P3603

        J Appl Physiol 1994 Jan;76(1):39-44

        Inotropic effects of aminophylline on canine diaphragm are enhanced by

        hyperinflation.

        Gayan-Ramirez G, Palecek F, Chen Y, Janssens S, Decramer M.

        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.