Acute stress and recovery responses to an Ironman triathlon

Körperliche Aktivität bewirkt eine Reihe von günstigen physiologischen Effekten und beugt damit erwiesenermaßen chronischen Erkrankungen vor. Paradoxerweise deuten indes einige Daten auf mögliche Gesundheitsrisiken (wie z.B. kumulativen oxidativen Stress) durch extreme sportliche Ausdauerbelastungen hin. Das Hauptziel des vom Österreichischen Wissenschaftsfonds geförderten Forschungsprojekts Risikobeurteilung von Teilnehmern eines Ironman Triathlons war daher, einen umfassenden Einblick in biochemische, physiologische und molekular-biologische Stressreaktionen nach einem Ironman Triathlon (3,8 km Schwimmen, 180 km Radfahren, 42 km Laufen) als einem Prototyp einer Ultra-Ausdauerbelastung zu gewinnen. Als Teil dieses Projekts wurden folgende Aspekte im Rahmen der vorliegenden Dissertation untersucht: 1.) Oxidativer Stress und antioxidative Reaktionen, 2.) Entzündungs-, immuno-endokrine und (skelett-)muskuläre Reaktionen sowie 3.) Wechselwirkungen dieser Reaktionen mit belastungsbedingten Effekten auf die DNA-Stabilität. Das Studienkollektiv bestand aus 42 gut trainierten, männlichen, sogenannten “Altersklasse” Triathleten (VO2 peak am Fahrradergometer: 56,6ml ± 6.2ml * kg–1 * min–1, Mittelwert ± Standardabweichung). Blutproben wurden 2 Tage vor dem Ironman Triathlon, unmittelbar nach Beendigung sowie 1 Tag, 5 und 19 Tage nach dem Ironman entnommen. Neben dem hämatologischen Profil wurden im Blutplasma folgende Parameter analysiert: Marker für oxidativen Stress, die gesamte Antioxidantienkapazität, nutritive und endogene Antioxidantien, immun-endokrine/inflammatorische Parameter und Muskelschädigungsmarker. Weiters wurden die Aktivitäten antioxidativen Enzyme in Erythrozyten untersucht. Korrelationsanalysen, einfaktorielle ANOVA und daran gekoppelte post hoc Tests wurden zur Eruierung potentieller Wechselwirkungen zwischen antioxidativen Reaktionen, oxidativem Stress, immun-endokrinen und Entzündungsreaktionen, skelett-muskulären Schäden und belastungsinduzierten Effekten auf Endpunkte für die DNA-Stabilität herangezogen (die im Rahmen einer weiteren Dissertation von Stefanie Reichhold untersucht wurden). Diese Studie dokumentiert, dass die Belastung eines Ironman Triathlons, trotz vorübergehender Anstiege bei den meisten Markern für oxidativen Stress, zu keiner nachhaltigen oxidativen Schädigung an zellulären Bestandteilen und Lipiden im Blut führt. Die Studienresultate weisen auf protektive Veränderungen im antioxidativen Schutzsystem hin, welche sowohl durch Training als auch durch die akute Belastung induziert werden. Darüber hinaus veranschaulichen die vorliegenden Ergebnisse, dass der Bedarf von Ultra-Ausdauerathleten an nutritiven Antioxidantien weitgehend über eine vielfältige, ausgewogene und in der Energiebilanz ausgeglichene Ernährung gedeckt werden kann. Allerdings erfordert die Antioxidantienaufnahme sowohl während als auch in der frühen Regenerationsphase nach einer Ultra-Ausdauerbelastung spezielles Augenmerk. Die durch den Ironman Triathlon initiierte markante systemische Entzündungsreaktion nahm rasch ab. Dahingegen geben die bis mindestens 5 Tage nach dem Triathlon moderat, aber signifikant erhöhten Entzündungsparameter sowie Korrelationen mit Muskelschädigungsmarkern, Hinweise auf Entzündungsvorgänge infolge noch nicht abgeschlossener Reparaturprozesse in der Skelettmuskulatur. Die Ergebnisse lassen auf keine ursächliche Zusammenhänge zwischen DNA Effekten in Lymphozyten und belastungsbedingten Entzündungsreaktionen schließen. Eine oxidative DNA-Schädigung durch eine erhöhte Bildung von reaktiven Sauerstoffspezies von an Entzündungsvorgängen beteiligten Leukozyten wurde vermutlich durch verstärkte antioxidative Reaktionen verhindert. In Summe weisen diese Daten auf eine sowohl durch Training als auch die akute Belastung induzierten Adaptationen von z.B. endogenen antioxidativen Schutzsystem und/oder Reparatursystemen hin. Diese Anpassungen protektiver Mechanismen dürften nachhaltigen Schäden durch oxidativen Stress und DNA Schädigungen entgegenwirken. Diese Resultate sind ein Indiz dafür, dass die Vorbereitungen auf und Teilnahme an einem Ultra-Ausdauerwettkampf