Published Online
on October 4, 2004

A more recent version of this article appeared on October 12, 2004

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Submitted on January 12, 2004
Revised on April 15, 2004
Accepted on April 15, 2004

Differential Effects of Theophylline on Sympathetic Excitation, Hemodynamics, and Breathing in Congestive Heart Failure

Stefan Andreas MD, Hartwig Reiter MD^*, Lars Lüthje MD, André Delekat , Rolf W. Grunewald MD, Gerd Hasenfuss MD, and Virend K. Somers MD, PhD

From the Department of Cardiology and Pneumology (S.A., H.R., L.L., A.D., G.H.) and the Department of Nephrology (R.W.G.), Georg-August-Universität, Göttingen, Germany; and the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn (V.K.S.).

^* To whom correspondence should be addressed. E-mail: sandreas{at}med.uni-goettingen.de.

Background--Patients with heart failure have high levels of central sympathetic outflow and also have a high prevalence of sleep-related breathing disorders, predominantly central sleep apnea. The options for treating central sleep apnea in heart failure are limited and include theophylline. Whether theophylline alters sympathetic activity in heart failure patients is not known.

Methods and Results--Using a single-blinded, randomized, placebo-controlled study design, we investigated the sympathetic, hemodynamic, neurohumoral, and ventilatory effects of theophylline in patients with congestive heart failure compared with healthy control subjects closely matched for age, sex, and body mass index. Theophylline increased muscle sympathetic nerve activity and lowered transcutaneous CO₂ in the control subjects but only lowered transcutaneous CO₂ in the heart failure patients. Theophylline nearly doubled plasma renin concentration in both the healthy subjects (P<0.01) and the heart failure patients (P<0.02).

Conclusions--Our study shows that in heart failure patients, there are differential effects of theophylline: in contrast to healthy subjects, theophylline does not increase sympathetic activity in heart failure, whereas increases in plasma renin and ventilation are still evident. These novel findings may have important implications for understanding the potential harmful and beneficial effects of theophylline and related substances in heart failure patients.

Key words: heart failure • theophylline • nervous system, sympathetic • ventilation • sleep apnea

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