Introdução: Baixos níveis de atividade física vêm sendo constatados nas diversas classes e faixas etárias da população brasileira, inclusive entre os jovens que anualmente se alistam para ingressar nas Forças Armadas. Este quadro compromete diretamente a saúde e a qualidade de vida destes jovens adultos, enquanto a realização de uma rotina de treinamento físico está relacionada com a prevenção de diversas doenças. O treinamento intervalado de alta intensidade (HIIT) é um método que tem demostrado ser eficiente para melhorar os níveis de aptidão e atividade física, bem como de indicadores de saúde como % gordura, % massa magra, aptidão cardiorrespiratória (VO2pico), perfis lipídico e glicêmico, em diversas populações. Partindo desta premissa, o presente estudo teve por objetivo analisar e comparar os efeitos crônicos de diferentes protocolos de treinamento de alta intensidade sobre indicadores de saúde e desempenho em jovens adultos militares. Metodologia: Dois grupos, compostos por militares homens entre 18 e 20 anos, foram submetidos durante 12 semanas, três vezes por semana, a dois diferentes protocolos de treinamento de HIIT previstos nos manuais do Exército: o treinamento intervalado aeróbio (TIA), e a corrida variada (CV). Os indivíduos foram avaliados pré e pósintervenção, sendo analisadas variáveis cardiorrespiratórias, antropométricas, glicêmicas e lipídicas relacionadas à saúde e ao desempenho, bem como teste de Cooper e salto vertical em plataforma de força. Resultados: Observou-se em ambos os grupos uma redução das dobras cutâneas (-12,7% e -7,1%, respectivamente para os grupos TIA e CV, p=0,002), assim como um aumento da massa livre de gordura (MLG) (TIA = 4,0%, CV = 2,2%), com esta diferença sendo significativamente maior para o grupo TIA (p=0,045). Também foi verificada uma melhora pós-intervenção no VO2pico (p=0,028), tanto para o grupo TIA (2,9%) como para o grupo CV (5,5%), havendo diferença significativa em favor do grupo CV (p=0,013). Da análise bioquímica, constatou-se que os dois treinamentos foram capazes de aumentar os níveis de HDL (TIA=10,3% e CV=20,7%, p=0,001) e diminuir a glicemia de jejum (TIA=-4,23% e CV=-4,33%, p=0,025). Adicionalmente, o grupo TIA apresentou um aumento significativo no teste squat jump (10,5%, p=0,011) e na potência de membros inferiores (8,1%, p=0,016). Os dois protocolos apresentaram um ganho significativo e tamanho de efeito muito grande no teste de Cooper (p<0,001, TIA d=1,865 e CV d=1,394), assim como um aumento significativo e tamanho de efeito grande para velocidade de segundo limiar ventilatório (vLV2) (p=0,001, TIA d=1,016 e CV d=1,173), velocidade deVO2pico (vVO2pico) (p<0,001, TIA d=1,047 e CV d=0,885) e velocidade máxima no teste ergométrico (vMáx) (p<0,001, TIA d=0,875 e CV d=0,773). Conclusão: Ambos os protocolos de treinamento foram efetivos em promover a melhora da composição corporal, do perfil lipídico e glicêmico, contribuindo para uma manutenção dos indicadores de saúde, sendo o treinamento intervalado mais eficaz no ganho de massa livre de gordura. Além disso, os dois tipos de treino parecem influenciar positivamente nas variáveis de desempenho, com destaque para a CV no ganho cardiorrespiratório, e para o TIA no aumento da potência de membros inferiores. / Introduction: Low levels of physical activity have been observed in the different groups of the Brazilian population, including the young people who annually join the Armed Forces. This framework influence directly health and quality of life of those young adults, while the carrying out of a physical training is related to prevention of various diseases. High intensity interval training (HIIT) is a method that has been shown to be efficient in improving fitness and physical activity levels, as well as health indicators such as fat mass, lean mass, cardiorespiratory fitness (VO2peak), lipid profile and glycemic control in several populations. Based on this premise, this study aimed to analyze and compare the chronic effects of different high intensity training protocols on health and performance indicators in young military adults. Methods: Two training groups, consisting of military men between the ages of 18 and 20, underwent two different HIIT protocols, foreseen in the Army manuals: aerobic interval training (TIA), and varied running (CV). Individuals were evaluated before and after the intervention period, in cardiorespiratory, anthropometric, glycemic and lipid parameters related to health and performance, as well as the Cooper’s test and vertical jump tests in force platform. Results: There was a reduction of skin folds in both groups (-12.7% and - 7.1%, respectively for TIA and CV groups, p = 0.002), as well as an increase in free fat mass (MLG) (TIA = 4.0%, CV = 2.2%), with significant difference for TIA group (p = 0.045). VO2peak improvement (p = 0.028) was also observed for both TIA group (2.9%) and CV group (5.5%), with significant difference in favor of CV group (p = 0.013). From blood analysis, it was found that both training protocols were able to increase HDL levels (TIA = 10.3% and CV = 20.7%, p = 0.001) and to decrease fasting glycaemia (TIA = -4, 23% and CV = -4.33%, p = 0.025). In addition, TIA group showed a significant increase in squat jump test (10.5%, p = 0.011) and lower limbs power (8.1%, p = 0.016). The two protocols showed a significant improve and very large effect size in Cooper's test (p <0.001, TIA d = 1.865 and CV d = 1.394), as well as a significant increase and large effect size for second ventilatory threshold speed (vLV2) (p = 0.001, TIA = 1.016 and CV d = 1.173), VO2peak speed (vVO2peak) (p <0.001, TIA d = 1.047 and CV d = 0.885) and ergometric test maximum speed vMáx (p <0.001, TIA d = 0.875 and CV d = 0.773). Conclusion: Both training protocols are effective in improve body composition, lipid and glycemic profile, contributing to maintain health indicators, with TIA method being more effective in free-fat mass increase. Besides, the two training seem to influence positively the performance variables, with emphasis on CV method in cardiorespiratory improvement, and on TIA method in lower limbs power increase.

