title: Chronic intermittent hypoxia exposure improves left ventricular contractility in transgenic mice with heart failure.
abstract: We previously reported the unexpected finding that 4 wk 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 present study was to assess the impact of 4 wk of 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 (wild type) and transgenic mice with cardiac overexpression of tumor necrosis factor α (TNF-αTG) at 10-12 wk of age were exposed to 4 wk of IH (nadir inspired oxygen 5-6% at 60 cycles/h for 12 h 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 were 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 atrial natriuretic peptide and brain natriuretic peptide compared with wild-type mice. When wild-type FVB mice were exposed to IH, they exhibited increases in arterial pressure and dP/dt(max), 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 4 wk 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.
authors: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors: Jahan
authors: J
authors: Naghshin
authors: Rosa H
authors: RH
authors: Rodriguez
authors: Eric M
authors: EM
authors: Davis
authors: Lia C
authors: LC
authors: Romano
authors: Kenneth R
authors: KR
authors: McGaffin
authors: Christopher P
authors: CP
authors: O'Donnell
mesh_terms: D000818:Animals; D002908:Chronic Disease; D006333:Heart Failure / Q000235:genetics* / Q000503:physiopathology*; D000860:Hypoxia / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000502:physiology*; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha