Impact of Acute High-Altitude Exposure on the Timing of Tranexamic Acid Administration in Rabbits with Traumatic Hemorrhagic Shock

Liu, Zhen, Chao Nie, Lijia Yuan, Hui Jiang, Chuanchuan Liu, Yi Zhang, and Minghua Liu.Impact of Acute High-Altitude Exposure on the Timing of Tranexamic Acid Administration in Rabbits with Traumatic Hemorrhagic Shock. <i>High Alt Med Biol.</i> 00:00-00, 2025. <b><i>Background:</i></b> Acute exposure to high altitude (≤3 days)-induced physiological changes may shorten the therapeutic time window for tranexamic acid (TXA) administration after traumatic hemorrhagic shock (THS). This study aims to compare the differences in the TXA therapeutic time window between THS patients with acute high-altitude exposure and those in low-altitude regions. <b><i>Methods:</i></b> Forty-two anesthetized rabbits were divided into three groups: low-altitude THS (l-THS), high-altitude sham, and high-altitude THS. All h-THS groups were housed for 3 days in 10% oxygen chambers (simulating 5,000 m altitude) before experimentation. THS models were established by reducing mean arterial pressure from 105 to 55 mmHg through blood loss combined with left tibiofibular fracture. Animals received single-dose TXA (90 mg/kg) with the following subgroups: l-THS-2h and l-THS-3h (TXA administered 2 hours/3 hours post-THS), h-THS-1h, h-THS-2h, h-THS-3h and h-THS-4h (TXA administered 1 hours/2 hours/3 hours/4 hours post-THS). Comparative analyses included hemodynamic parameters, complete blood counts, coagulation-fibrinolysis function, endothelial injury markers, inflammatory cytokines, and pulmonary histopathological changes. <b><i>Results:</i></b> High-altitude exposure required less blood loss to achieve THS compared with low-altitude conditions (51.00 ± 2.45 ml vs. 59.60 ± 3.65 ml, <i>p</i> < 0.05). At 6 hours post-THS, compared to the l-THS-2h group [TIC risk (INR:1.34 ± 0.09), anaerobic oxidation levels, inflammatory response levels, and lung injury score (1.8 (1.0, 2.0))], the l-THS-3h group [INR:1.51 ± 0.08; 2.6 (2.0, 3.0)], h-THS-2h group [1.45 ± 0.06; 2.8 (2.0, 3.5)], h-THS-3h group [INR:1.75 ± 0.11; 5.6 (4.5, 6.5)], and h-THS-4h group [INR:1.99 ± 0.06; 6.2 (6.0, 6.5)] all showed significantly higher values. For the same observational indicators, compared with the l-THS-3h group, the h-THS-1h group had lower values, while the h-THS-3h and h-THS-4h groups showed higher values. No statistically significant differences were observed between the l-THS-2h and h-THS-1h groups, or between the l-THS-3h and h-THS-2h groups for all parameters. <b><i>Conclusion:</i></b> The optimal time window for TXA administration in traumatic hemorrhagic shock may be shorter at high altitude compared with low-altitude area. These findings could influence therapeutic guidelines for TXA administration at high altitudes in humans.