Hintergrund: Bei der Herzinsuffizienz mit erhaltener Ejektionsfraktion (HFpEF) handelt es sich um ein komplexes Krankheitsbild, das mit steigenden Hospitalisierungsraten an immer zunehmender Bedeutung im Gesundheitssystem gewinnt. Trotz hoher Mortalitätsraten hat sich keine Standardtherapie etabliert und bisher existieren keine erfolgreichen Behandlungsmaßnahmen. Zudem macht die HFpEF die Hälfte aller Herzinsuffizienzfälle aus, was die Zweckmäßigkeit der Erforschung einer effektiven Therapie hervorhebt. Als ein der entscheidenden Faktoren in der Pathophysiologie der Erkrankung wird die endotheliale Störung gestellt. Mit Reduktion der NO-Bioverfügbarkeit im Endothelium führt die endotheliale Störung zur LV -Versteifung mit diastolischer Dysfunktion des Herzens. Das körperliche Training und daraus resultierende Scherkräfte im Blutgefäß triggern eine HDL-vermittelte Stickstoffmonoxid Synthese. Die vasodilatative, eNOS-steigernde Funktion des HDL kann bei Herzinsuffizienten gestört sein. Eine entsprechende Trainingsmodalität könnte sich jedoch als Endothelium-schützend zeigen. Fragestellung: Ziel dieser Dissertation ist die Erforschung, ob die HDL-Funktion von Patienten mit HFpEF durch das Hochintensive Intervalltraining (90-95 % der maximalen HF) oder Moderat-Intensives Kontinuierliches Ausdauertraining (60-70 % der maximalen HF) beeinflussbar ist. Im Fokus der Untersuchungen stehen die HDL-gesteuerte eNOS- Funktion (Funktion der endothelialen Stickstoffmonoxid-Synthase), die durch die Phosphorylierung an unterschiedlichen Aminosäureresten im Molekül ausgewertet wird, die PON-1 Aktivität (Paraoxonase-1), die für anti-oxidative Rolle des HDL spricht, sowie die Konzentrationen von TBARS (Thiobarbitursäure-reaktive Substanzen), die als Indikatoren der gesteigerten Lipidperoxidation dienen. Material und Methoden: Um die Fragen zu klären, wurden die Probanden in drei Gruppen randomisiert: 1) HIIT (Hochintensives Intervalltraining), 2) MCT (Moderat-Intensives Kontinuierliches Ausdauertraining) und 3) CG (Kontrollgruppe). Vor, während und nach den verschiedenen Trainingsinterventionen wurde das HDL durch Ultrazentrifugation aus dem Blutserum der Probanden isoliert. Im Anschluss daran erfolgte die Inkubation der gewonnenen HDL-Isolate mit humanen Aortenendothelzellen. Mittels Western Blot wurde die HDL-induzierte eNOS-Phosphorylierung an der aktivierenden Position Ser1177 (die zur Steigerung der eNOS-Aktivität führt) und an der deaktivierenden Position Thr 495 (die zur Hemmung der eNOS-Aktivität führt) ermittelt. Aktivierende Phosphorylierung der eNOS geht mit einer gesteigerten NO-Produktion einher. Zur Klärung, wie weit modifizierbar die Endothelium-schützende Rolle des HDL ist und welche Korrelationen damit einhergehen, wurde anti-oxidative Funktion des HDL gemessen. Dazu diente die Messung der Aktivität des assoziierten Enzymes - Paraoxonase-1 (PON-1), das die Lipoproteine vor oxidativer Modifikation schützt. Die protektive Eigenschaft des HDL lässt sich unter anderem durch reaktive Sauerstoffspezies modifizieren. Die reduzierte PON-1 Aktivität kann mit gesteigerter Lipidperoxidation mit daraus entstehenden Fettsäure-Radikale einhergehen. Als Indikator wurde in der vorliegenden Studie die Konzentration an Thiobarbitursäure- reaktiver Substanzen (TBARS) gemessen. Ergebnisse/ Beobachtungen: Durch das körperliche Training konnte man einen Anstieg der eNOS-Phosphorylierung an Ser1177 hervorrufen. Nach dem ersten supervidierten Teil des HIIT kam es zu einer signifikanten HDL-induzierten eNOS-Phosphorylierung an Ser 1177. Weder nach HIIT noch nach MCT konnte jedoch ein signifikanter Rückgang der eNOS Phosphorylierung an der deaktivierenden Position Thr495 festgestellt werden. Bei der Betrachtung der eNOS-Phosphorylierung in der MCT- und Kontrollgruppe fielen keine signifikanten Unterschiede auf. Bei HIIT Probanden ergaben sich signifikant erhöhte Werte von PON-1 Aktivität sowohl im Serum als auch im HDL. In MCT- und Kontrollgruppe konnten hingegen keine signifikante Steigerung der PON-1 Aktivität nachgewiesen werden. Bei der Betrachtung von erhobenen Daten dieser Arbeit fallen erhöhte Werte von TBARS- Konzentrationen bei allen Probanden auf. Es kam allerdings zu keinen signifikanten Unterschieden nach den Trainingsinterventionen. Schlussfolgerungen: Die vorliegende Studie liefert die Erkenntnisse, dass das Hochintensive Intervalltraining eine signifikant gesteigerte HDL-vermittelte eNOS Phosphorylierung, die ebenfalls mit signifikant erhöhter PON-1 Aktivität einhergeht, bei HFpEF-Erkrankten induziert. Ferner aus den erhobenen Daten lässt sich ableiten, dass die Compliance bei allen Probandengruppe jeweils höher während eines überwachten Trainings als während