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Induction and Characterization of Pulmonary Hypertension in Mice using the Hypoxia/SU5416 Model
Published on: June 3, 2020
Chronic intermittent hypoxia increases left ventricular contractility in C57BL/6J mice
Jahan Naghshin1, Kenneth R McGaffin, William G Witham
1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|July 11, 2009
Summary
Intermittent hypoxia (IH) unexpectedly increased left ventricular (LV) contractility in mice, independent of hypertrophy. Beta-adrenergic pathways partially mediated this enhanced cardiac function, contrary to initial hypotheses.
Area of Science:
- Cardiology
- Physiology
- Sleep Medicine
Background:
- Obstructive sleep apnea (OSA) is linked to cardiovascular pathology.
- Intermittent hypoxia (IH), a hallmark of OSA, is suspected to impair cardiac function.
- Previous studies in rats suggested IH reduces left ventricular (LV) ejection fraction.
Purpose of the Study:
- To investigate the impact of IH on LV contractility in C57BL/6J mice.
- To determine if beta-adrenergic receptor blockade modifies the cardiac response to IH.
- To challenge the prevailing hypothesis that IH causes cardiac dysfunction.
Main Methods:
- Adult male mice were exposed to 4 weeks of IH or intermittent air (IA) control.
- Cardiac function assessed via echocardiography and pressure-volume (PV) loop analysis.
- Effect of propranolol (beta-blocker) on IH response evaluated.
Main Results:
- Contrary to expectations, IH exposure increased LV ejection fraction and contractility.
- No changes observed in contractile proteins, atrial natriuretic peptide, or heart weight.
- Elevated cAMP levels and attenuated IH-induced contractility with propranolol.
Conclusions:
- IH exposure for 4 weeks enhances LV contractility in C57BL/6J mice.
- This effect is independent of ventricular hypertrophy.
- Cardiac beta-adrenergic pathways play a partial role in mediating IH-induced contractility increase.
