Delayed myonuclear addition, myofiber hypertrophy, and increases in strength with high-frequency low-load blood flow restricted training to volitional failure

J Appl Physiol (1985). 2019 Mar 1;126(3):578-592. doi: 10.1152/japplphysiol.00397.2018. Epub 2018 Dec 13.


The purpose of the present study was to investigate muscle hypertrophy, strength, and myonuclear and satellite cell (SC) responses to high-frequency blood flow-restricted resistance exercise (BFRRE). Thirteen individuals [24 ± 2 yr (mean ± SD), 9 men] completed two 5-day blocks of 7 BFRRE sessions, separated by a 10-day rest period. Four sets of unilateral knee extensions to voluntary failure at 20% of one repetition maximum (1RM) were conducted with partial blood flow restriction (90-100 mmHg). Muscle samples obtained before, during, 3 days, and 10 days after training were analyzed for muscle fiber area (MFA), myonuclei, SC, and mRNA and miRNA expression. Muscle size was measured by ultrasonography and magnetic resonance imaging and strength with 1RM knee extension. With the first block of BFRRE, SC number increased in both fiber types (70%-80%, P < 0.05), whereas type I and II MFA decreased by 6 ± 7% and 15 ± 11% ( P < 0.05), respectively. With the second block of training, muscle size increased by 6%-8%, whereas the number of SCs (type I: 80 ± 63%, type II: 147 ± 95%), myonuclei (type I: 30 ± 24%, type II: 31 ± 28%), and MFA (type I: 19 ± 19%, type II: 11 ± 19%) peaked 10 days after the second block of BFRRE, whereas strength peaked after 20 days of detraining (6 ± 6%, P < 0.05). Pax7- and p21 mRNA expression were elevated during the intervention, whereas myostatin, IGF1R, MyoD, myogenin, cyclinD1 and -D2 mRNA did not change until 3-10 days postintervention. High-frequency low-load BFRRE induced robust increases in SC, myonuclei, and muscle size but modest strength gains. Intriguingly, the responses were delayed and peaked 10-20 days after the training intervention, indicating overreaching. NEW & NOTEWORTHY In line with previous studies, we demonstrate that high-frequency low-load blood flow-restricted resistance exercise (HF-BFRRE) can elicit robust increases in satellite cell and myonuclei numbers, along with gains in muscle size and strength. However, our results also suggest that these processes can be delayed and that with very strenuous HF-BFRRE, there may even be transient muscle fiber atrophy, presumably because of accumulated stress responses. Our findings have implications for the prescription of BFR exercise.

Keywords: Kaatsu; ischemic exercise; muscle hypertrophy; myogenic stem cells; myonuclei.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Exercise / physiology*
  • Female
  • Humans
  • Hypertrophy / metabolism
  • Hypertrophy / physiopathology*
  • Male
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / physiology*
  • Muscle Strength / physiology*
  • RNA, Messenger / metabolism
  • Regional Blood Flow / physiology*
  • Resistance Training / methods
  • Young Adult


  • RNA, Messenger