Effect of intravenous aminophylline on plasma levels of catecholamines and related cardiovascular and metabolic responses in man.

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Abstract
Theophylline is thought to act by inhibiting the activity of phosphodiesterase, with a resultant increase in intracellular cyclic AMP. However, this concept is largely based on in vitro studies using concentrations of theophylline which greatly exceed therapeutic plasma concentrations. To investigate the relationship of the cardiovascular and metabolic effects of theophylline to activation of the sympathetic nervous system, i.v. aminophylline was administered to six healthy males under basal conditions. Each subject received four infusions. Mean theophylline concentrations (+/- SEM) of 4.5 +/- 0.2, 10.0 +/- 0.5, 14.0 +/- 0.5 and 20.0 +/- 1.2 micrograms/ml were achieved. Plasma epinephrine increased 262% (from 29 +/- 4 to 105 +/- 14 pg/ml, p less than 0.01) and plasma norepinephrine increased 64% (from 190 +/- 18 to 312 +/- 51 pg/ml, p less than 0.05) during the high-dose infusion. The increases in circulating catecholamines were dose-related (p less than 0.001 by analysis of variance). Dose-related increases in heart rate, systolic blood pressure, plasma glucose, free fatty acids and insulin were also observed (p less than 0.001 by analysis of variance). Although the duration of total electromechanical systole (QS2) and left ventricular ejection time adjusted for heart rate fell during the aminophylline infusions, this positive inotropic response was not influenced by dose, except possibly the high dose. Echocardiographic ejection fraction was not changed by the aminophylline infusions. We conclude that the acute cardiovascular and metabolic effects of theophylline may be mediated in part by stimulation of the sympathetic nervous system.