einer home-basierten Intervention war. Insgesamt kann man daraus spekulieren, dass HIIT eine verbesserte endotheliale Funktion des HDL hervorrufen könnte und eine mögliche effektive Therapiemethode der HFpEF in Zukunft darstellen würde. Eine Nutzung dieser Methode bleibt offen und bedarf weiterer Forschungen.:Inhaltsverzeichnis I Tabellenverzeichnis IV Abbildungsverzeichnis V Abkürzungsverzeichnis VI 1 Einleitung 3 1.1 Die Herzinsuffizienz mit erhaltener Ejektionsfraktion 3 1.1.1 Definition der Herzinsuffizienz, Klinisches Bild, Einteilung nach der Pathophysiologie 3 1.1.2 Epidemiologie der HFpEF 3 1.1.3 Pathomechanismus der HFpEF 4 1.1.4 HFpEF vs. HFrEF 11 1.1.5 Diagnose der HFpEF 12 1.1.6 Behandlungsmöglichkeiten 12 1.2 Körperliches Training 14 1.2.1 Belastungsintoleranz bei HFpEF 14 1.2.2 Hochintensives Intervalltraining (HIIT) und Moderat-Intensives Kontinuierliches Ausdauertraining (MCT) 15 1.3 High density lipoproteins 16 1.3.1 HDL bei Herzinsuffizienz 16 1.3.2 Funktionen und Bedeutung von HDL-Partikeln 17 1.4 Zielsetzung und Fragestellung 19 2 Material 20 2.1 Serum 20 2.2 Zellkulturmaterial 20 2.3 Kulturmedium 20 2.4 Chemikalien und Lösungen 20 2.5 Färbelösungen 20 2.6 Antikörper 20 2.7 Chemilumineszenz 20 2.8 Sonstige Materialien 21 2.9 Geräte 21 2.10 Software 21 3 Methoden 22 3.1 Studiendesign 22 3.2 Trainingsintervention 23 3.3 Isolation des HDL 24 3.3.1 Vorarbeiten 24 3.3.2 HDL Isolation 24 3.3.3 HDL Aufreinigung 25 3.4 Bestimmung der Proteinkonzentration nach der BCA-Methode 25 3.5 Stimulation der Zellen 26 3.6 Western Blot 26 3.7 Gelelektrophorese 27 3.8 Proteintransfer 28 3.9 Immundetektion 29 3.10 Chemilumineszenz 29 3.11 PON-1 Aktivität 30 3.12 TBARS 30 3.13 Statistische Analyse 30 4 Ergebnisse 31 4.1 Charakterisierung der Patienten 31 4.2 Patientendaten 32 4.3 Qualität des isolierten HDL 38 4.4 Die HDL-induzierte eNOS-Phosphorylierung 40 4.5 Aktivität der Paraoxonase 1 (PON-1) 44 4.6 TBARS-Konzentration im Serum 47 5 Diskussion 49 5.1 Hauptaussagen 49 5.1.1 Endotheliale Effekte des Trainings via HDL 50 5.1.2 Trainingsmodalitäten als potentielle Therapie 52 5.1.3 Denkbarer molekularer Mechanismus für die Regulation von endothelialen Funktionen des HDL 55 5.1.4 Quantitative vs. qualitative Auswertung der HDL Funktion 57 5.1.5 Unterschiede bei der Einhaltung der verschiedenen Trainingsprotokollen 59 5.1.6 Ausblick für zukünftige Forschungsarbeiten 61 5.1.7 Studienlimitationen 63 6 Zusammenfassung 65 7 Summary 67 8 Literaturverzeichnis 69 9 Anlage 1 88 10 Anlage 2 89 11 Curriculum vitae 90 12 Danksagung 91 Tabellenverzeichnis Tabelle 1: Reagenzien zur Vorbereitung eines 8 % und 12 % SDS-Polyacrylamidgels 27 Tabelle 2: Die verwendeten Antikörper zur Detektion der Proteine 29 Tabelle 3: Patientendaten zu Beginn der Studie -V1 32 Tabelle 4: Patientendaten zu den Zeitpunkten V1, V2, V3 33 Tabelle 5: Medikation 34 Tabelle 6: Lipidprofil 36 Tabelle 7: Ergospirometrie 37 Abbildungsverzeichnis Abbildung 1: Pathomechanismus der myokardialen Dysfunktion (übernommen aus Paulus & Tschöpe, 2013) 6 Abbildung 2: Entstehung der myokardialen Dysfunktion durch Veränderungen innerhalb extrazellulärer Matrix und Kardiomyozyten bei Übergewicht und Diabetes mellitus (DM) 7 Abbildung 3: Komorbiditäten bei HFpEF als Trigger für diastolische Dysfunktion 9 Abbildung 4: NO Synthese als Antwort auf Shear Stress 10 Abbildung 5: Schematische Darstellung, wie ein körperliches Training das Krankheitsfortschreiten sowie HDL-induzierte NO-Produktion beeinflusst (übernommen aus Adams et al., 2013) 18 Abbildung 6: Studiendesign 22 Abbildung 7: Trainingsprotokoll, MCT-Moderat-Intensives Kontinuierliches Ausdauertraining, HIIT- Hochintensives Intervalltraining, HRpeak- maximale Herzfrequenz (übernommen aus Suchy et al., 2014) 23 Abbildung 8: Positionieren der Kanülenspitze und Entnahme des HDL 25 Abbildung 9: SDS-Page nach Färbung mit Coomassie-Blau zum Nachweis von HDL mit Größenmarker, BSA-Standard und den HDL-Proben (10 μg, 20 μg und 30 μg des Proteins) 38 Abbildung 10: Die Immundetektion der gebundenen Antikörper Apo-Protein A 1 durch eine Chemilumineszenz-Reaktion mit Größenmarker (M) zum Nachweis von HDL. Apo-AI, das Hauptprotein des HDL, mit einer Molekülgröße von 28 kDa wurde in 1,95 μg, 0,99 μg, 0,5 μg und 0,099 μg des HDL-Isolates identifiziert 39 Abbildung 11: Die eNOS-Phosphorylierung an Ser1177 zu den Zeitpunkten V1, V2, V3 bei der HIIT-(C), MCT-(B) und CG-Gruppe-(A) 40 Abbildung 12: Die eNOS-Phosphorylierung an Thr495 zu den Zeitpunkten V1, V2, V3 bei der HIIT-(F), MCT-(E) und CG-Gruppe(D) 42 Abbildung 13: Aktivität der Paraoxonase-1 im HDL 45 Abbildung 14: Aktivität der Paraoxonase-1 im Serum 46 Abbildung 15: TBARS-Konzentration im Serum [μmol/l] 48 / Background: Heart failure with preserved ejection fraction (HFpEF) is a complex disease. Due to its increasing hospitalization rates, HFpEF is gaining importance in the healthcare system. Despite the high mortality rate, there is no successful treatment procedure and no standard therapy has been established. Moreover, HFpEF makes up half of all heart failure cases, which underlines the usefulness of finding the effective therapy. One of the determining factors of HFpEF pathophysiology is endothelial dysfunction. The reduction of NO-bioavailability in endothelium and consequently endothelial dysfunction provides to LV stiffness and diastolic dysfunction of the heart. The exercise training triggers shear stress inside the blood vessels and results in HDL-mediated nitric oxide synthesis. In heart failure patients, the eNOS-increasing and vasodilative function of HDL can be impaired. However, a suitable training modality could work as endothelium-protective. Aims: The present doctoral thesis aims to investigate the influence of high-intensity interval training (peak HR 90-95%) and moderate-intensity continuous training (peak HR 60-70%) on the function of HDL by HFpEF patients. This study focuses on HDL-regulated eNOS function (function of endothelial nitric oxide synthesis), which is evaluated by phosphorylation of different aminoacids residues in the molecule. Furthermore, we determined the activity of PON-1 (paraoxonase-1), which speaks of the antioxidative role of HDL, as well the concentration of TBARS (thiobarbituric acid reactive substances), which indicate increased lipid peroxidation. Material and methods: To clarify the questions, the probands were randomized to three groups: 1) HIIT (high-intensity interval training, 2) MCT (moderate-intensity continuous training) and 3) CG (control group). Before, during, and after different training interventions the HDL was isolated from the blood serum of probands by ultracentrifugation. Further, the HDL isolates were incubated with human aortic endothelial cells. The HDL-induced eNOS phosphorylation at the activating position Ser1177 (which results in increased activity of eNOS) and deactivating Thr495 (which results in inhibition of eNOS activity) were assessed by western blotting. The activated phosphorylation of eNOS leads to increased NO production. Subsequently, to investigate how modifiable the endothelial-protective role of HDL is and to find the possible correlation, the antioxidative function of HDL was evaluated. The latter was assessed by measuring the activity of the associated enzyme PON-1 (paraoxonase-1), which protects the lipoproteins against oxidative modifications. The protective property of HDL might be among others modified by reactive oxygen species. The reduced activity of PON-1 can be associated with increased lipid peroxidation and therefrom resulting fatty acids radicals. In this study, the amount of fatty acids radicals was indicated by the concentration of TBARS (thiobarbituric acid-reactive substances). Results and observations: Exercise training can increase phosphorylation at Ser1177. Indeed, the first supervised part of HIIT resulted in a significant increase of HDL-induced eNOS-Phosphorylation at Ser1177. However, neither after HIIT nor after MCT any significant decline of eNOS phosphorylation at deactivated position Thr495 could be demonstrated. Regarding the eNOS phosphorylation after MCT and in CG, no significant changes were observed. Furthermore, significantly increased activity of PON-1 in serum as well as in HDL was observed after HIIT. But, neither in MCT nor in the control group any significant increase in PON-1 activity was observed. The increased concentration of TBARS was detected in all groups. After the interventions, no significant differences concerning the concentration of TBARS were demonstrated in any group. Conclusions: High-intensity interval training by HFpEF patients results in increased HDL- induced eNOS phosphorylation, which is accompanied by significantly increased activity of PON-1. Therefore, we can speculate that HIIT could enhance the endothelial function of HDL and would be in the future one of the possible effective treatment methods for HFpEF. Furthermore, this study derives that compliance in all groups was higher during the supervised training than during home-based intervention. Eventually, the usefulness of HIIT in clinical settings requires further investigation.:Inhaltsverzeichnis I Tabellenverzeichnis IV Abbildungsverzeichnis V Abkürzungsverzeichnis VI 1 Einleitung 3 1.1 Die Herzinsuffizienz mit erhaltener Ejektionsfraktion 3 1.1.1 Definition der Herzinsuffizienz, Klinisches Bild, Einteilung nach der Pathophysiologie 3 1.1.2 