"Living High-Training Low" for Olympic Medal Performance: What Have We Learned 25 Years After Implementation?

BACKGROUND: Altitude training is often regarded as an indispensable tool for the success of elite endurance athletes. Historically, altitude training emerged as a key strategy to prepare for the 1968 Olympics, held at 2300 m in Mexico City, and was limited to the "Live High-Train High" method for endurance athletes aiming for performance gains through improved oxygen transport. This "classical" intervention was modified in 1997 by the "Live High-Train Low" (LHTL) model wherein athletes supplemented acclimatization to chronic hypoxia with high-intensity training at low altitude. PURPOSE: This review discusses important considerations for successful implementation of LHTL camps in elite athletes based on experiences, both published and unpublished, of the authors. APPROACH: The originality of our approach is to discuss 10 key "lessons learned," since the seminal work by Levine and Stray-Gundersen was published in 1997, and focusing on (1) optimal dose, (2) individual responses, (3) iron status, (4) training-load monitoring, (5) wellness and well-being monitoring, (6) timing of the intervention, (7) use of natural versus simulated hypoxia, (8) robustness of adaptative mechanisms versus performance benefits, (9) application for a broad range of athletes, and (10) combination of methods. Successful LHTL strategies implemented by Team USA athletes for podium performance at Olympic Games and/or World Championships are presented. CONCLUSIONS: The evolution of the LHTL model represents an essential framework for sport science, in which field-driven questions about performance led to critical scientific investigation and subsequent practical implementation of a unique approach to altitude training.

The Achilles Tendon: Imaging Diagnoses and Image-Guided Interventions-AJR Expert Panel Narrative Review.

The Achilles tendon is commonly affected by both chronic repetitive overuse and traumatic injuries. Achilles tendon injuries can potentially affect any individual but have a particularly high incidence in professional athletes. Appropriate imaging evaluation and diagnosis are paramount to guiding appropriate management. In this AJR Expert Panel Narrative Review, we discuss the role of various imaging modalities (particularly ultrasound and MRI) in the assessment of Achilles tendon pathology, focusing on the modalities' relative advantages and technical considerations. We describe the most common diagnoses affecting the Achilles tendon and adjacent structures, highlighting key imaging findings and providing representative examples. Various image-guided interventions that may be used in the management of Achilles tendon pathology are also reviewed, including high-volume injection, tendon fenestration, prolotherapy, and corticosteroid injection. The limited evidence supporting such interventions are summarized, noting an overall paucity of large-scale studies showing benefit. Finally, a series of consensus statements by the panel on imaging and image-guided intervention for Achilles tendon pathology are provided.

1 Year HIIT and Omega-3 Fatty Acids to Improve Cardiometabolic Risk in Stage-A Heart Failure.

OBJECTIVES: This study aims to determine whether 1 year of high-intensity interval training (HIIT) and omega-3 fatty acid (n-3 FA) supplementation would improve fitness, cardiovascular structure/function, and body composition in obese middle-aged adults at high-risk of heart failure (HF) (stage A). BACKGROUND: It is unclear if intensive lifestyle interventions begun in stage A HF can improve key cardiovascular and metabolic risk factors. METHODS: High-risk obese adults (n = 80; age 40 to 55 years; N-terminal pro-B-type natriuretic peptide >40 pg/mL or high-sensitivity cardiac troponin T >0.6 pg/mL; visceral fat >2 kg) were randomized to 1 year of HIIT exercise or attention control, with n-3 FA (1.6 g/daily omega-3-acid ethyl esters) or placebo supplementation (olive oil 1.6 g daily). Outcome variables were exercise capacity quantified as peak oxygen uptake (V.O2), left ventricular (LV) mass, LV volume, myocardial triglyceride content (magnetic resonance spectroscopy), arterial stiffness/function (central pulsed-wave velocity; augmentation index), and body composition (dual x-ray absorptiometry scan). RESULTS: Fifty-six volunteers completed the intervention. There was no detectible effect of HIIT on visceral fat or myocardial triglyceride content despite a reduction in total adiposity (Δ: -2.63 kg, 95% CI: -4.08 to -0.46, P = 0.018). HIIT improved exercise capacity by ∼24% (ΔV.O2: 4.46 mL/kg per minute, 95% CI: 3.18 to 5.56; P < 0.0001), increased LV mass (Δ: 9.40 g, 95% CI: 4.36 to 14.44; P < 0.001), and volume (Δ: 12.33 mL, 95 % CI: 5.61 to 19.05; P < 0.001) and reduced augmentation index (Δ: -4.81%, 95% CI: -8.63 to -0.98; P = 0.009). There was no independent or interaction effect of n-3 FA on any outcome. CONCLUSIONS: One-year HIIT improved exercise capacity, cardiovascular structure/function, and adiposity in stage A HF with no independent or additive effect of n-3 FA administration. (Improving Metabolic Health in Patients With Diastolic Dysfunction [MTG]; NCT03448185).

