Low-intensity pulsed ultrasound mitigates acute extremity compartment syndrome by mediating ferroptosis suppression

Acute extremity compartment syndrome (AECS) is a severe surgical emergency with no effective non-invasive therapies available. Here, we demonstrate that low-intensity pulsed ultrasound (LIPUS) attenuates muscle damage by suppressing oxidative stress and ferroptosis. In skeletal muscle cells following hypoxia-reoxygenation (H/R), LIPUS reduced reactive oxygen species (ROS), malondialdehyde, lipid peroxides, and ferrous iron accumulation. In a rat AECS model, LIPUS (1 MHz, 0.5 W/cm², 20% duty cycle) mitigated histopathological injury and iron deposition compared with untreated controls, without affecting healthy muscle. Mechanistically, LIPUS activated the Nrf2/Gpx4 antioxidant pathway and downregulated p53 expression. These findings identify LIPUS as a non-invasive intervention that inhibits ferroptosis and improves tissue outcomes in AECS, suggesting its potential as a bedside therapeutic strategy to complement surgical management.