Epidemiologie der HFpEF 3 1.1.3 Pathomechanismus der HFpEF 4 1.1.4 HFpEF vs. HFrEF 11 1.1.5 Diagnose der HFpEF 12 1.1.6 Behandlungsmöglichkeiten 12 1.2 Körperliches Training 14 1.2.1 Belastungsintoleranz bei HFpEF 14 1.2.2 Hochintensives Intervalltraining (HIIT) und Moderat-Intensives Kontinuierliches Ausdauertraining (MCT) 15 1.3 High density lipoproteins 16 1.3.1 HDL bei Herzinsuffizienz 16 1.3.2 Funktionen und Bedeutung von HDL-Partikeln 17 1.4 Zielsetzung und Fragestellung 19 2 Material 20 2.1 Serum 20 2.2 Zellkulturmaterial 20 2.3 Kulturmedium 20 2.4 Chemikalien und Lösungen 20 2.5 Färbelösungen 20 2.6 Antikörper 20 2.7 Chemilumineszenz 20 2.8 Sonstige Materialien 21 2.9 Geräte 21 2.10 Software 21 3 Methoden 22 3.1 Studiendesign 22 3.2 Trainingsintervention 23 3.3 Isolation des HDL 24 3.3.1 Vorarbeiten 24 3.3.2 HDL Isolation 24 3.3.3 HDL Aufreinigung 25 3.4 Bestimmung der Proteinkonzentration nach der BCA-Methode 25 3.5 Stimulation der Zellen 26 3.6 Western Blot 26 3.7 Gelelektrophorese 27 3.8 Proteintransfer 28 3.9 Immundetektion 29 3.10 Chemilumineszenz 29 3.11 PON-1 Aktivität 30 3.12 TBARS 30 3.13 Statistische Analyse 30 4 Ergebnisse 31 4.1 Charakterisierung der Patienten 31 4.2 Patientendaten 32 4.3 Qualität des isolierten HDL 38 4.4 Die HDL-induzierte eNOS-Phosphorylierung 40 4.5 Aktivität der Paraoxonase 1 (PON-1) 44 4.6 TBARS-Konzentration im Serum 47 5 Diskussion 49 5.1 Hauptaussagen 49 5.1.1 Endotheliale Effekte des Trainings via HDL 50 5.1.2 Trainingsmodalitäten als potentielle Therapie 52 5.1.3 Denkbarer molekularer Mechanismus für die Regulation von endothelialen Funktionen des HDL 55 5.1.4 Quantitative vs. qualitative Auswertung der HDL Funktion 57 5.1.5 Unterschiede bei der Einhaltung der verschiedenen Trainingsprotokollen 59 5.1.6 Ausblick für zukünftige Forschungsarbeiten 61 5.1.7 Studienlimitationen 63 6 Zusammenfassung 65 7 Summary 67 8 Literaturverzeichnis 69 9 Anlage 1 88 10 Anlage 2 89 11 Curriculum vitae 90 12 Danksagung 91 Tabellenverzeichnis Tabelle 1: Reagenzien zur Vorbereitung eines 8 % und 12 % SDS-Polyacrylamidgels 27 Tabelle 2: Die verwendeten Antikörper zur Detektion der Proteine 29 Tabelle 3: Patientendaten zu Beginn der Studie -V1 32 Tabelle 4: Patientendaten zu den Zeitpunkten V1, V2, V3 33 Tabelle 5: Medikation 34 Tabelle 6: Lipidprofil 36 Tabelle 7: Ergospirometrie 37 Abbildungsverzeichnis Abbildung 1: Pathomechanismus der myokardialen Dysfunktion (übernommen aus Paulus & Tschöpe, 2013) 6 Abbildung 2: Entstehung der myokardialen Dysfunktion durch Veränderungen innerhalb extrazellulärer Matrix und Kardiomyozyten bei Übergewicht und Diabetes mellitus (DM) 7 Abbildung 3: Komorbiditäten bei HFpEF als Trigger für diastolische Dysfunktion 9 Abbildung 4: NO Synthese als Antwort auf Shear Stress 10 Abbildung 5: Schematische Darstellung, wie ein körperliches Training das Krankheitsfortschreiten sowie HDL-induzierte NO-Produktion beeinflusst (übernommen aus Adams et al., 2013) 18 Abbildung 6: Studiendesign 22 Abbildung 7: Trainingsprotokoll, MCT-Moderat-Intensives Kontinuierliches Ausdauertraining, HIIT- Hochintensives Intervalltraining, HRpeak- maximale Herzfrequenz (übernommen aus Suchy et al., 2014) 23 Abbildung 8: Positionieren der Kanülenspitze und Entnahme des HDL 25 Abbildung 9: SDS-Page nach Färbung mit Coomassie-Blau zum Nachweis von HDL mit Größenmarker, BSA-Standard und den HDL-Proben (10 μg, 20 μg und 30 μg des Proteins) 38 Abbildung 10: Die Immundetektion der gebundenen Antikörper Apo-Protein A 1 durch eine Chemilumineszenz-Reaktion mit Größenmarker (M) zum Nachweis von HDL. Apo-AI, das Hauptprotein des HDL, mit einer Molekülgröße von 28 kDa wurde in 1,95 μg, 0,99 μg, 0,5 μg und 0,099 μg des HDL-Isolates identifiziert 39 Abbildung 11: Die eNOS-Phosphorylierung an Ser1177 zu den Zeitpunkten V1, V2, V3 bei der HIIT-(C), MCT-(B) und CG-Gruppe-(A) 40 Abbildung 12: Die eNOS-Phosphorylierung an Thr495 zu den Zeitpunkten V1, V2, V3 bei der HIIT-(F), MCT-(E) und CG-Gruppe(D) 42 Abbildung 13: Aktivität der Paraoxonase-1 im HDL 45 Abbildung 14: Aktivität der Paraoxonase-1 im Serum 46 Abbildung 15: TBARS-Konzentration im Serum [μmol/l] 48

