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1.  Increased longitudinal contractility and diastolic function at rest in well-trained amateur Marathon runners: a speckle tracking echocardiography study 
Regular physical activity reduces cardiovascular risk. There is concern that Marathon running might acutely damage the heart. It is unknown to what extent intensive physical endurance activity influences the cardiac mechanics at resting condition.
Eighty-four amateur marathon runners (43 women and 41 men) from Berlin-Brandenburg area who had completed at least one marathon previously underwent clinical examination and echocardiography at least 10 days before the Berlin Marathon at rest. Standard transthoracic echocardiography and 2D strain and strain rate analysis were performed. The 2D Strain and strain rate values were compared to previous published data of healthy untrained individuals.
The average global longitudinal peak systolic strain of the left ventricle was -23 +/- 2% with peak systolic strain rate -1.39 +/- 0.21/s, early diastolic strain rate 2.0 +/- 0.40/s and late diastolic strain rate 1.21 +/- 0.31/s. These values are significantly higher compared to the previous published values of normal age-adjusted individuals. In addition, no age-related decline of longitudinal contractility in well-trained athletes was observed.
There is increased overall longitudinal myocardial contractility at rest in experienced endurance athletes compared to the published normal values in the literature indicating a preserved and even supra-normal contractility in the athletes. There is no age dependent decline of the longitudinal 2D Strain values. This underlines the beneficial effects of regular physical exercise even in advanced age.
PMCID: PMC3975967  PMID: 24571726
2.  Heart Rate Recovery After Exercise and Neural Regulation of Heart Rate Variability in 30-40 Year Old Female Marathon Runners 
The aim of the present study was to examine the effects of endurance training on heart rate (HR) recovery after exercise and cardiac autonomic nervous system (ANS) modulation in female marathon runners by comparing with untrained controls. Six female marathon runners (M group) aged 32-40 years and eight age-matched untrained females (C group) performed a maximum-effort treadmill running exercise. Maximal oxygen uptake (VO2max) was measured during the exercise with a gas analyzer connected to subjects through a face mask. Heart rate, blood pressure and blood lactate were measured before and after the exercise. Rating of perceived exertion (RPE) to the exercise was obtained immediately after the exercise. Holter ECG was recorded and analyzed with power spectral analysis of heart rate variability (HRV) to investigate the cardiac ANS modulation. The M group had significantly higher VO2max, faster HR recovery after exercise, higher Mean RR, SDRR, HF power and lower LF/HF ratio at rest compared with the C group. The M group also presented greater percent decrease of blood pressure after exercise, although their blood pressure after exercise was higher than the C group. It is suggested that endurance training induced significant alterations in cardiac ANS modulation at rest and significant acceleration of HR recovery after exercise in female marathon runners. Faster HR recovery after exercise in the female marathon runners should result from their higher levels of HRV, higher aerobic capacity and exaggerated blood pressure response to exercise compared with untrained controls.
Key PointsThe effects of endurance training on HR recovery after exercise and cardiac ANS modulation were investigated in female marathon runners by comparing with untrained controls.Time and frequency domain analysis of HRV was used to investigate cardiac ANS modulation.As compared with untrained controls, the female marathon runners showed faster HR recovery after exercise, which should result from their higher levels of HRV, higher aerobic capacity and exaggerated blood pressure response to exercise.
PMCID: PMC3880089  PMID: 24431956
Heart rate recovery; heart rate variability; female marathon runner
3.  Whole blood coagulation and platelet activation in the athlete: A comparison of marathon, triathlon and long distance cycling 
Serious thrombembolic events occur in otherwise healthy marathon athletes during competition. We tested the hypothesis that during heavy endurance sports coagulation and platelets are activated depending on the type of endurance sport with respect to its running fraction.
Materials and Methods
68 healthy athletes participating in marathon (MAR, running 42 km, n = 24), triathlon (TRI, swimming 2.5 km + cycling 90 km + running 21 km, n = 22), and long distance cycling (CYC, 151 km, n = 22) were included in the study. Blood samples were taken before and immediately after completion of competition to perform rotational thrombelastometry. We assessed coagulation time (CT), maximum clot firmness (MCF) after intrinsically activation and fibrin polymerization (FIBTEM). Furthermore, platelet aggregation was tested after activation with ADP and thrombin activating peptide 6 (TRAP) by using multiple platelet function analyzer.
Complete data sets were obtained in 58 athletes (MAR: n = 20, TRI: n = 19, CYC: n = 19). CT significantly decreased in all groups (MAR -9.9%, TRI -8.3%, CYC -7.4%) without differences between groups. In parallel, MCF (MAR +7.4%, TRI +6.1%, CYC +8.3%) and fibrin polymerization (MAR +14.7%, TRI +6.1%, CYC +8.3%) were significantly increased in all groups. However, platelets were only activated during MAR and TRI as indicated by increased AUC during TRAP-activation (MAR +15.8%) and increased AUC during ADP-activation in MAR (+50.3%) and TRI (+57.5%).
