Outcomes After Endovascular Therapy With Procedural Sedation vs General Anesthesia in Patients With Acute Ischemic Stroke: The AMETIS Randomized Clinical Trial.

Importance: General anesthesia and procedural sedation are common practice for mechanical thrombectomy in acute ischemic stroke. However, risks and benefits of each strategy are unclear. Objective: To determine whether general anesthesia or procedural sedation for anterior circulation large-vessel occlusion acute ischemic stroke thrombectomy are associated with a difference in periprocedural complications and 3-month functional outcome. Design, Setting, and Participants: This open-label, blinded end point randomized clinical trial was conducted between August 2017 and February 2020, with final follow-up in May 2020, at 10 centers in France. Adults with occlusion of the intracranial internal carotid artery and/or the proximal middle cerebral artery treated with thrombectomy were enrolled. Interventions: Patients were assigned to receive general anesthesia with tracheal intubation (n = 135) or procedural sedation (n = 138). Main Outcomes and Measures: The prespecified primary composite outcome was functional independence (a score of 0 to 2 on the modified Rankin Scale, which ranges from 0 [no neurologic disability] to 6 [death]) at 90 days and absence of major periprocedural complications (procedure-related serious adverse events, pneumonia, myocardial infarction, cardiogenic acute pulmonary edema, or malignant stroke) at 7 days. Results: Among 273 patients evaluable for the primary outcome in the modified intention-to-treat population, 142 (52.0%) were women, and the mean (SD) age was 71.6 (13.8) years. The primary outcome occurred in 38 of 135 patients (28.2%) assigned to general anesthesia and in 50 of 138 patients (36.2%) assigned to procedural sedation (absolute difference, 8.1 percentage points; 95% CI, -2.3 to 19.1; P = .15). At 90 days, the rate of patients achieving functional independence was 33.3% (45 of 135) with general anesthesia and 39.1% (54 of 138) with procedural sedation (relative risk, 1.18; 95% CI, 0.86-1.61; P = .32). The rate of patients without major periprocedural complications at 7 days was 65.9% (89 of 135) with general anesthesia and 67.4% (93 of 138) with procedural sedation (relative risk, 1.02; 95% CI, 0.86-1.21; P = .80). Conclusions and Relevance: In patients treated with mechanical thrombectomy for anterior circulation acute ischemic stroke, general anesthesia and procedural sedation were associated with similar rates of functional independence and major periprocedural complications. Trial Registration: ClinicalTrials.gov Identifier: NCT03229148.

Sedation versus general anaesthesia in endovascular therapy for anterior circulation acute ischaemic stroke: the multicentre randomised controlled AMETIS trial study protocol.

INTRODUCTION: Endovascular thrombectomy is the standard of care for anterior circulation acute ischaemic stroke (AIS) secondary to emergent large vessel occlusion in patients who qualify. General anaesthesia (GA) or conscious sedation (CS) is usually required to ensure patient comfort and avoid agitation and movement during thrombectomy. However, the question of whether the use of GA or CS might influence functional outcome remains debated. Indeed, conflicting results exist between observational studies with better outcomes associated with CS and small monocentric randomised controlled trials favouring GA. Therefore, we aim to evaluate the effect of CS versus GA on functional outcome and periprocedural complications in endovascular mechanical thrombectomy for anterior circulation AIS. METHODS AND ANALYSIS: Anesthesia Management in Endovascular Therapy for Ischemic Stroke (AMETIS) trial is an investigator initiated, multicentre, prospective, randomised controlled, two-arm trial. AMETIS trial will randomise 270 patients with anterior circulation AIS in a 1:1 ratio, stratified by centre, National Institutes of Health Stroke Scale (≤15 or >15) and association of intravenous thrombolysis or not to receive either CS or GA. The primary outcome is a composite of functional independence at 3 months and absence of perioperative complication occurring by day 7 after endovascular therapy for anterior circulation AIS. Functional independence is defined as a modified Rankin Scale score of 0-2 by day 90. Perioperative complications are defined as intervention-associated arterial perforation or dissection, pneumonia or myocardial infarction or cardiogenic acute pulmonary oedema or malignant stroke evolution occurring by day 7. ETHICS AND DISSEMINATION: The AMETIS trial was approved by an independent ethics committee. Study began in august 2017. Results will be published in an international peer-reviewed medical journal. TRIAL REGISTRATION NUMBER: NCT03229148.

