New Findings
What is the central question of this study?
Is the magnitude of neuromuscular fatigue dependent upon exercise intensity above critical power (CP) when W′ (the curvature constant of the ...power–duration relationship) is depleted?
What is the main finding and its importance?
The magnitude of neuromuscular fatigue is the same after two bouts of supra‐CP cycling (3 versus 12 min) when controlling for W′ depletion but is larger for individuals of greater anaerobic capacity after the shorter bout and smaller for individuals of greater aerobic capacity after the longer exercise bout. These findings provide new insight into the mechanisms underpinning exercise above CP.
The aim of the present study was to test whether the development of neuromuscular fatigue within the severe‐intensity domain could be linked to the depletion of the curvature constant (W′) of the power–duration relationship. Twelve recreationally active men completed tests to determine peak oxygen consumption, critical power (CP) and W′, followed by two randomly assigned constant‐load supra‐CP trials set to deplete W′ fully in 3 (P‐3) and 12 min (P‐12). Pre‐ to postexercise changes in maximal voluntary contraction, potentiated quadriceps twitch force evoked by single (Qpot) and paired high‐ (PS100) and low‐frequency (PS10) stimulations and voluntary activation were determined. Cycling above CP reduced maximal voluntary contraction (P‐3, −20 ± 10% versus P‐12, −15 ± 7%), measures associated with peripheral fatigue (Qpot, −35 ± 13 versus −31 ± 14%; PS10, −38 ± 13 versus −37 ± 17%; PS100, −18 ± 9 versus −13 ± 8% for P‐3 and P‐12, respectively) and voluntary activation (P‐3, −12 ± 3% versus P‐12, −13 ± 3%; P < 0.05), with no significant difference between trials (P > 0.05). Changes in maximal voluntary contraction and evoked twitch forces were inversely correlated with CP and peak oxygen consumption after P‐12, whereas W′ was significantly correlated with changes in Qpot and PS10 after P‐3 (P < 0.05). Therefore, the magnitude of neuromuscular fatigue does not depend on exercise intensity when W′ is fully exhausted during severe‐intensity exercise; nonetheless, exploration of inter‐individual variations suggests that mechanisms underpinning exercise tolerance within this domain differ between short‐ and long‐duration exercise.
New Findings
What is the central question of this study?
Does the magnitude of neuromuscular fatigue depend on the amount of work done (W′) at task failure when cycling above critical power (CP)?
...What is the main finding and its importance?
Creatine supplementation increases W′ and enhances supra‐CP performance, but induces similar magnitudes of neuromuscular fatigue at task failure compared to placebo. Increased W′ does not lead to higher levels of neuromuscular fatigue. This supports the notion of a critical level of neuromuscular fatigue at task failure and challenges a direct causative link between W′ depletion and neuromuscular fatigue.
The present study examined the effect of creatine supplementation on neuromuscular fatigue and exercise tolerance when cycling above critical power (CP). Eleven males performed an incremental cycling test with four to five constant‐load trials to task failure (TTF) to obtain asymptote (CP) and curvature constant (W′) of the power–duration relationship, followed by three constant‐load supra‐CP trials: (1) one TTF following placebo supplementation (PLA); (2) one TTF following creatine supplementation (CRE); and (3) one trial of equal duration to PLA following creatine supplementation (ISO). Neuromuscular assessment of the right knee extensors was performed pre‐ and post‐exercise to measure maximal voluntary contraction (MVC), twitch forces evoked by single (Qpot) and paired high‐ (PS100) and low‐ (PS10) frequency stimulations and voluntary activation. Creatine supplementation increased TTF in CRE vs. PLA by ∼11% (P = 0.017) and work done above CP by ∼10% (P = 0.015), with no difference (P > 0.05) in reductions in MVC (−24 ± 8% vs. −20 ± 9%), Qpot (−39 ± 13% vs. −32 ± 14%), PS10 (−42 ± 14% vs. −36 ± 13%), PS100 (−25 ± 10% vs. −18 ± 12%) and voluntary activation (−7 ± 8% vs. −5 ± 7%). No significant difference was found between ISO and either PLA or CRE (P > 0.05). These findings suggest similar levels of neuromuscular fatigue can be found following supra‐CP cycling despite increases in performance time and amount of work done above CP, supporting the notion of a critical level of neuromuscular fatigue and challenging a direct causative link between W′ depletion and neuromuscular fatigue.
