title: Transition from acute to chronic hypercapnia in patients with periodic breathing: predictions from a computer model.
abstract: Acute hypercapnia may develop during periodic breathing from an imbalance between abnormal ventilatory patterns during apnea and/or hypopnea and compensatory ventilatory response in the interevent periods. However, transition of this acute hypercapnia into chronic sustained hypercapnia during wakefulness remains unexplained. We hypothesized that respiratory-renal interactions would play a critical role in this transition. Because this transition cannot be readily addressed clinically, we modified a previously published model of whole-body CO2 kinetics by adding respiratory control and renal bicarbonate kinetics. We enforced a pattern of 8 h of periodic breathing (sleep) and 16 h of regular ventilation (wakefulness) repeated for 20 days. Interventions included varying the initial awake respiratory CO2 response and varying the rate of renal bicarbonate excretion within the physiological range. The results showed that acute hypercapnia during periodic breathing could transition into chronic sustained hypercapnia during wakefulness. Although acute hypercapnia could be attributed to periodic breathing alone, transition from acute to chronic hypercapnia required either slowing of renal bicarbonate kinetics, reduction of ventilatory CO2 responsiveness, or both. Thus the model showed that the interaction between the time constant for bicarbonate excretion and respiratory control results in both failure of bicarbonate concentration to fully normalize before the next period of sleep and persistence of hypercapnia through blunting of ventilatory drive. These respiratory-renal interactions create a cumulative effect over subsequent periods of sleep that eventually results in a self-perpetuating state of chronic hypercapnia.
authors.affiliation: Divisions of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine/Bellevue Medical Center, New York, NY 10016, USA. robert.norman@med.nyu.edu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Norman
authors.forename: Roberta M
authors.initials: RM
authors.lastname: Goldring
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Clain
authors.forename: Beno W
authors.initials: BW
authors.lastname: Oppenheimer
authors.forename: Alan N
authors.initials: AN
authors.lastname: Charney
authors.forename: David M
authors.initials: DM
authors.lastname: Rapoport
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Berger
mesh_terms: D000208:Acute Disease; D001049:Apnea / Q000097:blood / Q000503:physiopathology*; D001639:Bicarbonates / Q000652:urine; D002245:Carbon Dioxide / Q000097:blood; D002908:Chronic Disease; D003198:Computer Simulation; D006801:Humans; D006935:Hypercapnia / Q000097:blood / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology; D008433:Mathematics; D008954:Models, Biological; D010507:Periodicity; D012123:Pulmonary Ventilation / Q000502:physiology; D012119:Respiration; D012137:Respiratory System / Q000503:physiopathology; D013997:Time Factors; D014851:Wakefulness / Q000502:physiology
chemical_list: D001639:Bicarbonates; D002245:Carbon Dioxide