Cardiovascular Risks Associated with Gender and Aging.

The aging and elderly population are particularly susceptible to cardiovascular disease. Age is an independent risk factor for cardiovascular disease (CVD) in adults, but these risks are compounded by additional factors, including frailty, obesity, and diabetes. These factors are known to complicate and enhance cardiac risk factors that are associated with the onset of advanced age. Sex is another potential risk factor in aging adults, given that older females are reported to be at a greater risk for CVD than age-matched men. However, in both men and women, the risks associated with CVD increase with age, and these correspond to an overall decline in sex hormones, primarily of estrogen and testosterone. Despite this, hormone replacement therapies are largely shown to not improve outcomes in older patients and may also increase the risks of cardiac events in older adults. This review discusses current findings regarding the impacts of age and gender on heart disease.

Impact of hyperoxia on cardiac pathophysiology.

Mechanical ventilation with high oxygen therapy (hyperoxia) is widely implemented in critical care and ICU settings. Although supplemental oxygen is beneficial to treat hypoxia, its use is also associated with poor outcomes and high mortality in patients. Lung injury due to hyperoxia exposure has been well-documented in patients, including in adults and neonates. Thus, lung injury due to hyperoxia has been extensively researched in both preclinical and clinical studies. However, hyperoxia has also been shown to be associated with hemodynamic changes in patients in ICU, including reductions in heart rate, stroke volume, and cardiac output. In addition, certain experimental studies report that hyperoxia exposure in neonates results in cardiac dysfunction in later adult life. Despite this, until recently, the impact of hyperoxia within the heart has not been well studied, or reported, specifically in adult experimental models. To close this significant gap, our lab has sought to clarify hyperoxia-induced cardiac pathophysiology in adult murine models. This review discusses the current findings regarding the cardiovascular impact of hyperoxia exposure.

Sex differences in murine cardiac pathophysiology with hyperoxia exposure.

Hyperoxia (>90% oxygen) is commonly implemented in mechanically ventilated patients. Reports suggest that hyperoxia is directly associated with in-hospital mortality in ventilated patients. Certain studies also show that mortality in women undergoing mechanical ventilation is significantly higher than that in men. Additionally, females are predisposed to certain cardiac electrophysiological risks, including QTc prolongation. In this study, we assessed the impact of hyperoxia in male and female mice (C57BL/6J) at age 8-10 weeks. On completion of either hyperoxia or normoxia exposures, physical, hemodynamic, biochemical, functional, electrophysiological, and molecular assessments were conducted. Hyperoxia-exposed mice lost a significant amount of body mass, compared with normoxia controls, in both sexes. However, while both genders developed brady-arrhythmia after hyperoxia exposure, female mice exhibited significantly reduced heart rates compared with males, with significantly elevated RR intervals. Additionally, 50% mortality was observed in females, whereas no mortality was reported in males. Furthermore, unlike in male mice, we observed no hypertrophy upon hyperoxia exposure in female mice. We reported that both hyperoxia-treated male and female mice exhibit significant hyperdynamic left ventricular ejection fraction, which is marked by % ejection fraction > 70 compared with the normoxia controls. We also noted significant reductions in stroke volume and cardiac output in both mice with hyperoxia. Surface ECG also demonstrated that hyperoxia exposure significantly augments RR, PR, QRS, QTc, and JT intervals in both sexes. Molecular analysis of left ventricular tissue demonstrated dysregulation of potassium ion channels in hyperoxia-treated males and females. In summary, we determined that sex differences are present with 72 hr hyperoxia exposure.