L-leucine stimulation of glucose uptake and utilization involves modulation of glucose - lipid metabolic switch and improved bioenergetic homeostasis in isolated rat psoas muscle ex vivo.

The antidiabetic effect of l-leucine has been attributed to its modulatory effect on glucose uptake and lipid metabolism in muscles. However, there is a dearth on its effect on glucose metabolism in muscles. Thus, the present study investigated the effect of l-leucine - stimulated glucose uptake on glucose metabolism, dysregulated lipid metabolic pathways, redox and bioenergetic homeostasis, and proteolysis in isolated psoas muscle from Sprague Dawley male rats. Isolated psoas muscles were incubated with l-leucine (30-240 µg/mL) in the presence of 11.1 mMol glucose at 37 ˚C for 2 h. Muscles incubated in only glucose served as the control, while muscles not incubated in l-leucine and/or glucose served as the normal control. Metformin (6.04 mM) was used as the standard antidiabetic drug. Incubation with l-leucine caused a significant increase in muscle glucose uptake, with an elevation of glutathione levels, superoxide dismutase, catalase, E-NTPDase and 5'nucleotidase activities. It also led to the depletion of malondialdehyde and nitric oxide levels, ATPase, chymotrypsin, acetylcholinesterase, glycogen phosphorylase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and lipase activities. There was an alteration in lipid metabolites, with concomitant activation of glycerolipid metabolism, fatty acid metabolism, and fatty acid elongation in mitochondria in the glucose-incubated muscle (negative control). Incubation with l-leucine reversed these alterations, and concomitantly deactivated the pathways. These results indicate that l-leucine-enhanced muscle glucose uptake involves improved redox and bioenergetic homeostasis, with concomitant suppressed proteolytic, glycogenolytic and gluconeogenetic activities, while modulating glucose - lipid metabolic switch.

Statin use, development of sarcopenia, and long-term survival after endovascular aortic repair.

OBJECTIVE: Statin therapy, associated with improved short-term survival after treatment of abdominal aortic aneurysms, may also predispose to muscle side effects. Evidence on statin-related sarcopenia is limited mainly to muscle function, and it is subject to several sources of bias. In the long term, postoperative development of sarcopenia is linked to mortality after endovascular repair (EVAR). We investigated statin use and long-term postoperative mortality after EVAR in relation to objective measurable markers of sarcopenia (psoas muscle surface area and density). METHODS: Altogether 216 abdominal aortic aneurysm patients treated with EVAR between 2006 and 2014 at Tampere University Hospital (Finland) were retrospectively studied. Psoas muscle parameters at the L3 level were evaluated from baseline and mainly 1- to 3-year follow-up computed tomography studies. Cox regression was used to study the association between statin medication, psoas muscle changes, and all-cause mortality. RESULTS: The majority of patients were male (87%), and the mean age was 77.7 years (standard deviation, 7.4). The median duration of follow-up was 6.3 years (interquartile range, 3.5) with a total mortality of 54.2% (n = 117). Regardless of a higher burden of comorbidities, statin users (n = 119) had lower mortality when compared with nonusers (multivariable hazard ratio [HR]: 0.69, 95% confidence interval: 0.48-0.99, P = .048). Furthermore, statin use was not associated with inferior muscle parameter values, and the relative change in psoas muscle area was actually lower in statin users compared with nonusers (-15.7% and -21.1%, P < .046). CONCLUSIONS: Statin use is associated with lower long-term mortality among patients undergoing EVAR without predisposing to increased sarcopenia.

Medical management of psoas muscle deep endometriosis: A case report.

Endometriosis is a common gynaecological pathology characterized by the presence of endometrial tissue outside the uterine cavity, and the most frequent locations of endometriosis are ovaries and posterior compartment of the pelvis. In this paper we report the case of a rare bilateral endometriosis location of posas muscle diagnosed and treated in a 25-year-old patient. This is the third case of psoas endometriosis location reported, but the first one successfully treated by hormone estrogen-progestogen treatment alone. Psoas endometriosis is a rare location and the medical management in first line can be an alternative to surgery and provide optimal patient relief.