A Moderate Supplementation of Native Whey Protein Promotes Better Muscle Training and Recovery Adaptations Than Standard Whey Protein - A 12-Week Electrical Stimulation and Plyometrics Training Study.

The purpose of this study was to assess if native whey protein (NW) supplementation could promote recovery and training adaptations after an electrostimulation (ES) training program combined to plyometrics training. Participants were allocated into three groups, supplemented 5 days/week, either with 15 g of carbohydrates + 15 g of NW (n = 17), 15 g of carbohydrates + 15 g of standard whey protein (SW; n = 15), or placebo (PLA; 30 g of carbohydrates; n = 10), while undergoing a 12-week ES training program of the knee extensors. Concentric power (Pmax) was evaluated before, immediately after, as well as 30 min, 60 min, 24 h, and 48 h after the 1st, 4th and last ES training session. The maximal voluntary contraction torque (MVC), twitch amplitude, anatomical cross-sectional area (CSA) and maximal voluntary activation level (VA) were measured before (T0), and after 6 (T1) and 12 weeks of training (T2). P max recovery kinetics differed between groups (p < 0.01). P max started to recover at 30 min in NW, 24 h in SW and 48 h in PLA. Training adaptations also differed between groups: MVC increased between T0 and T2 in NW (+11.8%, p < 0.001) and SW (+7.1%, p < 0.05), but not PLA. Nevertheless, the adaptation kinetics differed: MVC increased in NW and SW between T0 and T1, but an additional gain was only observed between T1 and T2 in NW. VA declined at T1 and T2 in PLA (-3.9%, p < 0.05), at T2 in SW (-3.5%, p < 0.05), and was unchanged in NW. CSA increased, but did not differ between groups. These results suggest that NW could promote a faster recovery and neuromuscular adaptations after training than SW. However, the mechanisms underlying this effect remain to be identified.

Nutritional and exercise interventions variably affect estrogen receptor expression in the adipose tissue of male rats.

Energy-dense food consumption and lack of physical activity are implicated in the development of the current obesity epidemic. The role of estrogen in adiposity and fuel partitioning is mediated mainly though the estrogen receptor α (ERα) isoform. We hypothesized that nutritional adaptation and exercise training, either individually or combined, could impact ERα expression in adipose tissue relative to glucose tolerance. Seventy-two Wistar rats were submitted to a high-fat, high-sucrose (HF-HS) diet for 16weeks. The first phase of our study was to investigate the effect of an HF-HS diet on whole-body glucose tolerance, as well as on body composition and ERα expression in different adipose tissues. Second, we investigated the effect of switching to a well-balanced diet, with or without exercise training for 8 weeks, on those same parameters. After the first part of this study, HF-HS-fed rats were fatter (8%) than control rats. Despite a decrease in glucose tolerance, ERα expression in adipose tissues was not significantly altered by an HF-HS diet. The return to a well-balanced diet significantly increased ERα expression in perirenal and epididymal adipose tissue, but there was no effect of diet or exercise training on whole-body glucose tolerance. The present findings suggest that diet is a powerful modulator of ERα expression in adipose tissue, as nutritional modulation after an HF-HS diet strongly affects ERα expression, particularly in perirenal and epididymal adipose tissue. However, ERα expression in adipose tissue does not appear to be associated with whole-body glucose tolerance.

Exercise training and return to a well-balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats.

