Effect of theophylline on the velocity of diaphragmatic muscle shortening

The present study examined the effect of theophylline on the shortening velocity of submaximally activated diaphragmatic muscle (i.e., muscles were activated by the use of a level of stimulation, 50 Hz, within the range of phrenic neural firing frequencies achieved during breathing, whereas maximum activation is achieved at 300 Hz). Experiments were performed in vitro on strips of diaphragmatic muscle obtained from 21 Syrian hamsters. Muscle shortening velocity was assessed during isotonic contractions against a range of afterloads, and Hill's characteristic equation was used to calculate velocity at zero load. In addition, unloaded shortening velocity was also measured by the slack test, i.e., from the time required for muscles to take up slack after a sudden reduction in muscle length. Theophylline (160 mg/l) increased the velocity of muscle shortening against a wide range of external loads (0-14 N/cm²) and increased the extrapolated unloaded velocity of shortening from 6.4 ± 0.9 to 7.9 ± 1.1 (SE) lengths/s (P < 0.01). Theophylline reduced the time required to take up slack for any given step change in muscle length, increasing the unloaded velocity of shortening assessed by the slack test from 7.6 ± 0.9 to 9.3 ± 1.1 lengths/s (P < 0.002). The effect of theophylline on diaphragmatic shortening velocity was evident at concentrations as low as 40 mg/l and increased progressively as theophylline concentrations were increased to 320 mg/l. Theophylline increased the shortening velocity of fatigued as well as fresh muscles. In keeping with previous reports, theophylline also increased the isometric force generated in response to 50-Hz electrical stimulation from 14.5 ± 2.5 to 15.6 ± 2.7 (SE) N/cm² (P < 0.05). These data indicate that theophylline increases the velocity of submaximally activated diaphragmatic muscle as well as its ability to generate force.