Etiopathogenetic Mechanisms of Pulmonary Hypertension in Sleep-Related Breathing Disorders

Abstract

Obstructive sleep apnea syndrome is a common disorder with significant health consequences and is on the rise in consonance with the obesity pandemic. In view of the association between sleep-disordered breathing and pulmonary hypertension as depicted by multiple studies, current clinical practice guidelines categorize obstructive sleep apnea as a risk factor for pulmonary hypertension and recommend an assessment for sleep disordered breathing in evaluating patients with pulmonary hypertension. The dysregulatory mechanisms associated with hypoxemic episodes observed in sleep related breathing disorders contribute to the onset of pulmonary hypertension and identification of these potentially treatable factors might help in the reduction of overall cardiovascular mortality.

Obstructive sleep apnea in children: a critical update

“…However, it is unclear whether pulmonary hypertension will develop only in the severest cases, such that increased recognition and awareness of sleep disordered breathing in children would lead to a reduced likelihood of long-standing disease and concurrent pulmonary hypertension, or whether the current techniques for noninvasive assessment of the pulmonary circulation in children are insufficiently sensitive to detect much milder involvement of the pulmonary vasculature. Furthermore, it is also unclear whether chronic mild intermittent hypoxia may result in lesser recruitment of the pulmonary vascular network than following exposures to sustained hypoxia of similar duration 47,48. This issue merits further research, particularly considering that the occurrence of intermittent hypoxia and mobilization of the lung capillary endothelial network may promote long-term susceptibility to pulmonary hypertension even during adulthood 49.…”

Inflammatory Response Mechanisms Exacerbating Hypoxemia in Coexistent Pulmonary Fibrosis and Sleep Apnea

“…Free oxygen radicals released from polymorphonuclear leukocytes during hypoxemic episodes further propagate this vascular oxidative stress. Occurrence of episodic hypoxemia from nocturnal desaturations also activates carotid chemoreceptors, thereby triggering arteriolar vasoconstriction and systemic catecholamine secretion [ 18 ].…”

“…Often, these chronic conditions which are also present in patients with OSA contribute to the amplification of hypoxemia by the release of chemoattractants, hormones, and specific inflammatory mediators which alter the fibrotic pathway within the pulmonary parenchyma. The coexistence of moderate to severe OSA results in episodes of hypoxic stress which directly modulates expression of cell adhesion molecules responsible for mediating leukocyte adhesion to endothelial cells [ 18 ]. Repetitive hypoxemia in OSA patients with fibrotic lung diseases ultimately leads to significantly increased levels of these cell adhesion molecules.…”

“…(2) Obesity, often associated with dysregulation of metabolic pathways, is frequently present in patients with OSA, IPF, or both. Adipocytes produce increased levels of leptin, a hormone responsible for regulating appetite suppression but which may induce platelet regulation and occurs in OSA at much higher levels [ 18 ]. Effective treatment of OSA has been demonstrated to reduce the acumulation of visceral fat and predisposition to weight gain [ 21 – 23 ].…”

Efectos inducidos por la hipoxia crónica intermitente en rata y cobaya como modelos animales de la apnea obstructiva del sueño

“…Además de las alteraciones cardiovasculares la apnea del sueño conlleva la aparición de otras co-morbilidades en pacientes con dicho trastorno del sueño. Una de las patologías asociadas, aunque no exenta de controversia, es la aparición de hipertensión pulmonar 320 . La HCS produce hipertensión pulmonar pero los efectos de la HCI están menos claros.…”