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Obstructive sleep apnea (OSA) is associated with significant cardiovascular consequences, including pulmonary hypertension, yet little is known about its effects on pulmonary microvascular perfusion. To investigate effects of OSA on pulmonary microvascular perfusion, we clamped the tracheal cannulas of anesthetized, spontaneously breathing rats to simulate obstructive apnea. The clamp remained in place for 10 breaths before it was released to allow the animals to again breathe spontaneously. We repeated this protocol every 20 s until the rat experienced a total of five apneic episodes of 10 breaths each. We then infused into a femoral vein 10 8 fluorescent latex particles (4 µm diameter), which became trapped within the pulmonary microcirculation. We removed the lungs, allowed them to air-dry, and quantified the particle distributions in sections of the lungs using dispersion index (DI) analysis, a method we developed previously. The log of the DI (logDI) is a measure of perfusion maldistribution. Greater log(DI) values correspond to greater maldistribution. Apneic lungs had average logDI values of 1.28 (SD 0.24). Rats not subjected to apnea had average logDI values of 0.85 (SD 0.08) ( P ≤ 0.05). Rats that received latex particles 10 min or 24 h after apnea had average logDI values of 0.97 (SD 0.31) and 0.84  (SD 0.38), respectively (not significant). Our results demonstrate, for the first time, that a few apneic events produced significant, but temporary, perfusion maldistribution within the pulmonary microcirculation. Repeated nightly episodes of apnea over months and years may explain why human patients with OSA suffer from significantly greater cardiovascular disease than those without OSA.

Study objectiveObstructive sleep apnea is prevalent among people with asthma, but underlying mechanisms remain unknown. Inhaled corticosteroids may contribute. We tested the effects of orally inhaled fluticasone propionate (FP) on upper airway (UAW) during sleep and wakefulness.Study design16-week single-arm study.Participants18 (14 females, mean [ ± SD] age 26 ± 6 years) corticosteroid-naïve subjects with mild asthma (FEV1 89 ± 8% predicted).InterventionsHigh dose (1,760 mcg/day) inhaled FP.Measurements(1) UAW collapsibility (passive critical closing pressure [Pcrit]); (2) tongue strength (maximum isometric pressure-Pmax, in KPa) and endurance-time (in seconds) able to maintain 50% Pmax across 3 trials (Ttot)-at anterior and posterior locations; (3) fat fraction and volume around UAW, measured by magnetic resonance imaging in three subjects.ResultsPcrit overall improved (became more negative) (mean ± SE) (-8.2 ± 1.1 vs. -12.2 ± 2.2 cm H2O, p = 0.04); the response was dependent upon baseline characteristics, with older, male gender, and worse asthma control predicting Pcrit deterioration (less negative). Overall, Pmax increased (anterior p = 0.02; posterior p = 0.002), but Ttot generally subsided (anterior p = 0.0007; posterior p = 0.06), unrelated to Pcrit response. In subjects studied with MRI, fat fraction and volume increased by 20.6% and 15.4%, respectively, without Pcrit changes, while asthma control appeared improved.ConclusionsIn this study of young, predominantly female, otherwise healthy subjects with well-controlled asthma and stiff upper airways, 16-week high dose FP treatment elicited Pcrit changes which may be dependent upon baseline characteristics, and determined by synchronous and reciprocally counteracting local and lower airway effects. The long-term implications of these changes on sleep disordered breathing severity remain to be determined.

Asthma and obstructive sleep apnea (OSA) are highly prevalent chronic conditions, and both are associated with systemic hypertension. Additionally, asthma and OSA reciprocally interact, mutually exacerbating each other. In this study, we tested the effect of allergen-induced lower airway inflammation and concurrent chronic intermittent hypoxia (CIH) on systemic blood pressure (BP), pulmonary function, and proinflammatory cytokines, in a rat model. Brown Norway rats were exposed to 43 days of normoxia (NORM) or CIH, concurrent with weekly house dust mite (HDM) challenges. BP was measured 1 day after the last HDM challenge. On day 44, pulmonary function was tested, and blood for Th-2 and Th-1 cytokine levels was collected. HDM significantly increased mean (P = 0.002), systolic (P = 0.003), and diastolic (P = 0.004) BP compared with saline-challenged controls. Higher mean BP significantly correlated to increased total respiratory system resistance (R2 = 0.266, P = 0.002), driven by an association with parenchymal tissue dampening (R2 = 0.166, P = 0.016). HDM relative to saline-challenged controls increased the expression of serum IL-6 (P = 0.008), but no relationships of systemic BP with IL-6 or any other cytokines were found. CIH did not alter the allergen-induced responses on BP, although it tended to increase the expression of serum IL-6 (P = 0.06) and monocyte chemoattractant protein-1 (MCP-1, P = 0.09), regardless of HDM challenge. Chronic allergen-induced airway inflammation results in systemic hypertension that is correlated to the degree of distal airway obstruction induced by the allergen. These effects do not appear to be explained by the associated systemic inflammation. [ABSTRACT FROM AUTHOR]