EFFECTS OF FATIGUE, FIBER LENGTH, AND AMINOPHYLLINE ON HUMAN DIAPHRAGM CONTRACTILITY

The clinical relevance of methylxanthines as therapeutic agents for im proving diaphragmatic contractility is controversial. In a double-blin d, placebo-controlled trial, we investigated the effect of aminophylli ne on the contractility of fresh and fatigued human diaphragm at diffe rent lung volumes, and therefore as a function of fiber length. The di aphragmatic contractility of normal subjects was assessed by measureme nts of transdiaphragmatic pressure changes (Pdi,T) in response to sing le, bilateral, supramaximal phrenic-nerve shocks during relaxation fro m total lung capacity (TLC) to functional residual capacity (FRC). Fat igue was induced by resistive breathing. Therapeutic levels of theophy lline were reached in all subjects. Underfresh (i.e., nonfatigue) cond itions, aminophylline significantly increased Pdi,T at lung volumes ab ove 75% of the inspiratory capacity (IC). Fatigue in the absence of am inophylline caused a disproportionately greater reduction of Pdi,Tat h igh than at low lung volume (J. Appl. Physiol. 1992; 72:1064), which w as rapidly reversible with rest. With aminophylline, the disproportion ate decrease in diaphragmatic contractility at short fiber lengths was not observed. Aminophylline potentiates diaphragmatic contractility t o 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.