AQ-AH 208, a New Bradycardic Agent, Increases Coronary Collateral Blood Flow to Ischemic Myocardium

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Abstract
Summary: The effect of AQ-AH 208 [3,4-dihydro-6,7-dimethoxy-2-(3 - ((2-(3,4-dimethoxyphenyl)ethyl)-aminomethyl)propyl)-1(2H)-isoquinolinone], a new selective bradycardic agent, on coronary collateral perfusion was investigated in anesthetized open-chest dogs following acute occlusion of the left anterior descending coronary artery. AQ-AH 208 (0.3 mg/kg i.v.), propranolol (0.3 mg/kg i.v.), and N-dimethylpropranolol (DMP; 2.5 mg/kg i.v.) were equieffective in reducing heart rate ˜15%. AQ-AH 208 increased collateral flow to the subepicardium, midmyocardium, and subendocardium by 24, 46, and 35% (p < 0.05), respectively, while propranolol and DMP had no effect. Atrial pacing to predrug levels in the presence of AQ-AH 208 reduced the increases in collateral flow to the different myocardial layers to 16, 25, and 30%, respectively; however, these increases were still significantly greater than control. It is concluded that part of the AQ-AH 208-induced increase in collateral perfusion is due to an increase in diastolic duration. The nature of the frequency-independent component of the effect is unknown but may be explained by a selective decrease in extravascular coronary resistance in the ischemic zone or an increase in the conductance of large epicardial coronary or collateral vessels.