mit keinen erhöhten Gesundheitsrisiken in Form von Herz-Kreislauferkrankungen oder Erkrankungen im Zusammenhang mit DNA Schädigungen verbunden sein dürften. Diese enorme physiologische Belastungsverträglichkeit und Regenerationsfähigkeit setzt allerdings einen entsprechenden Trainingszustand der Athleten voraus.There is compelling evidence that physical activity harvests numerous beneficial physiological effects and plays a key role in the prevention of various modern chronic diseases. However, some data imply that there are potentially harmful effects as a result of exceptional high volumes of exercise such as cumulative oxidative stress. In this context the Austrian Science Fund-funded research project Risk Assessment of Participants of an Ironman Triathlon was aimed to get a broader picture of biochemical, physiological and molecular-biological stress responses to an Ironman triathlon (3.8 km swimming, 180 km cycling, 42 km running) as a prototype of ultra-endurance exercise. As a part of this project the following specific issues have been addressed within the scope of the present doctoral thesis: 1.) oxidative stress and antioxidant responses, 2.) inflammatory, immuno-endocrine and (skeletal) muscular responses, and 3.) interactions of these responses with exercise-induced effects on DNA stability. Blood samples were taken from 42 well-trained, male, so called “age-group” (i.e. non-professional) triathletes (cycling VO2 peak: 56.6 ± 6.2 ml * kg –1 * min –1, mean ± SD) 2 days (d) before an Ironman triathlon, then immediately post-race, 1, 5 and 19 d later. Beside for the haematological profile, blood plasma was analyzed for oxidative stress markers, total plasma antioxidant capacity, nutritive and endogenous antioxidants, immune-endocrine/inflammatory parameters and muscle damage markers. Additionally, activities of antioxidative enzymes were determined in erythrocytes. Correlation analyses and one-factorial ANOVA plus post hoc tests were applied to assess significant associations among antioxidant, oxidative stress, inflammatory, immune-endocrine responses, muscle damage and exercise-induced effects on endpoints of DNA stability (analyzed within the framework of another published doctoral thesis by Stefanie Reichhold). Results from this study indicate that despite a temporary increase in most oxidative stress markers, there is no persistent oxidative damage to blood cell compounds and blood lipids in response to an Ironman triathlon, probably due to training- and exercise-induced protective alterations in the antioxidant defense system. Furthermore, findings from the current investigation illustrates that requirements by ultra-endurance athletes for nutritive antioxidants, to a great extend, can be achieved by a diversified, balanced and energy-sufficient diet, while the antioxidant intake during and in the early recovery phase after ultra-endurance exercise requires specific attention. The pronounced initial systemic inflammatory response induced by the acute bout of ultra-endurance exercise declines rapidly, but a low-grade systemic inflammation persisted until at least 5 d post-race, possibly reflecting incomplete muscle recovery. Moreover, the current results indicate that DNA effects in lymphocytes are not responsible for exercise-induced inflammatory responses, and that, vice versa, inflammatory processes do not promote DNA damage. Oxidative DNA damage via an increased formation of ROS derived from inflammatory cells might have been prevented by enhanced antioxidant responses. The general picture that emerges from the data of this research project is that training- and acute exercise-induced adaptations in protective mechanisms including improved endogenous antioxidant defences and repair systems counteract severe oxidative stress and persistent DNA damage. Based on these findings, training for and participating in an ultra-endurance event such as an Ironman triathlon, might not be associated with a higher risk of developing cardiovascular disease or diseases through DNA damage. However, the enormous capability to cope with and recover from certain forms of physiological stress implies an adequate training status

