Cardiovascular effects of enprofylline and theophylline

The cardiovascular effects of enprofylline (with no adenosine receptor antagonism) and of theophylline (with adenosine receptor antagonism) were compared in six normal subjects in a double‐blind trial at steady‐state concentrations of theophylline (12.5 ± 1.6 mg/L) and enprofylline (2.7 ± 0.3 mg/L). The mean (± SD) recumbent heart rate (HR) was higher (P < 0.04) after enprofylline (70 ± 14 bpm) than after theophylline (58 ± 13 bpm) or saline solution (57 ± 10 bpm). Forearm arterial resistance determined by plethysmography was lowered (P < 0.01) by theophylline (− 37% ± 14%) and enprofylline (—43% ± 24%) but not by saline solution (−6% ± 16%). In the semiupright position, the mean arterial pressure was lower (P < 0.01) after enprofylline (93 ±15 mm Hg) than after theophylline (108 ± 16 mm Hg). The cardiac index (CI) and left ventricular ejection fraction (LVEF) determined by radionuclide angiocardiography and the left ventricular end‐systolic pressure/volume ratio were not different for any regimen. During maximal exercise, HR was higher (P < 0.01) after both enprofylline (176 bpm) and theophylline (175 bpm) than after saline solution (161 bpm), but the increases in mean arterial pressure (18% to 32%), CI (153% to 167%), and LVEF (34% to 74%) were similar for all three regimens. Both theophylline and enprofylline lowered forearm arterial resistance without an increase in CI, LVEF, or cardiac inotropy, although enprofylline tended to cause a lower blood pressure and higher HR than did theophylline. Clinical Pharmacology and Therapeutics (1986) 39, 395–402; doi: 10.1038/clpt.1986.61