Human Serum Albumin Dimerization Enhances the S2 Emission of Bound Cyanine IR806.

Cyanine molecules are important phototheranostic compounds given their high fluorescence yield in the near-infrared region of the spectrum. We report on the frequency and time-resolved spectroscopy of the S2 state of IR806, which demonstrates enhanced emission upon binding to the hydrophobic pocket of human serum albumin (HSA). From excitation-emission matrix spectra and electronic structure calculations, we identify the emission as one associated with a state having the polymethine chain twisted out of plane by 103°. In addition, we find that this configuration is significantly stabilized as the concentration of HSA increases. Spectroscopic changes associated with the S1 and S2 states of IR806 as a function of HSA concentration, as well as anisotropy measurements, confirm the formation of HSA dimers at concentrations greater than 10 µM. These findings imply that the longer-lived S2 state configuration can lead to more efficient phototherapy agents, and cyanine S2 spectroscopy may be a useful tool to determine the oligomerization state of HSA.

Medicine in Extreme Environments: A New Medical Student Elective Class for Wilderness, Aerospace, Hyperbaric, Exercise, and Combat Medicine.

We developed an elective course titled Medicine in Extreme Environments (MEE) at the University of Texas Southwestern Medical Center for first- and second-year medical students. This course covered physiology, research, clinical practice, and career guidance regarding the fields of wilderness, space, hyperbaric, combat, and exercise medicine. The primary aim was to generate interest in and awareness of these seldom covered fields of medicine by exposing medical students to these disciplines during their preclinical years. A postcourse questionnaire was implemented to investigate whether the MEE course increased awareness of, interest in, and knowledge in the fields of medicine included in the curriculum. Through 2 iterations of the class, a total of 67 students enrolled in the course, and 38 students completed the questionnaire. After course completion, 95% felt they better understood the work and lifestyle of the fields covered, 100% learned more about concepts of each field, and 74% agreed that the elective influenced the direction of their future careers to include some part of the fields emphasized. Although only a limited number of students enrolled in this course, these initial findings suggest that the MEE curriculum may have some utility in promoting awareness of and interest in these medical disciplines among students who attend the course. With continued student and faculty support, this course will likely be continued annually at our institution. We believe that certain aspects of this course may be useful in helping develop similar courses at other medical schools.

A phase 2B randomised trial of hyperbaric oxygen therapy for ulcerative colitis patients hospitalised for moderate to severe flares.

BACKGROUND: Hyperbaric oxygen has been reported to improve disease activity in hospitalised ulcerative colitis (UC) patients. AIM: To evaluate dosing strategies with hyperbaric oxygen for hospitalised UC patients. METHODS: We enrolled UC patients hospitalised for acute flares (Mayo score 6-12). Initially, all patients received 3 days of hyperbaric oxygen at 2.4 atmospheres (90 minutes with two air breaks) in addition to intravenous steroids. Day 3 responders (reduction of partial Mayo score ≥ 2 points and rectal bleeding score ≥ 1 point) were randomised to receive a total of 5 days vs 3 days of hyperbaric oxygen. RESULTS: We treated 20 patients with hyperbaric oxygen (75% prior biologic failure). Day 3 response was achieved in 55% (n = 11/20), with significant reductions in stool frequency, rectal bleeding and CRP (P < 0.01). A more significant reduction in disease activity was observed with 5 days vs 3 days of hyperbaric oxygen (P = 0.03). Infliximab or colectomy was required in only three patients (15%) despite a predicted probability of 80% for second-line therapy. Day 3 hyperbaric oxygen responders were less likely to require re-hospitalisation or colectomy by 3 months vs non-responders (0% vs 66%, P = 0.002). No treatment-related adverse events were observed. CONCLUSION: Hyperbaric oxygen appears to be effective for optimising response to intravenous steroids in UC patients hospitalised for acute flares, with low rates of re-hospitalisation or colectomy at 3 months. An optimal clinical response is achieved with 5 days of hyperbaric oxygen. Larger phase 3 trials are needed to confirm efficacy and obtain labelled approval.

Hyperbaric Oxygen Therapy in Sports Musculoskeletal Injuries.

