Determinant role of the severity of hypoxia in the induction of reoxygenation injury in cat lung

ABSTRACT

Although reoxygenation is the best way to salvage hypoxic tissues, reduced oxygen species (ROS) generated during reoxygenation are known to cause further tissue injuries and the induction of heat shock proteins (HSPs). The present study was undertaken to determine any causal relationship between the severity of hypoxia and the opposite outcomes, either beneficial or detrimental, of the subsequent reoxygenation by measuring the HSP72. To this aim, one group (6 male cats, 2.5 ~ 3.5 kg) was subjected to a 5-min episode of hypoventilation (H, ventilation rate: 5/min) for the induction of slight hypoxia and the other group (6 male cats, 2.4-3.7 kg) was subjected to a 5-min episode of apnea (A) for severe hypoxia. Each 3 animals from both groups received a 10-min episode of ventilation with 95% O2 (O), whereas the remainder did not. After these procedures, all animals were allowed to be ventilated within physiological range for 1, 4, or 8 hours (1H, 1HO, 4H, 4HO, 8H, 8HO, 1A, 1AO, 4A, 4AO, 8A and 8AO groups). Control animals did not receive any manipulation. The arterial blood pCO2 was significantly higher just after apnea than hypoventilation, while pO2 and pH were significantly lower just after apnea than hypoventilation. Western blot analysis revealed that the magnitude of HSP72 synthesis is larger in 1H, 4H and 8H groups than in 1HO, 4H and 8HO groups, respectively. In contrast, 1AO, 4AO and 8AO groups more induced HSP72 than 1A, 4A and 8A groups, respectively. These results suggest that the reoxygenation is beneficial after slight hypoxia but detrimental after severe hypoxia.