Cardiac Response to Chronic Intermittent Hypoxia with a Transition from Adaptation to Maladaptation:The Role of Hydrogen Peroxide

Abstract

Obstructive sleep apnea (OSA) is a highly prevalent respiratory disorder of sleep, and associated with chronic intermittent hypoxia (CIH). Experimental evidence indicates that CIH is a unique physiological state with potentially “adaptive” and “maladaptive” consequences for cardio-respiratory homeostasis. CIH is also a critical element accounting for most of cardiovascular complications of OSA. Cardiac response to CIH is time-dependent, showing a transition from cardiac compensative (such as hypertrophy) to decompensating changes (such as failure). CIH-provoked mild and transient oxidative stress can induce adaptation, but severe and persistent oxidative stress may provoke maladaptation. Hydrogen peroxide as one of major reactive oxygen species plays an important role in the transition of adaptive to maladaptive response to OSA-associated CIH. This may account for the fact that although oxidative stress has been recognized as a driver of cardiac disease progression, clinical interventions with antioxidants have had little or no impact on heart disease and progression. Here we focus on the role of hydrogen peroxide in CIH and OSA, trying to outline the potential of antioxidative therapy in preventing CIH-induced cardiac damage.

Protective effects of quercetin from oxidative/nitrosative stress under intermittent hypobaric hypoxia exposure in the rat’s heart

“…Exposure to IHH increases RONS generation in the myocardium, which appears to be the main cause of myocardial damage. RONS produced in excess in the myocardium cause cardiomyocyte injury, apoptosis, and cell necrosis (42). In this study, cardiac hypertrophy was observed after long-term exposure to IHH, as evidenced by the significant increase in the heart weight-to-body weight ratio.…”

Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment

“…The examples below indicate that hypoxia may cause profound physiological changes; in humans, hypoxia is known inter alia from obstructive sleep apnoea. Chronic intermittent hypoxia may cause cardiovascular deterioration in animals and humans that may be due to oxidative stress, systemic inflammation, sympathetic activation, decrease of bone marrow-derived endothelial progenitor cell mobilization, which decreases repair of endothelial injuries, systemic and pulmonary arterial hypertension, and heart failure (Dumitrascu et al 2013; Wang et al 2013b; Yin et al 2012, 2014). In the lungs, hypoxia can induce oxidative stress and inflammation that can cause bronchial vasoconstriction, pulmonary oedema, vascular remodelling and pulmonary hypertension (Araneda and Tuesta 2012).…”

Effect of age on the cardiovascular remodelling induced by chronic intermittent hypoxia as a murine model of sleep apnoea

“…34 The cardiovascular response to CIH depends on the severity, frequency and duration of IH exposure and generally progresses from adaptation to maladaptation. 5,[35][36][37] Moderate IH has been associated with a beneficial response at the cardiovascular level, 38 including a protective or ischaemic preconditioning effect, while severe CIH exacerbates injury. 35,39 Here, we studied a long-term severe pattern of IH simulating severe OSA.…”