EFFECTS OF HYPOXEMIA, NORMOXIA, AND MODERATE TO SEVERE HYPEROXEMIA ON BRAIN-LUNG CROSSTALK IN A FOCAL ISCHEMIC STROKE MODEL

Abstract

Introduction: Patients with acute focal ischemic stroke (AIS) often require intensive care management, including mechanical ventilation and supplemental oxygen. Observational studies suggest a "U"-shaped relationship between PaO2 levels and mortality in AIS, yet the mechanisms driving cerebral and pulmonary damage across different oxygen levels are not well understood. Objective: This study aimed to evaluate the extent of brain and lung injury following exposure to varying PaO2 levels in an experimental model of focal AIS. Methods: Thirty-two male Wistar rats (CEUA 131/23) underwent focal AIS induced by thermocoagulation of pial blood vessels. After 24 hours, rats were randomly assigned to one of four groups (n=8 per group): normoxia (NORMO: PaO2 = 80-120 mmHg), hypoxia (HYPO: PaO2 < 80 mmHg), moderate hyperoxia (MOD: PaO2 = 121-299 mmHg), or severe hyperoxia (SEV: PaO2 ≥ 300 mmHg). Rats were ventilated for two hours with a positive end-expiratory pressure of 1 cmH2O and tidal volume (VT) of 6 ml/kg. Lung function was assessed at INITIAL and FINAL of the experiment. Lungs and brains were gathered for histological analysis. Results: PaO2 levels at FINAL were 95±15 mmHg in the NORMO group, 51±6 mmHg in the HYPO group, 184±52 mmHg in the MOD group, and 350±47 mmHg in the SEV group (p<0.001). Peak and plateau airway pressures increased over time across all groups (p<0.001), with no significant differences among groups. Diffuse alveolar damage (DAD) score was higher in MOD and SEV than NORMO groups (p=0.042, p=0.048; respectively). DAD score showed a positive and significative correlation with PaO2 levels (r=0.48, p=0.005). In the brain, inflammatory infiltration in ischemic penumbra indicated blood-brain barrier dysfunction, according to PaO2 levels. Conclusion: This study showed an association between lung structural changes and PaO2 levels. In the brain, it was observed inflammatory infiltration in ischemic area according to PaO2 levels.