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Ventilation and thoracoabdominal asynchrony during halothane anesthesia in infants.

To evaluate the ventilatory consequences of high chest wall compliance during anesthesia in infants, we assessed the effects of halothane at different fractions of minimal alveolar concentration (0.75, 1.0, and 1.5 MAC) on ventilation and movements of the rib cage and abdomen in infants < or = 12 mo of age (group I) and children (group II) > or = 12 mo of age. Minute ventilation decreased in group I, (20.6%, 0.75 to 1.5 MAC), but the change in group II did not reach the level of statistical significance. Tidal volume decreased with halothane level between 0.75 and 1.5 MAC, and its fall was greater in group I (32.7 +/- 11.2 vs. 22.6 +/- 9.3% in group II, P < 0.05). Duty cycle, or ratio of inspiratory to total time (TI/TT), increased in group II with halothane level but did not change in group I, resulting in a decreased TI in group I at higher halothane levels. Thoracic paradox increased with halothane level in group I but not group II. The increase in thoracic paradox in association with the fall in tidal volume between 0.75 and 1.5 MAC was greater in group I than group II (P < 0.05). We conclude that smaller infants depend more on inspiratory intercostal muscle activity to stabilize the thorax, leading to a greater degree of depression of ventilation during halothane depression of inspiratory intercostal activity.

Abdominal Muscles↗

Intracellular ionized calcium concentration in muscles from humans with malignant hyperthermia.

Ca2+ selective microelectrodes have been used to determine the free myoplasmic [Ca2+] in human skeletal muscle obtained from patients who had developed early signs associated with malignant hyperthermia (MH) during anesthesia. Intercostal muscle biopsies were performed under local anesthesia in four MH patients 15 days to 4 months after developing the MH crisis and in three control subjects. We used only microelectrodes that showed a Nernstian response between pCa3 and pCa7 (30.5 mV per decade at 37 degrees C). Membrane resting potential (V(m)) and calcium potential (V(Ca)) were obtained from superficial fibers. The free cytosolic [Ca2+] was 0.39 +/- 0.1 microM (mean +/- SEM, n = 18) in muscle fibers obtained from malignant hyperthermic patients, whereas in control subjects it was 0.11 +/- 0.02 microM (n = 10). These results suggest that this syndrome might be related to an abnormally high myoplasmic free resting calcium concentration, probably due to a defective function of the plasma membrane or the sarcoplasmic reticulum.

Adolescent↗

Thoracic epidural analgesia via the caudal approach using nerve stimulation in an infant with CATCH22.

PURPOSE: To illustrate insertion of an epidural catheter via caudal route in a small infant under electrical stimulation guidance. CLINICAL FEATURES: A six month old boy, weighting 4.25 kg, with a diagnosis of CATCH22 (Cardiac abnormality/abnormal faces, T cell deficit due to thymic hypoplasia, cleft palate, hypocalcemia due to hypoparathyroidism resulting from 22q11 deletion) was scheduled for fundoplication and gastrostomy tube (G-tube) insertion. A combined light general anesthesia and continuous epidural anesthesia technique was selected. Following induction of general anesthesia and tracheal intubation with 1.5 mg midazolam, 10 microg fentanyl and 10 mg succinylcholine, a 16G intravenous catheter was inserted into the caudal space. A 19G epidural catheter (Arrow Flextip Plus) epidural catheter was then inserted up cranially. A low electrical current (1-10mA) was then applied through the catheter. The level of motor movement was advanced from the lower limb muscles to the upper abdominal muscles as the catheter was threaded cranially. After 19 cm of epidural catheter had been inserted, intercostal muscle movement (T9-10 level) was observed at 4.2mA. The tip of the catheter was later confirmed to be at the T9-10 interspace by radiographical imaging. The patient awakened without distress and the trachea was extubated the same evening. The infant was discharged to the ward next morning with good pain relief from a continuous epidural infusion of bupivacane 0.1% with 1 microg x ml(-1) at 1.6 ml(-1). CONCLUSION: Epidural stimulation may help placement of the epidural catheter at the appropriate dermatome for effective anesthesia and analgesia.

