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Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

Expression of a muscle-specific, nitric oxide synthase transgene prevents muscle membrane injury and reduces muscle inflammation during modified muscle use in mice.

Nitric oxide (NO) can function as either a pro-inflammatory or anti-inflammatory molecule, depending upon its concentration and the microenvironment in which it is produced. We tested whether muscle-derived NO affects muscle inflammation and membrane lysis that occur in modified muscle use. Transgenic mice with muscle-specific over-expression of neuronal NO synthase (nNOS) were generated in which transgene expression was driven by the human skeletal muscle actin promoter. Transgenic mice and non-transgenic littermates were subjected to hindlimb muscle unloading followed by reloading, which causes muscle inflammation and membrane lysis. NOS expression decreased in transgenic and non-transgenic mice during muscle unloading. Muscle inflammation was assessed by immunohistochemistry after 24 h of muscle reloading following 10 days of unloading. Soleus muscles of non-transgenic mice showed significant increases in the concentrations of neutrophils (4.8-fold) and macrophages (11.3-fold) during reloading, compared to mice that experienced unloading only. Muscles of transgenic mice showed 51 % fewer neutrophils in reloaded muscles than those of non-transgenic mice, but macrophage concentrations did not differ from non-transgenic mice. Muscle membrane damage was determined by measuring influx of an extracellular marker dye. Significantly more membrane damage occurred in muscles of non-transgenic mice experiencing reloading than in ambulatory controls. However, membrane damage in the reloaded muscles of transgenic mice did not differ from that in ambulatory mice. In vitro cytotoxicity assays confirmed that mouse neutrophils lyse muscle cell membranes, and showed that inhibition of NOS in muscle and neutrophil co-cultures significantly increased neutrophil-mediated lysis of muscle cells. Together, these data show that muscle-derived NO can function as an anti-inflammatory molecule in muscle that experiences modified loading, and that NO can prevent neutrophil-mediated damage of muscle cell membranes in vivo and in vitro.

Animals↗

Transfected muscle and non-muscle actins are differentially sorted by cultured smooth muscle and non-muscle cells.

We have analyzed by immunolabeling the fate of exogenous epitope-tagged actin isoforms introduced into cultured smooth muscle and non-muscle (i.e. endothelial and epithelial) cells by transfecting the corresponding cDNAs in transient expression assays. Exogenous muscle actins did not produce obvious shape changes in transfected cells. In smooth muscle cells, transfected striated and smooth muscle actins were preferentially recruited into stress fibers. In non-muscle cells, exogenous striated muscle actins were rarely incorporated into stress fibers but remained scattered within the cytoplasm and frequently appeared organized in long crystal-like inclusions. Transfected smooth muscle actins were incorporated into stress fibers of epithelial cells but not of endothelial cells. Exogenous non-muscle actins induced alterations of cell architecture and shape. All cell types transfected by non-muscle actin cDNAs showed an irregular shape and a poorly developed network of stress fibers. beta- and gamma-cytoplasmic actins transfected into muscle and non-muscle cells were dispersed throughout the cytoplasm, often accumulated at the cell periphery and rarely incorporated into stress fibers. These results show that isoactins are differently sorted: not only muscle and non-muscle actins are differentially distributed within the cell but also, according to the cell type, striated and smooth muscle actins can be discriminated for. Our observations support the assumption of isoactin functional diversity.

Actins↗

Coexistence of fast-muscle-type and slow-muscle-type troponin T isoforms in single chimeric muscle fibers induced by muscle transplantation.

Regenerated muscle fibers which appeared after transplantation of chicken slow muscle (anterior latissimus dorsi) into breast fast muscle (pectoralis major) of the same animal were studied by two-dimensional SDS-polyacrylamide gel electrophoresis, immunoblotting, and immunostaining with antisera against fast-muscle-type troponin T and slow-muscle-type troponin T. In the transplanted muscle, degeneration of muscle fibers was followed by regeneration of slow muscle, which was revealed by detecting slow-muscle-type troponin T with the antiserum. Furthermore, coexistence of fast-muscle-type and slow-muscle-type troponin T isoforms in single chimeric muscle fibers composed of partly fast and partly slow fibers was observed in the regenerated muscle. We suggested that the chimeric fibers were originated from the fusion of fast and slow myoblasts during regeneration after muscle transplantation and that two nuclei differently determined in troponin T expression were working independently in a single cell.

