title: Central contribution to hypoventilation during severe inspiratory resistive loads.
abstract: OBJECTIVE
  Recent observations suggest that central hypoventilation with slowing of respiratory frequency contributes to hypoventilation during severe inspiratory resistive loads. We carried out a study to further characterize this bradypneic response.
  
  
  METHODS
  Prospective, controlled laboratory study.
  
  
  METHODS
  Basic science laboratory of a university hospital.
  
  
  METHODS
  Anesthetized adult cats (loading experiment n = 7, nonloaded hypercapnic controls n = 11).
  
  
  METHODS
  Experimental inspiratory loads increased transdiaphragmatic pressure to 75% of the maximum for each animal. Respiratory responses were observed at midrun or moderate conditions of respiratory insufficiency (defined as PaCO2 > or = 60 torr [> or = 8.0 kPa]) and failure (PaCO2 > or = 80 torr [> or = 10.6 kPa]). Nonloaded hypercapnic controls were studied with similar durations of exposure to CO2 in the same CO2 range.
  
  
  METHODS
  Inspiratory airflow, tidal volume, respiratory frequency, airway pressure, transdiaphragmatic pressure, transdiaphragmatic pressure response to phrenic nerve electrical stimulation, blood gas analysis. Severe inspiratory loads were applied to anesthetized adult cats to determine whether bradypnea could be observed in an anesthesized model that eliminated conscious responses. Experiments were performed in hyperoxic conditions to determine whether bradypnea develops in the absence of hypoxia. An additional control group was studied under hypercapnic conditions without loading to determine whether comparable hypercapnia is a sufficient stimulus to elicit bradypnea.
  
  
  RESULTS
  From midrun until failure, minute ventilation decreased by 16% in loaded animals. Hypoventilation was associated with a decrease in respiratory frequency from 40.1 to 29.9 breaths/min, whereas tidal volume, spontaneous transdiaphragmatic pressure, and transdiaphragmatic pressure response to phrenic nerve electrical stimulation remained unchanged. Control animals had no significant reduction in ventilation or respiratory frequency over similar levels and durations of hypercapnia.
  
  
  CONCLUSIONS
  Centrally mediated bradypnea contributed to hypoventilation in respiratory failure associated with inspiratory loading. Bradypnea preceded evidence of muscle fatigue. This change in respiratory cycle timing occurred under anesthesia, and thus, did not depend on conscious perception of dyspnea. Bradypnea does not depend on either hypercapnia or hypoxia.
authors.affiliation: Department of Pediatrics, State University of New York Health Science Center, Syracuse 13210.
authors.forename: R K
authors.initials: RK
authors.lastname: Kanter
authors.forename: W E
authors.initials: WE
authors.lastname: Fordyce
mesh_terms: D000403:Airway Resistance; D000818:Animals; D001784:Blood Gas Analysis; D002245:Carbon Dioxide / Q000097:blood; D002415:Cats; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006935:Hypercapnia / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D007040:Hypoventilation / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D000860:Hypoxia / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D010791:Phrenic Nerve; D012131:Respiratory Insufficiency / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D015656:Respiratory Mechanics; D012132:Respiratory Muscles / Q000294:innervation / Q000503:physiopathology; D014939:Work of Breathing
chemical_list: D002245:Carbon Dioxide