Abnormalities, Multiple↗

New potent mexiletine and tocainide analogues evaluated in vivo and in vitro as antimyotonic agents on the myotonic ADR mouse.

The antimyotonic activity of chiral derivatives of mexiletine and tocainide, selected as potent use-dependent blockers of skeletal muscle sodium channels, was evaluated in vivo acutely in myotonic ADR mice. The compounds had either aromatic (Me4 and Me6) or branched isopropyl groups (Me5 and To1) on the asymmetric centre, or had this latter one methylene apart from the amino group (Me2). Therapeutic doses of mexiletine (5-10 mg/kg) and tocainide (7-20 mg/kg) significantly reduced the long time of righting reflex (TRR), typical of ADR mice. Me4, Me5 and Me6 were 2-fold more potent than mexiletine. To1 fully normalised the TRR at 7 mg/kg. The electromyographic analysis confirmed a muscle-based activity for drug effectiveness on TRR. All the compounds reduced the myotonic hyperexcitability of intercostal muscle fibres when tested in vitro by current-clamp recordings, with a potency correlated with their action on sodium channels. On stimulus-evoked firing, the isopropyl analogues were 2-4-fold more potent than parent compounds, while the aromatic analogues were about 10-fold more potent than mexiletine. Patch-clamp recordings confirmed a normal-like pharmacological sensitivity of sodium channels of native ADR muscle fibres. Finally, the in vivo antimyotonic activity is due to the block of sodium channels and divergences with in vitro potency can be related to structure-based changes in drug pharmacokinetics.

Action Potentials↗

Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles.

Antisense oligonucleotide-mediated alternative splicing has great potential for treatment of Duchenne muscular dystrophy (DMD) caused by mutations within nonessential regions of the dystrophin gene. We have recently shown in the dystrophic mdx mouse that exon 23, bearing a nonsense mutation, can be skipped after intramuscular injection of a specific 2'-O-methyl phosphorothioate antisense oligoribonucleotide (2OMeAO). This skipping created a shortened, but in-frame, transcript that is translated to produce near-normal levels of dystrophin expression. This expression, in turn, led to improved muscle function. However, because DMD affects muscles body-wide, effective treatment requires dystrophin induction ideally in all muscles. Here, we show that systemic delivery of specific 2OMeAOs, together with the triblock copolymer F127, induced dystrophin expression in all skeletal muscles but not in cardiac muscle of the mdx dystrophic mice. The highest dystrophin expression was detected in diaphragm, gastrocnemius, and intercostal muscles. Large numbers of fibers with near-normal level of dystrophin were observed in focal areas. Three injections of 2OMeAOs at weekly intervals enhanced the levels of dystrophin. Dystrophin mRNA lacking the targeted exon 23 remained detectable 2 weeks after injection. No evidence of tissue damage was detected after 2OMeAO and F127 treatment either by serum analysis or histological examination of liver, kidney, lung, and muscles. The simplicity and safety of the antisense protocol provide a realistic prospect for treatment of the majority of DMD mutations. We conclude that a significant therapeutic effect may be achieved by further optimization in dose and regime of administration of antisense oligonucleotide.

Animals↗

Thoracic epidural analgesia via the lumbar approach using nerve stimulation in a pediatric patient with Down syndrome.

This case illustrates the threading of an epidural catheter with electrical stimulation guidance from the lumbar epidural space to the thoracic space in a pediatric patient. A 17-year-old boy with Down syndrome, weighing 48 kg, was scheduled to undergo a laparotomy for duodenal obstruction and gastrostomy tube insertion. Combined general and continuous epidural anesthesia was selected for his anesthetic. Following the induction of general anesthesia and tracheal intubation, a 17G Tuohy needle (Arrow International, Inc., Reading, PA) was inserted into the lumbar space (L3-4) using loss of resistance with air. A 20G styletted epidural catheter was then inserted and threaded cranially. As the catheter was advanced, a low electrical current (1-10mA) was applied to the catheter. Motor response was observed from the lower limb muscles to the upper abdominal muscles as the catheter advanced cranially. After 22 cm of the epidural catheter had been inserted, intercostal muscle movement (T9 - 10) was observed at 3.0 mA. Radiographical imaging later confirmed the catheter tip at T10. The patient awoke without distress and was discharged to the ward with subsequent good pain control from a continuous epidural infusion of bupivacaine 0.1% with 1 microg ml(-1) fentanyl at 4-6 ml(-1).