Animals↗

Skeletal muscle injury induced by eccentric muscle action: muscle proteins as markers of muscle fiber injury.

Muscular overuse after high force eccentric muscle action is associated with structural damage of the contractile apparatus that can be observed as Z-line steaming and myofibrillar disruption. Mechanical stress is the major contributing factor for inducing muscle injury, which initiates a cascade of processes resulting in skeletal muscle damage. Disturbances in Ca2+ homeostasis with elevated intracellular [Ca2+] activates the nonlysomal cysteine protease, calpain. Calpain is assumed to play an important role in triggering the response of skeletal muscle protein breakdown, of inflammatory changes, and of regeneration processes in response to eccentric muscle action. The inflammatory response is attributed to changes in hormone and cytokine levels in blood and skeletal muscle. To assess the amount of skeletal muscle damage, plasma CK activity and plasma myoglobin levels have been widely used as markers for muscle injury. As the cytosolic proteins do not necessarily reflect the amount of structural damage, structurally bound proteins such as myosin heavy chains and troponin have been investigated. This paper briefly reviews the cascade of events causing muscle cell injury after unaccustomed eccentric muscle action and the potential of muscle proteins as markers of skeletal muscle damage.

Animals↗

Expression of functional CXCR4 by muscle satellite cells and secretion of SDF-1 by muscle-derived fibroblasts is associated with the presence of both muscle progenitors in bone marrow and hematopoietic stem/progenitor cells in muscles.

We found that the murine cell lines C2C12 and G7 derived from muscle satellite cells, which are essential for muscle regeneration, express the functional CXCR4 receptor on their surface and that the specific ligand for this receptor, alpha-chemokine stromal-derived factor 1 (SDF-1), is secreted in muscle tissue. These cell lines responded to SDF-1 stimulation by chemotaxis, phosphorylation of mitogen-activated protein kinase (MAPK) p42/44 and AKT serine-threonine kinase, and calcium flux, confirming the functionality of the CXCR4 receptor. Moreover, supernatants derived from muscle fibroblasts chemoattracted both satellite cells and human CD34(+) hematopoietic stem/progenitor cells. In a similar set of experiments, supernatants from bone marrow fibroblasts were found to chemoattract CXCR4(+) satellite cells just as they chemoattract CD34(+) cells. Moreover, preincubation of both muscle satellite cells and hematopoietic stem/progenitor CD34(+) cells before chemotaxis with T140, a specific CXCR4 inhibitor, resulted in a significantly lower chemotaxis to media conditioned by either muscle- or bone marrow-derived fibroblasts. Based on these observations, we postulate that the SDF-1-CXCR4 axis is involved in chemoattracting circulating CXCR4(+) muscle stem/progenitor and circulating CXCR4(+) hematopoietic CD34(+) cells to both muscle and bone marrow tissues. Thus, it appears that tissue-specific stem cells circulating in peripheral blood could compete for SDF-1(+) niches, and this would explain, without invoking the concept of stem cell plasticity, why hematopoietic colonies can be cultured from muscles and early muscle progenitors can be cultured from bone marrow.

Animals↗

Muscle substrate levels, muscle enzyme activities and muscle morphology in the vastus lateralis and deltoideus muscles in normal children and in children with coarctation of the aorta.

Muscle biopsies from the deltoideus dx and vastus lat. dx muscles were taken in 17 children with coarctation of the aorta, aged 5.0 to 13.8 years, prior to surgery. Higher concentrations of glycogen, ATP and CP were found in the vastus lat. muscle compared to the deltoideus muscle. The same differences between these two muscles were also found in healthy controls. No differences were found between the patients with coarctation of the aorta and the control group. Nor were any differences found for the other variables studied; glucose, glucose-6-phosphate, lactate, muscle enzyme activities (SDH, LDH and phosphorylase), muscle fibre composition or fibre sizes. It seems reasonable to assume that the differences in muscle substrate levels found between the vasus lat. and the deltoideus muscles in the two groups were due to a higher degree of activity during daily life for the legs as compared to the arms. Patients with coarctation of the aorta do not seem to be influenced by the altered haemodynamic situation with regard to the studied variables.

Adenosine Triphosphate↗

Comparisons of muscle substrate levels, muscle enzyme activities and muscle morphology in arm and leg muscles in normal subjects and in patients operated upon for coarctation of the aorta in childhood.

Muscle biopsies from the upper and the lower part of the body (m. deltoideus dx and m. vastus lat dx) were taken in young men, 17-28 years of age, who had been operated upon for coarctation of the aorta in childhood. Significant differences regarding SDH-activity and some muscle substrate levels were found, with higher values in the leg muscle. The same differences were found in ten healthy controls. It is concluded that arm and leg muscle differ in these respects but that the haemodynamic difference remaining after coarctectomy does not seem to influence this situation.

Adenosine Triphosphate↗

Determinative mechanisms in secondary muscle lineages of ascidian embryos: development of muscle-specific features in isolated muscle progenitor cells.

Muscle cells of the ascidian larva originate from three different lines of progenitor cells, the B-line, A-line and b-line. Experiments with 8-cell embryos have indicated that isolated blastomeres of the B-line (primary) muscle lineage show autonomous development of a muscle-specific enzyme, whereas blastomeres of the A-line and b-line (secondary) muscle lineage rarely develop the enzyme in isolation. In order to study the mechanisms by which different lines of progenitors are determined to give rise to muscle, blastomeres were isolated from embryos of Halocynthia roretzi at the later cleavage stages when conspicuous restriction of the developmental fate of blastomeres had already occurred. Partial embryos derived from B-line muscle-lineage cells of the 64-cell embryo (B7.4, B7.5 and B7.8) showed autonomous expression of specific features of muscle cells (acetylcholinesterase, filamentous actin and muscle-specific antigen). In contrast, b-line muscle-lineage cells, even those isolated from the 110-cell embryo (b8.17 and b8.19), did not express any muscle-specific features, even though their developmental fate was mainly restricted to generation of muscle. Isolated A-line cells from the 64-cell embryos (A7.8) did not show any features of muscle differentiation, whereas some isolated A-line cells from the 110-cell embryos (A8.16) developed all three above-mentioned features of muscle cells. This transition was shown to occur during the eighth cell cycle. These results suggest that the mechanism involved in the process of determination of the secondary-lineage muscle cells differs from that of the primary-lineage muscle cells. Interaction with cells of other lineages may be required for the determination of secondary precursors to muscle cells. The presumptive b-line and A-line muscle cells that failed to express muscle-specific features in isolation did not develop into epidermal cells. Thus, although interactions between cells may be required for muscle determination in secondary lineages, the process may represent a permissive type of induction and may differ from the processes of induction of mesoderm in amphibian embryos.

Acetylcholinesterase↗

Contraction-induced muscle fiber damage is increased in soleus muscle of streptozotocin-diabetic rats and is associated with elevated expression of brain-derived neurotrophic factor mRNA in muscle fibers and activated satellite cells.

The expression of brain-derived neurotrophic factor (BDNF) is elevated in the soleus muscle of streptozotocin-diabetic rats. To determine whether this diabetes-induced elevation was associated with or enhanced by muscle activity we have induced high-intensity muscle contraction by electrically stimulating the sciatic nerve. In 6-week diabetic rats, intense contraction of the soleus muscle resulted in a two- to four-fold elevation of BDNF mRNA and increased plasma levels of creatine kinase that were associated with severe focal muscle fiber damage and concomitant satellite cell activation. Focal muscle fiber damage and concomitant satellite cell activation were also observed in the soleus muscle of nonstimulated diabetic rats, but to a much lesser extent. No effects of muscle contraction, i.e., experimentally induced or during normal daily activity, on muscle fiber structure or BDNF mRNA expression were seen in diabetic extensor digitorum longus (EDL) muscle. Using a nonradioactive in situ hybridization technique for electron microscopy, the elevated expression of BDNF mRNA in the diabetic soleus muscle was localized within muscle fibers as well as activated satellite cells. This study shows that diabetic soleus muscle, in contrast to diabetic EDL and to soleus and EDL muscle of normal animals, is highly susceptible to contraction-induced damage. Intense contraction and the associated muscle fiber damage in the diabetic soleus muscle result in an upregulation of BDNF mRNA in muscle fibers and activated satellite cells, which may be involved in the restoration and/or maintenance of nerve/muscle integrity.

