Chronic intermittent hypercapnic hypoxia increases pulmonary arterial pressure and haematocrit in rats

Abstract

Chronic intermittent hypercapnic hypoxia increases pulmonary arterial pressure and haematocrit in rats. M. McGuire, A. Bradford. #ERS Journals Ltd 2001. ABSTRACT: Sleep-disordered breathing is associated with pulmonary hypertension and raised haematocrit. The multiple episodes of apnoea in this condition cause chronic intermittent hypoxia and hypercapnia but the effects of such blood gas changes on pulmonary pressure or haematocrit are unknown. The present investigation tests the hypothesis that chronic intermittent hypercapnic hypoxia causes increased pulmonary arterial pressure and erythropoiesis.Rats were treated with alternating periods of normoxia and hypercapnic hypoxia every 30 s for 8 h per day for 5 days per week for 5 weeks, as a model of the intermittent blood gas changes which occur in sleep-disordered breathing in humans. Haematocrit, red blood cell count and haemoglobin concentration were measured each week and systemic and pulmonary arterial blood pressure and heart weight were measured after 5 weeks.In relation to control, chronic intermittent hypercapnic hypoxia caused a significant increase in systemic (104.3¡4.7 mmHg versus 121.0¡10.4 mmHg) and pulmonary arterial pressure (20.7¡6.8 mmHg versus 31.3¡7.2 mmHg), right ventricular weight (expressed as ratios) and haematocrit (45.2¡1.0% versus 51.5¡1.5%).It is concluded that the pulmonary hypertension and elevated haematocrit associated with sleep-disordered breathing is caused by chronic intermittent hypercapnic hypoxia. Sleep disordered breathing affects 1-4% of adults [1]. It is associated with multiple episodes of hypoxia and hypercapnia due to hypopnoea or apnoea, which are either caused by intermittent collapse of the upper airway (UA), termed obstructive sleep apnoea (OSA; the most common form of sleep disordered breathing), or a reduced drive to breath, termed central apnoea [2]. The condition is associated with a number of cardiovascular changes, including increased pulmonary and systemic arterial blood pressure, right ventricular hypertrophy, cardiac arrhythmias and increased haematocrit. Diurnal pulmonary hypertension is present in 17-42% of OSA patients [3][4][5][6][7] and represents a serious threat to long-term outcome in these patients [8]. The cause of pulmonary hypertension in these patients is unknown. During an apnoeic event, pulmonary arterial pressure is acutely increased [9], presumably due to hypoxic pulmonary vasoconstriction, so that repetitive episodes of increased pressure may ultimately give rise to daytime pulmonary hypertension [10]. In support of this, it has recently been shown that chronic intermittent hypocapnic hypoxia in rats causes right ventricular hypertrophy, suggesting that pulmonary arterial pressure is increased [11]. However, apnoeas are accompanied by hypercapnia as well as hypoxia [12], but the effects of this combination of chronic intermittent blood gas changes on pulmonary arterial pressure are unknown. It is known that chronic continuous hypercapnia protects against the effects of continuous hypoxia...

Pulmonary haemodynamics in patients with OSAS or an overlap syndrome

“…How can the discrepancy between clinical observations and the results of recent animal studied showing development of PH after exposure to short repetitive episodes of hypoxia similar to those observed in patients with OSAS [11,12] be explained? Early studies on animal models demonstrated that short amounts of exposure, lasting only few hours per day, to hypoxia may imitate nocturnal desaturation in COPD patients which has also resulted in the development of permanent PH [25,26].…”

“…Recently, McGuire and Bradford [11] demonstrated the development of pulmonary hypertension in rats exposed to short bursts of hypoxia and hypercapnia imitating apnoeic episodes. Fagan [12] studied the effect of intermittent hypoxia in mice and also concluded that mice develop pulmonary hypertension in response to the repetitive hypoxia-reoxygenation.…”

Sleep apnoea syndrome in 2011: current concepts and future directions

“…Many biological and pathophysiological changes have been linked to intermittent hypoxia, i.e. alteration in baroreflex activity [91], increase in pulmonary arterial pressure and haematocrit [92], changes in heart structure and function [93], and an alteration in endothelial dependent vasodilation in cerebral and muscular arteries [94]. In addition, an increased response to endothelin (ET)-1 was also demonstrated [89], presumably almost exclusively mediated by ET-A receptors [95].…”

Intermittent hypoxia and sleep-disordered breathing: current concepts and perspectives

“…A variety of biological and pathophysiological changes have also been demonstrated, i.e. altered baroreflex activity [56], increased pulmonary arterial pressure and haematocrit [57], changes in heart structure and function [58], altered endothelium-dependent vasodilation in cerebral and muscular arteries [59], and an increased response to endothelin (ET)-1 [54], presumably mediated almost exclusively by ETA receptors [60]. During IH, both blood pressure (BP) and myocardial changes might be critically dependent upon ET-1.…”