Characterization of a Rabbit Model of Traumatic Hemorrhagic Shock under High-Altitude Cold Conditions

High-altitude hypoxia and cold often co-occur in traumatic hemorrhagic shock (THS), yet time-resolved models that quantify their interaction with blood loss are scarce. We established a composite-trauma THS model in New Zealand rabbits at ≈ 5,000 m equivalent altitude and 8 ± 2 °C. Animals were randomized to six groups (HS (hemorrhagic shock); HS + COL (hemorrhagic shock + cold); HS+HYP (hemorrhagic shock + hypoxia); HS+HYP+COL (hemorrhagic shock + hypoxia + cold); Sham (normoxia, normothermia, no HS); HYP+COL (hypoxia + cold, no HS) ). Trauma comprised partial hepatectomy, total splenectomy, and femoral fracture; controlled hemorrhage lowered mean arterial pressure (MAP) to 35-40 mmHg for 5-10 min without resuscitation or active warming. At Pre/0/30/60/90/120 min, we recorded vital signs, blood gases/metabolites, coagulation-fibrinolysis, electrolytes/complete blood count (CBC), liver-kidney indices, cytokines, and terminal histology. Group × time mixed models revealed stable dose-response behavior and supra-additive injury in HS+HYP+COL: lactate ≈9.33 ± 0.17 mmol/L at 120 min, nadir arterial pH ≈6.52 ± 0.03, progressive Na⁺↓/Cl⁻↑/K⁺↑/iCa²⁺↓, hypocoagulability with secondary fibrinolysis (prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were prolonged; fibrinogen and antithrombin↓; D-dimer/fibrin(ogen) degradation products (FDP)↑), and early hepatorenal injury with concurrent TNF-α/IL-6/IL-1β/IL-10 surges. This reusable, quantifiable, time-resolved platform reveals that high-altitude hypoxia and cold amplify inflammation-endothelium-coagulation-metabolic imbalance beyond hemorrhage alone and supports evaluation of multi-axis strategies, including rewarming/oxygenation, balanced low-chloride fluids with electrolyte-stratified care, endothelial/glycocalyx protection, and immune-fibrinolysis modulation.