Supplemental oxygen induced cardiovascular pathophysiology in an end-of-life care model in mice.

Supplemental oxygen in critical care patients is associated with increased mortality. We previously reported hyperoxia-induces cardiac pathophysiology influenced by age, metabolic status, sex, and duration of exposure. The present study investigated the dose-dependent effects of oxygen on cardiac remodeling in very aged mice (>100 weeks), a model relevant to end-of-life physiology and clinical decision-making. Mice were exposed to graded oxygen concentrations or normal air for 72 h followed by comprehensive assessment of cardiac function and electrophysiology. Exposure to 70% O2 led to significant reduction in ejection fraction (82.5% ± 2.1% to 59.8% ± 3.4%) and cardiac output (38.2 ± 1.5 mL/min to 12.8 ± 1.2 mL/min in males and 8.1 ± 0.9 mL/min in females). A significant electrical remodeling (QTc 57.2 ± 1.8 ms to 78.4 ± 2.5 ms) was also observed. Although females exhibited higher baseline cardiac function than males, they demonstrated greater functional decline and earlier onset of electrical abnormalities at lower oxygen concentrations. These findings indicate that oxygen concentration is a critical determinant of cardiac dysfunction in advanced age, with heightened susceptibility in females. Collectively, this study highlights the potential risks of supplemental oxygen and underscores the importance of precision oxygen therapy in end-of-life care settings.