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This Article Full Text Full Text (PDF) All Versions of this Article: 107/3/787    most recent 91256.2008v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Naghshin, J. Articles by O'Donnell, C. P. PubMed PubMed Citation Articles by Naghshin, J. Articles by O'Donnell, C. P.

Chronic intermittent hypoxia increases left ventricular contractility in C57BL/6J mice

¹Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, ²Cardiovascular Institute, and ³Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania

Submitted 19 September 2008 ; accepted in final form 6 July 2009

Intermittent hypoxia (IH) commonly occurs in patients with obstructive sleep apnea and can cause a wide range of pathology, including reduced left ventricular (LV) ejection fraction in rats as determined by echocardiography, in rodent models. We utilized echocardiography and pressure-volume (PV) loop analyses to determine whether LV contractility was decreased in inbred C57BL/6J mice exposed to IH and whether blockade of β-adrenergic receptors modified the response to hypoxia. Adult male 9- to 10-wk-old mice were exposed to 4 wk of IH (nadir inspired O₂ 5–6% at 60 cycles/h for 12 h during the light period) or intermittent air (IA) as control. A second group of animals were exposed to the same regimen of IH or IA, but in the presence of nonspecific β-blockade with propranolol. Cardiac function was assessed by echocardiography and PV loop analyses, and mRNA and protein expression in ventricular homogenates was determined. Contrary to our expectations, we found with PV loop analyses that LV ejection fraction (63.4 ± 3.5 vs. 50.5 ± 2.6%, P = 0.015) and other measures of LV contractility were increased in IH-exposed animals compared with IA controls. There were no changes in contractile proteins, atrial natriuretic peptide levels, LV posterior wall thickness, or heart weight with IH exposure. However, cAMP levels were elevated after IH, and propranolol administration attenuated the increase in LV contractility induced by IH exposure. We conclude that, contrary to our hypothesis, 4 wk of IH exposure in C57BL/6J mice causes an increase in LV contractility that occurs independent of ventricular hypertrophy and is, in part, mediated by activation of cardiac β-adrenergic pathways.

blood pressure; cAMP; echocardiography; ejection fraction; pressure-volume loop; propranolol; sympathetic activation