While coagulation is activated during physical activity irrespective of type we observed significant platelet activation only during marathon and to a lesser extent during triathlon. We speculate that prolonged running may increase platelet activity, possibly, due to mechanical alteration. Thus, particularly prolonged running may increase the risk of thrombembolic incidents in running athletes.
PMCID: PMC3352046  PMID: 20452885
4.  Decrease in eccentric hamstring strength in runners in the Tirol Speed Marathon 
British Journal of Sports Medicine  2006;40(10):850-852.
The local muscular endurance of knee flexors, during eccentric work in particular, is important in preventing or delaying kinematic changes associated with fatigue during treadmill running. This result, however, may not be transferable to overground running.
To test the hypothesis that overground running is associated with eccentric hamstring fatigue.
Thirteen runners (12 male and one female) performed an isokinetic muscle test three to four days before and 18 hours after a marathon. Both legs were tested. The testing protocol consisted of concentric and eccentric quadriceps and hamstring contractions.
There were no significant differences between peak torque before and after the race, except that eccentric peak hamstring torque (both thighs) was reduced.
Overground running (running a marathon) is associated with eccentric hamstring fatigue. Eccentric hamstring fatigue may be a potential risk factor for knee and soft tissue injuries during running. Eccentric hamstring training should therefore be introduced as an integral part of the training programme of runners.
PMCID: PMC2465081  PMID: 16825267
fatigue; concentric; eccentric; hamstring; musculoskeletal injury
5.  Acute metabolic responses to a 24-h ultra-marathon race in male amateur runners 
European Journal of Applied Physiology  2011;112(5):1679-1688.
The study was conducted to evaluate the metabolic responses to a 24 h ultra-endurance race in male runners. Paired venous and capillary blood samples from 14 athletes (mean age 43.0 ± 10.8 years, body weight 64.3 ± 7.2 kg, VO2max 57.8 ± 6.1 ml kg−1 min−1), taken 3 h before the run, after completing the marathon distance (42.195 km), after 12 h, and at the finish of the race, were analyzed for blood morphology, acid–base balance and electrolytes, lipid profile, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and serum enzyme activities. Mean distance covered during the race was 168.5 ± 23.1 km (range 125.2–218.5 km). Prolonged ultra-endurance exercise triggered immune and inflammatory responses, as evidenced by a twofold increase in total leukocyte count with neutrophils and monocytes as main contributors, nearly 30-fold increase in serum IL-6 and over 20-fold rise in hsCRP. A progressive exponential increase in mean creatine kinase activity up to the level 70-fold higher than the respective pre-race value, a several fold rise in serum activities of aspartate aminotransferase and alanine aminotransferase, and a fairly stable serum γ-glutamyl transferase level, were indicative of muscle, but not of liver damage. With duration of exercise, there was a progressive development of hyperventilation-induced hypocapnic alkalosis, and a marked alteration in substrate utilization towards fat oxidation to maintain blood glucose homeostasis. The results of this study may imply that progressive decline in partial CO2 pressure (hypocapnia) that develops during prolonged exercise may contribute to increased interleukin-6 production.
PMCID: PMC3324692  PMID: 21879351
Ultra-endurance exercise; Muscle damage; Inflammatory response; Interleukin-6
6.  The foot in multistage ultra-marathon runners: experience in a cohort study of 22 participants of the Trans Europe Footrace Project with mobile MRI 
BMJ Open  2012;2(3):e001118.
67 runners participated in the Trans Europe FootRace 2009 (TEFR09), a 4487 km (2789 mi) multistage ultra-marathon covering the south of Europe (Bari, Italy) to the North Cape. Reports on ultra-marathons are lacking, but the literature reports overuse injuries in athletes, especially to the Achilles tendon (AT), ankle or hind foot. Bone oedema may be related to exposure and is present in fatigue fractures. Therefore, the aim of this study was to determine prospectively if sustained maximal load during an ultra-marathon leads to damage to the foot.
Design and participants
In a cohort study, repeated scanning of the 22 athletes participating in the study was performed before and during (approximately every 1000 km) the race. Using the obtained fat saturated inversion recovery sequence, two experienced readers blinded to the clinical data rated the images regarding foot lesions. Statistical analysis included regression analysis and computation of the inter-rater reliability.
The TEFR09 course. MRI scanning was performed according to prearranged schedules for every participant, using a mobile 1.5 Tesla MRI unit on a trailer following the race.
Primary outcome measures
MRI data such as AT diameter, bone or tendon lesions, subcutaneous, plantar fascia or intraosseous oedema.
The 22 study participants did not differ significantly from the total of the 67 TEFR09 runners regarding height, weight and age. The AT diameter increased significantly from 6.8 to 7.8 mm as did intraosseous signal, bone lesions and subcutaneous oedema. However, finishers differed only regarding plantar aponeurosis and subcutaneous oedema from participants aborting the TEFR09. Inter-rater reliability was 0.88–0.98.
