Am. J. Respir. Crit. Care Med., Vol 152, No. 1, 07 1995, 204-210.
Effects of fatigue, fiber length, and aminophylline on human diaphragm contractility
AP Gauthier, S Yan, P Sliwinski and PT Macklem
Meakins Christie Laboratories, Royal Victoria Hospital, Montreal Chest Hospital Centre, McGill University, Canada.
The clinical relevance of methylxanthines as therapeutic agents for
improving diaphragmatic contractility is controversial. In a double- blind,
placebo-controlled trial, we investigated the effect of aminophylline on
the contractility of fresh and fatigued human diaphragm at different lung
volumes, and therefore as a function of fiber length. The diaphragmatic
contractility of normal subjects was assessed by measurements of
transdiaphragmatic pressure changes (Pdi,T) in response to single,
bilateral, supramaximal phrenic-nerve shocks during relaxation from total
lung capacity (TLC) to functional residual capacity (FRC). Fatigue was
induced by resistive breathing. Therapeutic levels of theophylline were
reached in all subjects. Under fresh (i.e., nonfatigue) conditions,
aminophylline significantly increased Pdi,T at lung volumes above 75% of
the inspiratory capacity (IC). Fatigue in the absence of aminophylline
caused a disproportionately greater reduction of Pdi,T at high than at low
lung volume (J. Appl. Physiol. 1992; 72:1064), which was rapidly reversible
with rest. With aminophylline, the disproportionate decrease in
diaphragmatic contractility at short fiber lengths was not observed.
Aminophylline potentiates diaphragmatic contractility to a proportionately
greater extent at short than at long fiber lengths, under both fresh and
fatigued conditions. We explain these findings by known effects of muscle
shortening, fatigue, and methylxanthines on excitation-contraction coupling
mechanisms.