Different Concentrations of Ropivacaine under Ultrasound Guidance on Quadratus Lumbar Muscle Nerve Block in Elderly Patients with Hip Replacement.

OBJECTIVE: To compare the effect of ropivacaine in different concentrations under ultrasound guidance on lumbar muscle nerve blocking in elderly patients undergoing hip replacement surgery. METHODS: 60 elderly patients underwent hip replacement in our hospital over a period of April to December of 2019 were equally randomized into control and observation groups, with 30 each. Patients in the control group and observation group received 0.5% and 0.25% ropivacaine to block psoas muscle nerve, respectively. The anesthetic effect of ropivacaine at different concentrations was evaluated by time of sensory block onset and recovery and time of motor block onset and regression, blood pressure, heart rate, visual analogy scale, and postoperative nerve blocking degree. RESULTS: The onset time of sensory and motor block in the observation group was dramatically higher than that in the control group (P < 0.05), while the recovery time of sensory and motor was significantly shorter than that of the control group (P < 0.05). The heart rate in the observation group was notably lower than that in the control group, while the average blood pressure was remarkably higher (P < 0.05). After surgery, the degree of nerve block in the observation group was much lower compared with the control group (P < 0.05), while no marked difference in the visual analogue scale in the control group before and after surgical intervention was observed (P > 0.05). CONCLUSION: The 0.25% ropivacaine method has distinctive advantages over 0.50% ropivacaine psoas nerve anesthesia in hip replacement surgery in elderly patients.

Impact of measurement of skeletal muscle mass on clinical outcomes in patients with esophageal cancer undergoing esophagectomy after neoadjuvant chemotherapy.

BACKGROUND: Some studies have reported that sarcopenia is linked to clinical outcomes in multiple types of malignancies, but this association has not been established in esophageal cancer. We assessed how sarcopenia affects clinical outcomes of multidisciplinary treatments for esophageal cancer. METHODS: We included 165 esophageal cancer patients who had undergone neoadjuvant chemotherapy followed by esophagectomy. Computed tomography was used for cross-sectional measurement of the psoas muscle at the third lumbar vertebra; we then calculated the height-adjusted psoas muscle index. Pre- and postneoadjuvant chemotherapy psoas muscle indices were evaluated for associations with neoadjuvant chemotherapy response and neoadjuvant chemotherapy -related adverse events and postoperative complications, in addition to survival. Psoas muscle index cutoffs were 6.36 cm2/m2 for men and 3.92 cm2/m2 for women. RESULTS: Psoas muscle index decreased after neoadjuvant chemotherapy (from 7.17 to 6.96 cm2/m2; P = .0008), and specifically in men (from 7.45 to 7.23 cm2/m2; P = .0001) but not in women (from 5.21 to 5.17 cm2/m2; P = .810). Preneoadjuvant chemotherapy psoas muscle index (low versus high) was associated with neoadjuvant chemotherapy response (response rate: 65.1% vs 80.3%; P = .0494) and neoadjuvant chemotherapy-related adverse events (neutropenia: 93.0% vs 78.7%; P = .0337; febrile neutropenia: 53.5% vs 34.3%; P = .0278; hyponatremia: 51.2% vs 31.2%; P = .0190). Post-neoadjuvant chemotherapy psoas muscle index correlated with postoperative rate of complications (56.9% vs 33.3%; P = .0046), especially pneumonia (31.4% vs 9.7% P = .0008). Psoas muscle index was not associated with survival. CONCLUSION: Cross sectional measures of sarcopenia before and after neoadjuvant chemotherapy could predict tumor response, neoadjuvant chemotherapy -related adverse events, and postoperative complications in multidisciplinary treatments for esophageal cancer.

Force generated by myosin cross-bridges is reduced in myofibrils exposed to ROS/RNS.