Adolescent↗

The effect of voluntary diaphragmatic activation on back lifting.

The effect of increased intraabdominal pressure upon the activation of the erector spinae muscles during back lifting was studied in 10 healthy volunteers. The intraabdominal pressure was increased by voluntary prelifting coactivation of the diaphragm and the abdominal muscles. EMG was recorded with surface electrodes over the diaphragm and the erector spinae, abdominal and intercostal muscles. The EMG signals were rectified and averaged from 20 lifts of 10 kg with and without pressurization to give mean level of activity during 2 s before lifting and during successive angular positions of the trunk during lifting. In 7 of the 10 subjects the pre-lifting coactivation of diaphragm and abdominal muscles reduced erector spinae activity at lift-off and/or during the trunc erecting movement. An increased intraabdominal pressure thus often has an unloading effect on the erector spinae muscle during back lifting.

Abdomen↗

[A case of empyema with a bronchopleural fistula treated by a pedicle muscle flap with the thick parietal pleura].

A 65-year-old male with a bronchopleural fistula of 10 mm in diameter underwent thoracoplasty combined with a pedicle muscle flap following open thoracic window. He had been treated by gastrectomy and right upper lobectomy because of gastric perforation and lung tuberculosis before empyema. Sterilization for the empyema cavity through the thoracic window was done for 255 days, obliteration of the empyema cavity was achieved by a muscle flap with the thick parietal pleura. The parietal pleura which was not separated from the intercostal pleura which was not separated from the intercostal muscle was used for reinforcement of the muscle flap against the high intra-tracheal pressure. There was no postoperative relapse of empyema for 9 months.

Aged↗

Are MuSK antibodies the primary cause of myasthenic symptoms?

OBJECTIVE: To investigate the morphologic, electrophysiologic, and molecular correlates of muscle-specific tyrosine kinase-seropositive [MuSK(+)] myasthenia gravis (MG). BACKGROUND: Anti-MuSK antibodies are detected in some of acetylcholine receptor-seronegative [AChR(-)] patients with MG with prominent facial, bulbar, and respiratory muscle involvement. The morphologic and electrophysiologic correlates of MuSK(+) MG have not been investigated to date. METHODS: Immunohistochemistry, electron microscopy, and in vitro electrophysiology studies were performed on an intercostal muscle specimen of a patient with MuSK(+) MG and in control subjects. MUSK was directly sequenced, and the nucleotide changes were traced with allele-specific PCR in control subjects. RESULTS: A man aged 34 years has had facial weakness since childhood and progressive bulbar and respiratory muscle weakness and intermittent diplopia since age 21 years. He has thin temporalis and masseter muscles, a high-arched palate, and an atrophic tongue. EMG shows a 36% decrement in facial muscles. His mother has similar facial features. His endplates (EPs) show no AChR or MuSK deficiency, but the amplitudes of the miniature EP potentials and currents are reduced to 35% and 55% of normal, respectively. EP ultrastructure is well preserved, but some junctional folds immunostain faintly for immunoglobulin G. Mutation analysis of MUSK reveals one rare and two common DNA polymorphisms. CONCLUSIONS: 1) The circulating anti-muscle-specific tyrosine kinase antibodies caused neither muscle-specific tyrosine kinase nor acetylcholine receptor deficiency at the endplates; 2) the reduced intercostal miniature endplate potential and current amplitudes were not accounted for by acetylcholine receptor deficiency; 3) the faint immunoglobulin G deposits at the endplates may or may not represent anti-muscle-specific tyrosine kinase antibodies; and 4) the anti-muscle-specific tyrosine kinase antibodies may not be the primary cause of myasthenic symptoms in this patient.

Adult↗

[Aortic valve operations through an upper partial sternotomy].

