Adenosine mediates the antiarrhythmic effect of ischemic preconditioning in isolated rat hearts.
Adenosine appears to mediate the preconditioning-induced reduction in infarct size in rabbits and dogs, but little is known about the role of adenosine in preconditioning-induced protection against ischemia-induced arrhythmias. We compared the effects of preconditioning induced by 2 cycles of 5 min of global ischemia and 2 cycles of 5 min of perfusion with either adenosine (100 mumol/L) or the adenosine A1-selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 100 nmol/L) in protecting against ischemia-induced arrhythmias in Langendorff-perfused rat hearts. Preconditioning reduced the incidence of ventricular tachycardia (VT) from 100 to 58% and the incidence of sustained VT or ventricular fibrillation (VF) from 92 to 33%. Perfusion with adenosine reduced the incidence of VT from 100 to 55%, the incidence of VF from 67 to 9% and the incidence of sustained VT or VF from 92 to 9%. CCPA reduced the incidence of sustained VT or VF from 92 to 25%. These interventions provided a true reduction in the severity of arrhythmias, rather than merely a delay in the onset. Our results suggest that the stimulation of A1 receptor by adenosine is involved in triggering ischemic preconditioning-induced protection against ischemia-induced arrhythmias in rats.
Miyatake
Y
Y
First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Kusama
Y
Y
Kishida
H
H
Hayakawa
H
H
D000241:Adenosine / Q000008:administration & dosage*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D004285:Dogs; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D010477:Perfusion; D058906:Purinergic P1 Receptor Agonists; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
D000889:Anti-Arrhythmia Agents; D058906:Purinergic P1 Receptor Agonists; D000241:Adenosine