Animals↗

The complete amino acid sequence of actins from bovine aorta, bovine heart, bovine fast skeletal muscle, and rabbit slow skeletal muscle. A protein-chemical analysis of muscle actin differentiation.

Complete amino acid sequences for four mammalian muscle actins are reported: bovine skeletal muscle actin, bovine cardiac actin, the major component of bovine aorta actin, and rabbit slow skeletal muscle actin. The number of different actins in a higher mammal for which full amino acid sequences are now available is therefore increased from two to five. Screening of different smooth muscle tissues revealed in addition to the aorta type actin a second smooth muscle actin, which appears very similar if not identical to chicken gizzard actin. Since the sequence of chicken gizzard actin is known, six different actins are presently characterized in a higher mammal. The two smooth muscle actins--bovine aorta actin and chicken gizzard actin--differ by only three amino acid substitutions, all located in the amino-terminal end. In the rest of their sequences both smooth muscle actins share the same four amino acid substitutions, which distinguish them from skeletal muscle actin. Cardiac muscle actin differs from skeletal muscle actin by only four amino acid exchanges. No amino acid substitutions were found when actins from rabbit fast and slow skeletal muscle were compared. In addition we summarize the amino acid substitution patterns of the six different mammalian actins and discuss their tissue specificity. The results show a very close relationship between the four muscle actins in comparison to the nonmuscle actins. The amino substitution patterns indicate that skeletal muscle actin is the highest differentiated actin form, whereas smooth muscle actins show a noticeably cloer relation to nonmuscle actins. By these criteria cardiac muscle actin lies between skeletal muscle actin and smooth muscle actins.

Actins↗

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

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

Adult↗

E-box sites and a proximal regulatory region of the muscle creatine kinase gene differentially regulate expression in diverse skeletal muscles and cardiac muscle of transgenic mice.

Previous analysis of the muscle creatine kinase (MCK) gene indicated that control elements required for transcription in adult mouse muscle differed from those required in cell culture, suggesting that distinct modes of muscle gene regulation occur in vivo. To examine this further, we measured the activity of MCK transgenes containing E-box and promoter deletions in a variety of striated muscles. Simultaneous mutation of three E boxes in the 1,256-bp MCK 5' region, which abolished transcription in muscle cultures, had strikingly different effects in mice. The mutations abolished transgene expression in cardiac and tongue muscle and caused a reduction in expression in the soleus muscle (a muscle with many slow fibers) but did not affect expression in predominantly fast muscles: quadriceps, abdominals, and extensor digitorum longus. Other regulatory sequences with muscle-type-specific activities were found within the 358-bp 5'-flanking region. This proximal region conferred relatively strong expression in limb and abdominal skeletal muscles but was inactive in cardiac and tongue muscles. However, when the 206-bp 5' enhancer was ligated to the 358-bp region, high levels of tissue-specific expression were restored in all muscle types. These results indicate that E boxes and a proximal regulatory region are differentially required for maximal MCK transgene expression in different striated muscles. The overall results also imply that within skeletal muscles, the steady-state expression of the MCK gene and possibly other muscle genes depends on transcriptional mechanisms that differ between fast and slow fibers as well as between the anatomical and physiological attributes of each specific muscle.

Animals↗

[Muscle strength and muscle blood flow of the quadriceps muscle].

