Influence of cerebral blood flow on breathing stability

Xie A, Skatrud JB, Barczi SR, Reichmuth K, Morgan BJ, Mont S, Dempsey JA. Influence of cerebral blood flow on breathing stability. J Appl Physiol 106: 850-856, 2009. First published December 31, 2008; doi:10.1152/japplphysiol. 90914.2008.-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 (Delta 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 similar to 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.