Skeletal muscle weakness is associated with oxidative stress and oxidative posttranslational modifications on contractile proteins. There is indirect evidence that reactive oxygen/nitrogen species (ROS/RNS) affect skeletal muscle myofibrillar function, although the details of the acute effects of ROS/RNS on myosin-actin interactions are not known. In this study, we examined the effects of peroxynitrite (ONOO-) on the contractile properties of individual skeletal muscle myofibrils by monitoring myofibril-induced displacements of an atomic force cantilever upon activation and relaxation. The isometric force decreased by ~50% in myofibrils treated with the ONOO- donor (SIN-1) or directly with ONOO-, which was independent of the cross-bridge abundancy condition (i.e., rigor or relaxing condition) during SIN-1 or ONOO- treatment. The force decrease was attributed to an increase in the cross-bridge detachment rate (gapp) in combination with a conservation of the force redevelopment rate (kTr) and hence, an increase in the population of cross-bridges transitioning from force-generating to non-force-generating cross-bridges during steady-state. Taken together, the results of this study provide important information on how ROS/RNS affect myofibrillar force production which may be of importance for conditions where increased oxidative stress is part of the pathophysiology.

Modulatory effects of Caralluma fimbriata extract against high-fat diet induced abnormalities in carbohydrate metabolism in Wistar rats.

The present study was aimed to evaluate the modulatory effects of hydroalcoholic extract of Caralluma fimbriata (CFE) by assaying the activities of key enzymes of carbohydrate metabolism and changes in glycogen content (liver and muscle) in high-fat (HF) diet-induced diabetic rats. In vitro glucose uptake studies were carried out in both psoas muscle and adipose tissue. The inhibitory effect of the extract on α-amylase was determined in in vitro studies. Male Wistar rats of body weight around 180g were divided into five groups (n=8), two of these groups were fed with standard pellet diet and the other three groups were fed with HF- (60%) diet. CFE (200mg/kg body weight/day) was administered through oral route to each group of standard pellet diet rats and HF-fed rats and Metformin (Met) (20mg/kg body weight/day) was administered through oral route to HFD+Met group for 90 days. At the end of the experimental period, biochemical parameters related to glycogen content in liver and muscle, and intestinal disaccharidases like maltase, sucrase and lactase were assayed. Alterations in the activities of enzymes of glucose metabolism (hexokinase, phosphorfructoki nase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glucose-6-phosphate dehydrogenase), intestinal disaccharidases and glycogen content as observed in the high fat diet-fed rats were prevented with CFE/Met administration. From this study, we observed that CFE/Met could significantly restore the levels of glycogen in liver and muscle and key enzymes of carbohydrate metabolism to near normal in groups-HFD+CFE and HFD+Met. The skeletal muscle of HF-diet fed rats showed degenerative changes of muscle myofibers with fat deposition. These changes were attenuated in the HFD group treated with CFE/Met and retained their normal structure appearance. It can be concluded from these results that CFE might be of value in reducing the alterations related to carbohydrate metabolism under high calorie diet consumption.

Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study.

The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC50 = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU50 = 2.68 ± 0.75 %) or without (GU50 = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.

Unanticipated Motor Weakness with Ultrasound-Guided Transversalis Fascia Plane Block.

The transversalis fascia plane block is a relatively new truncal block that targets the iliohypogastric and ilioinguinal nerves. It is gaining wider usage for its reliability to block these nerves as compared with the transversus abdominis plane block. The case presented here appears to be the first time that motor weakness has resulted from this block technique. It is suspected that central and proximal spread of local anesthetic toward the psoas muscle may have resulted in a partial lumbar plexus block.

Change in skeletal muscle mass after administering entecavir in patients with hepatitis B.

