Hematological and biochemical responses to extreme hypoxia exposure after hypoxia preconditioning in Sprague–Dawley rats

Abstract

Hypoxia preconditioning (HP) is postulated to induce adaptive changes in the body for endurance and hypoxic acclimatization. Its dosage (severity, intermittence, duration) determines its effectiveness. Male SD rats were subjected to HP by exposing them to intervals of hypoxia for different durations in a normobaric hypoxia chamber at 12 % FiO₂ for 4h consecutively for 1, 2, 3, 4 and 5 days. To assess the acclimating effect of HP, the animals were further subjected to severe hypoxic exposure to 8 % FiO₂ for 6h. Physiological variables (peripheral oxygen saturation-SpO₂, heart rate-HR, and respiratory rate-RR), protein expression parameters (HIF-1α, EPO, VEGF, and uNOS), biochemical metabolites and hematology and blood gas variables were studied during the course of the hypoxia preconditioning schedule. All the statistical comparisons were performed using one-way ANOVA following Tukey's correction. It was found Day 3-HP was associated with a greater SpO₂ level (p < 0.05) compared with those of other hypoxia preconditioned groups, the percentage of NRBC was lowest in day 3-HP. PCO₂ was lower during days 2, 3 and 4-HP. Circulatory metabolites (nitrate + nitrite-NO, L-arginine, citrulline, succinate, blood urea nitrogen, and L-lactate) changed significantly with different durations of hypoxia preconditioning. HIF-1α showed peak expression on HP-3 day, whereas EPO was highest during HP-2 day, and VEGF was significantly lower at p < 0.001 as compared to extreme hypoxia without HP. Reduced oxidative stress (ROS) and inflammation (histopathology) were observed during HP-3 day. Hypoxia preconditioning at 12 % FiO₂ for 3 days can be postulated to be a potent non-pharmacological modality for inducing physiological and molecular responses that can influence hypoxic acclimatization during exposure to extremely hypoxic conditions.