title: Long acting calcium antagonist anipamil limits myocardial necrosis and penetrates the ischemic zone during 24 h of coronary artery occlusion in the dog.
abstract: This study examined the effect of the long acting calcium antagonist anipamil on the extent of myocardial necrosis during 24 h of coronary artery occlusion in the dog. Forty dogs had coronary artery occlusion with a 2 mm embolus injected into the left coronary system; 141 cerium microspheres were used to delineate the ischemic zone immediately following occlusion. Twenty dogs received no drug (controls) and 20 received anipamil (two boluses of 0.25 mg/kg intravenously, one within 5 mins of occlusion and the other 12 h later). Arterial pressure and heart rate were monitored for 24 h. A subgroup of five controls and four anipamil treated dogs had injections of a second microsphere (113 tin or 46scandium) at 24 h to show changes in bloodflow. At 24 h the surviving dogs were sacrificed, their hearts sectioned, the risk zones delineated by autoradiography and the necrotic zones delineated by tetrazolium staining. Samples were taken from the normal myocardium and the risk zones for a determination of tissue anipamil content and measurement of regional bloodflow. In the control hearts, 76 +/- 4% of the risk zones became necrotic after 24 h, compared with 53 +/- 4% in the anipamil treated group (P less than 0.005). Anipamil had no effect on the heart rate or the arterial pressure. In the control dogs, the bloodflow to the tissue that became necrotic was 17% of the normal flow immediately after coronary occlusion, and 16% at 24 h; flow in the viable (subepicardial) tissue was also unchanged (49 versus 54%).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Cardiovascular Research, Rayne Institute, St Thomas' Hospital London, United Kingdom.
authors.forename: A R
authors.initials: AR
authors.lastname: Denniss
authors.forename: J G
authors.initials: JG
authors.lastname: Kingma
authors.forename: D J
authors.initials: DJ
authors.lastname: Hearse
authors.forename: J M
authors.initials: JM
authors.lastname: Downey
authors.forename: D M
authors.initials: DM
authors.lastname: Yellon
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003692:Delayed-Action Preparations; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D009336:Necrosis; D011437:Propylamines / Q000378:metabolism / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D011437:Propylamines; C045313:anipamil