Role of cardiac energetics in aortic stenosis disease progression: identifying the high-risk metabolic phenotype

Background: Severe aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and cardiac metabolic alterations with evidence of steatosis and impaired myocardial energetics. Despite this common phenotype, there is an unexplained and wide individual heterogeneity in the degree of hypertrophy and progression to myocardial fibrosis and heart failure. We sought to determine whether the cardiac metabolic state may underpin this variability. Methods: We recruited 74 asymptomatic participants with AS and 13 healthy volunteers. Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to adenosine triphosphate ratio. Myocardial lipid content was determined using proton spectroscopy. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging. Results: Phosphocreatine/adenosine triphosphate was reduced early and significantly across the LV wall thickness quartiles (Q2, 1.50 [1.21–1.71] versus Q1, 1.64 [1.53–1.94]) with a progressive decline with increasing disease severity (Q4, 1.48 [1.18–1.70]; P=0.02). Myocardial triglyceride content levels were overall higher in all the quartiles with a significant increase seen across the AV pressure gradient quartiles (Q2, 1.36 [0.86–1.98] versus Q1, 1.03 [0.81–1.56]; P=0.034). While all AS groups had evidence of subclinical LV dysfunction with impaired strain parameters, impaired systolic longitudinal strain was related to the degree of energetic impairment (r=0.219; P=0.03). Phosphocreatine/adenosine triphosphate was not only an independent predictor of LV wall thickness (r=−0.20; P=0.04) but also strongly associated with myocardial fibrosis (r=−0.24; P=0.03), suggesting that metabolic changes play a role in disease progression. The metabolic and functional parameters showed comparable results when graded by clinical severity of AS. Conclusions: A gradient of myocardial energetic deficit and steatosis exists across the spectrum of hypertrophied AS hearts, and these metabolic changes precede irreversible LV remodeling and subclinical dysfunction. As such, cardiac metabolism may play an important and potentially causal role in disease progression

Determinants of left ventricular mass in obesity; a cardiovascular magnetic resonance study

<p>Abstract</p> <p>Background</p> <p>Obesity is linked to increased left ventricular mass, an independent predictor of mortality. As a result of this, understanding the determinants of left ventricular mass in the setting of obesity has both therapeutic and prognostic implications. Using cardiovascular magnetic resonance our goal was to elucidate the main predictors of left ventricular mass in severely obese subjects free of additional cardiovascular risk factors.</p> <p>Methods</p> <p>38 obese (BMI 37.8 ± 6.9 kg/m²) and 16 normal weight controls subjects, (BMI 21.7 ± 1.8 kg/m²), all without cardiovascular risk factors, underwent cardiovascular magnetic resonance imaging to assess left ventricular mass, left ventricular volumes and visceral fat mass. Left ventricular mass was then compared to serum and anthropometric markers of obesity linked to left ventricular mass, i.e. height, age, blood pressure, total fat mass, visceral fat mass, lean mass, serum leptin and fasting insulin level.</p> <p>Results</p> <p>As expected, obesity was associated with significantly increased left ventricular mass (126 ± 27 vs 90 ± 20 g; p < 0.001). Stepwise multiple regression analysis showed that over 75% of the cross sectional variation in left ventricular mass can be explained by lean body mass (β = 0.51, p < 0.001), LV stroke volume (β = 0.31 p = 0.001) and abdominal visceral fat mass (β = 0.20, p = 0.02), all of which showed highly significant independent associations with left ventricular mass (overall R²= 0.77).</p> <p>Conclusion</p> <p>The left ventricular hypertrophic response to obesity in the absence of additional cardiovascular risk factors is mainly attributable to increases in lean body mass, LV stroke volume and visceral fat mass. In view of the well documented link between obesity, left ventricular hypertrophy and mortality, these findings have potentially important prognostic and therapeutic implications for primary and secondary prevention.</p

Regional differences in health care of patients with inflammatory bowel disease in Germany

