title: Diaphragmatic neuromechanical coupling and mechanisms of hypercapnia during inspiratory loading.
abstract: We hypothesized that improved diaphragmatic neuromechanical coupling during inspiratory loading is not sufficient to prevent alveolar hypoventilation and task failure, and that the latter results primarily from central-output inhibition of the diaphragm and air hunger rather than contractile fatigue. Eighteen subjects underwent progressive inspiratory loading. By task failure all developed hypercapnia. Tidal transdiaphragmatic pressure (ΔPdi) and diaphragmatic electrical activity (ΔEAdi) increased during loading - the former more than the latter; thus, neuromechanical coupling (ΔPdi/ΔEAdi) increased during loading. Progressive increase in extra-diaphragmatic muscle contribution to tidal breathing, expiratory muscle recruitment, and decreased end-expiratory lung volume contributed to improved neuromechanical coupling. At task failure, subjects experienced intolerable breathing discomfort, at which point mean ΔEAdi was 74.9±4.9% of maximum, indicating that the primary mechanism of hypercapnia was submaximal diaphragmatic recruitment. Contractile fatigue was an inconsistent finding. In conclusion, hypercapnia during acute loading primarily resulted from central-output inhibition of the diaphragm suggesting that acute loading responses are controlled by the cortex rather than bulbopontine centers.
authors.affiliation: Edward Hines, Jr. Veterans Affairs Hospital, Hines, IL, United States; Loyola University, Maywood, IL, United States. Electronic address: flaghi@lumc.edu.
authors.forename: Franco
authors.initials: F
authors.lastname: Laghi
authors.affiliation: Edward Hines, Jr. Veterans Affairs Hospital, Hines, IL, United States; Loyola University, Maywood, IL, United States. Electronic address: hameeda.shaikh@va.gov.
authors.forename: Hameeda S
authors.initials: HS
authors.lastname: Shaikh
authors.affiliation: Edward Hines, Jr. Veterans Affairs Hospital, Hines, IL, United States. Electronic address: danielfm2@hotmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Morales
authors.affiliation: Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Canada; Department of Medicine, Interdepartmental Division of Critical Care Medicine, University of Toronto, Canada. Electronic address: sinderbyc@smh.ca.
authors.forename: Christer
authors.initials: C
authors.lastname: Sinderby
authors.affiliation: Edward Hines, Jr. Veterans Affairs Hospital, Hines, IL, United States; Loyola University, Maywood, IL, United States. Electronic address: ajubran@lumc.edu.
authors.forename: Amal
authors.initials: A
authors.lastname: Jubran
authors.affiliation: Edward Hines, Jr. Veterans Affairs Hospital, Hines, IL, United States; Loyola University, Maywood, IL, United States. Electronic address: mtobin2@lumc.edu.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Tobin
mesh_terms: D034861:Abdominal Wall / Q000503:physiopathology; D000328:Adult; D000388:Air; D001921:Brain / Q000503:physiopathology; D002245:Carbon Dioxide / Q000378:metabolism; D003964:Diaphragm / Q000503:physiopathology*; D004417:Dyspnea / Q000503:physiopathology; D004576:Electromyography; D045853:Exhalation / Q000502:physiology; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology*; D001239:Inhalation / Q000502:physiology*; D008176:Lung Volume Measurements; D008297:Male; D008959:Models, Neurological; D018763:Muscle Fatigue / Q000502:physiology; D010812:Physical Stimulation / Q000009:adverse effects*; D011312:Pressure; D012132:Respiratory Muscles / Q000503:physiopathology
chemical_list: D002245:Carbon Dioxide
keywords: Breathing pattern; Dyspnea; Hypercapnia; Muscle fatigue; Phrenic nerve; Respiratory muscles