OBJECTIVE: Cachexia, or disease-related loss of muscle mass, is a complication of chronic liver disease that modifies its clinical course. The aim of this study was to determine whether improvement in liver function and cachexia through control of the hepatitis B virus (HBV) increases skeletal muscle mass. METHODS: The blood tests and cross-sectional area (mm(2)) of the psoas major muscle on computed tomography were measured before and after long-term entecavir therapy (median, 39 mo; range, 14-76 mo) in patients with hepatitis B (17 men, 13 women; mean age, 63 ± 13 y). RESULTS: The anti-HBV effect was good in 30 patients given entecavir, and most patients had undetectable serum HBV-DNA levels (93%) and alanine aminotransferase normalization (83%) within a median of 32 mo. Overall, no significant change in the area of the psoas major muscle was seen in any of the patients, although a significant increase was seen when limited to cases of protein malnutrition defined as serum albumin (Alb) <4 g/dL. A positive correlation was seen for the amount of change (Δ) in the psoas major muscle and the amount of change (Δ) in Alb. CONCLUSIONS: The present findings suggest that skeletal muscle mass may fluctuate in parallel with Alb levels. An improvement in low muscle mass may thus be expected from antiviral therapy for viral liver disease, especially in patients with cachexia.

Early pharmacokinetic of ropivacaine without epinephrine after injection into the psoas compartment.

BACKGROUND: Large amounts of local anaesthetics (LA) are used during psoas compartment block (PCB), especially if combined with sciatic nerve block. Data regarding early pharmacokinetics of ropivacaine for PCB are lacking, notably when a vasoconstrictive agent has not been added. METHODS: PCB was established in 11 patients using 150 mg ropivacaine without epinephrine. Free and total arterial plasma concentrations of ropivacaine were measured at nine time points during the following 30 min. Also total protein, albumin, and α1-acid glycoprotein concentrations were analysed. RESULTS: Ropivacaine plasma concentrations were found in all patients within 30 s after injections. Maximum measured plasma concentrations were measured in all but two patients within the first 10 min. One patient experienced partial intravascular injection. Plasma concentrations showed wide inter-individual variability. Ranges of maximum measured plasma concentrations of total and free ropivacaine were 422-3905 and 5-186 ng ml(-1), respectively. The Pearson correlation between total and free concentrations was 0.96. No obvious relationship between concentrations of different plasma proteins (total protein, albumin, α1-acid glycoprotein) and ropivacaine concentrations was found. Maximal 5% of the measured ropivacaine was unbound. All blocks were successful and no signs of toxicity were observed. CONCLUSIONS: Maximum measured plasma concentrations of ropivacaine after PCB must be expected within 10 min. Although plasma concentrations stayed below toxic thresholds, our study demonstrates the risk of this regional anaesthesia technique. CLINICAL TRIAL REGISTRATION: The clinical study was not registered because enrolment of study patients occurred in 2006.

Calcium sensitivity of residual force enhancement in rabbit skinned fibers.

Isometric force after active stretch of muscles is higher than the purely isometric force at the corresponding length. This property is termed residual force enhancement. Active force in skeletal muscle depends on calcium attachment characteristics to the regulatory proteins. Passive force has been shown to influence calcium attachment characteristics, specifically the sarcomere length dependence of calcium sensitivity. Since one of the mechanisms proposed to explain residual force enhancement is the increase in passive force that results from engagement of titin upon activation and stretch, our aim was to test if calcium sensitivity of residual force enhancement was different from that of its corresponding purely isometric contraction and if such a difference was related to the molecular spring titin. Force-pCa curves were established in rabbit psoas skinned fibers for reference and residual force-enhanced states at a sarcomere length of 3.0 µm 1) in a titin-intact condition, 2) after treatment with trypsin to partially eliminate titin, and 3) after treatment with trypsin and osmotic compression with dextran T-500 to decrease the lattice spacing in the absence of titin. The force-pCa curves of residual force enhancement were shifted to the left compared with their corresponding controls in titin-intact fibers, indicating increased calcium sensitivity. No difference in calcium sensitivity was observed between reference and residual force-enhanced contractions in trypsin-treated and osmotically compressed trypsin-treated fibers. Furthermore, calcium sensitivity after osmotic compression was lower than that observed for residual force enhancement in titin-intact skinned fibers. These results suggest that titin-based passive force regulates the increase in calcium sensitivity of residual force enhancement by a mechanism other than reduction of the myofilament lattice spacing.