KEY POINTS: Some studies suggest that neuregulin 1 (NRG1) could be involved in the regulation of skeletal muscle energy metabolism in rodents. Here we assessed whether unbalanced diet is associated with alterations of the NRG1 signalling pathway and whether exercise and diet might restore NRG1 signalling in skeletal muscle of obese rats. We show that diet-induced obesity does not impair NRG1 signalling in rat skeletal muscle. We also report that endurance training and a well-balanced diet activate the NRG1 signalling in skeletal muscle of obese rats, possibly via a new mechanism mediated by the protease ADAM17. These results suggest that some beneficial effects of physical activity and diet in obese rats could be partly explained by stimulation of the NRG1 signalling pathway. ABSTRACT: Some studies suggest that the signalling pathway of neuregulin 1 (NRG1), a protein involved in the regulation of skeletal muscle metabolism, could be altered by nutritional and exercise interventions. We hypothesized that diet-induced obesity could lead to alterations of the NRG1 signalling pathway and that chronic exercise could improve NRG1 signalling in rat skeletal muscle. To test this hypothesis, male Wistar rats received a high fat/high sucrose (HF/HS) diet for 16 weeks. At the end of this period, NRG1 and ErbB expression/activity in skeletal muscle was assessed. The obese rats then continued the HF/HS diet or were switched to a well-balanced diet. Moreover, in both groups, half of the animals also performed low intensity treadmill exercise training. After another 8 weeks, NRG1 and ErbB expression/activity in skeletal muscle were tested again. The 16 week HF/HS diet induced obesity, but did not significantly affect the NRG1/ErbB signalling pathway in rat skeletal muscle. Conversely, after the switch to a well-balanced diet, NRG1 cleavage ratio and ErbB4 amount were increased. Chronic exercise training also promoted NRG1 cleavage, resulting in increased ErbB4 phosphorylation. This result was associated with increased protein expression and phosphorylation ratio of the metalloprotease ADAM17, which is involved in NRG1 shedding. Similarly, in vitro stretch-induced activation of ADAM17 in rat myoblasts induced NRG1 cleavage and ErbB4 activation. These results show that low intensity endurance training and well-balanced diet activate the NRG1-ErbB4 pathway, possibly via the metalloprotease ADAM17, in skeletal muscle of diet-induced obese rats.

A well-balanced diet combined or not with exercise induces fat mass loss without any decrease of bone mass despite bone micro-architecture alterations in obese rat.

The association of a well-balanced diet with exercise is a key strategy to treat obesity. However, weight loss is linked to an accelerated bone loss. Furthermore, exercise is known to induce beneficial effects on bone. We investigated the impact of a well-balanced isoenergetic reducing diet (WBR) and exercise on bone tissue in obese rats. Sixty male rats had previously been fed with a high fat/high sucrose diet (HF/HS) for 4months to induce obesity. Then, 4 regimens were initiated for 2months: HF/HS diet plus exercise (treadmill: 50min/day, 5days/week), WBR diet plus exercise, HF/HS diet plus inactivity and WBR diet plus inactivity. Body composition and total BMD were assessed using DXA and visceral fat mass was weighed. Tibia densitometry was assessed by Piximus. Bone histomorphometry was performed on the proximal metaphysis of tibia and on L2 vertebrae (L2). Trabecular micro-architectural parameters were measured on tibia and L2 by 3D microtomography. Plasma concentration of osteocalcin and CTX were measured. Both WBR diet and exercise had decreased global weight, global fat and visceral fat mass (p<0.05). The WBR diet alone failed to alter total and tibia bone mass and BMD. However, Tb.Th, bone volume density and degree of anisotropy of tibia were decreased by the WBR diet (p<0.05). Moreover, the WBR diet had involved a significant lower MS/BS and BFR/BS in L2 (p<0.05). Exercise had significantly improved BMD of the tibia possibly by inhibiting the bone resorption, as evidenced by no change in plasma osteocalcin levels, a decrease of CTX levels (p<0.005) and trabecular osteoclast number (p<0.05). In the present study a diet inducing weight and fat mass losses did not affected bone mass and BMD of obese rats despite alterations of their bone micro-architecture. The moderate intensity exercise performed had improved the tibia BMD of obese rats without any trabecular and cortical adaptation.

Impact of an obesogenic diet program on bone densitometry, micro architecture and metabolism in male rat.

