Hyperoxia-induced cardiotoxicity and ventricular remodeling in type-II diabetes mice.
Hyperoxia-induced cardiotoxicity and ventricular remodeling in type-II diabetes mice.
复制标题
高氧诱导的 II 型糖尿病小鼠心脏毒性和心室重塑。
DOI：
10.1007/s00380-017-1100-6
复制
发表时间：
2018
影响因子：
1.5
通讯作者：
Panguluri,SivaKumar
中科院分区：
文献类型：
--
作者：
Rodgers,JenniferLeigh;Samal,Eva;Mohapatra,Subhra;Panguluri,SivaKumar
高氧，或补充氧气，经常用于ICU危重患者的临床环境。然而，最近的几项研究已经证明了这种治疗对重症监护患者的负面影响，包括肺和心脏损伤的发生率增加以及死亡率增加。本研究的目的是确定高氧治疗导致的2型糖尿病小鼠模型（db/db）中心律失常和电重构的易感性。为此，将db/db及其杂合子对照用高氧（> 90%氧气）或常氧（正常空气）处理72小时。在高氧或常氧处理后，立即对小鼠进行体表ECG。使用切除的左心室评估离子通道表达，包括Kv1.4、Kv1.5、Kv4.2和KChIP 2。同时测定血清心肌标志物，包括心肌肌钙蛋白I和乳酸脱氢酶。我们的结果表明，db/db小鼠对心律失常的敏感性增加。常氧处理db/db小鼠表现出心律失常的特征，包括QTc和JT延长以及QRS延长。与高氧处理的杂合对照小鼠相比，在高氧处理的db/db小鼠中也观察到QRS延长显著增加。Db/db小鼠也表现出离子通道失调，如在高氧条件下Kv1.5、Kv4.2和KChIP 2下调所示。从这些结果，我们得出结论：（1）糖尿病小鼠表现出不同的病理生理学，当与杂合子对照相比，无论是在正常氧和高氧条件。(2)糖尿病小鼠在正常空气条件下更容易发生心律失常;这种影响在高氧条件下加剧。(3)与杂合子对照组不同，糖尿病小鼠没有表现出高氧导致的心脏肥大。(4)在高氧条件下，db/db小鼠也观察到类似于其杂合对照的离子通道重塑。
Hyperoxia, or supplemental oxygen, is regularly used in the clinical setting for critically ill patients in ICU. However, several recent studies have demonstrated the negative impact of this treatment in patients in critical care, including increased rates of lung and cardiac injury, as well as increased mortality. The purpose of this study was to determine the predisposition for arrhythmias and electrical remodeling in a type 2 diabetic mouse model (db/db), as a result of hyperoxia treatment. For this, db/db and their heterozygous controls were treated with hyperoxia (> 90% oxygen) or normoxia (normal air) for 72-h. Immediately following hyperoxia or normoxia treatments, mice underwent surface ECG. Excised left ventricles were used to assess ion channel expression, including for Kv1.4, Kv1.5, Kv4.2, and KChIP2. Serum cardiac markers were also measured, including cardiac troponin I and lactate dehydrogenase. Our results showed that db/db mice have increased sensitivity to arrhythmia. Normoxia-treated db/db mice displayed features of arrhythmia, including QTc and JT prolongation, as well as QRS prolongation. A significant increase in QRS prolongation was also observed in hyperoxia-treated db/db mice, when compared to hyperoxia-treated heterozygous control mice. Db/db mice were also shown to exhibit ion channel dysregulation, as demonstrated by down-regulation in Kv1.5, Kv4.2, and KChIP2 under hyperoxia conditions. From these results, we conclude that: (1) diabetic mice showed distinct pathophysiology, when compared to heterozygous controls, both in normoxia and hyperoxia conditions. (2) Diabetic mice were more susceptible to arrhythmia at normal air conditions; this effect was exacerbated at hyperoxia conditions. (3) Unlike in heterozygous controls, diabetic mice did not demonstrate cardiac hypertrophy as a result of hyperoxia. (4) Ion channel remodeling was also observed in db/db mice under hyperoxia condition similar to its heterozygous controls.