Influence of cerebral blood flow on breathing stability

Abstract

Our previous work showed a diminished cerebral blood flow (CBF) response to changes in Pa_{CO2 in congestive heart failure patients with central sleep apnea compared with those without apnea. Since the regulation of CBF serves to minimize oscillations in H⁺ and Pco2 at the site of the central chemoreceptors, it may play an important role in maintaining breathing stability. We hypothesized that an attenuated cerebrovascular reactivity to changes in PaCO2 would narrow the difference between the eupneic PaCO2 and the apneic threshold PaCO2 (ΔPaCO2), known as the CO2 reserve, thereby making the subjects more susceptible to apnea. Accordingly, in seven normal subjects, we used indomethacin (Indo; 100 mg by mouth) sufficient to reduce the CBF response to CO2 by ∼25% below control. The CO2 reserve was estimated during non-rapid eye movement (NREM) sleep. The apnea threshold was determined, both with and without Indo, in NREM sleep, in a random order using a ventilator in pressure support mode to gradually reduce PaCO2 until apnea occurred. results: Indo significantly reduced the CO2 reserve required to produce apnea from 6.3 ± 0.5 to 4.4 ± 0.7 mmHg ( P = 0.01) and increased the slope of the ventilation decrease in response to hypocapnic inhibition below eupnea (control vs. Indo: 1.06 ± 0.10 vs. 1.61 ± 0.27 l·min⁻¹·mmHg⁻¹, P < 0.05). We conclude that reductions in the normal cerebral vascular response to hypocapnia will increase the susceptibility to apneas and breathing instability during sleep.}