Cardiovascular Disease
Conditions
Keywords
muscle plasticity, exercise, rehabilitation, perfusion, ACE, genotype, hypertension, molecular biology
Brief summary
The study aims to systematically investigate the interaction between training modality, ACE genotype and disease in heart patients whom complete a cardiovascular rehabilitation program. This is carried out with the goal to improve the benefit of cardiovascular rehabilitation for the patient by maximising adjustments in muscle structure and function with the intervention. A population of healthy individuals will be recruited who will carry out the same training program, in order to compare the training effects respective to the general population.
Detailed description
Pharmacological inhibition of angiotensin converting enzyme modifies exercise-induced pro-angiogenic and mitochondrial gene transcript expression. Exercise-induced muscle plasticity importantly interacts with the insertion/deletion genotype of ACE and the training modality and intensity. The aim of this study is to systematically investigate the interaction between training modality, ACE genotype and disease in heart patients whom complete a cardiovascular rehabilitation program. There are two training modalities being used: The first modality involves cardiovascular training by an interval type of protocol that includes a high repetition number of shortening (i.e. concentric) type contractions on a softrobotic device. The second modality includes a high repetition number of lengthening (i.e. eccentric) type contractions on a softrobotic device. In both training modalities the same muscle groups are exercised over the same range of motion, with the same speed of movement, but with widely differing pedal force. Total absolute external mechanical work will be matched. In order to assess the baseline values and the effect size of the muscle and training adjustments made, healthy male and female volunteers will be included who are matched with respect to age and sex to the patient population and undergo the same training program.
Interventions
BEHAVIORALconcentric cardiovascular training
Subjects will carry out 8 weeks of cardiovascular training by an interval type of protocol that includes a high repetition number of concentric type contractions on a softrobotic device.
BEHAVIORALeccentric cardiovascular training
Subjects will carry out 8 weeks of cardiovascular training by an interval type of protocol that includes a high repetition number of eccentric type contractions on a softrobotic device.
GENETICACE genotyping
Subjects will be genotyped for the ACE-I/D gene polymorphism.
Sponsors
University of Zurich
Balgrist University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Patient group inclusion criteria: * stable coronary heart patients/heart patients without ischemia * Left ventricular ejection fraction \> 50% * Drug therapy with ACE inhibitors * V̇O2peak \<86% of the medical reference value Voluntary participation * Written informed consent of the subject to participate in the study
Exclusion criteria
* relevant valvular heart disease * arterial hypertension (blood pressure at rest\> 140/90) * arrhythmogenic cardiomyopathy * ACE inhibitor intolerance * contraindication for ethical reasons * known or suspected non-compliance with the curriculum * smoker * drug or alcohol disease * inability of the patient to follow the study procedures (e.g. because of language problems, mental illness, dementia) * participation in another clinical trial within the last 30 days prior to confinement and during the study * other, clinically significant comorbidities (cardiac arrhythmia, renal insufficiency, hepatic dysfunction, connective tissue disease \[Marfan syndrome, Ehlers-Danlos syndrome\]) Healthy subject group inclusion criteria: * inconspicuous ECG under exercise (persons in whom the exercise ECG is abnormal will be referred for a cardiological evaluation recessed to the University Hospital Zurich) * V̇O2peak \<50 ml O2 min-1 kg-1 * Voluntary participation * Written informed consent of the subject to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ACE I/D genotype | 975 days: May 2016-January 2019 | Genotype of the assessed insertion/deletion gene polymorphism of angiotensin converting enzyme ACE, i.e. ACE-II, ACE-ID or ACE-DD. |
| Molecular muscle characteristics - mRNA | 975 days: May 2016-January 2019 | • mRNA expression of VEGF, HIF-1a, HIF-1b, tenascin-C, Angpt1, Angpt1R, neuropilin, midkine, restin, COX4-1, COX4I-2, CPTI, LPL, LIPE, FATP, CD36 \[relative expression per 28S rRNA\] |
| Molecular muscle characteristics- protein | 975 days: May 2016-January 2019 | • Protein content of FAK, FRNK, p70S6K, mTOR, JNK, NDUFA9, SDH, UQCRC1, COX4I1, COX4I2, ATP5A1, VEGF, HIF-1a, CD31, MHC-1, MHC-2A, MHC-2X, MyoD, myogenin, CaMKII \[pixel counts per actin\] |