Antihyperglycemic activity of Caralluma tuberculata in streptozotocin-induced diabetic rats.

The current study aimed at evaluating the potential and mechanisms of the antidiabetic activity of the methanolic extract (ME) of Caralluma tuberculata as well as its chloroform (CF), n-butanol (BF) and the remaining water fractions (RFs) in streptozotocin-induced diabetic rats. The antidiabetic activity was evaluated through assessing fasting blood glucose (FBG), insulin levels, oral glucose tolerance test (OGTT), glucose utilization by isolated rat psoas muscle, gut glucose absorption and G-6-Pase activity in isolated rat liver microsomes. Both ME and RF showed the highest potency, where ME had superior activity. The mechanism underlying the observed antihyperglycemic activity of ME could be attributed, at least in part, to enhanced skeletal muscle utilization of glucose, inhibition of hepatic gluconeogenesis and stimulation of insulin secretion. ME was standardized through LC-MS analysis for its major pregnanes.

Resistance exercise combined with essential amino acid supplementation improved walking ability in elderly people.

We investigated the effects of resistance exercise combined with essential amino acid supplementation on psoas major muscle (PMM) hypertrophy and walking ability in elderly individuals. Twenty-nine healthy elderly individuals were assigned to 3 groups: (1) E (exercise), (2) A3 (exercise combined with 3.0 g of essential amino acid supplementation), and (3) A6 (exercise combined with 6.0 g of essential amino acid supplementation). To evaluate walking ability, the participants underwent the following 3 types of tests: the (1) 10-meter walk (10-W), (2) 10-meter walk involving crossing of obstacles (10-W + O), and (3) 6-minute walk (6M-W) tests. The 6-month training program resulted in significant PMM hypertrophy in all groups independent of amino acid supplementation. The extent of hypertrophy in the participants who took amino acids was dose-dependent, although the differences were not significant. Groups A3 and A6 demonstrated improvements in the 10-W and 10-W + O tests, whereas no improvement was observed in group E, regardless of PMM hypertrophy. Furthermore, group A6 showed an improvement in the 6M-W test. These results suggest that our training program causes PMM hypertrophy, whereas the training program combined with essential amino acid supplementation improves walking ability.

Kinetic mechanism of Ca²âº-controlled changes of skeletal troponin I in psoas myofibrils.

Conformational changes in the skeletal troponin complex (sTn) induced by rapidly increasing or decreasing the [Ca(2+)] were probed by 5-iodoacetamidofluorescein covalently bound to Cys-133 of skeletal troponin I (sTnI). Kinetics of conformational changes was determined for the isolated complex and after incorporating the complex into rabbit psoas myofibrils. Isolated and incorporated sTn exhibited biphasic Ca(2+)-activation kinetics. Whereas the fast phase (k(obs)∼1000 s(-1)) is only observed in this study, where kinetics were induced by Ca(2+), the slower phase resembles the monophasic kinetics of sTnI switching observed in another study (Brenner and Chalovich. 1999. Biophys. J. 77:2692-2708) that investigated the sTnI switching induced by releasing the feedback of force-generating cross-bridges on thin filament activation. Therefore, the slower conformational change likely reflects the sTnI switch that regulates force development. Modeling reveals that the fast conformational change can occur after the first Ca(2+) ion binds to skeletal troponin C (sTnC), whereas the slower change requires Ca(2+) binding to both regulatory sites of sTnC. Incorporating sTn into myofibrils increased the off-rate and lowered the Ca(2+) sensitivity of sTnI switching. Comparison of switch-off kinetics with myofibril force relaxation kinetics measured in a mechanical setup indicates that sTnI switching might limit the rate of fast skeletal muscle relaxation.

Mouse compound muscle action potential assay: an alternative method to conduct the LD50 botulinum toxin type A potency test.

