Mitochondria-targeted protection against cardiac dysfunction in an embryonic model of obstructive sleep apnoea during development

Obstructive sleep apnoea (OSA) is a chronic disorder caused by the dynamic collapse of the upper airway during sleep. Around 20% of pregnant women with obesity have obstructive sleep apnoea (OSA). Besides obesity, some physiological changes include upper airway edema and elevated chief pregnancy hormones leading to upper airway pressures and OSA during pregnancy. OSA is characterized by episodes of apnoeas associated with cyclical reduction of blood oxygenation levels and intermittent hypoxemia (IH). Data from animal studies support mechanistic links between IH and oxidative stress through increased production of reactive oxygen species leading to myocardial infarction and cardiovascular disease. However, the effect of IH on fetal cardiac health during pregnancy is completely unknown. In this study, the effects of IH on growth and cardiac function were investigated in the chicken embryo model, which permits isolation of the direct effects of IH incubation on the embryo during development, independent of effects on the mother and/or the placenta. Therefore, the aim of this thesis was to determine the impact of IH during development on somatic growth and cardiovascular function and to investigate the effect of the mitochondria-targeted antioxidant MitoQ against cardiovascular dysfunction programmed by IH in the chicken embryo. Relative to embryos incubated under normoxic conditions (controls), embryos incubated under IH conditions showed asymmetric growth restriction with left ventricular hypertrophy. Compared to controls, IH embryos displayed significant cardiac systolic and diastolic dysfunction, cardiac sympathetic dominance and a blunted coronary flow response to adenosine. Treatment of IH embryos with MitoQ protected against fetal growth restriction, cardiac systolic and diastolic dysfunction, cardiac sympathetic dominance and the reduced coronary blood flow response to adenosine. In conclusion, the data support that MitoQ treatment protects against the adverse effects of IH on growth and cardiovascular dysfunction in early development. Therefore, MitoQ may be useful therapy to protect the fetus in human pregnancy complicated by IH resulting from maternal OSA.