Protection from myocardial stunning by ischaemia and hypoxia with the adenosine A3 receptor agonist, IB-MECA.

Abstract

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.

• Authors: Helen L Maddock, Neil M Gardner, Nassirah Khandoudi, Antoine Bril, Kenneth J Broadley
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 477 Issue 3 Pg. 235-45 (Sep 23 2003) ISSN: 0014-2999 [Print] Netherlands
• PMID: 14522362 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine A3 Receptor Agonists
• Receptor, Adenosine A3
• Xanthines
• BW A522
• N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine
• Adenosine
• Oxygen

Topics

• Adenosine (analogs & derivatives, antagonists & inhibitors, pharmacology, therapeutic use)
• Adenosine A3 Receptor Agonists
• Animals
• Coronary Circulation (drug effects, physiology)
• Endothelium, Vascular (drug effects, injuries)
• Guinea Pigs
• Heart Atria (drug effects, physiopathology)
• Hypoxia (complications, drug therapy)
• Male
• Myocardial Ischemia (complications, drug therapy)
• Myocardial Stunning (complications, drug therapy, prevention & control)
• Oxygen (pharmacology)
• Papillary Muscles (drug effects, physiopathology)
• Perfusion
• Receptor, Adenosine A3 (physiology)
• Reperfusion Injury (complications, drug therapy, physiopathology)
• Time Factors
• Xanthines (adverse effects)