PURPOSE: We performed a prevalidation of the compound muscle action potential (CMAP) assay to determine the potency of botulinum neurotoxin type A (BoNT/A) with the aim of substituting for the mouse lethality test (LD50), which is used for quality control. METHODS: Prevalidation experiments were performed to demonstrate the specificity, linearity, accuracy, precision, range, limit of quantitation (LOQ), and robustness of the assay. For specificity, toxin detection ability was determined in the presence of neutralizing antibodies (0.8 and 8 IU/mL). Linearity of this assay was determined by measuring CMAP amplitude using nine concentrations (n = 3) in the range of 1-100 U/mL (n = 3). Accuracy was assessed using five concentrations (n = 3) in the range of 4-40 U/mL. Intermediate precision was confirmed by analyzing individually prepared reagents on multiple days by one operator (n = 3). Different body weights (23-25 and 25-27 g) and measurement times (3-5 and 5-7 min) after anesthetic induction were tested to assess robustness. RESULTS: This assay might have BoNT/A specificity, based on the CMAP amplitude recovery using a concentration of neutralizing antibodies. The calibration curves were linear over the range of 2-40 U/mL (R² = 0.982). The accuracy of 14 determinations was within the range of 89.8-118.6% compared to the theoretical values among 15 determinations, except one (131.3%). Assay variability was acceptable with coefficients of variation of 4.3-14.4%. The range of quantification and the LOQ were 4-40 U/mL and 4 U/mL, respectively. Different body weights and measurement times after inducing anesthesia had no effect on CMAP amplitude. CONCLUSIONS: These results suggest that the mouse CMAP assay is an alternative method to the standard LD50 potency test and meets the requirement of the three Rs (particularly refinement and reduction).

[Infiltration of the psoas muscles with botulinum toxin guided by computerised axial tomography: a series of cases]. / Infiltración del psoas con toxina botulínica guiada por tomografía axial computarizada: serie de casos.

AIM: To evaluate the effectiveness and safety of infiltrating the psoas muscle with botulinum toxin guided by computerised tomography (CT) in order to reduce dynamic contracture in bending the hip. PATIENTS AND METHODS: The study involves a series of five children diagnosed with spastic cerebral palsy and bilateral involvement. All the children were able to walk and they presented an attitude on bending the hips and knees consisting in the typical 'crouch gait' together with a dynamic contracture of the hips and knees. They did not present any contraindications for the use of botulinum toxin and their parents gave their consent. Under CT control and anaesthetic sedation, both psoas muscles were infiltrated with a dose of 3 U/kg of body weight; later, both ischiotibial muscles were infiltrated using 3 U/kg doses. The patients were evaluated both prior to and four weeks after infiltration; the muscular range was assessed by means of goniometry, muscular tone was evaluated using the modified Ashworth scale, spasticity was measured using Tardieu's dynamic test and the attitude in bending the hips and knees under a load was assessed by goniometric measurement. Likewise, adverse secondary effects to the puncture or to the use of the toxin were recorded. RESULTS: The five patients reported an improvement in both mobility (with a reduction of tone and contracture) and the posture when standing. CONCLUSIONS: Infiltration of the psoas muscle guided by CT is an effective, safe technique for reducing spasticity in bending the hip, which, if accompanied by infiltration of the ischiotibial muscles, improves the attitude on bending the hip and knee.

Sarcomere length-dependent Ca2+ activation in skinned rabbit psoas muscle fibers: coordinated regulation of thin filament cooperative activation and passive force.

