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Nathan Goodyear

Exercise-induced right ventricular dysfunction and structural remodelling in endurance ... - 0 views

  • In a cohort of well-trained athletes, we demonstrated that intense endurance exercise causes an acute reduction in RV function that increases with race duration and correlates with increases in biomarkers of myocardial injury
  • no relationship between LV function and biomarker levels
  • focal gadolinium enhancement and increased RV remodelling were more prevalent in those athletes with a longer history of competitive sport, suggesting that repetitive ultra-endurance exercise may lead to more extensive RV change and possible myocardial fibrosis
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  • he cardiac impact of both acute and cumulative exercise is greatest on the RV.
  • Greater reductions in RV function occurred in those athletes competing for a longer duration, suggesting that the heart has a finite capacity to maintain the increased work demands of exercise
  • cardiac injury is greatest in the least trained
  • Previous investigators have documented reductions in RV function in less trained subjects over the marathon distance
  • We enrolled elite and subelite athletes and found a significant association between fitness (VO2max) and the reduction in post-race RVEF
  • Even after many years of detraining, cardiac dilation may not completely regress in elite athletes
  • The focus on well-trained athletes may be of particular relevance, given that they perform exercise of highest intensity and duration most frequently, and, thus, may be at a greater risk of cumulative injury.
  • The lack of correlation between increases in troponin and changes in LV function seen in this study has been previously interpreted as evidence that post-exercise elevations in cardiac biomarkers are benign.
  • a significant correlation between changes in RVEF and post-race biomarker levels and this relationship was even stronger in the athletes who completed the race of longest duration, the ultra-triathlon
  • The correlations with RVEF, but not LVEF, provide further evidence of the differential effects of intense exercise on RV and LV function
  • BNP release during intense exercise is associated with greater relative increases in RV systolic pressures, but not LV pressures
  • BNP may provide a measure of both acute RV load and the resultant fatigue which occurs when this load is sustained
  • It has been demonstrated that ventricular load increases with exercise intensity and is greater for the RV than the LV,29 thus potentially explaining why the RV is more susceptible to fatigue after prolonged exercise.
  • This study demonstrates, for the first time, an association between endurance exercise of increasing duration and structural, functional, and biochemical markers of cardiac dysfunction in highly trained athletes
  • Functional abnormalities were confined to the RV and were largely reversible 1 week following the event
  • there remained a significant minority of athletes in whom there was evidence of myocardial fibrosis in the interventricular septum
  • RV abnormalities may be acquired through cumulative bouts of intense exercise and provides direction for prospective investigations aimed at elucidating whether extreme exercise may promote arrhythmias in some athletes.
  • the acute injury and chronic remodelling of the myocardium both disproportionately affect the RV and it remains possible that the two are linked.
  • focal DGE was confined to the interventricular septum and commonly at the site of RV attachment
  • emerging evidence that intense endurance exercise may be associated with an excess in arrhythmic disorders, the mechanisms for which remain unexplained
  • RVEF (and not LVEF) was reduced in athletes with complex ventricular arrhythmias when compared with healthy athletes and non-athletes without arrhythmias
  • it is premature to conclude that these changes may represent a proarrhythmic substrate
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    Study finds endurance racing results in reduce Right ventricle ejection fraction even in elite athletes.  This post-race RVEF reduction is associated with VO2max.
Nathan Goodyear

An integrative analysis reveals coordinated reprogramming of the epigenome and the tran... - 0 views

