Effects of theophylline on hemodynamics and tissue oxygenation in patients with cirrhosis.
Since adenosine may play a role in the hyperdynamic circulation of cirrhosis, we examined the effects of theophylline (an adenosine receptor antagonist) on systemic and splanchnic hemodynamics, tissue oxygenation and sympathoadrenal activity in patients with cirrhosis and liver failure. Theophylline (aminophylline) was administered intravenously for 30 min. Six patients received a dose of 3 mg/kg and eight others a dose of 6 mg/kg. The low dose caused plasma theophylline concentrations of 7.4 +/- 1.8 mg/ml (mean +/- S.E.), and induced a significant increase in heart rate from 84 +/- 5 to 93 +/- 8 beats/min. This dosage did not significantly change other hemodynamic values, oxygen (O2) consumption, or sympathoadrenal activity. The high dose elicited plasma theophylline concentrations of 15.8 +/- 4.0 mg/ml. This dose significantly increased heart rate from 78 +/- 5 to 87 +/- 7 beats/min and significantly decreased right atrial pressure from 2.5 +/- 1.0 to 1.4 +/- 0.8 mmHg, stroke volume from 52 +/- 3 to 47 +/- 5 ml.beat-1.m-2 and systolic arterial pressure from 140 +/- 5 to 129 +/- 6 mmHg. In contrast, O2 consumption, sympathoadrenal activity, and all other hemodynamic values (including azygos blood flow) were not significantly modified. As a result, we conclude that, in patients with cirrhosis, theophylline may cause decreased stroke volume which lowers systolic arterial pressure. In our patients theophylline also had a positive chronotropic effect but no vasoconstrictor effect on systemic and splanchnic circulation. Finally, theophylline did not improve tissue oxygenation in patients with cirrhosis.
Moreau
R
R
Laboratoire d'Hémodynamique Splanchnique, Unité de Recherches de Physiopathologie Hépatique (INSERM U-24), Hôpital Beaujon, Clichy, France.
Champigneulle
B
B
Gaudin
C
C
Poo
J L
JL
Kleber
G
G
Bacq
Y
Y
Lebrec
D
D
D000328:Adult; D002395:Catecholamines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000502:physiology; D013318:Stroke Volume / Q000187:drug effects; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology*
D002395:Catecholamines; D013806:Theophylline