BENEFICIAL-EFFECTS OF 2 SPECIFIC BRADYCARDIC AGENTS AQ-A39 (FALIPAMIL) AND AQ-AH-208 ON REVERSIBLE MYOCARDIAL REPERFUSION DAMAGE IN ANESTHETIZED DOGS

  • 1 August 1986
    • journal article
    • research article
    • Vol. 238  (2) , 422-428
Abstract
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 interior descending coronary occlusion followed by 3 hr of reperfusion. AQ-A39 (2.5-mg/kg bolus + 100 .mu.g/kg/min i.v.) and AQ-AH 208 (0.5 mg/kg bolus + 25 .mu.g/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 < .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.

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