  • contribution to the training response of the epigenome as a mediator between genes and environment
  • Differential DNA methylation was predominantly observed in enhancers, gene bodies and intergenic regions and less in CpG islands or promoters
  • highly consistent and associated modifications in methylation and expression, concordant with observed health-enhancing phenotypic adaptations, are induced by a physiological stimulus
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  • The health benefits following exercise training are elicited by gene expression changes in skeletal muscle, which are fundamental to the remodeling process
  • there is increasing evidence that more short-term environmental factors can influence DNA methylation
  • dietary factors have the potency to alter the degree of DNA methylation in different tissues, 9,10 including skeletal muscle
  • In one study, a single bout of endurance-type exercise was shown to affect methylation at a few promoter CpG sites
  • In the context of diabetes, exercise training has been shown to affect genome-wide methylation pattern in skeletal muscle,13 as well as in adipose tissue.
  • physiological stressors can indeed affect DNA methylation
  • training intervention reshapes the epigenome and induces significant changes in DNA methylation
  • the findings from this tightly controlled human study strongly suggest that the regulation and maintenance of exercise training adaptation is to a large degree associated to epigenetic changes, especially in regulatory enhancer regions
  • Endurance training [after training (T2) vs. before training (T1)] induced significant (false discovery rate, FDR< 0.05) methylation changes at 4919 sites across the genome in the trained leg
  • identified 4076 differentially expressed genes
  • a complementary approach revealed that over 600 CpG sites correlated to the increase in citrate synthase activity, an objective measure of training response (Figure S4 and Dataset S14). This might imply that some of these sites could influence the degree of training response.
  • As expected by a physiological environmental trigger on adult tissue, the observed effect size on DNA methylation was small in comparison to disease states such as cancer
  • a preferential localization outside of CpG Islands/Shelves/Shores
  • endurance training especially influences enhancers
  • negative correlation was more prominent for probes in promoter/5′UTR/1st exon regions, while gene bodies had a stronger peak of positive correlation
  • The significant changes in DNA methylation, that primarily occurred in enhancer regions, were to a large extent associated with relevant changes in gene expression
  • The main findings of this study were that 3 months of endurance training in healthy human volunteers induced significant methylation changes at almost 5000 sites across the genome and significant differential expression of approximately 4000 genes
  • DMPs that increased in methylation were mainly associated to structural remodeling of the muscle and glucose metabolism, while the DMPs with decreased methylation were associated to inflammatory/immunological processes and transcriptional regulation
  • This suggests that the changes in methylation seen with training were not a random effect across the genome but rather a controlled process that likely contributes to skeletal muscle adaptation to endurance training
  • Correlation of the changes in DNA methylation to the changes in gene expression showed that the majority of significant methylation/expression pairs were found in the groups representing either increases in expression with a concomitant decrease in methylation or vice versa
  • The fraction of genes showing both significant decrease in methylation and upregulation was 7.5% of the DEGs or 2.3% of all genes detected in muscle tissue with at least one measured DNA methylation position. Correspondingly, 7.0% of the DEGs or 2.1% of all genes showed both significant increase in methylation and downregulation
  • we show that DNA methylation changes are associated to gene expression changes in roughly 20% of unique genes that significantly changed with training
  • Examples of structural genes include COL4A1, COL4A2 and LAMA4. These genes have also been identified as important for differences in responsiveness to endurance training
  • methylation status could be part of the mechanism behind variable training response
  • Among the metabolic genes, MDH1 catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle and NDUFA8 plays an important role in transferring electrons from NADH to the respiratory chain
  • PPP1R12A,
  • In the present study, methylation predominantly changed in enhancer regions with enrichment for binding motifs for different transcription factors suggesting that enhancer methylation may be highly relevant also in exercise biology
  • Of special interest in the biology of endurance training may be that MRFs, through binding to the PGC-1α core promoter, can regulate this well-studied co-factor for mitochondrial biogenesis
  • That endurance training led to an increased methylation in enhancer regions containing motifs for the MRFs and MEFs is somewhat counterintuitive since it should lead to the repression of the action of the above discussed transcription factors
  • decrease with training in this study, including CDCH15, MYH3, TNNT2, RYR1 and SH3GLB1
  • expression of MEF2A itself decreased with training
  • this study demonstrates that the transcriptional alterations in skeletal muscle in response to a long-term endurance exercise intervention are coupled to DNA methylation changes
  • We suggest that the training-induced coordinated epigenetic reprogramming mainly targets enhancer regions, thus contributing to differences in individual response to lifestyle interventions
  • a physiological health-enhancing stimulus can induce highly consistent modifications in DNA methylation that are associated to gene expression changes concordant with observed phenotypic adaptations
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    Exercise alters gene expression via methylation--the power of epigenetics.  Interestingly, the majority of the methylation was outside the CPG island regions.  This 3 month study found methylation of 5,000 sites across the genome resulting in altered expression of apps 4,000 genes.  The altered muscle changes of the endurance training was linked to DNA methylation changes.
Nathan Goodyear

Metabolic characteristics of keto-adapted ultra-endurance runners - Metabolism - Clinic... - 0 views

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    full study of previous abstract: low carb and high fat diet found to maintain muscle glycogen equal to high carb diet in endurance athletes.  Endurance athletes have high fat oxidation and this probably only applies to these endurance athletes; I would suspect this high fat oxidation would not be found in other short interval sports i.e. sprinting, football....
Nathan Goodyear

The human metabolic response to chronic ketosis without caloric restriction: preservati... - 0 views

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    ketogenic diet found to not deplete muscle glycogen in endurance athletes.  The metabolism of the endurance athletes can do this via the high fat oxidation--estimates of 80%.
Nathan Goodyear