This study was conducted to measure muscle blood flow changes during increased muscle strength in order to determine what characteristic parameters of muscle strength were most closely correlated with increased muscle blood flow. The muscle blood flow and muscle strength in the quadriceps femoris were measured simultaneously during isokinetic extension of the knee joints in two groups--one with knee-joint-disease and the other of healthy volunteers. Muscle blood flow was measured by the heated thermocouple technique, while parameters of muscle strength were evaluated utilizing curves calculated by a Cybex II. The test results showed a positive correlation between parameters of muscle strength (peak torque, total work and average power) and peak blood flow. However, both the muscle strength and the muscle blood flow values were less in the group with knee joint disease than in the group of healthy volunteers. In both groups, the muscle blood flow was greatest when the knee was extended at an increased angular velocity. Although the muscle blood flow was greatest at this time, only the parameter of average power increased while the parameter of peak torque and total work decreased. As a result, the average power was correlated most closely with the increased muscle blood flow. In patients with a knee joint disease, the increase in the muscle blood flow was much higher than expected despite the fact that there was little increase in average power during knee movement at an increased angular velocity. It appeared that the pathological condition in these patients' quadriceps femoris required increased blood flow despite an inability of the muscle to perform increased muscle work.

Adolescent↗

[Contractile properties of the striated muscle fibres of esophageal muscle in comparison with skeletal muscle in rats].

The contractile properties of the striated oesophageal muscle of the rat were studied in vitro at 35 degrees C and 25 degrees C. They were compared with those of the slow-twitch soleus muscle and the fast-twitch extensor digitorum longus (EDL) muscle of the same animals. The contraction time of the oesophageal muscle is 30 msec (+/- 2.5 msec S.E.) at 35 degrees C. It is little but significantly longer than those of the soleus muscle. It is remarkable that the twitch-tetanus ratio of the oesophageal muscle fibres is approximately twice that of the skeletal muscles. Immediately after a tetanic stimulation the amplitude of a single twitch of the fast EDL is increased (posttetanic potentiation); in the slow soleus muscle it is unchanged or decreased, however. Also the muscle fibres of the oesophagus exhibit a post-tetanic-potentiation, but this is smaller than in EDL. A decrease of the temperature of the bathing solution causes in preparations of the fast EDL a higher tension developed by a single twitch (cold potentiation). This is not detectable in preparations of the slow soleus muscle. The oesophageal muscle shows also a remarkable cold potentiation, but it is smaller than in EDL. An increase of the extracellular K+-concentration evokes a short-lasting contracture in the investigated rat muscles. The mechanical thresholds of the oesophageal muscle fibres are clearly higher than those of the soleus muscle but lower than those of the EDL. The striated oesophageal muscle fibres of the rat in spite of their low speed of contraction show some properties of muscle fibres of the fast twitch type.

Animals↗

Roles of muscle activity and load on the relationship between muscle spindle length and whole muscle length in the freely walking cat.

The objective of this research was to compare the length of muscle spindles to the length of the whole muscle, during normal movements. Pairs of piezoelectric crystals were implanted near the origin and insertion of muscle fibres in the medial gastrocnemius (MG) muscle of cats. The distance between crystals was measured with pulsed ultrasound, the origin-to-insertion length of the MG muscle was measured with a transducer made of saline-filled silicone tubing, MG force was measured with a tendon force transducer and EMG activity was selectively recorded in the vicinity of implanted crystals. These signals were simultaneously recorded during posture or locomotion on a motorized treadmill. Three periods were identified in the step cycle, during which the relation between muscle length and spindle length changed dramatically. In period I (roughly corresponding to the late F and E1 phases of swing), the MG muscle and spindles followed similar length changes: both were stretched and then shortened by about 6 mm. In period II (corresponding to the stance phase, E2-E3) the MG muscle yielded under the weight of the body and was stretched by 1-3 mm, whereas the MG spindles typically continued shortening. In period III, the MG muscle shortened rapidly by 6-8 mm after the foot left the ground and then stretched again by about the same amount, whereas the spindles could remain nearly isometric. We attribute these large discrepancies in muscle and spindle length to the architecture of the MG muscle and the compliance of long tendinous elements in series with the spindles. We conclude that the length changes imposed on muscle spindles during voluntary movements are not simply related to the parent muscle length changes and cannot be estimated without taking into account the muscle architecture, the location of the spindle within the muscle, the level of muscle activation and the external load.

