms responded partially to pyridostigmine, but the abnormal fatigability did not. Tests for anti-AChR antibodies were negative. A younger sister had elements of the same disease. An intercostal muscle specimen was obtained from the propositus at age 9 years for endplate studies. The quantal content of the endplate potential was normal. Miniature endplate currents were abnormally large and their decay time constant was abnormally short. AChR channel properties were studied by analysis of acetylcholine-induced current noise. The mean single-channel conductance was increased 1.7-fold and the mean channel open time was 30% shorter than normal. The number of AChR per endplate was normal. Electron microscopy of most endplates showed no abnormality, but a few were degenerating or simplified. The channel abnormality may stem from a point mutation in an AChR subunit affecting a single amino acid residue lining the pore of the AChR channel. The mechanism by which the physiological abnormality produces clinical symptoms is not known, but possible explanations are considered.

Adult↗

Localization of the DMDL gene-encoded dystrophin-related protein using a panel of nineteen monoclonal antibodies: presence at neuromuscular junctions, in the sarcolemma of dystrophic skeletal muscle, in vascular and other smooth muscles, and in proliferating brain cell lines.

mAbs have been raised against different epitopes on the protein product of the DMDL gene, which is an autosomal homologue of the X-linked DMD gene for dystrophin. These antibodies provide direct evidence that DMDL protein is localized near acetylcholine receptors at neuromuscular junctions in normal and mdx mouse intercostal muscle. The primary location in tissues other than skeletal muscle is smooth muscle, especially in the vascular system, which may account for the wide tissue distribution previously demonstrated by Western blotting. The DMDL protein was undetectable in the nonjunctional sarcolemma of normal human muscle, but was observed in nonjunctional sarcolemma of Duchenne muscular dystrophy patients, where dystrophin itself is absent or greatly reduced. The expression of DMDL protein is not restricted to smooth and skeletal muscle, however, since relatively large amounts are present in transformed brain cell lines of both glial and Schwann cell origin. This contrasts with the low levels of DMDL protein in adult brain tissue.

Animals↗

Conduction velocities in single fibers of diseased human muscle.

Focal sarcolemmal lesions, segmental degeneration, and fiber splitting are observed in Duchenne muscular dystrophy and have been proposed to be major contributory causes of dysfunction of this disease. The presence of these abnormalities should affect impulse conduction along the sarcolemma. To test this prediction, we measured conduction velocities of the action potential in normal and diseased human intercostal muscle fibers by means of intracellular microelectrodes. The resting potentials of fibers from patients with Duchenne dystrophy, Becker dystrophy, and motor neuron disease were partially depolarized, and conduction velocities in these fibers were slower than normal. When the membrane potential was artifically hyperpolarized, the conduction velocity in Becker dystrophy fibers was not significantly different from normal. However, conduction velocity values in Duchenne dystrophy or motor neuron disease fibers were significantly lower than normal regardless of the level of membrane hyperpolarization. These data are analyzed in light of the presence of morphologic lesions in the diseased muscle fibers.

Action Potentials↗

Activity of respiratory muscles in upright and recumbent humans.

It is established that during tidal breathing the rib cage expands more than the abdomen in the upright posture, whereas the reverse is usually true in the supine posture. To explore the reasons for this, we studied nine normal subjects in the supine, standing, and sitting postures, measuring thoracoabdominal movement with magnetometers and respiratory muscle activity via integrated electromyograms. In eight of the subjects, gastric and esophageal pressures and diaphragmatic electromyograms via esophageal electrodes were also measured. In the upright postures, there was generally more phasic and tonic activity in the scalene, sternocleidomastoid, and parasternal intercostal muscles. The diaphragm showed more phasic (but not more tonic) activity in the upright postures, and the abdominal oblique muscle showed more tonic (but not phasic) activity in the standing posture. Relative to the esophageal pressure change with inspiration, the inspiratory gastric pressure change was greater in the upright than in the supine posture. We conclude that the increased rib cage motion characteristic of the upright posture owes to a combination of increased activation of rib cage inspiratory muscles plus greater activation of the diaphragm that, together with a stiffened abdomen, acts to move the rib cage more effectively.

Abdominal Muscles↗

Myoplasmic calcium regulation in myotubes from horses with recurrent exertional rhabdomyolysis.

OBJECTIVE: To determine whether alterations in myoplasmic calcium regulation can be identified in muscle cell cultures (myotubes) and intact muscle fiber bundles derived from Thoroughbreds affected with recurrent exertional rhabdomyolysis (RER). ANIMALS: 6 related Thoroughbreds with RER and 8 clinically normal (control) Thoroughbred or crossbred horses. PROCEDURES: Myotube cell cultures were grown from satellite cells obtained from muscle biopsy specimens of RER-affected and control horses. Fura-2 fluorescence was used to measure resting myoplasmic calcium concentration as well as caffeine- and 4-chloro-m-cresol (4-CMC)-induced increases in myoplasmic calcium. In addition, intact intercostal muscle fiber bundles were prepared from both types of horses, and their sensitivities to caffeine- and 4-CMC-induced contractures were determined. RESULTS: Myotubes of RER-affected and control horses had identical resting myoplasmic calcium concentrations. Myotubes from RER-affected horses had significantly higher myoplasmic calcium concentrations than myotubes from control horses following the addition of > or = 2mM caffeine; however, there was no difference in their response to 4-CMC (> or = 1 mM). Caffeine contracture thresholds for RER and control intact muscle cell bundles (2 vs 10mM, respectively) were significantly different, but 4-CMC contracture thresholds of muscle bundles from RER-affected and control horses (500 microM) did not differ. CONCLUSIONS AND CLINICAL RELEVANCE: An increase in caffeine sensitivity of muscle cells derived from a family of related RER-affected horses was detected in vitro by use of cell culture with calcium imaging and by use of fiber bundle contractility techniques. An alteration in muscle cell calcium regulation is a primary factor in the cause of this heritable myopathy.