BACKGROUND: The relationships between fat mass and bone tissue are complex and not fully elucidated. A high-fat/high-sucrose diet has been shown to induce harmful effects on bone micro architecture and bone biomechanics of rat. When such diet leads to obesity, it may induce an improvement of biomechanical bone parameters in rodent.Here, we examined the impact of a high-fat/high-sucrose diet on the body composition and its resulting effects on bone density and structure in male rats. Forty three Wistar rats aged 7 months were split into 3 groups: 1 sacrificed before diet (BD, n = 14); 1 subjected to 16 weeks of high-fat/high-sucrose diet (HF/HS, n = 14); 1 subjected to standard diet (Control, n = 15). Abdominal circumference and insulin sensitivity were measured and visceral fat mass was weighed. The bone mineral density (BMD) was analyzed at the whole body and tibia by densitometry. Microcomputed tomography and histomorphometric analysis were performed at L2 vertebrae and tibia to study the trabecular and cortical bone structures and the bone cell activities. Osteocalcin and CTX levels were performed to assess the relative balance of the bone formation and resorption. Differences between groups have been tested with an ANOVA with subsequent Scheffe post-hoc test. An ANCOVA with global mass and global fat as covariates was used to determine the potential implication of the resulting mechanical loading on bone. RESULTS: The HF/HS group had higher body mass, fat masses and abdominal circumference and developed an impaired glucose tolerance (p < 0.001). Whole body bone mass (p < 0.001) and BMD (p < 0.05) were higher in HF/HS group vs. Control group. The trabecular thickness at vertebrae and the cortical porosity of tibia were improved (p < 0.05) in HF/HS group. Bone formation was predominant in HF/HS group while an unbalance bone favoring bone resorption was observed in the controls. The HF/HS and Control groups had higher total and abdominal fat masses and altered bone parameters vs. BD group. CONCLUSIONS: The HF/HS diet had induced obesity and impaired glucose tolerance. These changes resulted in an improvement of quantitative, qualitative and metabolic bone parameters. The fat mass increase partly explained these observations.

Time-course changes of muscle protein synthesis associated with obesity-induced lipotoxicity.

The object of the study was to investigate the sequential changes of protein synthesis in skeletal muscle during establishment of obesity, considering muscle typology. Adult Wistar rats were fed a standard diet for 16 weeks (C; n = 14), or a high-fat, high-sucrose diet for 16 (HF16; n = 14) or 24 weeks (HF24; n = 15). Body composition was measured using a dual-energy X-ray absorptiometry scanner. The fractional synthesis rates (FSRs) of muscle protein fractions were calculated in tibialis anterior (TA) and soleus muscles by incorporation of l-13C-valine in muscle protein. Muscle lipid and mitochondria contents were determined using histochemical analysis. Obesity occurred in an initial phase, from 1 to 16 weeks, with an increase in weight (P < 0.05), fat mass (P < 0.001), muscle mass (P < 0.001) and FSR in TA (actin: 5.3 ± 0.2 vs. 8.8 ± 0.5% day−1, C vs. HF16, P < 0.001) compared with standard diet. The second phase, from 16 to 24 weeks, was associated with a weight stabilization, a decrease in muscle mass (P < 0.05) and a decrease in FSR in TA (mitochondrial: 5.6 ± 0.2 vs. 4.2 ± 0.4% day−1, HF16 vs. HF24, P < 0.01) compared with HF16 group. Muscle lipid content was increased in TA in the second phase of obesity development (P < 0.001). Muscle mass, lipid infiltration and muscle protein synthesis were differently affected, depending on the stage of obesity development and muscle typology. Chronic lipid infiltration in glycolytic muscle is concomitant with a reduction of muscle protein synthesis, suggesting that muscle lipid infiltration in response to a high-fat diet is deleterious for the incorporation of amino acid in skeletal muscle proteins.

Is protein metabolism changed with obesity?

PURPOSE OF REVIEW: Although it is well established that obesity is accompanied by various degrees of metabolic impairments especially in the regulation of carbohydrate and lipid metabolism, the influence of obesity on protein metabolism is not clearly understood. The purpose of this review is to present data describing the modification in protein metabolism that have been reported in the clinical setting of obesity. RECENT FINDINGS: Recent findings suggest that protein metabolism at the whole-body level is less sensitive to insulin action. Impairments in skeletal muscle protein synthesis rates in the postabsorptive state and in response to anabolic factors are reported in obese human. Finally, chronic excessive energy intake and increased adiposity in rats, without the appearance of other metabolic disturbances, do not induce any changes in tissue protein synthesis rates. SUMMARY: Body composition in obesity is characterized by elevated fat mass but also lean body mass which is considered either increased or decreased (in the case of sarcopenic obesity). Thus protein metabolism as reflected by changes in protein synthesis and breakdown might be modified in obese individuals but it is still largely debated. Only a few studies have investigated muscle protein kinetics during obesity and do not lead to the same conclusions prolonging the controversies. Indeed, obesity is associated with many metabolic disturbances which might constitute confounding factors differently affecting muscle protein metabolism.