The median sternotomy has been accepted as the most common approach to the heart, because this approach is easily opened and closed, and easy access to the entire heart is possible. Following the pioneering work by Cosgrove and colleagues of using a parasternal incision for aortic and mitral valve operations, several reports suggested that modified minimal access procedures are likely to be associated with reduced postoperative discomfort and faster recovery. Since July 1997, we have used an upper partial sternotomy and a limited skin incision for isolated aortic valve replacement (AVR) at our hospital. To demonstrate the benefits of this approach, we compared 14 AVR operations using our minimal access incision (group M) with 19 patients undergoing isolated AVR using a conventional sternotomy (group F). In the minimal access group of patients, a small skin incision was made from the second intercostal space to the fourth rib. The pectralis major and intercostal muscle was freed from the sternum, and then a transverse half sternotomy was made in the fourth intercostal space using a striker without injury to the right internal mammary artery. A median partial sternotomy from the supersternal notch to the level of the fourth intercostal space. Cardiopulmonary bypass was connected through the same access site to avoid cannulation of both groins. Conversion to median sternotomy was not necessary in any patient including reexploration for postoperative bleeding. There was no operative mortality, stroke, aortic dissection and perivalvular leaks due to technical factors. In group F, wound infection occurred in 1 patient. One patient in group M required reoperation to control postoperative bleeding. Although mean duration of operation, cardiopulmonary bypass, and cross clamp time in group M was not prolonged, the initiation of cardiopulmonary bypass and aortic crossclamp was delayed by difficulties of cannulations. The distance between the transverse sternotomy (lower edge of divided sternum) and the midpoint of aortic valve annulus was correlated with mean duration of cardiopulmonary bypass and cross clamp time. Our experience demonstrates that isolated AVR through an upper partial sternotomy allows the same quality operations as the full sternotomy, although more clinical experience is required to clarify the benefits of this approach. Excellent exposure of the aortic valve through a partial sternotomy may be attained, if an adequate approach can be selected by the position of aortic valve.

Aortic Valve↗

Parasternal and external intercostal responses to various respiratory maneuvers.

Recent studies suggest that the external intercostal (EI) muscles of the upper rib cage, like the parasternals (PA), play an important ventilatory role, even during eupneic breathing. The purpose of the present study was to further assess the ventilatory role of the EI muscles by determining their response to various static and dynamic respiratory maneuvers and comparing them with the better-studied PA muscles. Applied interventions included 1) passive inflation and deflation, 2) abdominal compression, 3) progressive hypercapnia, and 4) response to bilateral cervical phrenicotomy. Studies were performed in 11 mongrel dogs. Electromyographic (EMG) activities were monitored via bipolar stainless steel electrodes. Muscle length (percentage of resting length) was monitored with piezoelectric crystals. With passive rib cage inflation produced either with a volume syringe or abdominal compression, each muscle shortened; with passive deflation, each muscle lengthened. During eupneic breathing, each muscle was electrically active and shortened to a similar degree. In response to progressive hypercapnia, peak EMG of each intercostal muscle increased linearly and to a similar extent. Inspiratory shortening also increased progressively with increasing PCO2, but in a curvilinear fashion with no significant differences in response among intercostal muscles. In response to phrenicotomy, the EMG and degree of inspiratory shortening of each intercostal muscle increased significantly. Again, the response among intercostal muscles was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mechanics of the parasternal intercostals during occluded breaths in dogs.

The electrical activity and the respiratory changes in length of the third parasternal intercostal muscle were measured during single-breath airway occlusion in 12 anesthetized, spontaneously breathing dogs in the supine posture. During occluded breaths in the intact animal, the parasternal intercostal was electrically active and shortened while pleural pressure fell. In contrast, after section of the third intercostal nerve at the chondrocostal junction and abolition of parasternal electrical activity, the muscle always lengthened. This inspiratory muscle lengthening must be related to the fall in pleural pressure; it was, however, approximately 50% less than the amount of muscle lengthening produced, for the same fall in pleural pressure, by isolated stimulation of the phrenic nerves. These results indicate that 1) the parasternal inspiratory shortening that occurs during occluded breaths in the dog results primarily from the muscle inspiratory contraction per se, and 2) other muscles of the rib cage, however, contribute to this parasternal shortening by acting on the ribs or the sternum. The present studies also demonstrate the important fact that the parasternal inspiratory contraction in the dog is really agonistic in nature.

