Aminophylline increases respiratory muscle activity during hypercapnia in humans.
Theophylline is an old drug traditionally used as a bronchodilator, although it was recently shown to possess anti-inflammatory properties, enhance the actions of corticosteroid actions, and stimulate the respiratory neuronal network. Theophylline has been recognized as an important drug for not only asthma but also corticosteroid-insensitive chronic obstructive pulmonary disease (COPD). To clarify the role of theophylline in hypercapnic ventilatory responses in humans, we analyzed the effects of aminophylline administered at the usual clinical therapeutic doses on ventilation and augmentation of respiratory muscle contractility in room air and under 3 conditions of hypercapnia.



We performed electromyography (EMG) of the parasternal intercostal muscle (PARA) and transversus abdominis muscle (TA) in 7 healthy subjects and recorded both ventilatory parameters and EMG data in room air and under 3 conditions of hypercapnia before (control) and during aminophylline administration.



Before aminophylline administration (control), hypercapnic stimulation elicited ventilatory augmentation in a hypercapnia intensity-dependent manner. Ventilatory parameters (tidal volume, frequency of respiration, and minute ventilation) showed significant increases from lower PaCO2 levels during aminophylline administration when compared with the corresponding values before aminophylline administration. EMG activity of both PARA and TA increased significantly at each level of hypercapnia, and those augmentations were shown from lower PaCO2 levels during aminophylline administration.



Aminophylline administered at the usual clinical therapeutic dose increases ventilation and EMG activity of both inspiratory and expiratory muscles during hypercapnia in healthy humans.
Kitasato University School of Allied Health Sciences, Kanagawa, Japan; Division of Respiratory Medicine, Kitasato University Hospital, Kanagawa, Japan. Electronic address: myoko@kitasato-u.ac.jp.
Masanori
M
Yokoba
Kitasato University School of Allied Health Sciences, Kanagawa, Japan; Division of Respiratory Medicine, Kitasato University Hospital, Kanagawa, Japan.
Masato
M
Katagiri
Kitasato University Graduate School of Medical Sciences, Kanagawa, Japan; Rehabilitation Medicine, Tokai University Oiso Hospital, Kanagawa, Japan.
Tsuyoshi
T
Ichikawa
Division of Respiratory Medicine, Kitasato University Hospital, Kanagawa, Japan.
Akira
A
Takakura
Kitasato University School of Allied Health Sciences, Kanagawa, Japan.
Naohito
N
Ishii
Kitasato University School of Allied Health Sciences, Kanagawa, Japan.
Yoshifumi
Y
Kurosaki
Kitasato University Graduate School of Medical Sciences, Kanagawa, Japan.
Yuya
Y
Yamada
Department of Clinical Laboratories, Kitasato University Hospital, Kanagawa, Japan.
Tomoaki
T
Tsukushi
Division of Respiratory Medicine, Kitasato University Hospital, Kanagawa, Japan.
Noriyuki
N
Masuda
Critical Care Medicine, University of Calgary, Calgary, Alberta, Canada.
Paul A
PA
Easton
Yasuto
Y
Nishii
Yasumasa
Y
Okada
Tadashi
T
Abe
D000628:Aminophylline / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism; D004576:Electromyography / Q000379:methods; D006801:Humans; D006935:Hypercapnia / Q000188:drug therapy* / Q000503:physiopathology; D007366:Intercostal Muscles / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D012132:Respiratory Muscles / Q000187:drug effects* / Q000378:metabolism; D013990:Tidal Volume; D055815:Young Adult
D001993:Bronchodilator Agents; D002245:Carbon Dioxide; D000628:Aminophylline
Aminophylline; Electromyogram; Hypercapnia; Parasternal intercostal muscle; Transversus abdominis muscle