Under the extreme stress of the TEFR09, an increase of the AT diameter as well as bone signal are thought to be adaptive since only subcutaneous oedema and plantar fascia oedema were related to abortion of the race.
Trial registration number
University of Ulm, Germany Ethics Committee Number 78/08-UBB/se.
Article summary
Article focus
A study on effects of ultra-marathon running, in this case, the multistage Trans Europe FootRace covering a distance of 4487 km from Bari (Italy) to the North Cape.
Observational cohort study using MRI to look for possible lesions to the foot.
Key messages
During sustained maximal load, AT diameter and bone MRI short τ inversion recovery signal (hinting at subtle oedema) increases. This is thought to be adaptive.
Subcutaneous oedema and plantar fascia signal were related to abortion of the race. These measurements seem to be related to relevant changes leading to discontinuation of the run.
No relevant new foot joint or tendon lesions were detected during the race over 4487 km.
Strengths and limitations of this study
Repeated measurement prospectively during the run was possible only because of the mobile MRI unit used for this research project.
The number of included runners (22) is high compared with other MRI-based studies but may have been too small to detect less frequent lesions.
PMCID: PMC3364457  PMID: 22619270
7.  Performance and age of African and non-African runners in half- and full marathons held in Switzerland, 2000–2010 
Endurance running performance of African (AF) and non-African (NAF) athletes is investigated, with better performances seen for Africans. To date, no study has compared the age of peak performance between AF and NAF runners. The present research is an analysis of the age and running performance of top AF and NAF athletes, using the hypothesis that AF athletes were younger and faster than NAF athletes.
Age and performance of male and female AF and NAF athletes in half-marathons and marathons held in Switzerland in 2000–2010 were investigated using single and multilevel hierarchical regression analyses.
For half-marathons, male NAF runners were older than male AF runners (P = 0.02; NAF, 31.1 years ± 6.4 years versus AF, 26.2 years ± 4.9 years), and their running time was longer (P = 0.02; NAF, 65.3 minutes ± 1.7 minutes versus AF, 64.1 minutes ± 0.9 minutes). In marathons, differences between NAF and AF male runners in age (NAF, 33.0 years ± 4.8 years versus AF, 28.6 years ± 3.8 years; P < 0.01) and running time (NAF, 139.5 minutes ± 5.6 minutes versus AF, 133.3 minutes ± 2.7 minutes; P < 0.01) were more pronounced. There was no difference in age (NAF, 31.0 years ± 7.0 years versus AF, 26.7 years ± 6.0 years; P > 0.05) or running time (NAF, 75.0 minutes ± 3.7 minutes versus AF, 75.6 minutes ± 5.3 minutes; P > 0.05) between NAF and AF female half-marathoners. For marathoners, NAF women were older than AF female runners (P = 0.03; NAF, 31.6 years ± 4.8 years versus AF, 27.8 years ± 5.3 years), but their running times were similar (NAF, 162.4 minutes ± 7.2 minutes versus AF, 163.0 minutes ± 7.0 minutes; P > 0.05).
In Switzerland, the best AF male half-marathoners and marathoners were younger and faster than the NAF counterpart runners. In contrast to the results seen in men, AF and NAF female runners had similar performances. Future studies need to investigate performance and age of AF and NAF marathoners in the World Marathon Majors Series.
PMCID: PMC3871899  PMID: 24379724
endurance; running; ethnicity; road race; gender difference
8.  Evaluating the Influence of Massage on Leg Strength, Swelling, and Pain Following a Half-Marathon 
Journal of Sports Science & Medicine  2004;3(YISI 1):37-43.
Massage therapy is commonly used following endurance running races with the expectation that it will enhance post-run recovery of muscle function and reduce soreness. A limited number of studies have reported little or no influence of massage therapy on post-exercise muscle recovery. However, no studies have been conducted in a field setting to assess the potential for massage to influence muscle recovery following an actual endurance running race. To evaluate the potential for repeated massage therapy interventions to influence recovery of quadriceps and hamstring muscle soreness, recovery of quadriceps and hamstring muscle strength and reduction of upper leg muscle swelling over a two week recovery period following an actual road running race. Twelve adult recreational runners (8 male, 4 female) completed a half marathon (21.1 km) road race. On days 1,4, 8, and 11 post-race, subjects received 30 minutes of standardized massage therapy performed by a registered massage therapist on a randomly assigned massage treatment leg, while the other (control) leg received no massage treatment. Two days prior to the race (baseline) and preceding the treatments on post-race days 1, 4, 8, and 11 the following measures were conducted on each of the massage and control legs: strength of quadriceps and hamstring muscles, leg swelling, and soreness perception. At day 1, post-race quadriceps peak torque was significantly reduced (p < 0.05), and soreness and leg circumference significantly elevated (p < 0.05) relative to pre-race values with no difference between legs. This suggested that exercise-induced muscle disruption did occur. Comparing the rate of return to baseline measures between the massaged and control legs, revealed no significant differences (p > 0.05). All measures had returned to baseline at day 11. Massage did not affect the recovery of muscles in terms of physiological measures of strength, swelling, or soreness. However, questionnaires revealed that 7 of the 12 participants perceived that the massaged leg felt better upon recovery.
