title: Influence of cerebral blood flow on breathing stability.
abstract: Our previous work showed a diminished cerebral blood flow (CBF) response to changes in Pa(CO(2)) 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 Pco(2) 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(CO(2)) would narrow the difference between the eupneic Pa(CO(2)) and the apneic threshold Pa(CO(2)) (DeltaPa(CO(2))), known as the CO(2) 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 CO(2) by approximately 25% below control. The CO(2) 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(CO(2)) until apnea occurred. results: Indo significantly reduced the CO(2) 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 x min(-1) x 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.
authors.affiliation: Departments of Medicin, University of Wisconsin, Madison, Wisconsin 53705, USA. axie@facstaff.wisc.edu
authors.forename: Ailiang
authors.initials: A
authors.lastname: Xie
authors.forename: James B
authors.initials: JB
authors.lastname: Skatrud
authors.forename: Steven R
authors.initials: SR
authors.lastname: Barczi
authors.forename: Kevin
authors.initials: K
authors.lastname: Reichmuth
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Morgan
authors.forename: Sara
authors.initials: S
authors.lastname: Mont
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Dempsey
mesh_terms: D000293:Adolescent; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D002245:Carbon Dioxide / Q000008:administration & dosage; D002317:Cardiovascular Agents / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D006935:Hypercapnia; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology*; D012891:Sleep Apnea Syndromes / Q000139:chemically induced / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D002317:Cardiovascular Agents; D002245:Carbon Dioxide; D007213:Indomethacin