Traumatic brain injury (TBI) is a leading cause of disabilities resulting from cognitive and neurological deficits, as well as psychological disorders. Only recently, preclinical research on ...electrical stimulation methods as a potential treatment of TBI sequelae has gained more traction. However, the underlying mechanisms of the anticipated improvements induced by these methods are still not fully understood. It remains unclear in which stage after TBI they are best applied to optimize the therapeutic outcome, preferably with persisting effects. Studies with animal models address these questions and investigate beneficial long- and short-term changes mediated by these novel modalities.
In this review, we present the state-of-the-art in preclinical research on electrical stimulation methods used to treat TBI sequelae. We analyze publications on the most commonly used electrical stimulation methods, namely transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS) and vagus nerve stimulation (VNS), that aim to treat disabilities caused by TBI. We discuss applied stimulation parameters, such as the amplitude, frequency, and length of stimulation, as well as stimulation time frames, specifically the onset of stimulation, how often stimulation sessions were repeated and the total length of the treatment. These parameters are then analyzed in the context of injury severity, the disability under investigation and the stimulated location, and the resulting therapeutic effects are compared. We provide a comprehensive and critical review and discuss directions for future research. RESULTS AND CONCLUSION: We find that the parameters used in studies on each of these stimulation methods vary widely, making it difficult to draw direct comparisons between stimulation protocols and therapeutic outcome. Persisting beneficial effects and adverse consequences of electrical simulation are rarely investigated, leaving many questions about their suitability for clinical applications. Nevertheless, we conclude that the stimulation methods discussed here show promising results that could be further supported by additional research in this field.
Abstract Objectives Transcatheter Aortic Valve Implantation (TAVI) can be performed via the transaxillary approach, but data about complications and procedural outcome is limited. Introduction TAVI ...is an established treatment option for patients at high risk for conventional aortic valve replacement. Nowadays, the transfemoral approach is the most commonly used access for TAVI. Nevertheless, the transfemoral access is not suitable in many patients necessitating alternative approaches. Methods We analyzed the outcome of 100 consecutive cases receiving percutaneous transaxillary TAVI at two different hospitals. Data were retrospectively analyzed by means of procedural, hemodynamic and clinical outcome. In addition, 1st versus 2nd generation devices were analyzed. Results Mean age was 78.2 ± 2.1 years and the logEuroSCORE I was 24.6 ± 13.9%. Transaxillary TAVI was performed in 85% via the left and in 15% via the right axillary artery. Device success was achieved in 95%. In general, there was a clear learning curve with this approach. No patient experienced a major and 11% a minor access site complication. There was one procedural death (annular rupture) and one peri-procedural TIA. 23% of the patients received a new pacemaker. At discharge, effective orifice area was 1.94 ± 0.16 cm2 and the mean aortic gradient was 6.8 ± 2.1 mm Hg. Moderate aortic regurgitation/paravalvular leakage was documented in two patients. Mortality rates at 30 days and one year were 6% and 14.8%. Last but not least, 2nd generation devices showed improved procedural outcomes. Conclusions The percutaneous transaxillary access for TAVI is technically feasible and safe thereby yielding excellent clinical results. Condensed abstract We investigated In 100 consecutive patients undergoing percutaneous transaxillary transcatheter aortic valve implantation thereby demonstrating that this approach is technically feasible and safe with acceptable numbers of minor vascular complications.
The interventional treatment of mitral valve regurgitation by the MitraClip procedure has grown rapidly in Germany and Europe during the past years. The MitraClip procedure has the potential to treat ...high-risk patients with secondary mitral valve regurgitation and poor left ventricular function. Furthermore, patients with primary mitral valve regurgitation may be treated successfully by the MitraClip procedure in case of high surgical risk or in very old patients. At the same time it has been emphasised that the MitraClip interventional treatment is still at an early stage of clinical development. The largest clinical experience with the MitraClip procedure so far is probably present in some German cardiovascular centers, which here summarise their recommendations on the current indications and procedural steps of the MitraClip treatment. These recommendations of the AGIK and ALKK may present a basis for future development.
The size-dependent deposition of microparticles and nanoparticles after oral administration to rats using an experimental model colitis was examined. Local delivery of an entrapped drug could reduce ...side effects and would be a distinct improvement compared with existing colon delivery devices.
Ulcerative colitis was induced in Lewis rats with trinitrobenzenesulfonic acid. Fluorescent polystyrene particles with a size of 0.1, 1, or 10 microm were administered for 3 days. The animals then were sacrificed and their guts resected. Particle distribution in the colon was imaged by confocal laser scanning microscopy and quantified by fluorescence spectrophotometry.
