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Erschienen in:
05.12.2017 | Original Article
Hyperoxia-induced cardiotoxicity and ventricular remodeling in type-II diabetes mice
Erschienen in: Heart and Vessels | Ausgabe 5/2018
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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.