Seawater Immersion Hypothermia Triggers Cardiac Pyroptosis via the NF-κB/NLRP3 Inflammasome Axis: A Mechanistic Study...

Cold seawater immersion is a critical lethal risk in maritime accidents and military operations, frequently inducing fatal myocardial dysfunction. However, the mechanisms underlying this seawater immersion hypothermia-induced cardiac injury remain poorly defined. This study aimed to elucidate the pathological progression and underlying mechanisms of myocardial injury induced by cold seawater immersion. A male SD rat model was immersed in 15 °C seawater for 2 h. Echocardiography, transmission electron microscopy, transcriptomics, and Western blot were performed to assess cardiac function, mitochondrial ultrastructure, and molecular mechanisms. Cold stress triggered progressive bradycardia (~480 to ~100 bpm) with initial Frank-Starling compensation, followed by decompensation with reduced cardiac output and impaired diastolic function. Mitochondrial ultrastructural damage preceded histological lesions and was accompanied by elevated cardiac injury markers (cTnT, CK-MB, BNP). Cardiac tissue exhibited upregulated TNF-α, IL-1β, and IL-6, while transcriptomic analysis revealed enrichment of inflammatory pathways (TNF, NF-κB) and coordinated upregulation of pattern recognition receptors including scavenger receptor, Toll-like receptor, and NOD-like receptor families. The Western blot confirmed NF-κB activation, NLRP3 inflammasome assembly, and the N-terminal fragment of gasdermin D (GSDMD-NT) accumulation, indicating pyroptotic cell death. These findings demonstrate that cold seawater stress disrupts mitochondrial homeostasis and activates the NF-κB/NLRP3/pyroptosis cascade, contributing to inflammatory cardiomyocyte death and cardiac decompensation. This mechanistic insight may inform therapeutic strategies for seawater immersion hypothermia.