INTRACORONARY ALPHA-2-ADRENERGIC RECEPTOR BLOCKADE ATTENUATES ISCHEMIA IN CONSCIOUS DOGS DURING EXERCISE

Studies on the role of .alpha.-adrenergic constrictor tone in the coronary vascular bed during ischemia were performed in dogs running on a treadmill. The animals were instrumented with a left ventricular pressure transducer, and regional systolic wall thickening (%WTh) was assessed by sonomicrometry in the anteior and posterior walls of the left ventricle. An intracoronary catheter was implanted chronically in the circumflex coronary artery, and a hydraulic cuff was placed proximally around the artery. After .beta.-adrenergic blockade with propranolol (0.8 mg/kg i.v.), acute stenosis of the coronary artery was performed during running in five dogs to induce severe regional myocardial dysfunction in the posterior wall. Intracoronary infusion of the selective .alpha.2-adrenergic blocking agent idazoxan (80 .mu.g/kg) improved %WTh inthe ischemic region from 5.1 .+-. 1.6 to 10.8 .+-. 2.8% (p < 0.05), without any significant effect on the anterior wall. Blood flow to the subendocardium of the posterior wall (radioactive microspheres) increased from 0.17 .+-. 0.05 to 0.45 .+-. 0.30 (ml/min)/g (p < 0.05). It is concluded that in exercising dogs subjected to .beta.-adrenergic blockade, significant postjunctional .alpha.2-adrenergic receptor-mediated coronary vasoconstriction exists, even during severe ischemia. Regional .alpha.2-adrenergic receptor blockade can reduce regional ischemia and improve contractile function by attenuating exercise-induced sympathetic vasoconstriction in this conscious animal model.