Differential effects of theophylline on sympathetic excitation, hemodynamics, and breathing in congestive heart failure.
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.


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.
Andreas
Stefan
S
Department of Cardiology and Pneumology, Georg-August-Universität, Göttingen, Germany. sandreas@med.uni-goettingen.de
Reiter
Hartwig
H
Lüthje
Lars
L
Delekat
André
A
Grunewald
Rolf W
RW
Hasenfuss
Gerd
G
Somers
Virend K
VK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D002317:Cardiovascular Agents / Q000627:therapeutic use; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D058915:Purinergic P1 Receptor Antagonists; D012083:Renin / Q000097:blood; D012119:Respiration / Q000187:drug effects*; D016037:Single-Blind Method; D020182:Sleep Apnea, Central / Q000150:complications / Q000188:drug therapy; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013806:Theophylline / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D002317:Cardiovascular Agents; D019332:Endothelin-1; D010726:Phosphodiesterase Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D013806:Theophylline; D012083:Renin