| Molecular muscle characteristics- phosphorylation | 975 days: May 2016-January 2019 | • Phosphorylation of proteins phospho-Y397- FAK, phospho-T421/S424-P70S6K, phospho -T183/Y185-JNK, phospho-S2448-mTOR \[pixel counts per actin\] |
| Molecular muscle characteristics- ACE | 975 days: May 2016-January 2019 | • ACE activity \[fmol min-1\] |
| Cellular muscle characteristics - fiber type % | 975 days: May 2016-January 2019 | • Distribution of type I, IIA and IIX fibers \[%\] |
| Cellular muscle characteristics - fiber area % | 975 days: May 2016-January 2019 | • Area percentage of type I, IIA and IIX fibers \[% area\] |
| Cellular muscle characteristics - fiber type CSA | 975 days: May 2016-January 2019 | • Cross sectional area of type I, IIA and IIX fibers \[micrometer2\] |
| Cellular muscle characteristics - Capillary density | 975 days: May 2016-January 2019 | • Capillary density \[capillaries micrometer-2\] |
| Functional muscle characteristics - Reactive Power | 975 days: May 2016-January 2019 | • Reactive Power as estimated on the soft robotic device \[Watt\] |
| Cellular muscle characteristics - Capillary-to-fiber ratio | 975 days: May 2016-January 2019 | • Capillary-to-fiber ratio |
| Functional muscle characteristics - Maximal Power | 975 days: May 2016-January 2019 | • Maximal power during ramp test on ergometer \[Watt\] |
| Functional muscle characteristics - Critical Power | 975 days: May 2016-January 2019 | • Critical power in ramp test on ergometer \[Watt\] |
| Functional muscle characteristics - Real Power | 975 days: May 2016-January 2019 | • Real Power as estimated on the soft robotic device \[Watt\] |
| Functional muscle characteristics - Negative Power | 975 days: May 2016-January 2019 | • Negative Power as estimated on the soft robotic device \[Watt\] |
| Functional muscle characteristics - Maximal force | 975 days: May 2016-January 2019 | • Maximal force during the reactive power test on the soft robotic device \[Newton\] |
| Functional muscle characteristics - Maximal velocity | 975 days: May 2016-January 2019 | • Maximal velocity during the reactive power test on the soft robotic device \[m sec-1\] |
| Functional muscle characteristics - Rate of force development | 975 days: May 2016-January 2019 | • Rate of force development as estimated during the Real Power test on the soft robotic device \[meter sec-2\] |
| Muscle metabolism - muscle oxygenation ramp | 975 days: May 2016-January 2019 | • Muscle oxygenation (m. vastus lateralis, m. gastrocnemius, m. gluteus maximus) during ramp test on ergometer \[%\] |
| Muscle metabolism - muscle oxygenation robot exercise | 975 days: May 2016-January 2019 | • Muscle oxygenation (m. vastus lateralis, m. gastrocnemius, m. gluteus maximus) during exercise on soft robot \[%\] |
| Muscle metabolism - hemoglobin ramp | 975 days: May 2016-January 2019 | • Total hemoglobin during ramp test on ergometer \[%\] |
| Muscle metabolism - hemoglobin robot exercise | 975 days: May 2016-January 2019 | • Total hemoglobin during exercise on soft robot \[%\] |
| Muscle metabolism - lipid compounds | 975 days: May 2016-January 2019 | • Concentration of lipid compounds in m. vastus lateralis muscle during exercise on soft roboter |
| Muscle metabolism - metabolites | 975 days: May 2016-January 2019 | • Concentration of metabolites in m. vastus lateralis muscle during exercise on soft roboter |
| Muscle metabolism - serum glucose | 975 days: May 2016-January 2019 | • Concentration of glucose in serum during ramp test on ergometer \[mmol l-1\] |
| Muscle metabolism - serum lactate | 975 days: May 2016-January 2019 | • Concentration of lactate in serum during ramp test on ergometer \[mmol l-1\] |
| Cardiovascular function - Heart rate rest | 975 days: May 2016-January 2019 | • Heart rate at rest \[beats per minute\] |
| Cardiovascular function - Heart rate ramp | 975 days: May 2016-January 2019 | • Heart rate in ramp test on ergometer \[beats per minute\] |
| Cardiovascular function - cardiac output | 975 days: May 2016-January 2019 | • Cardiac output \[L min-1\] |
| Cardiovascular function - ejection fraction | 975 days: May 2016-January 2019 | • Ejection fraction |
| Cardiovascular function - Maximal oxygen uptake | 975 days: May 2016-January 2019 | • Maximal oxygen uptake (VO2max) during ramp test on ergometer \[ml O2 min-1 kg-1\] |
| Cardiovascular function - ventilation | 975 days: May 2016-January 2019 | • Ventilation during ramp test on ergometer \[L min-1\] |
| Cardiovascular function - ventilation frequency | 975 days: May 2016-January 2019 | • Ventilation frequency ramp test on ergometer \[min-1\] |
| Cardiovascular function - respiration quotient | 975 days: May 2016-January 2019 | • Respiration quotient during ramp test on ergometer \[ L O2 inspired / L CO2 expired\] |
| Cardiovascular function - endurance | 975 days: May 2016-January 2019 | Time-to-exhaustion in constant load on ergometer \[seconds\] |
Countries
Switzerland
Outcome results
None listed