Sex differences in murine cardiac pathophysiology with hyperoxia exposure

Area of Science:

• Physiology
• Cardiovascular Research
• Toxicology

Background:

• Mechanical ventilation often involves hyperoxia (>90% oxygen).
• Hyperoxia is linked to increased mortality in ventilated patients.
• Women undergoing mechanical ventilation show higher mortality and cardiac electrophysiological risks.

Purpose of the Study:

• To investigate the sex-specific effects of hyperoxia on male and female mice.
• To assess physical, hemodynamic, biochemical, functional, electrophysiological, and molecular impacts of hyperoxia.

Main Methods:

• Male and female C57BL/6J mice (8-10 weeks old) were exposed to either hyperoxia or normoxia.
• Comprehensive assessments including physical, hemodynamic, biochemical, functional, electrophysiological, and molecular analyses were performed.
• Electrocardiography (ECG) and molecular analysis of left ventricular tissue were conducted.

Main Results:

• Hyperoxia caused significant body mass loss in both sexes.
• Female mice exhibited lower heart rates, longer RR intervals, and 50% mortality, unlike males.
• Both sexes showed hyperdynamic left ventricular ejection fraction, reduced stroke volume, and cardiac output.
• ECG revealed prolonged RR, PR, QRS, QTc, and JT intervals in both sexes.
• Molecular analysis indicated dysregulation of potassium ion channels in both male and female mice.

Conclusions:

• Sex differences significantly influence the physiological response to 72-hour hyperoxia exposure.
• Female mice display heightened vulnerability to hyperoxia, evidenced by increased mortality and distinct cardiac alterations.
• Hyperoxia impacts cardiac electrophysiology and left ventricular function in a sex-dependent manner.