In skeletal muscle, active force production varies as a function of sarcomere length (SL). It has been considered that this SL dependence results simply from a change in the overlap length between the thick and thin filaments. The purpose of this study was to provide a systematic understanding of the SL-dependent increase in Ca(2+) sensitivity in skeletal muscle, by investigating how thin filament "on-off" switching and passive force are involved in the regulation. Rabbit psoas muscles were skinned, and active force measurements were taken at various Ca(2+) concentrations with single fibers, in the short (2.0 and 2.4 µm) and long (2.4 and 2.8 µm) SL ranges. Despite the same magnitude of SL elongation, the SL-dependent increase in Ca(2+) sensitivity was more pronounced in the long SL range. MgADP (3 mM) increased the rate of rise of active force and attenuated SL-dependent Ca(2+) activation in both SL ranges. Conversely, inorganic phosphate (Pi, 20 mM) decreased the rate of rise of active force and enhanced SL-dependent Ca(2+) activation in both SL ranges. Our analyses revealed that, in the absence and presence of MgADP or Pi, the magnitude of SL-dependent Ca(2+) activation was (1) inversely correlated with the rate of rise of active force, and (2) in proportion to passive force. These findings suggest that the SL dependence of active force in skeletal muscle is regulated via thin filament "on-off" switching and titin (connectin)-based interfilament lattice spacing modulation in a coordinated fashion, in addition to the regulation via the filament overlap.

Electron microscopy and x-ray diffraction evidence for two Z-band structural states.

In vertebrate muscles, Z-bands connect adjacent sarcomeres, incorporate several cell signaling proteins, and may act as strain sensors. Previous electron microscopy (EM) showed Z-bands reversibly switch between a relaxed, "small-square" structure, and an active, "basketweave" structure, but the mechanism of this transition is unknown. Here, we found the ratio of small-square to basketweave in relaxed rabbit psoas muscle varied with temperature, osmotic pressure, or ionic strength, independent of activation. By EM, the A-band and both Z-band lattice spacings varied with temperature and pressure, not ionic strength; however, the basketweave spacing was consistently 10% larger than small-square. We next sought evidence for the two Z-band structures in unfixed muscles using x-ray diffraction, which indicated two Z-reflections whose intensity ratios and spacings correspond closely to the EM measurements for small-square and basketweave if the EM spacings are adjusted for 20% shrinkage due to EM processing. We conclude that the two Z-reflections arise from the small-square and basketweave forms of the Z-band as seen by EM. Regarding the mechanism of transition during activation, the effects of Ca(2+) in the presence of force inhibitors suggested that the interconversion of Z-band forms was correlated with tropomyosin movement on actin.

Hemodynamic changes during a combined psoas compartment-sciatic nerve block for elective orthopedic surgery.

BACKGROUND: Hemodynamic variables can theoretically be influenced by a combined psoas compartment-sciatic nerve block (CPCSNB) owing to a relatively high systemic absorption of local anesthetics and extended vasodilatation in the anesthetized limb (hemisympatectomy). In this study we assessed and documented hemodynamic changes during CPCSNB for elective orthopedic surgery. METHODS: Twenty consecutive patients scheduled for a total hip arthroplasty revision surgery were subjected to a CPCSNB with 150 mg bupivacaine (with epinephrine 1:200.000) 90 minutes before surgery (2 separate single-injection blocks: 30 mg bupivacaine for the sciatic nerve block and 120 mg bupivacaine for the psoas compartment block). Cardiac index, invasive arterial blood pressure, and heart rate were measured at baseline and 60 minutes after puncture using a minimally invasive cardiac output monitoring device (FloTrac/Vigileo™ system (Edwards Lifesciences, Irvine, CA)). RESULTS: Cardiac index did not change after a CPCSNB (preblock cardiac index 2.98 ± 0.54 l · min(-1) · m(-2) versus postblock cardiac index 2.99 ± 0.60 l · min(-1) · m(-2)). There was a significant reduction in mean arterial blood pressure (108 ± 16 mm|Hg vs. 99 ± 16 mm|Hg (P < 0.001)) and diastolic blood pressure (75 ± 9 mm|Hg vs. 68 ± 10 mm|Hg (P = 0.001)). Heart rate increased significantly (68 ± 9 beats · min(-1) vs. 73 ± 10 beats · min(-1) (P = 0.001)). CONCLUSION: CPCSNB did not affect cardiac index. Changes in arterial blood pressure and heart rate, although statistically significant, remained within an acceptable clinical range (<10% variation). CPCSNB does not appear to induce clinically significant hemodynamic changes in this group of patients.