Cardiovascular response to increasing theophylline concentrations.

The circulatory effects of plateau plasma theophylline concentrations of 5, 10 and 20 mg/l were examined in normal male volunteers using forearm plethysmography, systolic time intervals and echocardiography. Systemic arterial and forearm venous pressures were not significantly altered during theophylline infusions. Forearm blood flow increased an average 9.4% at 5 mg/l, 15.3% at 10 mg/l and 41.2% at 20 mg/l. Forearm venous distensibility was maximally increased by 20.9% at 10 mg/l. Changes in heart rate and systolic time intervals were apparent only at concentrations between 10-20 mg/l. Heart rates increased from 3-16 beats/min. The left ventricular ejection time index and isovolumetric contraction time were significantly reduced with an increase in the PEP/LVET ratio consistent with a reduction in cardiac pre-load and an increase in inotropy. However, the interindividual variability in circulatory responses was great and consistent alterations in cardiac stroke volume and ejection fraction were not observed in either the supine or 60 degrees passive-tilt positions. The variable responses cannot be due to variations in drug disposition between subjects since the range of plasma theophylline values at each concentration plateau was narrow.