Hyperbaric oxygen therapy (HBOT) is a well-established treatment for a variety of conditions. Hyperbaric oxygen therapy is the administration of 100% oxygen breathing in a pressure vessel at higher than atmospheric pressure (1 atmosphere absolute = 101 kPa). Typically, treatment is given daily for between 1 and 2 h at pressures of 2.0 to 2.8 ATA, depending on the indication. Sporting injuries are often treated over 3 to 10 sessions. Hyperbaric oxygen therapy has been documented to be effective and is approved in 14 medical indications by the Undersea and Hyperbaric Medical Society, including, but not limited to, carbon monoxide poisoning, compromised skin grafts and flaps, crush injuries, necrotizing soft tissue infections, and nonhealing ulcers with arterial insufficiencies. Recently, HBOT for sports musculoskeletal injuries is receiving increased attention. Hyperbaric oxygen therapy may allow injured athletes to recover faster than normal rehabilitation methods. Any reduction in collegiate and professional athletes' rehabilitation period can be financially significant for top-level sports teams; however, further research is required to confirm HBOT's benefits on sports musculoskeletal injuries. The purpose of this review to discuss the current understanding of HBOT as a treatment modality for common musculoskeletal injuries in sport medicine. Moreover, we will highlight the advantages and disadvantages of this modality, as well as relevant clinical and research applications.

Iron insufficiency diminishes the erythropoietic response to moderate altitude exposure.

The effects of iron stores and supplementation on erythropoietic responses to moderate altitude in endurance athletes were examined. In a retrospective study, red cell compartment volume (RCV) responses to 4 wk at 2,500 m were assessed in athletes with low (n = 9, ≤20 and ≤30 ng/mL for women and men, respectively) and normal (n = 10) serum ferritin levels ([Ferritin]) without iron supplementation. In a subsequent prospective study, the same responses were assessed in athletes (n = 26) with a protocol designed to provide sufficient iron before and during identical altitude exposure. The responses to a 4-wk training camp at sea level were assessed in another group of athletes (n = 13) as controls. RCV and maximal oxygen uptake (V̇o2max) were determined at sea level before and after intervention. In the retrospective study, athletes with low [Ferritin] did not increase RCV (27.0 ± 2.9 to 27.5 ± 3.8 mL/kg, mean ± SD, P = 0.65) or V̇o2max (60.2 ± 7.2 to 62.2 ± 7.5 mL·kg-1·min-1, P = 0.23) after 4 wk at altitude, whereas athletes with normal [Ferritin] increased both (RCV: 27.3 ± 3.1 to 29.8 ± 2.4 mL/kg, P = 0.002; V̇o2max: 62.0 ± 3.1 to 66.2 ± 3.7 mL·kg-1·min-1, P = 0.003). In the prospective study, iron supplementation normalized low [Ferritin] observed in athletes exposed to altitude (n = 14) and sea level (n = 6) before the altitude/sea-level camp and maintained [Ferritin] within normal range in all athletes during the camp. RCV and V̇o2max increased in the altitude group but remained unchanged in the sea-level group. Finally, the increase in RCV correlated with the increase in V̇o2max [(r = 0.368, 95% confidence interval (CI): 0.059-0.612, P = 0.022]. Thus, iron deficiency in athletes restrains erythropoiesis to altitude exposure and may preclude improvement in sea-level athletic performance.NEW & NOTEWORTHY Hypoxic exposure increases iron requirements and utilization for erythropoiesis in athletes. This study clearly demonstrates that iron deficiency in athletes inhibits accelerated erythropoiesis to a sojourn to moderate high altitude and may preclude a potential improvement in sea-level athletic performance with altitude training. Iron replacement therapy before and during altitude exposure is important to maximize performance gains after altitude training in endurance athletes.

Does High-Intensity Endurance Training Increase the Risk of Atrial Fibrillation? A Longitudinal Study of Left Atrial Structure and Function.

