Upper-extremity blood flow restriction: the proximal, distal, and contralateral effects-a randomized controlled trial.

BACKGROUND: Blood flow restriction (BFR) training with low weight is purported to induce similar physiological changes to high-weight regimens with the benefit of less tissue stress. We hypothesized that low-weight training with BFR would produce increased gains in strength and hypertrophy for muscle groups proximal, distal, and contralateral to tourniquet placement compared with low-weight training alone. METHODS: In this prospective, randomized controlled trial, healthy subjects were randomized into a 6-week low-weight training program either with or without BFR on 1 extremity. Outcome measures included limb circumference and strength. Comparisons were made between the BFR and non-BFR extremities, BFR and control groups, and non-BFR extremity and control groups. RESULTS: A total of 24 subjects (14 BFR and 10 control subjects) completed the protocol. Significantly greater gains were observed in dynamometric strength both proximal (shoulder scaption [30% greater], flexion [23%], and abduction [22%]) and distal (grip strength [13%]) to the tourniquet in the BFR limb compared with both the non-BFR extremity and the control group (P < .05). Arm and forearm circumferences significantly increased in the BFR limb compared with the non-BFR limb and control group (P = .01). The non-BFR extremity demonstrated greater grip strength than the control group (9%, P < .01). No adverse events were reported. CONCLUSION: Low-weight BFR training provided a greater increase in strength and hypertrophy in the upper-extremity proximal and distal muscle groups compared with the control group. The non-BFR extremity showed a significant increase in grip strength compared with the control group, indicating a potential systemic effect.

Proximal, Distal, and Contralateral Effects of Blood Flow Restriction Training on the Lower Extremities: A Randomized Controlled Trial.

BACKGROUND:: Blood flow restriction (BFR) training involves low-weight exercises performed under vascular occlusion via an inflatable cuff. For patients who cannot tolerate high-load exercises, BFR training reportedly provides the benefits of high-load regimens, with the advantage of less tissue and joint stress. HYPOTHESIS:: Low-load BFR training is safe and efficacious for strengthening muscle groups proximal, distal, and contralateral to tourniquet placement in the lower extremities. STUDY DESIGN:: Randomized controlled trial. LEVEL OF EVIDENCE:: Level 1. METHODS:: This was a randomized controlled trial of healthy participants completing a standardized 6-week course of BFR training. Patients were randomized to BFR training on 1 extremity or to a control group. Patients were excluded for cardiac, pulmonary, or hematologic disease; pregnancy; or previous surgery in the extremity. Data collected at baseline and completion included limb circumferences and strength testing. RESULTS:: The protocol was completed by 26 patients, providing 16 BFR and 10 control patients (mean patient age, 27 years; 62% female). A statistically greater increase in strength was seen proximal and distal to the BFR tourniquet when compared with both the nontourniquet extremity and the control group ( P < 0.05). Approximately twice the improvement was seen in the BFR group compared with controls. Isokinetic testing showed greater increases in knee extension peak torque (3% vs 11%), total work (6% vs 15%), and average power (4% vs 12%) for the BFR group ( P < 0.04). Limb circumference significantly increased in both the thigh (0.8% vs 3.5%) and the leg (0.4% vs 2.8%) compared with the control group ( P < 0.01). Additionally, a significant increase occurred in thigh girth (0.8% vs 2.3%) and knee extension strength (3% vs 8%) in the nontourniquet BFR extremity compared with the control group ( P < 0.05). There were no reported adverse events. CONCLUSION:: Low-load BFR training led to a greater increase in muscle strength and limb circumference. BFR training had similar strengthening effects on both proximal and distal muscle groups. Gains in the contralateral extremity may corroborate a systemic or crossover effect. CLINICAL RELEVANCE:: BFR training strengthens muscle groups proximal, distal, and contralateral to cuff placement. Patients undergoing therapy for various orthopaedic conditions may benefit from low-load BFR training with the advantage of less tissue stress.

Anticonvulsant effects of the selective melatonin receptor agonist ramelteon.

OBJECTIVE: The endogenous hormone melatonin has previously been shown to exert anticonvulsant effects in a variety of experimental models. Accordingly, we asked whether ramelteon, a synthetic and selective melatonin receptor agonist, might also possess anticonvulsant and/or antiepileptogenic properties. METHODS: The effects of ramelteon (30 or 100 mg/kg intraperitoneally twice daily for 5 days) were evaluated in two animal models of epilepsy. In the rat rapid kindling model, baseline hippocampal afterdischarge properties, kindling progression, and hippocampal excitability in kindled animals were measured. Anti-ictogenic efficacy was assessed after acute administration in untreated kindled rats. In the spontaneously epileptic Kcna1-null mouse model, we determined seizure frequency and periodicity using continuous video/EEG monitoring over 72 hours. Further, circadian rest-activity rhythms in ramelteon-treated animals were studied with actigraphy. RESULTS: In kindled animals, ramelteon reversed kindling-induced hippocampal excitability; however, it did not modify baseline afterdischarge properties, the progression and establishment of the kindled state in the rapid kindling model. However, in Kcna1-null mice, ramelteon (200 mg/kg/day) significantly attenuated seizure periodicity and frequency and improved circadian rest-activity rhythms compared with control animals. CONCLUSIONS: The selective melatonin receptor agonist ramelteon possesses anticonvulsant properties in a chronic epilepsy model. Our findings provide further support for melatonin receptors being potential novel targets for anticonvulsant drug development.

Ketogenic diet treatment abolishes seizure periodicity and improves diurnal rhythmicity in epileptic Kcna1-null mice.

INTRODUCTION: Seizures are known to perturb circadian rhythms in humans as well as in animal models of epilepsy. However, it is unknown whether treatment of the underlying epilepsy restores normal biologic rhythms. We asked whether: (1) seizure activity is characterized by diurnal rhythmicity, (2) chronically epileptic mice exhibit impaired rest-activity rhythms, and (3) treatment with the anticonvulsant ketogenic diet (KD) improves such perturbations. METHODS: Chronically epileptic Kcna1-null mice were fed either a standard diet (SD) or KD for 4 weeks and subjected to continuous video-EEG (electroencephalography) and actigraphy monitoring for 3-5 days to assess seizure activity and rest-activity cycles. RESULTS: Seizure activity in Kcna1-null mice demonstrated diurnal rhythmicity, peaking at zeitgeber (ZT)2.30 +/- 1.52. Rest-activity rhythms of epileptic mice were significantly disrupted. Whereas locomotor activity for wild-type mice peaked at ZT15.45 +/- 0.28 (ZT14:26-ZT16:51), peak activity of epileptic mice was more unpredictable, occurring over a 12.4 h range (ZT06:33-ZT18:57). In six of nine epileptic mice, peak activity was delayed to ZT17.42 +/- 0.38, whereas peak activity was advanced to ZT10.00 +/- 1.26 in the remaining mice. Treatment with the KD abolished seizure periodicity and restored the rest-activity rhythm to values resembling those of wild-type mice (i.e., activity peaking at ZT16.73 +/- 0.67). CONCLUSIONS: Kcna1-null mice experience seizures with 24-h periodicity and impaired circadian behavior. KD reduces the number and periodicity of seizures and restores normal behavioral rhythms, suggesting that this nonpharmacologic therapy may benefit biologic rhythm disturbances in epileptic patients.