Animals↗

The pectoral muscle flaps in the treatment of bronchial stump fistula following pneumonectomy.

Between 1975 and June 1992, pneumonectomy was performed in 594 patients, of whom 33 (5.6%) developed bronchopleural fistulae postoperatively. Until 1989 25 cases were reoperated: 5 patients were treated by thoracoplasty primarily, 20 by repair of the stump with sutures and by covering the stump with pericardial tissue or intercostal muscle, of whom 10 suffered from empyema. In 5/20 patients (25%) chronic fistulae developed making further interventions necessary. Since 1989 seven patients with bronchial stump fistulae have been reoperated with a delay of less than 12 h after diagnosis. Surgery consisted of reclosure of the stump with sutures in five patients. In addition, every patient was treated with the intrathoracic transposition of a petiolated ipsilateral pectoral muscle graft, which was the only treatment in two patients. Neither recurrence of the bronchopleural fistula nor empyema was seen in this group of patients (0%). We conclude that bronchial stump fistulae in patients after pneumonectomy can be treated successfully by the use of pectoral muscle flaps either combined with a closure of the leak using sutures or as the only measure. The method proved to be simple, safe and without major impairment of the patient. In combination with early reintervention, postpneumonectomy empyema including a disfiguring thoracoplasty can thereby often be avoided.

Bronchial Fistula↗

Use of the dog model for Duchenne muscular dystrophy in gene therapy trials.

Golden retriever muscular dystrophy (GRMD) is an excellent model for the study of the efficacy of gene therapy in dystrophin deficient myopathies for there are many similarities between affected dogs and Duchenne muscular dystrophy (DMD) in boys. GRMD is not caused by deletion mutation but results from a point mutation in the consensus splice acceptor in intron 6 of the canine dystrophin gene. As a result exon 7 is skipped during processing of the GRMD dystrophin messenger RNA. We have developed a rapid test which makes direct use of exon 7 specific genomic PCR products. We have undertaken preliminary experiments on gene therapy using the mini-gene and the full length gene alone and in combination with lipofectin and/or the bacterial beta-galactosidase reporter gene Lac Z. Following direct injection of the Lac Z plasmid, either alone or with lipofectin, about 50% of the sites showed expression when biopsied some 14 days later. The beta-galactosidase activity was present in muscle and granulation tissue but was never abundant. Pups injected intraperitoneally with Lac Z were found to have positive material in their mesenteric lymph nodes, liver and spleen. Those injected with Lac Z and lipofectin also had positive material in the diaphragm, intercostal muscles and abdominal muscles, but again only a small amount of positive material was present at any of the sites. In animals directly injected into the muscle with the dystrophin mini-gene, half had positive staining for dystrophin in biopsies taken 14 days later. Of the 6 sites in the muscles of animals given the mini-gene and lipofectin only one had fibres positive for dystrophin when examined 14 days later. Six pups were injected directly with full-length gene construct and when biopsies were taken 10 days later two of the animals had strongly stained peripheries to a small number of fibres.

Adenoviridae↗

[New clinical method to evaluate the ventilatory and non-ventilatory functions of respiratory muscles].

New clinical methods have been developed to evaluate the ventilatory and non-ventilatory functions of respiratory muscles. Three-dimensional stereoscopic diaphragm imaging method: Using this method we found that the diaphragm is shaped like an elliptic cylinder with an ellipsoid dome. During ventilation with relatively small tidal volume (less than 1L) the diaphragm moves like a piston keeping the same configuration. Multiphasic analysis of chest wall configuration: By observing movements at the different local regions of the chest wall, the activity of the respiratory muscles can be estimated. The non-ventilatory functions can be evaluated by the relaxation and the iso-volume lines on the Konno-Mead diagram. Deviation of the chest wall configuration from the relaxation line means a conversion of the intercostal muscles from the fixator function to the ventilatory function. The movement of the chest wall along the iso-volume line seen during coughing or talking also indicates the non-ventilatory function of the respiratory muscles which generates antigravitational forces.

Cough↗

Neck breathing: a form of voluntary respiration for the spine-injured ventilator-dependent quadriplegic child.

Children with respirator-dependent quadriplegia because of C-2 spinal cord injuries are now surviving the acute stages of their injury. The major cause of mortality and morbidity in the chronic stage is due to respiratory complications. Surveillance, 24 h/d, is the best way to prevent accidental disconnection of respirator equipment from the patient and its inherent catastrophic consequences. The constant risk of disconnection adds tension to the home environment and takes away from the patient any degree of independence or privacy. Because of this, an alternative method of respiration using neck accessory muscles was developed to restore a patient-controlled, voluntary system of respiration. This method, neck breathing, is described in detail in seven children varying in age from 3 years to 16 years 3 months. All seven patients had complete paralysis of the intercostal muscles and the diaphragm. An eighth patient who was unable to learn the technique is also described. Neck breathing is also compared to glossopharygeal breathing, an alternative method of respiration developed during the polio era.

Adolescent↗