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Introduction : Au Canada, 80 % des personnes âgées (65 ans et plus) sont considérées comme physiquement inactives, en particulier celles ayant un diabète de type 2 (DT2). Auprès de cette population, l’entraînement par intervalles de haute intensité (HIIT) a récemment été préconisé pour sa courte durée et ses avantages pour la santé. Néanmoins, en raison de l’intensité élevée, le HIIT peut être perçu comme difficile, déplaisant et contribue à l’inactivité physique des personnes âgées. Cependant, aucune étude n’a examiné l’effet de la durée des intervalles sur les réponses affectives (c’est-à-dire, le plaisir-déplaisir) et la perception de l’effort chez les femmes âgées ayant un DT2. Objectif : Examiner les réponses affectives et la perception de l’effort de femmes âgées ayant un DT2, lors de deux conditions de HIIT(s) sur tapis roulant, l’une avec des intervalles courts et l’autre avec des intervalles longs. Méthode : Onze femmes âgées ayant un DT2 (âge : 70.18 ± 4.85 ans ; IMC : 33.30 ± 5.65 kg/m²) ont effectué deux conditions de HIIT(s) : 1) HIIT-10 (10 x 1 minute à 90 % de la fréquence cardiaque maximale) et 2) HIIT-4 (4 x 4 minute à 90 % de la fréquence cardiaque maximale). Mesures : La Feeling Scale a été utilisée pour mesurer les réponses affectives et l’échelle de Borg CR-10 pour la perception de l’effort. Les variables ont été évaluées à la fin de chaque intervalle à 25, 50, 65 et 90 % du temps total des conditions. Des modèles mixtes ont été utilisés pour analyser si les réponses affectives et la perception de l’effort augmentaient/diminuaient (effet temps) en fonction des conditions (effet d’interaction). Résultats : Pour les réponses affectives, il a été trouvé un effet temps [F(2, 124) = 19.51, p < .0001], pas d’effet de la condition (F(1, 124) = 0.01, p = .89) ni aucune interaction temps × condition (F(2, 124) = 0.39, p = .67). Ces résultats signifient que le plaisir a diminué de manière similaire dans les deux conditions de HIIT(s). Pour la perception de l’effort, il a été trouvé un effet temps [F(2, 160) = 87.58, p < .0001], un effet de la condition [F(1, 160) = 6.37, p = .01], mais aucune interaction temps × condition [F(2, 160) = 0.35, p = .69]. Ces résultats signifient que la perception de l’effort a augmenté, sans différence en fonction des conditions. Conclusion : Quelle que soit la durée de l’intervalle, les HIIT(s) ont conduit à une diminution significative du plaisir. Malgré les bénéfices prometteurs du HIIT, ce type d’entraînement ne semble pas être une solution unique pour favoriser l’adhésion à l’activité physique chez les femmes âgées ayant un DT2. / Introduction : In Canada, 80% of the elderly (aged 65 and over) are considered physically inactive, especially those with type 2 diabetes mellitus (T2DM). Among this population, high-intensity interval training (HIIT) has recently been advocated for its short duration and health benefits. Nevertheless, due to the high intensity, HIIT can be perceived as difficult, unpleasant and may contribute to physical inactivity in the elderly. However, no study has investigated the effect of interval duration on affective response (i.e., pleasure-displeasure) and perceived exertion in elderly women with T2DM. Objectif : To examine the affective response and perceived exertion of elderly women with T2DM in two treadmill HIIT conditions, one with short intervals and the other with long intervals. Methods: Eleven elderly women with T2DM (age : 70.18 ± 4.85 years; BMI: 33.3 ± 5.6 kg/m²) performed two HIIT conditions: 1) HIIT-10 (10 x 1 minute at 90% maximal heart rate) and 2) HIIT-4 (4 x 4 minutes at 90% maximal heart rate). Measurement: The Feeling Scale was used to measure affective responses and the Borg CR-10 for perceived exertion. Variables were assessed after intervals at 25, 50, 65, and 90% of the total condition time. Mixed models were used to analyze whether affective responses and perceived exertion increased/decreased (time effect) depending on conditions (interaction effect). Results: For affective responses, a time effect was found [F(2, 124) = 19.51, p < .0001], no condition effect (F(1, 124) = 0.01, p = .89) nor any time × condition interaction (F(2, 124) = 0.39, p = .67). These results mean that pleasure decreased similarly in both HIIT conditions. For perceived exertion, a time effect was found [F(2, 160) = 87.58, p < .0001], a condition effect [F(1, 160) = 6.37, p = .01], but no time × condition interaction [F(2, 160) = 0.35, p = .69]. These results mean that perceived exertion increased with no difference depending on the condition. Conclusion : Regardless of interval duration, HIIT led to a significant decrease in pleasure. Despite the promising benefits of HIIT, this type of training does not appear to be a solution solely for promoting adherence to physical activity in the elderly with T2DM.

