Optimal surgical timing after high-altitude de-adaptation: day-30 post-descent marks physiologic recalibration and improved small bowel repair in rats.

BACKGROUND: High-altitude de-adaptation following rapid transition from chronic hypoxia to normoxia has been associated with increased postoperative risk, yet its temporal physiological features and impact on intestinal repair remain poorly defined. METHODS: Male Sprague-Dawley rats (n = 84) were exposed to simulated high altitude (5,000 m) for 90 days and then relocated to normoxia. Standardized small bowel rupture repair was performed at 1, 10, 20, 30, 40, 50, or 60 days after relocation. Hypoxia adaptation and reversibility were assessed using arterial oxygen saturation, hematological indices, hypoxia-responsive molecular markers, respiratory rate, body weight, and behavior. Postoperative outcomes were evaluated 10 days after surgery, including inflammatory cytokines, oxidative stress markers, immune cell infiltration, and histopathology. RESULTS: Chronic hypoxia induced a stable hypoxia-adapted state characterized by reduced oxygen saturation, enhanced erythropoiesis, increased respiratory rate, and upregulation of intestinal HIF-1α and vascular endothelial growth factor, all of which progressively normalized after return to normoxia and resolved by approximately 30 days. Perioperative survival did not differ among groups. In contrast, systemic inflammatory cytokines and lipid peroxidation peaked at day 1 post-relocation and declined to nadir levels by day 30. This period was marked by reduced macrophage infiltration, peak fibroblast density, and more organized granulation tissue and collagen deposition. CONCLUSION: The duration of high-altitude de-adaptation is closely associated with intestinal repair quality. Approximately 30 days of normoxic re-acclimation correspond to coordinated resolution of hypoxia-related physiological perturbations and optimized tissue repair, identifying a critical post-relocation window relevant to surgical timing after descent from high altitude.