Intravenous Fluid Use in Athletes - 0 views

  • Treatment of exercise-associated hyponatremia with hypertonic IV infusion to correct plasma sodium levels is also a standard and accepted use of IV fluid infusions
  • athletes who present for medical care with hypernatremia who cannot tolerate oral fluids can benefit from IV fluids
  • Vaporization of sweat accounts for 80% of heat loss in hot, dry atmospheric conditions. This mechanism of water loss is the major contributor for exercise-associated dehydration
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  • The rate of water loss can be quantified through measurement of sweat rate
  • Pre- and postexercise body weight measurements are the most common means to estimate overall water loss but are condition specific
  • It appears that 1% to 2% body weight loss is well tolerated by the exercising athlete
  • Dehydration, defined as greater than 2% loss of body weight, can negatively affect performance
  • In highly trained endurance athletes, plasma volume and sodium serum concentration were preserved despite a 5% body weight loss
  • In Ironman triathletes, dehydration to 5% body weight loss did not correlate with occurrence of medical complications
  • hydration should begin hours prior to exercise, especially if known deficits are present, and fluids should be consumed at a slow, steady rate, with 5 to 7 mL/kg taken 4 hours prior to exercise
  • Sodium concentration did not produce significant changes in the rate of absorption but was primarily dependent on carbohydrate concentration
  • Replacing 150% of body weight loss over 60 minutes has been tolerated without complications
  • IV treatment of severe dehydration (>7% body weight loss), exertional heat illness, nausea, emesis, or diarrhea, and in those who cannot ingest oral fluids for other reasons, is clinically indicated
  • A recent survey of the National Football League teams revealed that 75% (24 of 32) of the teams utilized IV infusion of fluids for prehydration in at least some otherwise healthy individuals
  • In the National Football League, an average of 1.5 L of normal saline was administered approximately 2.5 hours prior to competition
  • after 2 hours of exercise, the rectal temperature was 0.6° higher in the group not receiving IV infusion. Also, stroke volume and cardiac output were 11% to 16% lower in the control group versus the IV infusion group.
  • Recent evidence suggests the etiology of EAMC is related to muscle fatigue and neuronal excitability
  • no correlation between hydration status or electrolyte concentrations with EAMC
  • there may be a subset of muscle cramping that is associated with a loss of both body fluid and sodium
  • Glycerol is the primary agent for oral hyperhydration
  • elevation of plasma volume by 200 to 300 mL via dextran infusion resulted in 15% increase in stroke volume, 4% increase in VO2 max, and an increase in the exercise time to fatigue
  • Neither the tonicity nor mode of hydration resulted in improved speed of rehydration, greater fluid retention, or improved performance
  • There are beneficial anecdotal reports of EAMC treatment in elite and professional-level athletes with IV hydration during the course of an event
  • Plasma volume was better restored during rehydration with IV fluids at preexercise and 5 minutes of exercise. At 15 minutes, there was no difference between IV and oral rehydration
  • More rapid restoration of plasma volume was accomplished in the IV treatment group with no advantages over oral rehydration in physiological strain, heat tolerance, ratings of perceived effort, or thermal sensations
  • No difference was found in exercise time to exhaustion. IV and oral rehydration methods were equally effective. Heart rates were statistically higher in the oral rehydration group through 75 minutes of exercise, and there were higher increases in norepinephrine plasma concentrations
  • No significant differences between the groups were found for time to recovery, number of days with pain, number of days with stiffness, sleep disturbance, fatigue, rectal temperature, and loss of appetite
  • The current data suggest that IV rehydration is faster than oral
  • There may be physiological benefits of decreased heart rate and norepinephrine in athletes rehydrated via IV route
  • Postexercise blood 1 hour and 24 hours showed no differences in circulating myoglobin or creatine kinase
  • The use of IV fluid may be beneficial for a subset of fluid sensitive athletes
  • this should be reserved for high-level athletes with strong histories of symptoms in well-monitored settings.
  • Volume expanders may also be beneficial for some athletes
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    to be read
Nathan Goodyear

Exercise-associated hyponatremia: role of cytokines. - PubMed - NCBI - 0 views

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    study links rhabdomyolysis to exercise induced hyponatremia.  This article links the depletion of glycogen to muscle release of IL-6 leading to increase in ECW and thus hyponatremia. The abstract discusses fluid restriction vs hypertonic 3% NaCL to reverse the more severe cases.  The first signs are of weight gain and thus weight should be monitored.  Decreased renal output is also associated with EAH.  Altered mental status is an early sign.
Nathan Goodyear

Cordyceps sinensis promotes exercise endura... [J Ethnopharmacol. 2011] - PubMed - NCBI - 0 views

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    Cordyceps supplementation at 200 mg/kg/day improves exercise endurance capacity.  Parameters found: angiogenesis, improved glucose uptake, improved lactate uptake.  This occurred in both those rats in the exercise arm and those in the non-exercise arm.
Nathan Goodyear

Exercise-associated hyponatremia. - PubMed - NCBI - 0 views

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    hyponatremia due to exercise, or exercise induced hyponatremia, is multifactorial: over-hydration, poor renal clearance, SIADH thus inhibition of renal fluid clearance, and excessive Na loss through sweat.
Nathan Goodyear

Omega-3 fatty acids supplementation improves endothelial function and maximal oxygen up... - 0 views