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<p>What a ride it has been. The ups and downs of the McMaster graduate program has been a sweet one. It has been a pleasure working with the Exercise Metabolism Research Group for the past 2 years, and I will miss being around the work that goes on in the trenches around the lab. I have leaned on many people for all types of guidance through this journey, and would like to thank everyone for their unprecedented support. I have grown as a person and student and will use everything I have learned at this fine establishment I’m sure at one point or another along the great path of life. I must thank my amazing parents, family, friends and of coarse Ashley for putting up with my work ethic throughout my studies; the long days that I would go missing. Without their support none of this would have been possible. I have to specially mention Melanie Wolfe for recommending myself, and ultimately Stu Phillips for presenting this opportunity that is coming to a close. I have had great senior support from Cam Mitchell, Tyler Churchward-Venne, Todd Prior and Michaela Devries in putting this document together, and would not be submitting this without their selfless assistance. It’s been a journey getting to this point, but I wouldn’t change it for the world, to the next chapter in life, cheers and God Bless.</p> / <p>Higher dietary protein intake, greater than the Recommended Dietary Allowance (RDA; 0.8 g protein/kg/d), coupled with resistive exercise has been shown to aid in preservation of muscle mass during hypocaloric diet-induced weight loss. We examined the impact of dietary protein supplementation at two levels (1.2 and 2.4 g/kg/d) on body composition during a 4wk hypocaloric dietary intervention that included 6d/wk of high intensity resistance exercise and interval training. In a single blind study, forty young men consumed 33±1.1 kcal/LBM (~40% reduction versus estimated energy requirements), and were randomly assigned to a group that consumed either 1.2g/kg/d protein or 2.4g/kg/d. Body composition was determined using DXA, Bod Pod, and Bio-impedance pre- and post-intervention to derive a 4-compartment model for body composition. Both groups retained lean mass (LM), but retention was greater in the higher protein group (p</p> / Master of Science (MSc)

This thesis is missing page 63 from all copies. -Digitization Centre / Manipulating carbohydrate (CHO) availability has been shown to alter acute exercise-induced changes in metabolic gene transcription and training-induced changes in oxidative capacity. The present study examined the effect of CHO availability on signalling pathways linked to mitochondrial biogenesis in response to high-intensity interval exercise (HIE). We hypothesized that reduced CHO availability would augment phosphorylation of AMP-activated protein kinase (AMPK), calcium/calmodulin-dependent kinase II (CaMKII), and p38 mitogen-activated protein kinase (p38) in response to HIE. Ten active men performed two experimental trials in random order, separated by 2:1 wk. During each trial, subjects performed two HIE sessions separated by 3 h (AM and PM sessions). Exercise sessions consisted of 5 x 4 min cycling bouts at a workload that elicited approximately 90% V02peak, with 2 min rest periods. Between sessions, subjects ingested -1.2 g CHO/kg b.w./h (HI-HI) or a taste-matched, non-energetic placebo (HI-LO). Muscle biopsies and blood samples were obtained before (Pre) and after (Post) the AM and PM HIE sessions. AMPK, CaMKII, and p38 MAPK phosphorylation increased from AM Pre to AM Post (p<0.01). During the PM exercise session, p38 phosphorylation increased in the HI-LO condition (-4.5-fold, p<0.001), whereas the HI-HI condition remained unchanged. PM HIE significantly increased CaMKII phosphorylation independent of condition, while no exercise or condition-mediated AMPK effects were observed. In summary, restricting CHO availability following an acute session of HIE augmented the exercise-induced increase in p38 phosphorylation during a subsequent HIE session. It remains to be determined whether chronic changes in p38 MAPK signalling are mechanistically linked to altered skeletal muscle remodelling observed after CHO-restricted exercise training. / Thesis / Master of Science (MS)

High-intensity interval training (HIIT) consists of short intervals of exercise at high intensity intermitted by intervals of lower intensity and is associated with improvement of body composition and metabolic health in adults. Studies in overweight adolescents are scarce. We conducted a randomized controlled trial in overweight adolescents to compare acceptance and attendance of HIIT with or without weekly motivational encouragement through text messages and access to a study website. HIIT was offered for six months (including summer vacation) twice a week (60 min/session). Participation rates were continuously assessed and acceptance was measured. Clinical parameters were assessed at baseline and after six months. Twenty-eight adolescents participated in this study (age 15.5 +/- 1.4; 54% female). The