We previously reported the unexpected finding that four weeks of exposure to intermittent hypoxia (IH), which simulates the hypoxic stress of obstructive sleep apnea, improved LV cardiac function in healthy lean C57BL/6J mice. The purpose of the current study was to assess the impact of four weeks IH on cardiac function in a transgenic murine model that exhibits a natural history of heart failure. We hypothesized that IH exposure would exacerbate cardiac decompensation in heart failure. Adult male FVB (wildtype) and transgenic mice with cardiac over expression of tumor necrosis factor alpha (TNF-αTG) at 10-12 weeks of age were exposed to four weeks of IH (nadir inspired oxygen 5-6% at 60 cycles hr-1 for 12 hr during light period) or intermittent air (IA) as control. Cardiac function was assessed by echocardiography and pressure-volume loop analyses and mRNA and protein expression was performed on ventricular homogenates. TNF-αTG mice exposed to IA exhibited impaired LV contractility and increased LV dilation associated with markedly elevated cardiac expression of ANP and BNP compared to wildtype mice. When wildtype FVB mice were exposed to IH they exhibited increases in arterial pressure and dP/dtmax LV contractility, consistent with our previous report in C57BL/6J mice. Surprisingly, we found that TNF-αTG mice exposed to IH showed a reduction in end-diastolic volume (38.7 ± 3.8 to 22.2 ± 2.1 uL; p < 0.01) and an increase in ejection fraction (29.4 ± 2.5 to 41.9 ± 3.1 %; p < 0.05). In contrast to our previous study in C56Bl/6J mice, neither FVB nor TNF-αTG mice exhibited an upregulation in β-adrenergic expression or cAMP in response to IH exposure. We conclude that four weeks of exposure to IH in mice induces adaptive responses that improve cardiac function in not only healthy animals, but also in animals with underlying heart failure.
- blood pressure
- heart failure
- intermittent hypoxia
- Copyright © 2012, Journal of Applied Physiology