Endogenous adenosine suppresses norepinephrine-induced ventricular arrhythmias in rat heart.
Adenosine is an antiarrhythmic substance particularly effective in catecholamine-dependent tachycardias. Although endogenous adenosine substantially accumulates in catecholamine-stimulated hearts, little is known about the antiarrhythmic potency of endogenous adenosine in this condition. Therefore, we sought to demonstrate a potential antifibrillatory effect of endogenous adenosine either by blockade of adenosine receptors with 8-phenyltheophylline (8-PT) or by suppression of endogenous adenosine release with nitrobenzyl-6-thioinosine (NBTI). The study was performed in spontaneously beating Langendorff-perfused rat hearts. Adenosine release into the effluent was determined by HPLC methods. Catecholamine stimulation was induced by perfusing the hearts with norepinephrine (1 mumol/l) for 30 min, which caused ventricular tachycardia (VT) in 31% and ventricular fibrillation (VF) in 25% of control hearts (n = 35). When 8-PT (10 mumol/l) was added to the perfusion buffer prior to norepinephrine, the incidence of VT and VF increased to 79 and 68%, respectively. The addition of 8-PT did not affect the catecholamine-dependent formation of adenosine. Perfusion of the hearts with NBTI (10 mumol/l) prior to norepinephrine reduced adenosine release and increased the occurrence of both VT (65%) and VF (40%). In summary, the results indicate that adenosine is an endogenous antiarrhythmic substance, which accumulates in catecholamine-stimulated myocardium to a level, which effectively suppresses the occurrence of ventricular arrhythmias.
Görge
B
B
Medizinische Klinik II, Medizinische Universität zu Lübeck, Germany.
Kurz
T
T
Katus
H A
HA
Richardt
G
G
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000139:chemically induced*
D058915:Purinergic P1 Receptor Antagonists; D014662:Vasoconstrictor Agents; D013868:Thioinosine; D013806:Theophylline; C028322:8-phenyltheophylline; C001789:4-nitrobenzylthioinosine; D000241:Adenosine; D009638:Norepinephrine