Pharmacological delayed preconditioning against ischaemia-induced ventricular arrhythmias: effect of an adenosine A(1)-receptor agonist.
1. The goal of this study was to investigate the effects of the delayed pharmacological preconditioning produced by an adenosine A(1)-receptor agonist (A(1)-DPC) against ventricular arrhythmias induced by ischaemia and reperfusion, compared to those of ischaemia-induced delayed preconditioning (I-DPC). 2. Eighty-nine instrumented conscious rabbits underwent a 2 consecutive days protocol. On day 1, rabbits were randomly divided into four groups: 'Control' (saline, i.v.), 'I-DPC' (six 4-min coronary artery occlusion/4-min reperfusion cycles), 'A(1)-DPC(100)' (N(6)-cyclopentyladenosine, 100 microg kg(-1), i.v.), and 'A(1)-DPC(400)' (N(6)-cyclopentyladenosine, 400 microg kg(-1), i.v.). On day 2, i.e., 24 h later, the incidence and severity of ventricular arrhythmias during a 30-min coronary artery occlusion and subsequent reperfusion were analysed in all animals, using an arrhythmia score. 3. I-DPC, A(1)-DPC(100) and A(1)-DPC(400) significantly reduced the infarct size (34+/-5, 42+/-3 and 43+/-7% of the area at risk, respectively) as compared to Control (55+/-3% of the area at risk). 4. During both ischaemia and reperfusion, neither the incidence nor the severity of ventricular arrhythmias were altered by A(1)-DPC(100), A(1)-DPC(400) or I-DPC as compared to Control. 5. Thus, despite reduction of infarct size induced by delayed preconditioning, A(1)-DPC as well as I-DPC failed to exert any anti-arrhythmic effect in the conscious rabbit model of ischaemia-reperfusion.
Tissier
R
R
Département de Pharmacologie, Faculté de Médecine Paris Sud and INSERM E 00.01, 63, rue Gabriel Péri, 94276 Le Kremlin-Bicêtre Cedex, France.
Souktani
R
R
Parent de Curzon
O
O
Lellouche
N
N
Henry
P
P
Giudicelli
J F
JF
Berdeaux
A
A
Ghaleh
B
B
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000150:complications; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D017202:Myocardial Ischemia / Q000150:complications*; D015425:Myocardial Reperfusion / Q000009:adverse effects; D058906:Purinergic P1 Receptor Agonists; D011817:Rabbits
D058906:Purinergic P1 Receptor Agonists; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine