Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA.
Cell Biology, Microbiology and Molecular Biology, College of Arts and Sciences, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA.
Cells. 2023 May 24;12(11):1457. doi: 10.3390/cells12111457.
Mechanical ventilation often results in hyperoxia, a condition characterized by excess SpO levels (>96%). Hyperoxia results in changes in the physiological parameters, severe cardiac remodeling, arrhythmia development, and alteration of cardiac ion channels, all of which can point toward a gradual increase in the risk of developing cardiovascular disease (CVD). This study extends the analysis of our prior work in young Akita mice, which demonstrated that exposure to hyperoxia worsens cardiac outcomes in a type 1 diabetic murine model as compared to wild-type (WT) mice. Age is an independent risk factor, and when present with a major comorbidity, such as type 1 diabetes (T1D), it can further exacerbate cardiac outcomes. Thus, this research subjected aged T1D Akita mice to clinical hyperoxia and analyzed the cardiac outcomes. Overall, aged Akita mice (60 to 68 weeks) had preexisting cardiac challenges compared to young Akita mice. Aged mice were overweight, had an increased cardiac cross-sectional area, and showed prolonged QTc and JT intervals, which are proposed as major risk factors for CVD like intraventricular arrhythmias. Additionally, exposure to hyperoxia resulted in severe cardiac remodeling and a decrease in Kv 4.2 and KChIP2 cardiac potassium channels in these rodents. Based on sex-specific differences, aged male Akita mice had a higher risk of poor cardiac outcomes than aged females. Aged male Akita mice had prolonged RR, QTc, and JT intervals even at baseline normoxic exposure. Moreover, they were not protected against hyperoxic stress through adaptive cardiac hypertrophy, which, at least to some extent, is due to reduced cardiac androgen receptors. This study in aged Akita mice aims to draw attention to the clinically important yet understudied subject of the effect of hyperoxia on cardiac parameters in the presence of preexisting comorbidities. The findings would help revise the provision of care for older T1D patients admitted to ICUs.
机械通气常常导致高氧血症，其特征是 SpO 水平过高（>96%）。高氧血症会导致生理参数改变、严重的心脏重构、心律失常的发展以及心脏离子通道的改变，所有这些都可能导致心血管疾病（CVD）风险逐渐增加。本研究扩展了我们之前在年轻 Akita 小鼠中的研究分析，该研究表明，与野生型（WT）小鼠相比，高氧暴露会使 1 型糖尿病小鼠模型的心脏结局恶化。年龄是一个独立的危险因素，当与 1 型糖尿病（T1D）等主要合并症同时存在时，它会进一步恶化心脏结局。因此，这项研究使老年 T1D Akita 小鼠暴露于临床高氧环境中，并分析了心脏结局。总的来说，与年轻的 Akita 小鼠相比，老年 Akita 小鼠（60 至 68 周龄）已经存在心脏挑战。老年小鼠超重，心脏横截面积增加，QTc 和 JT 间期延长，这些被认为是 CVD（如室内心律失常）的主要危险因素。此外，高氧暴露导致这些啮齿动物的严重心脏重构和 Kv 4.2 和 KChIP2 心脏钾通道减少。基于性别特异性差异，老年雄性 Akita 小鼠的心脏不良结局风险高于老年雌性。即使在基础正常氧暴露下，老年雄性 Akita 小鼠的 RR、QTc 和 JT 间期也延长。此外，它们不能通过适应性心脏肥大来防止高氧应激，至少在某种程度上，这是由于心脏雄激素受体减少所致。这项在老年 Akita 小鼠中的研究旨在引起人们对临床重要但研究不足的高氧对存在预先存在的合并症的心脏参数的影响的关注。这些发现将有助于修订对 ICU 收治的老年 T1D 患者的护理。