In the inflamed tissue, an increased adherence of particles was observed at the thicker mucus layer and in the ulcerated regions. A size dependency of the deposition was found, and an increased number of attached particles to the colon was determined compared with the control group. For 10-micorm particles, only fair deposition was observed (control group: 1.4 +/- 0.6%; colitis: 5.2 +/- 3.8% of administered particle mass). One-micrometer particles showed higher binding (control group: 2.0 +/- 0.8%; colitis: 9.1 +/- 4.2%). Highest binding was found for 0.1-microm particles (control group: 2.2 +/- 1.6%; colitis: 14.5 +/- 6.3%). The ratio of colitis/control deposition increased with smaller particle sizes.
The use of submicron-sized carriers holds promise for the targeted delivery of drugs to the inflamed colonic mucosal areas in inflammatory bowel disease.
Aims
Transcatheter mitral valve replacement (TMVR) with dedicated devices promises to fill the treatment gap between open-heart surgery and edge-to-edge repair for patients with severe mitral ...regurgitation (MR). We herein present a single-centre experience of a TMVR series with two transapical devices.
Methods and results
A total of 11 patients were treated with the Tendyne™ (
N
= 7) or the Tiara™ TMVR systems (
N
= 4) from 2016 to 2020 either as compassionate-use procedures or as commercial implants. Clinical and echocardiographic data were collected at baseline, discharge and follow-up and are presented in accordance with the Mitral Valve Academic Research Consortium (MVARC) definitions.
The study cohort age 77 years (73, 84); 27.3% male presented with primary (
N
= 4), secondary (
N
= 5) or mixed (
N
= 2) MR etiology. Patients were symptomatic (all NYHA III/IV) and at high surgical risk logEuroSCORE II 8.1% (4.0, 17.4). Rates of impaired RV function (72.7%), severe pulmonary hypertension (27.3%), moderate or severe tricuspid regurgitation (63.6%) and prior aortic valve replacement (63.6%) were high. Severe mitral annulus calcification was present in two patients. Technical success was achieved in all patients. In 90.9% (
N
= 10) MR was completely eliminated (i.e. no or trace MR). Procedural and 30-day mortality were 0.0%. At follow-up NYHA class was I/II in the majority of patients. Overall mortality after 3 and 6 months was 10.0% and 22.2%.
Conclusions
TMVR was performed successfully in these selected patients with complete elimination of MR in the majority of patients. Short-term mortality was low and most patients experienced persisting functional improvement.
Graphic abstract
Positive results of MitraClip in terms of improvement in clinical and left ventricular parameters have been described in detail. However, long-term effects on secondary pulmonary hypertension were ...not investigated in a larger patient cohort to date. 70 patients with severe mitral regurgitation, additional pulmonary hypertension, and right heart failure as a result of left heart disease were treated in the heart centers Hamburg and Göttingen. Immediately after successful MitraClip implantation, a reduction of the RVOT diameter from 3.52 cm to 3.44 cm was observed reaching a statistically significant value of 3.39 cm after 12 months. In contrast, there was a significant reduction in the velocity of the tricuspid regurgitation (TR) from 4.17 m/s to 3.11 m/s, the gradient of the TR from 48.5 mmHg to 39.3 mmHg, and the systolic pulmonary artery pressure (PAPsyst) from 58.6 mmHg to 50.0 mmHg. This decline continued in the following months (Vmax TR 3.09 m/s, peak TR 38.6 mmHg, and PAPsyst 47.4 mmHg). The tricuspid annular plane systolic excursion (TAPSE) increased from 16.5 mm to 18.9 mm after 12 months. MitraClip implantation improves pulmonary artery pressure, tricuspid regurgitation, and TAPSE after 12 months. At the same time, there is a decrease in the RVOT diameter without significant changes in other right ventricular and right atrial dimensions.
Zusammenfassung
Die Technik der Transkatheteraortenklappenimplantation (TAVI) hat einen festen Platz in der Therapie von inoperablen und Hochrisikopatienten mit symptomatischer, hochgradiger ...Aortenklappenstenose eingenommen. Eine Indikationsausweitung hin zu Patienten mit intermediärem Risikoprofil ist für die Zukunft wahrscheinlich. Inzwischen steht eine Vielzahl moderner, optimierter TAVI-Systeme zur Verfügung, mit denen eine differenzierte Therapie unter Berücksichtigung individueller klinischer und anatomischer Patientencharakteristika möglich ist. Dies hat, zusammen mit einer optimierten Prozedurplanung und gewachsener Anwendererfahrung, zu einer stetigen Verbesserung klinischer und hämodynamischer Ergebnisse nach TAVI geführt. Ein interdisziplinärer Heart-Team-Ansatz ist eine unverzichtbare Voraussetzung für die optimale Patientenversorgung.
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