Key PointsMassage does not appear to affect physiological indices of muscle recovery post exercise.Massage does appear to positively influence perceptions of recovery.More research needs to be completed on the purported benefits of massage.
PMCID: PMC3990931  PMID: 24778552
Recovery; running; perception; massage
9.  AQUA© as predictor of allergy in elite marathon runners 
The prevalence of allergy in athletes is increasing, and its risk varies across sports. The risk is dependent mainly on the ventilation rate and environmental factors; however, the prevalence of allergy in elite runners remains unknown. Therefore, the aim of this study was to screen allergy symptoms in elite marathon runners by using a validated questionnaire for screening allergy in athletes.
Two hundred and one elite marathoners, who participated in the most competitive Brazilian marathons and half-marathons during 2011, were invited to complete a validated self-report Allergy Questionnaire for Athletes (AQUA©), with additional questions pertaining to training history, such as running experience, running distance per week and their best race time in marathon or half-marathon events.
Sixty percent of the assessed athletes reported allergy symptoms as defined by a positive AQUA outcome (score [greater than or equal to] 5). No significant differences (p > 0.05) between groups (AQUA + and AQUA-) were observed for gender, age, running experience, weekly training volume and best performance time in the half-marathon and marathon. The most frequently reported symptoms were related to the respiratory tract and physical effort.
This study demonstrates that AQUA© can be used to predict allergy in elite marathon runners. In addition, these athletes have a higher prevalence of allergy symptoms to elite athletes from other sports.
PMCID: PMC3983857  PMID: 24708728
10.  Cardiac Output and Performance during a Marathon Race in Middle-Aged Recreational Runners 
The Scientific World Journal  2012;2012:810859.
Purpose. Despite the increasing popularity of marathon running, there are no data on the responses of stroke volume (SV) and cardiac output (CO) to exercise in this context. We sought to establish whether marathon performance is associated with the ability to sustain high fractional use of maximal SV and CO (i.e, cardiac endurance) and/or CO, per meter (i.e., cardiac cost). Methods. We measured the SV, heart rate (HR), CO, and running speed of 14 recreational runners in an incremental, maximal laboratory test and then during a real marathon race (mean performance: 3 hr 30 min ± 45 min). Results. Our data revealed that HR, SV and CO were all in a high but submaximal steady state during the marathon (87.0 ± 1.6%, 77.2 ± 2.6%, and 68.7 ± 2.8% of maximal values, respectively). Marathon performance was inversely correlated with an upward drift in the CO/speed ratio (mL of CO × m−1) (r = −0.65, P < 0.01) and positively correlated with the runner's ability to complete the race at a high percentage of the speed at maximal SV (r = 0.83, P < 0.0002). Conclusion. Our results showed that marathon performance is inversely correlated with cardiac cost and positively correlated with cardiac endurance. The CO response could be a benchmark for race performance in recreational marathon runners.
PMCID: PMC3356747  PMID: 22645458
11.  Gastrointestinal disturbances in marathon runners. 
The purpose of this survey was to investigate the prevalence of running-induced gastrointestinal (GI) disturbances in marathon runners. A questionnaire was completed by 471 of the estimated 1,750 competitors in the 1986 Belfast City Marathon. Eighty-three per cent of respondents indicated that they occasionally or frequently suffered one or more GI disturbances during or immediately after running. The urge to have a bowel movement (53%) and diarrhoea (38%) were the most common symptoms, especially among female runners (74% and 68% respectively). Upper GI tract symptoms were experienced more by women than men (p less than 0.05) and more by younger runners than older runners (p less than 0.01). Women also suffered more lower GI tract symptoms than men (p less than 0.05) with younger runners showing a similar trend. Both upper and lower tract symptoms were more common during a "hard" run than an "easy" run (p less than 0.01) and were equally as common both during and after running. Of those runners who suffered GI disturbances, 72% thought that running was the cause and 29% believed their performance to be adversely affected. There was no consensus among sufferers as to the causes of symptoms and a wide variety of "remedies" were suggested. GI disturbances are common amongst long-distance runners and their aetiology is unknown. Medical practitioners should be aware of this when dealing with patients who run.
PMCID: PMC1478552  PMID: 3167507
12.  Running Pace Decrease during a Marathon Is Positively Related to Blood Markers of Muscle Damage 
PLoS ONE  2013;8(2):e57602.
