The effect of theophylline on hypoxic, hypercapnic hamster diaphragm muscle in vitro

Hypoxic, hypercapnic acidosis (HHA) decreases tension and enhances fatigue in hamster diaphragm in vitro. We hypothesized that theophylline would decrease the harmful effect of HHA. Hamster diaphragm strips were studied in Krebs solution aerated with 21% O2 and 12% CO2. The force-frequency responses and the tension and relaxation of brief, submaximal contractions were studied. Mild fatigue was produced by a series of 45 submaximal contractions, after which recovery of force was followed for 15 min. Theophylline (0.55 mM) was added at the time of exposure to HHA (early theophylline) in half the strips and at the end of the fatigue run (late theophylline) in the others. In contrast to our hypothesis, early theophylline had a limited effect on force production in unfatigued HHA diaphragm strips and resulted in lower force production in the recovery period. Late theophylline improved force in the recovery period for low-frequency contractions. Thus the effect of theophylline in the setting of HHA depended on the time it was added and was beneficial only if added after the muscle stopped contracting.