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Impact of age and sex on hyperoxia-induced cardiovascular pathophysiology
Mechanisms of Ageing and Development ( IF 5.3 ) Pub Date : 2022-09-06 , DOI: 10.1016/j.mad.2022.111727
Riddhi Vichare 1 , Faizan Saleem 1 , Hussein Mansour 1 , Katarina Bojkovic 1 , Feng Cheng 1 , Manas Biswal 2 , Siva Kumar Panguluri 3
Affiliation  

Hyperoxia is characterized by pronounced inflammatory responses, pulmonary cell apoptosis, and adverse cardiac remodeling due to an excess supply of oxygen. Hyperoxic episodes are frequent in mechanically ventilated patients and are associated with in-hospital mortality. This study extends the analysis of prior published research by our group as it investigates the influence of age in male and female rodents exposed to hyperoxic conditions. Age is an independent cardiovascular risk factor, often compounded by variables like obesity, diabetes, and a decline in sex hormones and their receptors. This study simulates clinical hyperoxia by subjecting rodents to > 90 % of oxygen for 72 h and compares the changes in cardiac structural and functional parameters with those exposed to normal air. While in both sexes conduction abnormalities with ageing were discernible, aged females owing to their inherent higher baseline QTc, were at a higher risk of developing arrhythmias as compared to age-matched males. Quantitative real-time RT-PCR and western blot analysis reflected altered expression of cardiac potassium channels, resulting in conduction abnormalities in aged female rodents. Unaffected by age and sex, hyperoxia-treated mice had altered body composition, as evidenced by a considerable reduction in body weight. Interestingly, compensatory hypertrophy observed as a protective mechanism in young males was absent in aged males, whereas protection of hearts from hyperoxia-induced cardiac hypertrophy was absent in aged female mice, both of which may be at least in part due to a reduction in sex steroid receptors and the systemic steroid levels. Finally, statistical analysis revealed that hyperoxia had the greatest impact on most of the cardiac parameters, followed by age and then sex. This data established an imperative finding that can change the provision of care for aged individuals admitted to ICU by elucidating the impact of intrinsic aging on hyperoxia-induced cardiac remodeling.



中文翻译:


年龄和性别对高氧诱导的心血管病理生理学的影响



高氧症的特点是明显的炎症反应、肺细胞凋亡以及由于氧气供应过多而导致的不良心脏重塑。高氧发作在机械通气患者中很常见,并且与院内死亡率相关。这项研究扩展了我们小组之前发表的研究的分析,因为它调查了年龄对暴露于高氧条件的雄性和雌性啮齿动物的影响。年龄是一个独立的心血管危险因素,通常与肥胖、糖尿病和性激素及其受体下降等因素相结合。这项研究通过让啮齿类动物接受 > 90% 的氧气 72 小时来模拟临床高氧症,并将心脏结构和功能参数的变化与暴露于正常空气的情况进行比较。虽然两性随着年龄的增长都会出现传导异常,但老年女性由于其固有的较高基线 QTc,与年龄匹配的男性相比,发生心律失常的风险更高。定量实时 RT-PCR 和蛋白质印迹分析反映了心脏钾通道表达的改变,导致老年雌性啮齿动物的传导异常。不受年龄和性别影响,高氧治疗小鼠的身体成分发生了改变,体重大幅减轻就证明了这一点。有趣的是,在年轻雄性小鼠中观察到的作为保护机制的代偿性肥大在老年雄性小鼠中不存在,而在老年雌性小鼠中不存在对心脏免受高氧诱导的心脏肥大的保护,这两者可能至少部分归因于性别的减少类固醇受体和全身类固醇水平。 最后,统计分析显示,高氧对大多数心脏参数的影响最大,其次是年龄,然后是性别。该数据确立了一项迫切的发现,可以通过阐明内在衰老对高氧诱导的心脏重塑的影响,改变对入住 ICU 的老年人的护理服务。

更新日期:2022-09-09
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