Completing a marathon is one of the most challenging sports activities, yet the source of running fatigue during this event is not completely understood. The aim of this investigation was to determine the cause(s) of running fatigue during a marathon in warm weather.
Methodology/Principal Findings
We recruited 40 amateur runners (34 men and 6 women) for the study. Before the race, body core temperature, body mass, leg muscle power output during a countermovement jump, and blood samples were obtained. During the marathon (27 °C; 27% relative humidity) running fatigue was measured as the pace reduction from the first 5-km to the end of the race. Within 3 min after the marathon, the same pre-exercise variables were obtained.
Marathoners reduced their running pace from 3.5 ± 0.4 m/s after 5-km to 2.9 ± 0.6 m/s at the end of the race (P<0.05), although the running fatigue experienced by the marathoners was uneven. Marathoners with greater running fatigue (> 15% pace reduction) had elevated post-race myoglobin (1318 ± 1411 v 623 ± 391 µg L−1; P<0.05), lactate dehydrogenase (687 ± 151 v 583 ± 117 U L−1; P<0.05), and creatine kinase (564 ± 469 v 363 ± 158 U L−1; P = 0.07) in comparison with marathoners that preserved their running pace reasonably well throughout the race. However, they did not differ in their body mass change (−3.1 ± 1.0 v −3.0 ± 1.0%; P = 0.60) or post-race body temperature (38.7 ± 0.7 v 38.9 ± 0.9 °C; P = 0.35).
Running pace decline during a marathon was positively related with muscle breakdown blood markers. To elucidate if muscle damage during a marathon is related to mechanistic or metabolic factors requires further investigation.
PMCID: PMC3583862  PMID: 23460881
13.  Hypertrophic cardiomyopathy associated with sudden death during marathon racing. 
British Heart Journal  1979;41(5):624-627.
An experienced marathon runner died suddenly during a competitive race. At necropsy, ventricular hypertrophy but no asymmetrical septal hypertrophy was found. Histological studies showed features of hypertrophic cardiomyopathy. The coronary arteries were normal. We propose that the runner died from myocardial ischaemia, precipitated by marathon running on a background of hypertrophic cardiomyopathy. Excess cardiac work, induced by marathon running in the presence of mild congenital cardiac defects, could have contributed to the development of the cardiomyopathy.
PMCID: PMC482078  PMID: 157146
14.  Creatine kinase elevations in marathon runners: relationship to training and competition. 
Elevation of creatine kinase (CK) in serum after exertion is a reliable marker of skeletal muscle injury. Limited data exist on CK levels in conditioned athletes after endurance training and competition. Serum CK was measured by a kinetic UV method (normal < 100 U/L) in 15 long distance runners before (pre-race), 24 hours after (post-race) and four weeks following (post-race) the 1979 Boston Marathon. CK levels were elevated throughout the study. Mean values for all runners and for those finishing before and after three hours and 30 minutes are as follows: Post-race CK was significantly elevated among the ten faster as compared to the five slower runners (p = 0.025). Elevations of creatine kinase drawn 24 hours post-marathon are inversely related to finishing times among the runners tested.
PMCID: PMC2595821  PMID: 7445533
15.  Changes in thioredoxin concentrations: an observation in an ultra-marathon race 
Changes in plasma thioredoxin (TRX) concentrations before, during, and after a 130-km endurance race were measured with the aim of elucidating the relationship between exercise and oxidative stress (OS).
Blood samples were taken from 18 runners participating in a 2-day-long 130-km ultra-marathon during the 2 days of the race and for 1 week thereafter. There were six sampling time points: at baseline, after the goal had been reached on the first and second day of the endurance race, respectively, and on 1, 3, and 5/6 days post-endurance race. The samples were analyzed for plasma TRX concentrations, platelet count, and blood lipid profiles.
Concentrations of plasma TRX increased from 17.9 ± 1.2 ng/mL (mean ± standard error of the mean) at baseline to 57.3 ± 5.0 ng/mL after the first day’s goal had been reached and to 70.1 ± 6.9 ng/mL after the second day's goal had been reached; it then returned to the baseline level 1 day after the race. Platelet counts of 21.3 ± 1.2 × 104 cell/μL at baseline increased to 23.9 ± 1.5 × 104 cells/μL on Day 1 and to 26.1 ± 1.0 × 104 cells/μL on Day 2. On Day 7, the platelet counts had fallen to 22.1 ± 1.2 × 104 cell/μL. There was a significant positive correlation between plasma TRX and platelet count.
These data suggest that plasma TRX is an OS marker during physical exercise. Further studies are needed to determine the appropriate level of exercise for the promotion of health.
