Local and Systemic Effects of Blood Flow Restriction Therapy in an Animal Model

Abstract

Background: Blood flow restriction therapy (BFRT) has been increasingly applied to improve athletic performance and injury recovery. Validation of BFRT has lagged behind commercialization, and currently the mechanism by which this therapy acts is unknown. BFRT is one type of ischemic therapy, which involves exercising with blood flow restriction. Repetitive restriction of muscle blood flow (RRMBF) is another ischemic therapy type, which does not include exercise. Hypothesis/Purpose: The purpose was to develop a rat model of ischemic therapy, characterize changes to muscle contractility, and evaluate local and systemic biochemical and histologic responses of 2 ischemic therapy types. We hypothesized that ischemic therapy would improve muscle mass and strength as compared with the control group. Study Design: Controlled laboratory study. Methods: Four groups of 10 Sprague-Dawley rats were established: control, stimulation, RRMBF, and BFRT. One hindlimb of each subject underwent 8 treatment sessions over 4 weeks. To simulate exercise, the stimulation group underwent peroneal nerve stimulation for 2 minutes. The RRMBF group used a pneumatic cuff inflated to 100 mm Hg with a 48-minute protocol. The BFRT group involved 100–mm Hg pneumatic cuff inflation and peroneal nerve stimulation for a 5-minute protocol. Four methods of evaluation were performed: in vivo contractility testing, histology, immunohistochemistry, and ELISA. Analysis of variance with post hoc Tukey test and linear mixed effects modeling were used to compare the treatment groups. Results: There was no difference in muscle mass among groups ( P = .40) or between hindlimbs ( P = .73). In vivo contractility testing showed no difference in maximum contractile force among groups ( P = .64) or between hindlimbs ( P = .30). On histology, myocyte cross-sectional area was not different among groups ( P = .55) or between hindlimbs ( P = .44). Pax7 immunohistochemistry demonstrated no difference in muscle satellite cell density among groups ( P = .06) or between hindlimbs ( P = .046). ELISA demonstrated the RRMBF group as eliciting elevated GH levels as compared with the other groups ( P < .001). Conclusion: Ischemic therapy did not induce gains in muscle mass, contractility strength, fiber cross-sectional area, or satellite cell density locally or systemically in this model, although the RRMBF group did have elevated GH levels on ELISA. Clinical Relevance: This animal model does not support ischemic therapy as a method to improve muscle mass, function, or satellite cell density.

A Comprehensive Model of Blood Flow Restriction in the Post-surgical Rat

“…squats), but they are less applicable to studies of BFR due to their inability to generate hindlimb-specific movement, thus potentially introducing compensation by the non-targeted limbs. Other studies that combine BFR and resistance training in rats use low-current neuromuscular electrostimulation in anesthetized rats, which allows for careful control of occlusion pressure but only stimulates contraction of a single muscle 45,47,52 . Further, prolonged exposure to systemic anesthesia can cause reductions in body temperature and impact blood flow through distal vasculature, affecting accurate measurement of blood flow occlusion 53 .…”

“…Achieving external BFR in rats has typically been done on anesthetized and carefully positioned rats 45 . Rubber bands and cuffs have been used to create transient arterial occlusion 22,[46][47][48] , and direct surgical ligation is used for continuous arterial occlusion 49,50 .…”