Background: The regional availability of specialized physicians is an important aspect in healthcare of patients with IBD. The association between physician density and healthcare is not yet clear. Most studies did not consider district type, which reflects population density. Our research question was, “Do specialist density and district type influence the healthcare of IBD patients in Germany?” Methods: We combined a claims dataset from a German health insurance fund with population and physician data. Four main aspects were investigated: regular specialist visits, drug therapies, surveillance colonoscopy, and IBD-related hospitalizations. Various regression analyses were performed. Results: The study cohort was comprised of 21,771 individuals, including 9282 patients with Crohn disease and 12,489 patients with ulcerative colitis. Patients who were living in districts with higher specialist densities were more likely to attend specialist visits on a regular basis. No difference in the frequencies of TNF-alpha inhibitor therapies was found. However, individuals from urban areas were more likely to receive a permanent immunosuppressive therapy with continuous specialist support. Conclusions: The results revealed that some aspects had positive effects on the probability of implementing healthcare in accordance with pathways and guidelines. No clear evidence of a general healthcare undersupply in rural areas was found.DF

Nitrate: The Dr. Jekyll and Mr. Hyde of human health?

Background: Dietary nitrate has a controversial role in human health. For over half a century, the nitrate content of the three major dietary sources – vegetables, meat, and water – has been legislated, regulated, and monitored due to public health concerns over cancer risk. In contrast, a growing and compelling body of evidence indicates that dietary nitrate, particularly from vegetables, protects against cardiovascular disease and other chronic diseases. This evidence for the protective effect of nitrate is overshadowed by the potential for nitrate to form carcinogenic N-nitrosamines. Scope and approach: The nitrate content, regulations and estimated intake from vegetables, meat and water are described. The evidence that nitrate, through its effects on nitric oxide, improves cardiovascular disease outcomes, cognitive health, musculoskeletal health, and exercise performance as well as the potential to protect against other debilitating health outcomes (nitrate as Dr Jekyll) is discussed. The underlying assumption that all nitrate, irrespective of source, leads to the formation of carcinogenic N-nitrosamines and the evidence of an association between the different sources of nitrate and cancer (nitrate as Mr Hyde) is examined. Key findings and conclusions: The current theory that nitrate, is a carcinogenic contaminant in meat, water, and vegetables is not fully supported by available evidence. Definitive studies examining the beneficial or harmful effects of source-dependent nitrate have yet to be performed. Studies with improved exposure assessment and accurate characterization of factors that affect endogenous nitrosation are also needed to draw conclusions about risk of cancer from dietary nitrate intake

Observational study of regional aortic size referenced to body size: production of a cardiovascular magnetic resonance nomogram

Background: Cardiovascular magnetic resonance (CMR) is regarded as the gold standard for clinical assessment of the aorta, but normal dimensions are usually referenced to echocardiographic and computed tomography data and no large CMR normal reference range exists. As a result we aimed to 1) produce a normal CMR reference range of aortic diameters and 2) investigate the relationship between regional aortic size and body surface area (BSA) in a large group of healthy subjects with no vascular risk factors. Methods: 447 subjects (208 male, aged 19–70 years) without identifiable cardiac risk factors (BMI range 15.7–52.6 kg/m2) underwent CMR at 1.5 T to determine aortic diameter at three levels: the ascending aorta (Ao) and proximal descending aorta (PDA) at the level of the pulmonary artery, and the abdominal aorta (DDA), at a level 12 cm distal to the PDA. In addition, 201 of these subjects had aortic root imaging, allowing for measurements at the level of the aortic valve annulus (AV), aortic sinuses and sinotubular junction (STJ). Results: Normal diameters (mean ±2 SD) were; AV annulus male(♂) 24.4 ± 5.4, female (♀) 21.0 ± 3.6 mm, aortic sinus♂32.4 ± 7.7, ♀27.6 ± 5.8 mm, ST-junction ♂25.0 ± 7.4, ♀21.8 ± 5.4 mm, Ao ♂26.7 ± 7.7, ♀25.5 ± 7.4 mm, PDA ♂20.6 ± 5.6, +18.9 ± 4.0 mm, DDA ♂17.6 ± 5.1, ♀16.4 ± 4.0 mm. Aortic root and thoracic aortic diameters increased at all levels measured with BSA. No gender difference was seen in the degree of dilatation with increasing BSA (p > 0.5 for all analyses). Conclusion: Across both genders, increasing body size is characterized by a modest degree of aortic dilatation, even in the absence of traditional cardiovascular risk factors