PMCID: PMC2854340  PMID: 19960374
Lipid profile; Marathon runner; Oxidative stress; Platelet counts; Thioredoxin
16.  Gastrointestinal disturbances in marathon runners. 
To determine the prevalence of various gastrointestinal disturbances related to long-distance running and its effect on weight, diet and everyday digestive problems, we gave a questionnaire to 279 leisure-time marathon runners, comprising 10% of the participants in a local marathon race. Their answers disclosed a prevalence of dietary changes, weight reduction and altered bowel habits (mainly looser stools and/or more frequent defaecation) of 37, 38 and 48% respectively. A quarter reported earlier long lasting gastrointestinal problems, which improved in 41% of the runners after they started regular training. Thirty-four percent experienced gastrointestinal disturbances during or after running, 20% to such an extent that it seriously affected their performance.
PMCID: PMC1478906  PMID: 2097027
17.  SELDI-TOF-MS Serum Profiling Reveals Predictors of Cardiac MRI Changes in Marathon Runners 
Purpose. To utilize proteomics to discover proteins associated with significant cardiac magnetic resonance imaging (MRI) changes in marathon runners. Methods. Serum from 25 runners was analyzed by surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Proteomic profiles were compared in serum samples obtained prior to the race, at the finish line and within 7 hours after race to identify dynamic proteins correlated with cardiac MRI changes. Results. 693 protein/peptide clusters were identified using two ProteinChip surface chemistries and, of these, 116 were significantly different between the three time points. We identified 7 different patterns of protein expression change within the runners and 5 prerace protein peaks, 16 finish-line protein levels, and 15 postrace proteins which were correlated with significant postrace cardiac MRI changes. Conclusions. This study has identified baseline levels of proteins which may be predictive of risk of significant cardiac damage following a marathon race. Preliminary identification of the significant proteins suggested the involvement of cytokines and other proteins involved in stress and inflammatory response.
PMCID: PMC3439948  PMID: 22988506
18.  Prevalence of Hyponatremia, Renal Dysfunction, and Other Electrolyte Abnormalities Among Runners Before and After Completing a Marathon or Half Marathon 
Sports Health  2011;3(2):145-151.
Prior reports on metabolic derangements observed in distance running frequently have small sample sizes, lack prerace laboratory measures, and report sodium as the sole measure.
Metabolic abnormalities—hyponatremia, hypokalemia, renal dysfunction, hemoconcentration—are frequent after completing a full or half marathon. Clinically significant changes occur in these laboratory values after race completion.
Study Design:
Observational, cross-sectional study.
Consenting marathon and half marathon racers completed a survey as well as finger stick blood sampling on race day of the National Marathon to Fight Breast Cancer (Jacksonville, Florida, February 2008). Parallel blood measures were obtained before and after race completion (prerace, n = 161; postrace, n = 195).
The prevalence of prerace and postrace hyponatremia was 8 of 161 (5.0%) and 16 of 195 (8.2%), respectively. Hypokalemia was not present prerace but was present in 1 runner postrace (1 of 195). Renal dysfunction occurred prerace in 14 of 161 (8.7%) and postrace in 83 of 195 (42.6%). Among those with postrace renal dysfunction, 45.8% (38 of 83) were classified as moderate or severe. Hemoconcentration was present in 2 of 161 (1.2%) prerace and 6 of 195 (3.1%) postrace. The mean changes in laboratory values were (postrace minus prerace): sodium, 1.6 mmol/L; potassium, −0.2 mmol/L; blood urea nitrogen, 2.8 mg/dL; creatinine, 0.2 mg/dL; and hemoglobin, 0.3 g/dL for 149 pairs (except blood urea nitrogen, n = 147 pairs). Changes were significant for all comparisons (P < 0.01) except potassium (P = 0.08) and hemoglobin (P = 0.01).
Metabolic abnormalities are common among endurance racers, and they may be present prerace, including hyponatremia. The clinical significance of these findings is unknown.
Clinical relevance:
It is unclear which runners are at risk for developing clinically important metabolic derangements. Participating in prolonged endurance exercise appears to be safe in the majority of racers.
PMCID: PMC3445140  PMID: 23016001
marathon; hyponatremia; renal dysfunction; running; endurance sports
19.  Sudden cardiac arrest in a marathon runner. A case report 
Sudden cardiac death is a rare condition resulting from undetected cardiac abnormalities in athletes and non-athletes. Participant screening, immediate and advanced medical management can probably reduce mortality and ameliorate outcomes. In recent years, extracorporeal membrane oxygenation has emerged as a valuable therapeutic option in patients experiencing refractory cardiac arrest as a bridge to different types of outcome, including recovery, heart transplantation or ventricular assist device and organ donations. In this report we describe a case of a sudden cardiac arrest in a marathon runner treated with extracorporeal membrane oxygenation.
