Beneficial effects of two specific bradycardic agents AQ-A39 (falipamil) and AQ-AH 208 on reversible myocardial reperfusion damage in anesthetized dogs.

The effects of 2 specific bradycardic agents, AQ-A39 [5,6-dimethoxy-2-[3-([alpha-(3,4-dimethoxy)phenylethyl]methyl-amino) propyl]phthalimidine hydrochloride] and AQ-AH 208 [3,4-dihydro-6,7-dimethoxy-2-]3-[(2-[3, 4-dimethoxy-phenyl)-ethyl]-aminoethyl]propyl[-1(2H)isoquinone] were evaluated for their effects on subendocardial segment shortening (% SS) as measured by sonomicrometry and regional myocardial blood flow (radioactive microspheres) in anesthetized dogs subjected to a 15 min left anterior descending coronary occlusion followed by 3 hr of reperfusion. AQ-A39 (2.5-mg/kg bolus + 100 micrograms/kg/min i.v.) and AQ-AH 208 (0.5-mg/kg bolus + 25 micrograms/kg/min i.v.) were administered 15 min before coronary occlusion, during occlusion and throughout reperfusion. Both agents produced equivalent reductions in heart rate (24%) and the heart rate-systolic pressure product (27%) without any other significant hemodynamic changes. Collateral blood flow to the ischemic area was not different between the drug-treated and control groups. During coronary occlusion and throughout reperfusion, however, % SS was significantly (P less than .05) improved by both agents in the ischemic-reperfused area as compared to a control group. Thus, the beneficial actions of AQ-A39 and AQ-AH 208 on improving the recovery of subendocardial contractile function (% SS) may be explained partially by a reduction in myocardial oxygen requirements as a result of bradycardia. These results suggest that specific bradycardic agents may have potential for treatment of certain types of myocardial ischemia.