Inhaled nitric oxide as a rescue therapy in rat crush syndrome: translating bench research to field application

Abstract Crush syndrome (CS) is characterised by ischaemia/reperfusion-induced rhabdomyolysis, leading to systemic inflammation and high mortality. Building on our previous findings that intravenous nitric oxide (NO) donors improve survival in this condition, we investigated the therapeutic efficacy of inhaled NO delivered via a portable, controlled-release device in an experimental rat model of CS. Anaesthetised rats underwent bilateral hindlimb compression using rubber tourniquets for 5 h, followed by reperfusion. Among the various inhalation conditions tested, administration of NO (160 parts per million) for 2 h after reperfusion significantly increased survival rate from 20 to 90%. Improvements in haemodynamic parameters, biochemical markers, and histopathological findings correlated with enhanced survival outcomes. These results suggest that on-site NO inhalation therapy may serve as an effective first-line, emergency intervention for CS, particularly in disaster settings. Graphical abstract