Ischemic postconditioning reduces infarct size by activation of A1 receptors and K+(ATP) channels in both normal and hypercholesterolemic rabbits.
The effect of ischemic postconditioning (Postcon) in hypercholesterolemic animals is unknown. The objectives were to determine if ischemic preconditioning (IPC) and Postcon reduce infarct size in hypercholesterolemic animals and to assess if A1 receptors and K+(ATP) channels are involved in Postcon mechanisms. Isolated rabbit hearts were perfused according to the Langendorff technique and subjected to 30 minutes of ischemia and 30 minutes of reperfusion (G1). In Group 2, IPC was performed (1 cycle of 5 minutes ischemia/reperfusion) before 30 minutes of ischemia. In Group 3 (G3), Postcon was performed (2 cycles of 30-second reperfusion/ischemia) after 30 minutes of ischemia. The G3 protocol was repeated in G4 and G5, but during Postcon, an A1 receptor blocker (DPCPX, 200 nM) and glybenclamide (K+(ATP), blocker, 0.3 microM) were administered, respectively. The G1 to G5 protocols were repeated in animals fed with an enriched cholesterol diet (1%) for 4 weeks (G6 to G10). The infarct size was measured by triphenyltetrazolium. The infarct size was 16.6 +/- 4.6% in G1 and 25.8 +/- 7.3% in G6, and IPC and Postcon reduced the infarct area in both normal and hypercholesterolemic animals (G2: 5.1 +/- 1.7% [P < 0.05] and G3: 5.4 +/- 0.9% [P < 0.05] in normal animals; G7: 4.1 +/- 1.6% [P < 0.05] and G8 4.8 +/- 0.9% [P < 0.05], in hypercholesterolemic animals). Both DPCPX and glybenclamide abolished the effect reached by Postcon. Thus, Postcon reduces infarct size in normal and hypercholesterolemic animals through the activation of A1 and K+(ATP) channels.
Donato
Martín
M
Institute of Cardiovascular Pathophysiology, Faculty of Medicine, University of Buenos Aires, Argentina.
D'Annunzio
Verónica
V
Berg
Gabriela
G
Gonzalez
Germán
G
Schreier
Laura
L
Morales
Celina
C
Wikinski
Regina L W
RL
Gelpi
Ricardo J
RJ
D058916:Adenosine A1 Receptor Antagonists; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005905:Glyburide / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019157:Ischemic Preconditioning, Myocardial; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism*; D011817:Rabbits; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D017725:Ventricular Pressure / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
D058916:Adenosine A1 Receptor Antagonists; D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D043682:Receptor, Adenosine A1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D005905:Glyburide