A hypothesis-driven pulmonary-cerebral mechanistic framework of neurological decompression illness in repetitive breath-hold diving.

This hypothesis-driven narrative review synthesizes physiological, clinical, and neuroimaging evidence to advance an integrated pulmonary-cerebral framework for decompression illness (DCI) in repetitive breath-hold diving. Three unresolved features are addressed: the predominance of cerebral involvement, the characteristic localization of lesions to external watershed and distal arterial territories, and the gradual evolution of neurological deficits. Drawing on converging evidence from pulmonary vascular physiology and cerebral gas kinetics, we propose that venous nitrogen bubbles generated during repetitive dives intermittently bypass pulmonary filtration through transient recruitment of intrapulmonary arteriovenous anastomoses (IPAVA), providing a plausible route for episodic arterialization. Once lodged in distal cerebral arteries, these bubbles may enlarge through diffusion of nitrogen from supersaturated brain tissue, potentially contributing to progressive vascular obstruction, endothelial activation, blood-brain barrier disruption, and vasogenic edema. This review articulates a hypothesis-generating integrative framework in which IPAVA-mediated arterialization and diffusion-driven bubble enlargement may together provide a plausible physiological interpretation for the progressive, watershed-predominant cerebral injury unique to repetitive breath-hold diving. Although direct evidence remains limited-particularly regarding dynamic IPAVA behavior and quantitative nitrogen kinetics- the available data appear broadly compatible with a proposed mechanism centered on episodic arterialization followed by diffusion-driven bubble growth. By framing breath-hold diving-related DCI as a coupled pulmonary-cerebral process, this review proposes a testable conceptual foundation for future integrative research aimed at clarifying IPAVA dynamics, cerebral microvascular vulnerability, and nitrogen transport within supersaturated tissues.