Background: Hyperoxia or clinical oxygen (O-2) therapy is known to result in increased oxidative burden. Therefore, understanding susceptibility to hyperoxia exposure is clinically important. Bone morphogenetic proteins (BMPs) 2 and 4 are involved in cardiac development and may influence responses to hyperoxia.Methods: Bmp2(+/-), Bmp4(+/-) and wild-type mice were exposed to hyperoxia (100% O-2) for 24 hrs. Electrocardiograms (ECG) were recorded before and during exposure by radio-telemetry.Results: At baseline, a significantly higher low frequency (LF) and total power (TP) heart rate variability (HRV) were found in Bmp2(+/-) mice only (p<0.05). Twenty-four hours hyperoxia-induced strain-independent reductions in heart rate, QTcB and ST-interval and increases in QRS, LF HRV and standard deviation of RR-intervals were observed. In Bmp4(+/-) mice only, increased PR-interval (PR-I) (24 hrs), P-wave duration (P-d; 18 and 21-24 hrs), PR-I minus P-d (PR-Pd; 24 hrs) and root of the mean squared differences of successive RR-intervals (24 hrs) were found during hyperoxia (p50.05).Discussion: Elevated baseline LF and TP HRV in Bmp2(+/-) mice suggests an altered autonomic nervous system regulation of cardiac function in these mice. However, this was not related to strain specific differences in responses to 24 hrs hyperoxia. During hyperoxia, Bmp4(+/-) mice were the most susceptible in terms of atrioventricular conduction changes and risk of atrial fibrillation, which may have important implications for patients treated with O-2 who also harbor Bmp4 mutations. This study demonstrates significant ECG and HRV responses to 24 hrs hyperoxia in mice, which highlights the need to further work on the genetic mechanisms associated with cardiac susceptibility to hyperoxia.

Protein synthesis through the PI3k‐Akt pathway is reduced in aged skeletal muscle, leading to a decrease in fiber size and number. Phytoecdysteroids, in particular 20‐hydroxyecdysone (20E), from the plant Ajuga turkestanica increases protein synthesis in C2C12 skeletal muscle cells and muscle strength in young rats. The objective of this study was to determine if an extract from A. turkestanica (ATE), enriched in phytoecdysteroids, affects muscle fiber size and PI3k‐Akt signaling in skeletal muscle of aged mice. Aged male C57BL/6 mice (20 mo) received ATE, 20E, or vehicle (CT) only for 28 days. H&E staining revealed 41% and 30% larger fiber cross‐sectional area (CSA) in the triceps brachii (p=0.014) and plantaris (p=0.018) muscles of 20E‐treated sedentary mice, respectively, compared to CT. ATE treatment resulted in larger, but non‐significant differences in CSA of the triceps brachii (26%; p=0.088) and plantaris (8%; p=0.497) muscles, compared to CT. Western blotting performed on gastrocnemius muscles showed a significant increase in phosphorylation of Akt in 20E‐treated sedentary aged skeletal muscle, compared to CT (p=0.013). In conclusion, these data suggest that 20E rescues the loss of muscle fiber size and increases activation of the PI3k‐Akt pathway in sedentary aged skeletal muscle. Supported in part by a USDA Kannapolis Scholars Fellowship.