Protection from myocardial stunning by ischaemia and hypoxia with the adenosine A3 receptor agonist, IB-MECA.
Guinea pig isolated working hearts were exposed to 30-min ischaemia by reducing coronary flow to 10%, followed by reperfusion. Aortic output fell to 4.5+/-4.5% of the pre-ischaemic value at reperfusion, recovering to 48.2+/-14.6% at 20-min post-reperfusion; the index of myocardial stunning. IB-MECA (N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide, 3 x 10(-7) M), infused from 10 min into ischaemia, did not affect recovery of aortic output 20 min after reperfusion (41.9+/-1.9%). IB-MECA infused at reperfusion, however, significantly protected against stunning, aortic output recovering to 79.6+/-3.9% at 20-min post-reperfusion. Hypoxic gassing (5% CO(2) in nitrogen, 30 min) of guinea pig isolated paced left atria and papillary muscles reduced the developed tension, recovering to 75% 5 min after re-oxygenation. This myocardial stunning was unaffected by IB-MECA (3 x 10(-7) M) added 10 min into hypoxia. IB-MECA added at reoxygenation significantly improved recovery, which was prevented by the adenosine A(3) receptor antagonist, 1-propyl-3-(3-iodo-4-aminobenzyl)-8-(4-oxyacetate)phenylxanthine (I-ABOPX, 1 x 10(-5) M). Thus, stimulation of adenosine A(3) receptors at reperfusion/reoxygenation in guinea pig cardiac preparations protects against myocardial stunning.
Maddock
Helen L
HL
Department of Pharmacology, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cathays Park, Wales CF10 3XF, Cardiff, UK.
Gardner
Neil M
NM
Khandoudi
Nassirah
N
Bril
Antoine
A
Broadley
Kenneth J
KJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D058909:Adenosine A3 Receptor Agonists; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications* / Q000188:drug therapy; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications* / Q000188:drug therapy; D017682:Myocardial Stunning / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control*; D010100:Oxygen / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000503:physiopathology; D010477:Perfusion; D043684:Receptor, Adenosine A3 / Q000502:physiology; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D013997:Time Factors; D014970:Xanthines / Q000009:adverse effects
D058909:Adenosine A3 Receptor Agonists; D043684:Receptor, Adenosine A3; D014970:Xanthines; C086749:BW A522; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D000241:Adenosine; D010100:Oxygen