BACKGROUND: Exercise mitigates many cardiovascular risk factors associated with atrial fibrillation. Endurance training has been associated with atrial structural changes which can increase the risk for atrial fibrillation. The dose of exercise training required for these changes is uncertain. We sought to evaluate the impact of exercise on left atrial (LA) mechanical and electrical function in healthy, sedentary, middle-aged adults. METHODS: Sixty-one adults (52±5 years) were randomized to either 10 months of high-intensity exercise training or yoga. At baseline and post-training, all participants underwent maximal exercise stress testing to assess cardiorespiratory fitness, P-wave signal-averaged electrocardiography for filtered P-wave duration and atrial late potentials (root mean square voltage of the last 20 ms), and echocardiography for LA volume, left ventricular end-diastolic volume, and mitral inflow for assessment of LA active emptying. Post-training data were compared with 14 healthy age-matched Masters athletes. RESULTS: LA volume, Vo2 max, and left ventricular end-diastolic volume increased in the exercise group (15%, 17%, and 16%, respectively) with no change in control (P<0.0001). LA active emptying decreased post-exercise versus controls (5%; P=0.03). No significant changes in filtered P-wave duration or root mean square voltage of the last 20 ms occurred after exercise training. LA and left ventricular volumes remained below Masters athletes. The athletes had longer filtered P-wave duration but no difference in the frequency of atrial arrhythmia. CONCLUSIONS: Changes in LA structure, LA mechanical function, and left ventricular remodeling occurred after 10 months of exercise but without significant change in atrial electrical activity. A longer duration of training may be required to induce electrical changes thought to cause atrial fibrillation in middle-aged endurance athletes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique Identifier: NCT02039154.

Changing Systems Through Effective Teams: A Role for Simulation.

Teams are the building blocks of the healthcare system, with growing evidence linking the quality of healthcare to team effectiveness, and team effectiveness to team training. Simulation has been identified as an effective modality for team training and assessment. Despite this, there are gaps in methodology, measurement, and implementation that prevent maximizing the impact of simulation modalities on team performance. As part of the 2017 Academic Emergency Medicine Consensus Conference "Catalyzing System Change Through Health Care Simulation: Systems, Competency, and Outcomes," we explored the impact of simulation on various aspects of team effectiveness. The consensus process included an extensive literature review, group discussions, and the conference "workshop" involving emergency medicine physicians, medical educators, and team science experts. The objectives of this work were to: 1) explore the antecedents and processes that support team effectiveness, 2) summarize the current role of simulation in developing and understanding team effectiveness, and 3) identify research targets to further improve team-based training and assessment, with the ultimate goal of improving healthcare systems.

Altitude Training in Elite Swimmers for Sea Level Performance (Altitude Project).

INTRODUCTION: This controlled, nonrandomized, parallel-groups trial investigated the effects on performance, V˙O2 and hemoglobin mass (tHbmass) of four preparatory in-season training interventions: living and training at moderate altitude for 3 and 4 wk (Hi-Hi3, Hi-Hi), living high and training high and low (Hi-HiLo, 4 wk), and living and training at sea level (SL) (Lo-Lo, 4 wk). METHODS: From 61 elite swimmers, 54 met all inclusion criteria and completed time trials over 50- and 400-m crawl (TT50, TT400), and 100 (sprinters) or 200 m (nonsprinters) at best stroke (TT100/TT200). Maximal oxygen uptake (V˙O2max) and HR were measured with an incremental 4 × 200 m test. Training load was estimated using cumulative training impulse method and session RPE. Initial measures (PRE) were repeated immediately (POST) and once weekly on return to SL (PostW1 to PostW4). tHbmass was measured in duplicate at PRE and once weekly during the camp with CO rebreathing. Effects were analyzed using mixed linear modeling. RESULTS: TT100 or TT200 was worse or unchanged immediately at POST, but improved by approximately 3.5% regardless of living or training at SL or altitude after at least 1 wk of SL recovery. Hi-HiLo achieved greater improvement 2 (5.3%) and 4 wk (6.3%) after the camp. Hi-HiLo also improved more in TT400 and TT50 2 (4.2% and 5.2%, respectively) and 4 wk (4.7% and 5.5%) from return. This performance improvement was not linked linearly to changes in V˙O2max or tHbmass. CONCLUSIONS: A well-implemented 3- or 4-wk training camp may impair performance immediately but clearly improves performance even in elite swimmers after a period of SL recovery. Hi-HiLo for 4 wk improves performance in swimming above and beyond altitude and SL controls through complex mechanisms involving altitude living and SL training effects.

Alagebrium in combination with exercise ameliorates age-associated ventricular and vascular stiffness.

