Object
Title: Impact of interval blood flow restricted training on the process of angiogenesis and functions of vascular endothelium
Abstract:
Blood flow restriction exercise (BFRE), derived from the KAATSU technique, is gaining increasing application. The range of BFRE exercises includes both low and high loads, as well as various types of exercises, and the compression level ranges from 20 mmHg to even 300 mmHg. As a result of BFR exercises, even at low loads, the levels of lactic acid, growth hormone, and the remodeling of capillary vessels in skeletal muscles increase. Although it is hypothesized that the effect of reactive hyperemic blood perfusion, caused by the increase in shear stress induced by BFRE, leads to vasodilation and the stimulation of endothelial factors production, which could promote the improvement of endothelial function, these phenomena remain insufficiently studied. Atherosclerosis is a chronic inflammatory disease of the arteries characterized by the formation of lipid-rich atherosclerotic plaques within the inner layer of arterial walls. This disease, along with its complications, is a leading cause of death and disability among adults in developed countries. Its peripheral manifestation, known as peripheral artery disease (PAD), affects up to 60% of individuals aged 70 and above. The fundamental element of conservative treatment for PAD is physical exercise. Modifying and improving its forms, with particular emphasis on endothelial function and stimulation of angiogenesis, allows for bette ; r clinical outcomes in patients with PAD. Research objectives: 1. Assessment of endothelial function and angiogenesis activation in response to interval training with the use of blood flow restriction (BFR) in healthy volunteers. 2. Comparison of the impact of exercise with blood flow restriction (BFR) versus unrestricted flow (nonBFR) on vascular endothelial function and angiogenesis activation. 3. Evaluation of the application of exercise with restricted blood flow (BFR) in the patient with peripheral arterial disease. In Stage I, a prospective cross-over study was conducted on a group of healthy volunteers. During the training sessions, the participants performed 21-minute exercises in a seated position on an elliptical trainer, consisting of a 9-minute warm-up and 6 sprints lasting 30 seconds with increased resistance, separated by 90-second rest periods. In the case of BFR exercises, venous flow restriction was maintained throughout the training by using cooling pressure cuffs (40 mmHg for the arms and 65 mmHg for the thighs). Endothelial functions were assessed using non-invasive imaging studies, including flow-mediated dilation (FMD), reactive hyperemia index (RHI), and pulse wave analysis (PWA). Measurements of the concentrations of vascular endothelial growth factor receptor 2 (VEGF-R2), platelet endothelial cell adhesion molecule (PECAM-1), and transmembrane prot ; ein CD34 were performed to monitor angiogenesis processes. It was shown that endothelial vasodilatory functions improved significantly as a result of BFRE compared to non-BFR exercises. Vessel stiffness decreased under the influence of BFRE, while non-BFR exercises caused a slight increase. Both forms of training led to angiogenesis activation, but stimulation through BFRE was more effective than unrestricted blood flow. In the second stage, a systematic literature review was conducted in conjunction with a meta-analysis to enhance the strength of the obtained scientific evidence. Online databases, including the Cochrane Database of Systematic Reviews, PubMed, and Embase, were searched for articles published between January 2000 and November 2022. Original articles reporting the results of randomized or non-randomized clinical trials or prospective cross-over studies with an experimental group (BFRE) and a control group (non-BFR) were included for analysis. Only studies conducted on adult participants that included at least one vascular variable, such as endothelial function (FMD, IMT, RHI, AI, SI, RI, NO concentration), angiogenesis (VEGF, CD31/PECAM-1, CD106/VCAM-1, von Willebrand factor), or other vascular functions (Tcpo2, ABI, TBI, CAVI), were considered. A total of 851 literature references were identified, of which 38 met the inclusion criteria for analysis. Due to d ; ata quality, meta-analysis was only possible for the comparison of the effects of BFRE and non-BFRE on the following vascular variables: FMD (11 study populations), PWV (7), VEGF (7), ABI (8), systolic blood pressure (SBP) (24), and heart rate (HR) (23). The meta-analysis demonstrated a significant improvement in FMD and an increase in VEGF levels after BFR training compared to non-BFR exercises. The analysis of available literature revealed several limitations, including a small number of published reports, low sample sizes in the studied groups with high heterogeneity, heterogeneity of training protocols, and variations in the degree of blood flow restriction. Considering the results of Stages I and II, which indicate the effectiveness of BFR exercises in improving endothelial function and stimulating angiogenesis, Stage III involved conducting a pilot experimental form of exercise rehabilitation in a patient with peripheral artery disease (PAD) and intermittent claudication, for whom procedural treatment or conventional walking training was not applicable. A 62-year-old male patient with significant degenerative changes in the hip joint, as well as degenerative and discopathy in the lumbosacral spine, was scheduled for right hip arthroplasty due to lower limb ischemia. He presented with short-distance right-sided intermittent claudication in the calf (pain-free walking di ; stance, PFWD: 100m; maximum walking distance, MWD: 300m). Doppler ultrasound examination confirmed occlusion of the leg arteries. Due to limited mobility caused by joint dysfunction, standard walking training could not be performed, and the patient declined procedural treatment. An experimental exercise rehabilitation program with BFRE was introduced (lower limb cuff pressure: 20mmHg). The exercise protocol used in Stage I was applied, with sessions conducted three times a week for three months. The patient achieved an extension of claudication distance (PFWD: 600m, MWD: 1000m) and an increase in ABI (from 0.3 to 0.55) and TBI (from 0.0 to 0.2), allowing for orthopedic surgery and subsequent regular rehabilitation based on walking training. After three years, the patient walks without limitations or symptoms of claudication, and ABI and TBI have further improved (0.8 and 0.6, respectively). In summary, a single-center clinical study conducted on healthy volunteers demonstrated that training with restricted venous flow not only improves endothelial vasodilatory function and reduces vascular stiffness but also stimulates angiogenesis. Furthermore, the results of the meta-analysis confirmed these findings and indicated that these phenomena occur more intensively during physical activities with BFR compared to exercises without blood flow restriction. Low-intensity interval trai ; ning with BFR, applied experimentally in a PAD patient without other treatment options, yielded positive clinical outcomes in terms of hemodynamic indicators and patient health improvement.
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Degree discipline:
choroby układu krążenia ; rehabilitacja
Degree grantor:
Rada Dyscypliny Nauki medyczne
Promoter:
Śliwka, Agnieszka ; Jaworek, Magdalena
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Last modified:
Jul 25, 2024
In our library since:
Apr 25, 2024
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5
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http://dl.cm-uj.krakow.pl:8080/publication/5089
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| Edition name | Date |
|---|---|
| ZB-139671 | Jul 25, 2024 |
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