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

Abstract

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 beta-adrenergic receptors modified the response to hypoxia. Adult male 9- to 10-wk-old mice were exposed to 4 wk of IH (nadir inspired O(2) 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 beta-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 beta-adrenergic pathways.

S-nitrosylation: integrator of cardiovascular performance and oxygen delivery

“…Signaling via the β 2 -adrenergic receptor (β 2 -AR) coordinates hypoxic adaptation across multiple organs, including the lungs (improved ventilation/perfusion matching) (38)(39)(40)(41), skeletal muscle (hypoxic vasodilation [HVD]) (41)(42)(43), and heart (augmenting contractility) (44). Through its influence on β 2 -AR signaling, S-nitrosylation may regulate hypoxic responses.…”

Impact of the Chronic Repetitive Leg Ischemia on Left Ventricular Function and Severity of Coronary Atherosclerosis in Patients with Acute Coronary Syndrome

“…It is probable that moderate hemodynamic stress reduces the levels of inflammatory markers and increases flow-mediated vasodilation by ischemic preconditioning. In patients with CAD, it has been shown that increased walking ability is associated with improved LVEF [14,15] . The recently published study of Bøtker et al [16] has provided a promising result, showing that RIPC before hospital admission in the setting of ACS protects LV function.…”

The polymorphic and contradictory aspects of intermittent hypoxia

“…The possible role of ROS has been explained as depending on concentration, such that ROS emerge as cardioprotective at low levels but detrimental at high levels (36,165). In support of such assumptions, Naghshin and colleagues (118,119) reported that chronic IH treatment is sufficient to improve cardiac function in healthy mice and transgenic mice with underlying heart failure.…”