Advanced glycation end-products (AGEs) initiate cellular inflammation and contribute to cardiovascular disease in the elderly. AGE can be inhibited by Alagebrium (ALT), an AGE cross-link breaker. Moreover, the beneficial effects of exercise on aging are well recognized. Thus, we investigated the effects of ALT and exercise (Ex) on cardiovascular function in a rat aging model. Compared to young (Y) rats, in sedentary old (O) rats, end-systolic elastance (Ees) decreased (0.9±0.2 vs 1.7±0.4mmHg/µL, P<0.05), dP/dt(max) was attenuated (6054±685 vs 9540±939mmHg/s, P<0.05), ventricular compliance (end-diastolic pressure-volume relationship (EDPVR)) was impaired (1.4±0.2 vs 0.5±0.4mmHg/µL, P<0.05) and diastolic relaxation time (tau) was prolonged (21±3 vs 14±2ms, P<0.05). In old rats, combined ALT+Ex (4weeks) increased dP/dt(max) and Ees (8945±665 vs 6054±685mmHg/s, and 1.5±0.2 vs 0.9±0.2 respectively, O with ALT+Ex vs O, P<0.05 for both). Diastolic function (exponential power of EDPVR and tau) was also substantially improved by treatment with Alt+Ex in old rats (0.4±0.1 vs 0.9±0.2 and 16±2 vs 21±3ms, respectively, O with ALT+EX vs O, P<0.05 for both). Pulse wave velocity (PWV) was increased in old rats (7.0±0.7 vs 3.8±0.3ms, O vs Y, P<0.01). Both ALT and Ex alone decreased PWV in old rats but the combination decreased PWV to levels observed in young (4.6±0.5 vs 3.8±0.3ms, O with ALT+Ex vs Y, NS). These results suggest that prevention of the formation of new AGEs (with exercise) and breakdown of already formed AGEs (with ALT) may represent a therapeutic strategy for age-related ventricular and vascular stiffness.

Cardiac atrophy in women following bed rest.

Both chronic microgravity exposure and long-duration bed rest induce cardiac atrophy, which leads to reduced standing stroke volume and orthostatic intolerance. However, despite the fact that women appear to be more susceptible to postspaceflight presyncope and orthostatic hypotension than male astronauts, most previous high-resolution studies of cardiac morphology following microgravity have been performed only in men. Because female athletes have less physiological hypertrophy than male athletes, we reasoned that they also might have altered physiological cardiac atrophy after bed rest. Magnetic resonance imaging was performed in 24 healthy young women (32.1 +/- 4 yr) to measure left ventricular (LV) and right ventricular (RV) mass, volumes, and morphology accurately before and after 60 days of 6 degrees head-down tilt (HDT) bed rest. Subjects were matched and then randomly assigned to sedentary bed rest (controls, n = 8) or two treatment groups consisting of 1) exercise training using supine treadmill running within lower body negative pressure plus resistive training (n = 8), or 2) protein (0.45 g x kg(-1) x day(-1) increase) plus branched-chain amino acid (BCAA) (7.2 g/day) supplementation (n = 8). After sedentary bed rest without nutritional supplementation, there were significant reductions in LV (96 +/- 26 to 77 +/- 25 ml; P = 0.03) and RV volumes (104 +/- 33 to 86 +/- 25 ml; P = 0.02), LV (2.2 +/- 0.2 to 2.0 +/- 0.2 g/kg; P = 0.003) and RV masses (0.8 +/- 0.1 to 0.6 +/- 0.1 g/kg; P < 0.001), and the length of the major axis of the LV (90 +/- 6 to 84 +/- 7 mm. P < 0.001), similar to what has been observed previously in men (8.0%; Perhonen MA, Franco F, Lane LD, Buckey JC, Blomqvist Zerwekh JE, Peshock RM, Weatherall PT, Levine BD. J Appl Physiol 91: 645-653, 2001). In contrast, there were no significant reductions in LV or RV volumes in the exercise-trained group, and the length of the major axis was preserved. Moreover, there were significant increases in LV (1.9 +/- 0.4 to 2.3 +/- 0.3 g/kg; P < 0.001) and RV masses (0.7 +/- 0.1 to 0.8 +/- 0.2 g/kg; P = 0.002), as well as mean wall thickness (9 +/- 2 to 11 +/- 1 mm; P = 0.02). The interaction between sedentary and exercise LV and RV masses was highly significant (P < 0.0001). Protein and BCAA supplementation led to an intermediate phenotype with no change in LV or RV mass after bed rest, but there remained a significant reduction in LV volume (103 +/- 14 to 80 +/- 16 ml; P = 0.02) and major-axis length (91 +/- 5 to 88 +/- 7 mm; P = 0.003). All subjects lost an equivalent amount of body mass (3.4 +/- 0.2 kg control; 3.1 +/- 0.04 kg exercise; 2.8 +/- 0.1 kg protein). Cardiac atrophy occurs in women similar to men following sedentary 60 days HDT bed rest. However, exercise training and, to a lesser extent, protein supplementation may be potential countermeasures to the cardiac atrophy associated with chronic unloading conditions such as in spaceflight and prolonged bed rest.