Animals↗

Dantrolene sodium is able to reduce the resting ionic [Ca2+]i in muscle from humans with malignant hyperthermia.

Malignant hyperthermia (MH) is a hereditary myopathy, triggered when susceptible patients are exposed to a depolarizing muscle relaxant and/or potent volatile anesthetics. We have studied the effects of dantrolene on the free [Ca2+]i of intercostal muscle biopsies obtained from two MH-susceptible patients before and after administration of dantrolene orally (2.5 mg/kg for 3 days) and intravenously (1.0 mg/kg 2 hours before the biopsy). The free [Ca2+]i was measured by Ca2+-selective microelectrodes. The mean resting free [Ca2+]i in the MH-susceptible muscle before dantrolene treatment was 0.42 +/- 0.01 microM (mean +/- SEM, n = 12). The administration of dantrolene reduced this value to 0.27 +/- 0.01 microM (n = 14). There was no detectable difference in the resting membrane potential after dantrolene. These results represent the first direct demonstration that dantrolene is able to reduce the resting free [Ca2+]i in skeletal muscle of MH-susceptible patients.

Adult↗

The lateral limited thoracotomy incision: standard for pulmonary operations.

Four hundred sixty-eight consecutive thoracotomies for which the lateral limited thoracotomy incision was used are reviewed (1978 to 1988). The limited incision is a lateral muscle-splitting incision with preservation of the latissimus dorsi, splitting of the serratus anterior, and cutting of only the intercostal muscles without rib resection. Patients were designated unsuitable for operation if (1) biopsy-proved distant metastasis existed, (2) mediastinoscopy revealed extranodal metastasis, or (3) severe respiratory compromise resulted in shortness of breath at rest with a forced expiratory volume in 1 second of less than 0.75 L (four patients). Mean patient age was 60.9 (+/- 15.7) years. Surgical procedures included lobectomy (n = 317), pneumonectomy (n = 41), wedge resection (n = 82), resections of blebs or bullae (n = 17), thoracotomy and biopsy for unresectable lesion (n = 6), and decortication (n = 5). Pathologic analysis revealed 354 malignant tumors, 102 benign lesions, and 12 carcinoids. The perioperative mortality rate was 0.85% (4/468) and major morbidity was present in 2.9% (14/468). Mean operative time was 73.1 (+/- 32.2) minutes with a blood loss resulting in a mean decrease of the hematocrit value of 2.6 (+/- 2.5) gm; three patients were given a total of 7 units of blood. Most patients do not require a stay in the intensive care unit postoperatively (less than 10%). Hospital stay postoperatively was a mean of 6.1 (+/- 2.9 days. The limited incision is a significant factor in decreasing operative time, blood loss, postoperative pain and morbidity, and cost.

Aged↗

Bifid ribs observed in the third and the fourth ribs.

Three cases of bifid ribs were found in two cadavers during routine dissections at the Iwate Medical University School of Dentistry. All of the cases were found in the third or the fourth rib. The distal parts of the osseous rib bifurcated with an angle of 60 degrees and both of the branches had their own costal cartilage. The costal cartilage fused again to form the trunk which was connected to the sternum. The space between the two branches was filled with presumably normal intercostal muscles. Blood supply was maintained by a small branch from the interthoracic artery to the upper branches. However, the intercostal nerves did not branch toward the upper branch but only ran along the lower margins of the lower branches of the bifid ribs.

Aged↗

Evaluation of a digestion assay and determination of sample size and tissue for the reliable detection of Trichinella larvae in walrus meat.

