title: Celiprolol, a compound which attenuates myocardial acidosis and improves regional segmental function following ischemia in dogs: a comparison with propranolol.
abstract: Celiprolol, propranolol or saline were administered to separate groups (n = 5-6) of anesthetized dogs in which a critical stenosis was applied to the circumflex coronary artery for 90 min and then reperfused for 30 min. Test drugs were administered at 30 min poststenosis and the effects on pH, regional function and endocardiogram were monitored. A reduction in coronary flow of 54 +/- 2% (n = 27) yielded marked increases in hydrogen ion concentration (H+) of 17 +/- 2 X 10(-8) and ischemic endocardial ST segment of 6 +/- 1 mV while ischemic segmental shortening decreased 75 +/- 9%. Heart rate, arterial pressure and normal regional function were not altered. Celiprolol 0.1 and 1 mg/kg, i.v., reversed the alterations in H+ and ischemic ST segment to prestenosis values while improving ischemic segmental shortening 20 and 38%, respectively, and not affecting heart rate. Propranolol 0.1 and 1 mg/kg, i.v., reversed the alterations in H+ and ischemic ST segment to prestenosis values while further decreasing ischemic segmental shortening 66 and 30%, respectively. Upon reperfusion, ischemic segmental shortening returned to prestenosis values in the group treated with celiprolol 1 mg/kg, i.v., while the propranolol- and saline-treated groups further decreased. It is concluded that celiprolol is efficacious in normalizing myocardial function and ischemia-induced electrophysiological changes following coronary artery stenosis.
authors.affiliation: Department of Cardiovascular Pharmacology, Rorer Central Research, Horsham, Pa.
authors.forename: J A
authors.initials: JA
authors.lastname: Barrett
authors.forename: A M
authors.initials: AM
authors.lastname: Magistro
authors.forename: R D
authors.initials: RD
authors.lastname: Smith
authors.forename: T P
authors.initials: TP
authors.lastname: Pruss
authors.forename: P S
authors.initials: PS
authors.lastname: Wolf
mesh_terms: D000138:Acidosis / Q000188:drug therapy*; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D009202:Cardiomyopathies / Q000188:drug therapy*; D017272:Celiprolol; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008297:Male; D011412:Propanolamines / Q000627:therapeutic use*; D011433:Propranolol / Q000627:therapeutic use*
chemical_list: D000317:Adrenergic alpha-Antagonists; D011412:Propanolamines; D011433:Propranolol; D017272:Celiprolol