Animals↗

Striated muscle-type tropomyosin in a chordate smooth muscle, ascidian body-wall muscle.

Body-wall muscle tropomyosin (Tm) of a marine chordate, the ascidian Ciona intestinalis, was studied by protein and cDNA clone analyses. Our results indicate that body-wall muscle of Ciona contains one major Tm isoform encoded by a single gene. Unexpectedly, the sequence of this Tm resembles vertebrate-striated muscle Tm isoforms, rather than those of smooth muscle or nonmuscle tissues, despite the fact that body-wall muscle is a nonsarcomeric (i.e. smooth) muscle. We also found that an apparently identical Tm isoform, derived from the same gene, is expressed at high levels in Ciona heart, a striated muscle. This is the first example of an organism in which a single Tm isoform is prominently expressed in both sarcomeric and non-sarcomeric tissues. Our results demonstrate that the characteristic features of "sarcomeric" Tm isoforms are not primarily related to sarcomeric ultrastructure per se. Instead, because ascidian body-wall muscle, unlike vertebrate smooth muscle, contains troponin, we suggest that it is the interaction with troponin that generates the selective pressure to maintain the characteristic C-terminal structure of so-called sarcomeric Tm isoforms. Our results further document the remarkable molecular similarity between the nonsarcomeric ascidian body-wall muscle and vertebrate-striated muscle. We suggest that these muscle types represent sarcomeric and nonsarcomeric variants of a fundamental class of troponin/Tm-regulated muscles, contrary to the traditional smooth/striated classification of muscle types. The possible relationship of this class of muscle to vertebrate smooth muscle is discussed.

Amino Acid Sequence↗

[Cisatricurium in the orbicularis oculi muscle. Comparisn of the neuromuscular action of cisatracurium and atracurium in the orbicularis oculi muscle and the adductor pollicis muscle].

OBJECTIVES: Muscle relaxants have different pharmacodynamic profiles in various muscles. Therefore, results obtained for one muscle cannot be extrapolated to other muscles. In the adductor pollicis muscle cisatracurium exerts a pharmacodynamic profile comparable to atracurium, despite the known difference in onset time. However, studies evaluating the neuromuscular effect of cisatracurium in different muscles are lacking. Accordingly, this study compares the pharmacodynamic profile of cisatracurium and atracurium in the orbicularis oculi muscle (OO) - which shows a neuromuscular course similar to the diaphragm and the laryngeal muscles - and the adductor pollicis muscle (AP). METHODS: Forty-five patients (ASA I-II), scheduled for elective spinal surgery were anaesthetized with propofol and fentanyl. Endotracheal intubation was performed without using a muscle relaxant. Neuromuscular transmission was monitored using acceleromyography in both muscles. Patients received 0.1 mg/kg (2x ED(95)) or 0.15 mg/kg (3x ED(95)) cisatracurium, or 0.5 mg/kg atracurium (2x ED(95)) at random. Onset and recovery times were measured according to the recommendation of the Copenhagen Consensus Conference. RESULTS: Onset time was significantly shorter in the OO than in the AP following 0.15 mg/kg cisatracurium and 0.5 mg/kg atracurium (P<0.05). No differences in onset time between the two muscles were found after 0.1 mg/kg cisatracurium. The recovery of T(1) to 10% of its control was completed sooner in the OO than in the AP in all three groups (P<0.05). CONCLUSIONS: Cisatracurium shows a dose-dependent shorter onset time in the OO than in the AP. This is consistent with the current view that the onset of non-depolarizing neuromuscular blockers is more rapid in the OO than in the AP. However, at least a dose of 3x ED(95) of cisatracurium was necessary to show a difference in onset time between both muscles. In contrast, atracurium is reported to lead to a significantly shorter onset of neuromuscular block in the OO following 2x the ED(95). The more rapid recovery of T(1) to 10% of its control in all three groups in the OO is due to the relative resistance of this muscle to muscle relaxants.

Adult↗