Proteomic Evaluation of High-Intensity Interval Training Effects on Cardiac Fibrosis
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 12
- Primary Endpoint
- Left ventricular end-diastolic volume (LVEDV)
Study Overview
Brief Summary
The study aimed to highlight the effect of high-intensity interval training (HIIT) on cardiac fibrosis in cardiac patients. From 2009-2018, cardiac patients with measurements of VO2peak, b-type natriuretic peptide, quality of life questionnaire, cardiovascular magnetic resonance imaging with late gadolinium enhancement (CMR-LGE), and preserved serum before and after 36 times of HIIT were enrolled. The human cardiac fibroblast (CF) isolated from human adult ventricle is treated with sera before and after HIIT. Measurements of cell migration as well as cell proliferation and global cell protein profiles before and after HIIT will be performed.
Detailed Description
From January 1, 2009 to December 31, 2018, cardiac patients with stable clinical status for greater than 4 weeks have completed 36 times of HIIT. Subjects with clinical assessments (listed below) before and after HIIT will be included.
*Baseline information, including age, gender, body mass index, duration disease duration, co-morbidities and medication history were reviewed. Subjects with echocardiographic examination, short form-36 health survey (SF-36) for qualities of life, graded cardiopulmonary exercise test (CPET), cardiac magnetic resonance imaging with late gadolinium enhancement (CMR-LGE), blood chemistry tests (hematocrit, brain natriuretic peptide, high-sensitivity C-reactive protein, creatinine), and preserved sera before and after HIIT.*
Cell behaviors Human cardiac fibroblast (CF) isolated from human adult ventricle (HCF-av cell, ScienCell Research Laboratories, Carlsbad, CA, USA) are cultured in medium containing 10 % FBS, 1% fibroblast growth supplement, and 1% penicillin/streptomycin. Cells (1x10^5) were seeded in dishes of 10-cm diameter and were cultured in the above medium overnight. We used 10% of the patient serum in substitution for the 10% fetal bovine serum (FBS) to treat human cardiac fibroblast (CF) isolated from human adult ventricle (HCF-av cell, ScienCell Research Laboratories, Carlsbad, CA, USA), and serum effects on CF were evaluated.
Cell Culture Human cardiac fibroblasts (CFs) isolated from human adult ventricle (HCF-av cell, ScienCell Research Laboratories, Carlsbad, CA, USA) were cultured in medium containing 10 % FBS, 1% fibroblast growth supplement, and 1% penicillin/streptomycin. Cells (1x10^5) were seeded in dishes of 10-cm diameter and were cultured in the above medium overnight.
Cell migration assay The cell migration speed in the serum obtained from cardiac patients pre- and post-HIIT was determined as described previously. In brief, HCF-av cells of 3000 were plated on each 3.5-cm Petri dishes with polyacrylamide substrates and were harvest in media containing 10% of cardiac patient sera before and after HIIT. Phase contrast images were recorded using a cooled charge-coupled device camera (Photometrics, Tucson, AZ), attached to an Eclipse Ti-E inverted microscope system (Nikon Instruments Inc., Melville, NY) equipped with a 20X, numerical aperture 0.75 Achromat phase objective lens and a INU series stage top incubator (Tokai HIT Co., Ltd., Shizuoka-ken, Japan). The position of the cell was determined every 10 min for a period of 120-180 mins, based on the center of the nucleus. Migration speed was calculated based on the persistent random walk equation.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 21 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Heart failure patients, diagnosed according to the Framingham heart failure diagnostic criteria, with stable clinical status for greater than 4 weeks after conservative treatment or intervention were enrolled in the study.
Exclusion Criteria
- •Those who were
- •< 20 years
- •under anti-coagulant therapy
- •unable to exercise > 1 year owing to non-cardiovascular disease
- •pregnant or plan to be pregnant within one year
- •plan to have cardiac transplant within 6 months
- •uncorrected valvular heart disease related heart failure
- •congenital heart disease related heart failure
- •Other exercise contraindications：
- •unstable angina
- •resting systolic blood pressure> 200 mmHg or resting diastolic blood pressure> 110 mmHg
- •orthostatic blood pressure drop (systolic blood pressure drop > 20 mmHg)。
- •critical aortic stenosis stenosis (peak systolic pressure gradient> 50 mmHg and aortic valve opening < 0.75 cm2)。
- •acute fever
- •uncontrolled uncontrolled atrial or ventricular dysrhythmias
- •uncompensated congestive heart failure
- •3-degree AV block)
- •acute pericarditis and/or myocarditis
- •recent embolism < 6 months
- •thrombophlebitis
- •restin ST segment displacement > 2mm
- •patients with uncontrolled diabetes (resting serum glucose > 300mg/dL or > 250mg/dL with ketone body) was excluded in the study.
Arms & Interventions
Pre- and Post-HIIT
Participants will be evaluated before and after exercise training.
Intervention: High-intensity interval training (Behavioral)
Outcomes
Primary Outcomes
Left ventricular end-diastolic volume (LVEDV)
Time Frame: 3-4 months (for 36 times of exercise training)
LVEDV in milliliter measured by cardiac magnetic resonance imaging with late gadolinium enhancement before and after exercise training
Proteomics
Time Frame: 3-4 months (for 36 times of exercise training)
Protein level changes in fold change in cardiac fibroblast before and after exercise training
Cardiac output (CO)
Time Frame: 3-4 months (for 36 times of exercise training)
Cardiac output in milliliter per minute measured by cardiac magnetic resonance imaging with late gadolinium enhancement before and after exercise training
Left ventricular end-systolic volume (LVESV)
Time Frame: 3-4 months (for 36 times of exercise training)
LVESV in milliliter measured by cardiac magnetic resonance imaging with late gadolinium enhancement before and after exercise training
Extracellular volume fraction (ECV)
Time Frame: 3-4 months (for 36 times of exercise training)
ECV in percent (%) measured by cardiac magnetic resonance imaging with late gadolinium enhancement before and after exercise training
Cardiac mass
Time Frame: 3-4 months (for 36 times of exercise training)
Cardiac mass in gram measured by cardiac magnetic resonance imaging with late gadolinium enhancement before and after exercise training
Secondary Outcomes
- Brain natriuretic peptide (BNP)(3-4 months (for 36 times of exercise training))
- Peak cardiac output (CO)(3-4 months (for 36 times of exercise training))
- Oxygen uptake efficiency slope (OUES)(3-4 months (for 36 times of exercise training))
- Peak exercise capacity (VO2peak)(3-4 months (for 36 times of exercise training))
- Ventilation/VCO2 ratio (Ve-VCO2)(3-4 months (for 36 times of exercise training))
- Hematocrit (Hct)(3-4 months (for 36 times of exercise training))
- Creatinine (Cre)(3-4 months (for 36 times of exercise training))
- Physical component score (PCS)(3-4 months (for 36 times of exercise training))
- Mental component score (MCS)(3-4 months (for 36 times of exercise training))
- Migration speed(3-4 months (for 36 times of exercise training))
- Cell proliferation curve(3-4 months (for 36 times of exercise training))
- High-sensitivity C-reactive protein (hsCRP)(3-4 months (for 36 times of exercise training))