Myth-busting the zone of injury concept: a prospective study on the vascular response to high-energy lower extremity trauma

Abstract

Background: Although the zone of injury concept is widely accepted, no histologic studies of vessel wall changes causing the phenomena are reported. This prospective study investigated the vascular response to high-energy lower extremity trauma to evaluate the validity of the zone of injury concept. Methods: The histologic appearance of arterial and venous walls in the zone of injury was studied in 19 patients (median age 46 [interquartile range 29.5–62.5] years) who underwent osteosynthesis and free-flap reconstruction due to high-energy lower extremity open fracture. Vascular samples were harvested from the injured extremity and control samples were harvested from the free-flap donor site. Histologic and morphometric characteristics of the vessels were analyzed microscopically and using digital pathology QuPath software. Results: Vascular samples were harvested on post-injury days 1–11. Intimal thickness was >3 times greater in arteries harvested from the zone of injury than in control samples (P<0.01) and the intima/media ratio was 2-fold that in control samples (P=0.01). Arterial intimal fibrosis was more evident in vessels harvested from the zone of injury (P<0.01), but medial fibrosis and medial thickness did not differ significantly between groups. Venous intimal thickening (P<0.01) and the intima/media ratio (P=0.02) were superior in samples from the zone of injury. Fibrosis-related changes did not differ between groups (P=0.45). Conclusions: These findings support the validity of the zone of injury concept by providing a novel histologic basis for this phenomenon. Intimal thickening and arterial intimal fibrosis are prominent histologic features of vessels affected by major lower extremity trauma.