3D vascular mapping reveals multi-organ injury following severe acute pancreatitis.

RATIONALE: Severe acute pancreatitis (SAP) is a life-threatening disease with substantial mortality, primarily resulting from pancreatic microcirculatory failure that initiates multiple organ dysfunction syndrome (MODS). While early microvascular injury is widely recognized as a critical determinant of disease progression, the precise spatiotemporal dynamics and mechanisms underlying vascular damage remain largely elusive, limiting the development of effective therapeutic interventions. METHODS: An integrated imaging method that combines vascular labeling, tissue clearing, and light-sheet microscopy is proposed to realize 3D mapping and quantitative analysis of multi-organ vascular networks in a mouse model of SAP. RESULTS: We found that SAP induced systemic microvascular disruption accompanied by organ-specific perfusion deficits across multiple vital organs. As the primary site of injury, the pancreas exhibited the earliest and most severe hypoperfusion, whereas remote organs showed a delayed decline in perfusion, with different trends among organs. Specifically, perfusion in the lung, heart, and kidney decreased gradually with disease progression, perfusion in the liver and spleen remained stable within the first 6 hours and then decreased rapidly, while the brain perfusion showed a sharp decrease at the end stage. These distinct perfusion trajectories are consistent with sequential compensatory and decompensatory responses. More importantly, the administration of heparin sodium within 12 hours after SAP induction significantly improved survival, reversed multi-organ hypoperfusion, and preserved microvascular integrity across affected organs. CONCLUSIONS: This study identifies systemic vascular injury as a key driver of multiple organ dysfunction in SAP and provides a convincing evidence that early intervention with heparin sodium can improve multi-organ hypoperfusion, preserve microvascular integrity, and enhance survival.