Obstructive apnea causes microvascular perfusion maldistribution in the lungs of rats

Abstract

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 108 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.