Skeletal Muscle Microvascular Changes in Response to Short-Term Blood Flow Restricted Training—Exercise-Induced Adaptations and Signs of Perivascular Stress

Abstract

Aim: Previous reports suggest that low-load muscle exercise performed under blood flow restriction (BFR) may lead to endurance adaptations. However, only few and conflicting results exist on the magnitude and timing of microvascular adaptations, overall indicating a lack of angiogenesis with BFR training. The present study, therefore, aimed to examine the effect of short-term high-frequency BFR training on human skeletal muscle vascularization. Methods: Participants completed 3 weeks of high-frequency (one to two daily sessions) training consisting of either BFR exercise [(BFRE) n = 10, 22.8 ± 2.3 years; 20% one-repetition maximum (1RM), 100 mmHg] performed to concentric failure or work-matched free-flow exercise [(CON) n = 8, 21.9 ± 3.0 years; 20% 1RM]. Muscle biopsies [vastus lateralis (VL)] were obtained at baseline, 8 days into the intervention, and 3 and 10 days after cessation of the intervention to examine capillary and perivascular adaptations, as well as angiogenesis-related protein signaling and gene expression. Results: Capillary per myofiber and capillary area (CA) increased 21-24 and 25-34%, respectively, in response to BFRE (P < 0.05-0.01), while capillary density (CD) remained unchanged. Overall, these adaptations led to a consistent elevation (15-16%) in the capillary-to-muscle area ratio following BFRE (P < 0.05-0.01). In addition, evaluation of perivascular properties indicated thickening of the perivascular basal membrane following BFRE. No or only minor changes were observed in CON.

Functional and molecular adaptations of quadriceps and hamstring muscles to blood flow restricted training in patients with ACL rupture

“…Consistent with this notion VEGF ‐ A mRNA tended to be higher in vastus lateralis and semitendinosus muscles in the BFR than in the SHAM‐BFR group. Increased VEGF ‐ A expression in vastus lateralis muscle following LL‐BFR exercise was observed in healthy men, 14 which supports findings of other authors 14,32,33 that angiogenesis may contribute to enhanced endurance. However, in our study VEGF ‐ A mRNA tended to be increased in semitendinosus muscle without improvements in endurance.…”

“…Apart from its well‐studied effects on muscle strength and size, the LL‐BFR training has been also shown to enhance muscle endurance 7,9 by enhancing muscle microvascular function 14,32,33 and oxygenation 7 . Our recent clinical studies showed protective effects of short‐term preconditioning with LL‐BFR exercise on QF muscle endurance following arthroscopic ACL reconstruction, but not on its strength and size 8,9 .…”

Effects of Blood Flow Restriction Exercise and Possible Applications in Type 2 Diabetes

“…In addition, there is evidence that BFRT may trigger microvascular changes, including capillary neoformation and thickening of the perivascular basal membrane, as well as mitochondrial adaptations such as decreased mitochondrial reactive oxygen species (ROS) production within myocytes [13,14]. These adaptations may also make BFRT suitable for populations such as individuals with T2D, who suffer from vascular complications, alterations of mitochondrial function in several tissues, including skeletal muscle, and associated musculoskeletal problems such as muscle weakness [15].…”

Blood‐flow‐restricted exercise: Strategies for enhancing muscle adaptation and performance in the endurance‐trained athlete

“…In elite powerlifters, the number of capillaries around type I fibres increased in response to 6.5 weeks of high-frequency (daily) LLRE (∼30% 1RM) with BFR, but not after LLRE alone (Bjørnsen et al, 2019). An increase in capillary-to-fibre ratio (C:F; ∼23%) and capillary area (∼30%) in response to 3 weeks of high-frequency (one or two daily sessions) LLRE (20% 1RM) was observed with BFR performed to volitional failure, in comparison to work-matched, non-BFR exercise (Nielsen et al, 2020 Abbreviations: ACC, acetyl-CoA carboxylase; AMPK, 5′-adenosine monophosphate-activated protein kinase; AOP, arterial occlusion pressure; BFR, blood flow restriction; CaMKII, calmodulin-dependent protein kinase II; CON, control; CREB, cAMP response-element binding protein; CS, citrate synthase; COXIV, cytochrome C oxidase subunit IV; eNOS, endothelial nitric oxide synthase; β-HAD, 3-hydroxyacyl-CoA dehydrogenase; HIF-1α, hypoxia-inducible factor-1α; HLRE, high-load resistance exercise; iNOS, inducible nitric oxide synthase; LOP, limb occlusion pressure; nNOS, neuronal nitric oxide synthase; p38MAPK, p38 mitogen-activated protein kinase; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator 1-α; rep or reps, repetitions; 1RM, one repetition maximum; VEGF, vascular endothelial growth factor; VEGFR-2, vascular endothelial growth factor receptor-2.…”

“…In elite powerlifters, the number of capillaries around type I fibres increased in response to 6.5 weeks of high‐frequency (daily) LLRE (∼30% 1RM) with BFR, but not after LLRE alone (Bjørnsen et al., 2019). An increase in capillary‐to‐fibre ratio (C:F; ∼23%) and capillary area (∼30%) in response to 3 weeks of high‐frequency (one or two daily sessions) LLRE (20% 1RM) was observed with BFR performed to volitional failure, in comparison to work‐matched, non‐BFR exercise (Nielsen et al., 2020). These adaptations occurred alongside a proportional increase in muscle fibre area (Nielsen et al., 2012), resulting in a stable capillary density (number of capillaries per unit cross‐sectional area of muscle).…”