PMCID: PMC3484937  PMID: 23439699
ECLS; refractory cardiac arrest
20.  Regionally accentuated reversible brain grey matter reduction in ultra marathon runners detected by voxel-based morphometry 
During the 4,487 km ultra marathon TransEurope-FootRace 2009 (TEFR09), runners showed catabolism with considerable reduction of body weight as well as reversible brain volume reduction. We hypothesized that ultra marathon athletes might have developed changes to grey matter (GM) brain morphology due to the burden of extreme physical training. Using voxel-based morphometry (VBM) we undertook a cross sectional study and two longitudinal studies.
Prior to the start of the race 13 runners volunteered to participate in this study of planned brain scans before, twice during, and 8 months after the race. A group of matched controls was recruited for comparison. Twelve runners were able to participate in the scan before the start of the race and were taken into account for comparison with control persons. Because of drop-outs during the race, VBM could be performed in 10 runners covering the first 3 time points, and in 7 runners who also had the follow-up scan after 8 months. Volumetric 3D datasets were acquired using an MPRAGE sequence. A level of p < 0.05, family-wise corrected for multiple comparisons was the a priori set statistical threshold to infer significant effects from VBM.
Baseline comparison of TEFR09 participants and controls revealed no significant differences regarding GM brain volume. During the race however, VBM revealed GM volume decreases in regionally distributed brain regions. These included the bilateral posterior temporal and occipitoparietal cortices as well as the anterior cingulate and caudate nucleus. After eight months, GM normalized.
Contrary to our hypothesis, we did not observe significant differences between TEFR09 athletes and controls at baseline. If this missing difference is not due to small sample size, extreme physical training obviously does not chronically alter GM.
However, during the race GM volume decreased in brain regions normally associated with visuospatial and language tasks. The reduction of the energy intensive default mode network as a means to conserve energy during catabolism is discussed. The changes were reversible after 8 months.
Despite substantial changes to brain composition during the catabolic stress of an ultra marathon, the observed differences seem to be reversible and adaptive.
PMCID: PMC3896776  PMID: 24438692
Voxel based morphometry; VBM; Catabolism; Plasticity; Brain; Default mode network; MRI; Ultra marathon
21.  Competing risks of mortality with marathons: retrospective analysis 
BMJ : British Medical Journal  2007;335(7633):1275-1277.
Objective To determine from a societal perspective the risk of sudden cardiac death associated with running in an organised marathon compared with the risk of dying from a motor vehicle crash that might otherwise have taken place if the roads had not been closed.
Design Population based retrospective analysis with linked ecological comparisons of sudden death.
Setting Marathons with at least 1000 participants that had two decades of history and were on public roads in the United States, 1975-2004.
Main outcome measures Sudden death attributed to cardiac causes or to motor vehicle trauma.
Results The marathons provided results for 3 292 268 runners on 750 separate days encompassing about 14 million hours of exercise. There were 26 sudden cardiac deaths observed, equivalent to a rate of 0.8 per 100 000 participants (95% confidence interval 0.5 to 1.1). Because of road closure, an estimated 46 motor vehicle fatalities were prevented, equivalent to a relative risk reduction of 35% (95% confidence interval 17% to 49%). The net reduction in sudden death during marathons amounted to a ratio of about 1.8 crash deaths saved for each case of sudden cardiac death observed (95% confidence interval: 0.7 to 3.8). The net reduction in total deaths could not be explained by re-routing traffic to other regions or days and was consistent across different parts of the country, decades of the century, seasons of the year, days of the week, degree of competition, and course difficulty.
Conclusion Organised marathons are not associated with an increase in sudden deaths from a societal perspective, contrary to anecdotal impressions fostered by news media.
PMCID: PMC2151171  PMID: 18156224
22.  Alterations of Neuromuscular Function after the World's Most Challenging Mountain Ultra-Marathon 
PLoS ONE  2013;8(6):e65596.
We investigated the physiological consequences of the most challenging mountain ultra-marathon (MUM) in the world: a 330-km trail run with 24000 m of positive and negative elevation change. Neuromuscular fatigue (NMF) was assessed before (Pre-), during (Mid-) and after (Post-) the MUM in experienced ultra-marathon runners (n = 15; finish time  = 122.43 hours ±17.21 hours) and in Pre- and Post- in a control group with a similar level of sleep deprivation (n = 8). Blood markers of muscle inflammation and damage were analyzed at Pre- and Post-. Mean ± SD maximal voluntary contraction force declined significantly at Mid- (−13±17% and −10±16%, P<0.05 for knee extensor, KE, and plantar flexor muscles, PF, respectively), and further decreased at Post- (−24±13% and −26±19%, P<0.01) with alteration of the central activation ratio (−24±24% and −28±34% between Pre- and Post-, P<0.05) in runners whereas these parameters did not change in the control group. Peripheral NMF markers such as 100 Hz doublet (KE: −18±18% and PF: −20±15%, P<0.01) and peak twitch (KE: −33±12%, P<0.001 and PF: −19±14%, P<0.01) were also altered in runners but not in controls. Post-MUM blood concentrations of creatine kinase (3719±3045 Ul·1), lactate dehydrogenase (1145±511 UI·L−1), C-Reactive Protein (13.1±7.5 mg·L−1) and myoglobin (449.3±338.2 µg·L−1) were higher (P<0.001) than at Pre- in runners but not in controls. Our findings revealed less neuromuscular fatigue, muscle damage and inflammation than in shorter MUMs. In conclusion, paradoxically, such extreme exercise seems to induce a relative muscle preservation process due likely to a protective anticipatory pacing strategy during the first half of MUM and sleep deprivation in the second half.