standard deviation score for body mass index over all participants was 2.33 at baseline and decreased by 0.026 (95% CI - 0.048 to 0.10) units, p = 0.49. Waist to height ratio was 0.596 at baseline and decreased by 0.013 (95% CI 0.0025 to 0.024), p = 0.023. Participation within the first two months ranged from 65% to 75%, but fell to 15% within the last three months. Attendance in the intervention group was 14% (95% CI - 8 to 37), p = 0.18, higher than the control group. Overall program content was rated as \"good\" by participants, although high drop-out rates were observed. Summer months constitute a serious problem regarding attendance. The use of media support has to be assessed further in appropriately powered trials.

The aim of this master thesis is to evaluate the influence of a six-week HIIT (High intensity interval training) on body composition and both aerobic and anaerobic performance. A group of 9 men aged 28-51 years was gathered and who followed an exact six-week training programme according to the chosen hypothesis. The results of our study show that the chosen six-week programme led to statistically significant (p < 0,05) changes in body weight (kg), BMI (kg/m2 ), in FEV (l), and ANC/kg (J/kg). Changes in the other parameters were statistically not significant. Taking into account the size of group (n=9) we conclude that mainly effects on the individual level were attained.

Cardiac rehabilitation (CR) exercise training, which traditionally involves the prescription of moderate intensity continuous exercise, can slow the progression of heart disease and improve cardiorespiratory fitness (CRF). Cardiac function is typically investigated using calculations of ejection fraction (EF) from echocardiography, yet EF measures do not provide information about the unique twisting motion of the heart. Novel measures of cardiac function, such as LV twist, myocardial performance index (MPI) and global longitudinal strain (GLS), may provide additional information about changes in LV mechanics associated with exercise training for individuals with coronary artery disease (CAD). The aims of this study were to investigate the changes in cardiac function, using both standard and novel measures, at baseline (0 weeks; T1), post-initial training (4 weeks; T2), and post-training (12 weeks; T3) in response to either stair climbing-based high intensity interval training (STAIR) or traditional moderate intensity continuous training (TRAD). We recruited 16 individuals with CAD (61±7years; 1W) and randomized them into TRAD and STAIR groups (n=8/group). Standard (CRF and EF), and novel (LV twist, MPI, GLS), measures of cardiovascular function were assessed at all three timepoints. CRF improved in both groups, after 4 and 12 weeks (STAIR: T1:22.1±4.2, T2:24.7±4.9, T3:25.4±5.2 and TRAD: T1:22.8±2.5, T2:25.2±4.9, T3:26.0±5.0 mL/kg/min; P<0.005) of CR exercise. We observed an increase in apical rotation (P=0.01) and LV twist (P=0.03), but no changes in either traditional (EF P=0.15), or novel (MPI P=0.19; GLS P=0.81) measures of cardiac function over time, in either group. It is possible that the relatively short training period (12 weeks) was not sufficient to result in significant changes in cardiac function, despite improvements in CRF. Future research should assess both standard and novel indices of cardiac function over longer exercise training periods to determine the ideal indices for tracking changes over time with interventions in this population. / Thesis / Master of Science (MSc) / Cardiac rehabilitation exercise is an important part of recovery after a heart attack, and it has been shown to improve heart function measured using standard ultrasound assessments. Studies have suggested that novel measures of heart function may be more sensitive in comparison to these standard ultrasound measures, yet these novel measures have not been examined in individuals completing stair-climbing based high intensity cardiac rehabilitation exercise training. This work examined the changes in both novel and standard ultrasound measures of heart function after either stair climbing-based high intensity interval training or traditional moderate intensity exercise training in individuals who have heart disease. While this study found that both stair climbing based high intensity interval training and traditional cardiac rehabilitation both resulted in increases in cardiorespiratory fitness after 12 weeks of training, no changes were observed in any of the standard measures of heart function. Supporting the concept that novel measures of heart function might be more sensitive, as some training associated changes were observed in the novel measures of heart function.