A digestion assay was validated for the detection of Trichinella larvae in walrus (Odobenus rosmarus) meat, and appropriate samples for testing were determined using tissues from infected walruses harvested for food. Examination of muscles from 3 walruses showed that the tongue consistently contained approximately 2-6 times more larvae than the pectoral and intercostal muscles. Comparison of numbers of larvae in the root, body, and apex of the tongue from 3 walruses failed to identify a predilection site within the tongue, but the apex was considered an optimal tissue because of the high larval density within the tongue and the ease of collection. All 31 spiked samples weighing 50 g each and containing between 0.1 and 0.4 larvae per gram (lpg) were correctly identified as infected, indicating that the sensitivity of this procedure is adequate for diagnostic use. A sample size of 10 g consistently detected larvae in 2 walrus tongues containing > or = 0.3 lpg (n = 40), and until additional data are available, sample sizes from individual walrus tongues should be a minimum of 10 g. This study provides the preliminary data that were used for the development of a food safety analytical protocol for the detection of Trichinella in walrus meat in arctic communities.

Animals↗

Hypokalemic periodic paralysis: in vitro investigation of muscle fiber membrane parameters.

To study the mechanism of attacks in familial hypokalemic paralysis, we recorded resting membrane potentials, action potentials, current-voltage relationships, and isometric forces in intercostal muscle fibers from three patients. In normal extracellular medium, the resting potential was reduced, but membrane conductance was not different from control. Excitability was reduced and the action potentials had no overshoot. On exposure to a 1-mM potassium solution, with or without insulin, the cells depolarized to about -50 mV, and became inexcitable. Over the tested membrane potential range from -120 to -40 mV, the slope conductance in the 1-mM potassium solution was not different from that of control fibers in a 1-mM potassium solution. In particular, the potassium component conductance was not reduced. Depolarized fibers could not be completely repolarized by returning to a 3.5-mM potassium solution. An experimentally induced transient shift of the chloride equilibrium potential to a highly negative value caused stable repolarization. Paralysis could also be induced by replacement of extracellular chloride with an impermanent anion, a treatment which causes myotonia in healthy fibers. It was concluded that the basic defects are a reduced excitability and an increased sodium conductance, and that these defects are aggravated on reduction of the extracellular potassium concentration.

Adult↗

The effects of single afferent impulses on the probability of firing of external intercostal motoneurones in the cat.

1. Recordings of afferent discharges from external intercostal muscle spindles were made from in-continuity dorsal roots of anaesthetized, paralysed cats and the afferents were characterized as described in the preceding paper (Kirkwood & Sears, 1982).2. The strengths and time courses of the raised probabilities of firing of external intercostal motoneurones evoked by the synaptic actions of impulses in the afferents were measured by constructing cross-correlation histograms from the discharges of the individual afferents and the discharges of the motoneurones, which were simultaneously recorded from the cut central ends of intercostal nerve filaments. Other dorsal roots, apart from the rootlet containing the afferent fibre, were cut to prevent afferent synchronization from affecting the results.3. Cross-correlation histograms involving single efferent discharges showed narrow peaks (mean half-width 0.99 msec) at monosynaptic latencies.4. This mean half-width is slightly longer than the mean rise-time of the e.p.s.p.s described in the preceding paper, but much shorter than the mean half-width of those e.p.s.p.s. These measurements, together with the shapes of individual histogram peaks thus confirm the prediction of Kirkwood & Sears (1978) that the shape of such a peak should be approximated by the time differential of the underlying e.p.s.p. plus the e.p.s.p. time course itself. Amplitudes of the peaks were also consistent with the predictions of Kirkwood & Sears (1978).5. The cross-correlation histograms involving multi-unit efferent discharges were entirely consistent with those involving single efferent discharges and were used to demonstrate the patterns of projections of individual afferents to different groups of intercostal motoneurones.6. Individual afferents excited alpha motoneurones of all spike sizes in the intercostal filament recordings but excitation of gamma motoneurones was not detected.7. Individual afferents excited motoneurones of the same segment and both adjacent segments, but no projection beyond these was detected.8. The amplitude of the multi-unit cross-correlation peak was taken as a measure of the over-all strength of the connexions to a given segment. When this amplitude was measured for motoneurones of the same segment as the afferent, for sixteen out of nineteen afferents there was a highly significant positive correlation with the conduction velocity of the afferent. The remaining three afferents gave a strength of connexion which appeared to be much stronger than would be expected from the rest of the population of afferents.9. The strength of connexion to adjacent segments was generally lower than to the same segment.

Action Potentials↗