PMCID: PMC3694082  PMID: 23840345
23.  Alterations in Postural Control during the World's Most Challenging Mountain Ultra-Marathon 
PLoS ONE  2014;9(1):e84554.
We investigated postural control (PC) effects of a mountain ultra-marathon (MUM): a 330-km trail run with 24000 m of positive and negative change in elevation. PC was assessed prior to (PRE), during (MID) and after (POST) the MUM in experienced ultra-marathon runners (n = 18; finish time = 126±16 h) and in a control group (n = 8) with a similar level of sleep deprivation. Subjects were instructed to stand upright on a posturographic platform over a period of 51.2 seconds using a double-leg stance under two test conditions: eyes open (EO) and eyes closed (EC). Traditional measures of postural stability (center of pressure trajectory analysis) and stabilogram-diffusion analysis (SDA) parameters were analysed. For the SDA, a significantly greater short-term effective diffusion was found at POST compared with PRE in the medio-lateral (ML; Dxs) and antero-posterior (AP) directions (Dys) in runners (p<0.05) The critical time interval (Ctx) in the ML direction was significantly higher at MID (p<0.001) and POST (p<0.05) than at PRE in runners. At MID (p<0.001) and POST (p<0.05), there was a significant difference between the two groups. The critical displacement (Cdx) in the ML was significantly higher at MID and at POST (p<0.001) compared with PRE for runners. A significant difference in Cdx was observed between groups in EO at MID (p<0.05) and POST (p<0.005) in the ML direction and in EC at POST in the ML and AP directions (p<0.05).
Our findings revealed significant effects of fatigue on PC in runners, including, a significant increase in Ctx (critical time in ML plan) in EO and EC conditions. Thus, runners take longer to stabilise their body at POST than at MID. It is likely that the mountainous characteristics of MUM (unstable ground, primarily uphill/downhill running, and altitude) increase this fatigue, leading to difficulty in maintaining balance.
PMCID: PMC3897373  PMID: 24465417
24.  Neuromuscular Consequences of an Extreme Mountain Ultra-Marathon 
PLoS ONE  2011;6(2):e17059.
We investigated the physiological consequences of one of the most extreme exercises realized by humans in race conditions: a 166-km mountain ultra-marathon (MUM) with 9500 m of positive and negative elevation change. For this purpose, (i) the fatigue induced by the MUM and (ii) the recovery processes over two weeks were assessed. Evaluation of neuromuscular function (NMF) and blood markers of muscle damage and inflammation were performed before and immediately following (n = 22), and 2, 5, 9 and 16 days after the MUM (n = 11) in experienced ultra-marathon runners. Large maximal voluntary contraction decreases occurred after MUM (−35% [95% CI: −28 to −42%] and −39% [95% CI: −32 to −46%] for KE and PF, respectively), with alteration of maximal voluntary activation, mainly for KE (−19% [95% CI: −7 to −32%]). Significant modifications in markers of muscle damage and inflammation were observed after the MUM as suggested by the large changes in creatine kinase (from 144±94 to 13,633±12,626 UI L−1), myoglobin (from 32±22 to 1,432±1,209 µg L−1), and C-Reactive Protein (from <2.0 to 37.7±26.5 mg L−1). Moderate to large reductions in maximal compound muscle action potential amplitude, high-frequency doublet force, and low frequency fatigue (index of excitation-contraction coupling alteration) were also observed for both muscle groups. Sixteen days after MUM, NMF had returned to initial values, with most of the recovery process occurring within 9 days of the race. These findings suggest that the large alterations in NMF after an ultra-marathon race are multi-factorial, including failure of excitation-contraction coupling, which has never been described after prolonged running. It is also concluded that as early as two weeks after such an extreme running exercise, maximal force capacities have returned to baseline.
PMCID: PMC3043077  PMID: 21364944
25.  Marathon Runner with Acute Hyponatremia: A Neurological Disorder 
We report the case of an athletic 49-year-old female who has run the 2011 Marathon of Paris and was addressed to the hospital for a confusion. The investigations revealed a cerebral edema complicating a severe hyponatremia secondary to an exercise-associated hyponatremia (EAH). Using 3% hypertonic saline solution, the evolution the patient rapidly improve allowing discharge after 7 days. We then discuss the importance of EAH in long-term efforts.
PMCID: PMC3542923  PMID: 23326709

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