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    supplementation of 2.6 grams of n-3 found to increase NO and VO2max in elite cycling athletes.  This has applications for all endurance athletes.  
Nathan Goodyear

https://www.cayugamed.org/docs/Nutrition_Update_for_the_Ultraendurance_Athlete%208.pdf - 0 views

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    Nutrition for ultra endurance.  To be read.
Nathan Goodyear

Cordyceps sinensis promotes exercise endurance capacity of rats by activating skeletal ... - 0 views

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    mouse model finds cordyceps improves exercise endurance.  This has, largely, not translated to human studies, though very few studies are available.  
Nathan Goodyear

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1332190/pdf/brjsmed00019-0063.pdf - 0 views

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    study finds IV hydration with glucose and larger volume did not recover as well as those with 100 ml  of IV fluids.  This conclusion is incomplete as the time differences between the 2 groups was significant--group 2 (2.5 L fluid group) finished much faster and studies have shown that these endurance athletes are more prone to dehydration, more significant weight loss, adverse effects from the event.  This likely explains the difference between the 2 groups.
Nathan Goodyear

Metabolic characteristics of keto-adapted ultra-endurance runners - Metabolism - Clinic... - 0 views

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    For endurance athletes, low carb and high fat diet utilizes the high fat oxidation in these athletes compared to a high carb diet.  Glycogen stores did not differ between the two groups.  
Nathan Goodyear

Thieme E-Journals - International Journal of Sports Medicine / Abstract - 0 views

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    Ultra endurance athletic events associated with significant increase in systemic inflammation due to damaged gut.
Nathan Goodyear

The endurance athletes heart: acute stress and chronic adaptation -- George et al. 46 (... - 0 views

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    acute and chronic heart changes to endurance training/events.
Nathan Goodyear

Diagnosis and prevention of hyponatremia at an ultradistance triath... - PubMed - NCBI - 0 views

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    over hydration increases risk of hyponatremia.  Body weight is inversely associated with Na levels.  Weight evaluations are an appropriate means to evaluate.  Endurance triathlon athletes can lose up to 5% without any negative physiologic impact.
Nathan Goodyear

Endurance exercise performance: the physiology of champions - 0 views

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    great review on performance physiology.  This article reviews  how VO2 max, lactate threshold, performance VO2, and mitochondria contribute to peak endurance performance.
Nathan Goodyear

http://www.sportsperformancecentres.com/articles/interest/Endurance_Exercise_and_Protei... - 0 views

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    white paper on protein for endurance athletes.
Nathan Goodyear

http://www.msma.org/docs/communications/momed/Excessive_Endurance_Exercise_and_Heart_Di... - 0 views

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    great review of data on cardiac damage associated with extreme endurance training.  These EEEs, that they are called, are rare in those < 40 and usually involved genetic defects.  This article points to aggressive preventive testing in those > 50.
Nathan Goodyear

The Single Nucleotide Polymorphism Gly482Ser in the PGC-1α Gene Impairs Exerc... - 0 views

  • Oxidative slow-twitch type I fibres (henceforth briefly called ‘slow fibres’) contain MHC-Iβ. They use oxidative phosphorylation (OXPHOS) to generate ATP and are thus highly fatigue resistant and preferentially activated during endurance exercise. Slow fibres comprise high amounts of mitochondria, myoglobin and lipid droplets, and are well supplied by capillaries
  • there are three types of fast-twitch fibres (types IIA, IID/X, IIB, with the corresponding MHC isoforms IIa, IId/x, IIb) which are all used for rapid high-force generation. Oxidative-glycolytic fast-twitch type IIA fibres have intermediate amounts of mitochondria, lipid droplets and capillaries, and are intermediately resistant to fatigue (as compared to type I and types IIB and IID/X). Glycolytic fast-twitch type IID/X fibres are poor in mitochondria, lipids and capillaries and more susceptible to fatique than type IIA. Glycolytic fast-twitch type IIB fibres have the lowest amounts of mitochondria, lipid droplets and capillaries, but generate the highest contraction velocities
  • Several studies have shown that PGC-1α is upregulated after endurance training
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  • upregulation of PGC-1α expression enhances and/or maintains mitochondrial biogenesis, eventually leading to an increased mitochondrial content of the muscle fibres.
  • PGC-1α also plays an important role in the pathogenesis of insulin resistance and T2D
  • carriers of the Gly482Ser SNP have a reduced cardiorespiratory fitness and a higher risk for metabolic syndrome and T2D
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    Those that carry the risk SNP for Gly482Ser for the PGC-1alpha gene dont' transform type II to type I and thus decrease the effectiveness of aeorbic exercise training, decreased oxidative phosphorylation, decreased lipid oxidation, increased lipid accumulaiton in muscle, and increased risk of IR, obesity, and diabetes.
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