Journal of Applied Physiology, Vol 76, Issue 1 39-44, Copyright © 1994 by American Physiological Society
Inotropic effects of aminophylline on canine diaphragm are enhanced by hyperinflation
G. Gayan-Ramirez, F. Palecek, Y. Chen, S. Janssens and M. Decramer
Respiratory Muscle Research Unit, University Hospitals, Katholieke Universiteit Leuven, Belgium.
During acute hyperinflation, patients with chronic obstructive pulmonary
disease are likely to have foreshortened inspiratory muscles. Because the
effects of aminophylline on contractile properties of the foreshortened
diaphragm have never been studied in vivo, we compared these effects with
those obtained at functional residual capacity (FRC). In 12 anesthetized
dogs, bilateral phrenic nerve stimulation (1, 10, 20, and 100 Hz) was
performed at FRC and near total lung capacity (TLC) before and 1 h after
each injection of aminophylline, given in cumulative doses of 20, 40, and
80 mg/kg (serum levels of 18.7 +/- 6.3, 29.9 +/- 5.9, and 60.4 +/- 11.9
mg/l, respectively). Passive diaphragm shortening from FRC to TLC, measured
in eight animals, averaged 30 +/- 12% of the resting length and increased
to 35 +/- 12 and 34 +/- 13% after 40 and 80 mg/kg, respectively. After
aminophylline, the increase in transdiaphragmatic pressure at FRC did not
reach statistical significance, whereas near TLC transdiaphragmatic
pressure significantly increased with 80 mg/kg at all stimulus frequencies
(e.g., at 20 Hz from 4.4 +/- 2.9 to 6.7 +/- 2.9 cmH2O) and with 40 mg/kg at
10 and 20 Hz. Diaphragm length changes during stimulation were unchanged
after aminophylline both at FRC and near TLC. We conclude that
aminophylline has a pronounced inotropic effect on foreshortened canine
diaphragm, even at concentrations close to the therapeutic range in humans.
