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Influence of cerebral blood flow on breathing stability

Departments of ¹Medicine, ²Population Health Sciences, and ³Orthopedics and Rehabilitation, University of Wisconsin; and ⁴The Middleton Memorial Veterans Hospital, Genetic Research, Education and Clinic Center, Madison, Wisconsin

Submitted 16 July 2008 ; accepted in final form 30 December 2008

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 Pa_CO2 would narrow the difference between the eupneic Pa_CO2 and the apneic threshold Pa_CO2 (Pa_CO2), 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 Pa_CO2 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.

Pa_CO2; apnea

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