title: Differences in refractory-period response of canine subendocardium and subepicardium to bunazosin, an alpha1-adrenoceptor antagonist, and propranolol during myocardial ischemia.
abstract: Our objective was to investigate the effects of alpha1- or beta-adrenoceptor blockers on endocardial and epicardial refractory-period changes during myocardial ischemia in alpha-chloralose-anesthetized dogs. The first and second diagonal branches of the left anterior descending coronary artery were ligated. The refractory period was determined by an S1-S2 extrastimulus method. Dogs were treated with the alpha1-blocker bunazosin (0.1-0.2 mg/kg, i.v.; n = 16), the beta-blocker propranolol (0.2 mg/kg, i.v.; n = 15), or saline (n = 11). Dogs that developed ventricular tachycardia/fibrillation (VT/VF) during the experiment were excluded from the statistical assessment in refractory periods. In all groups, coronary ligation produced a significant shortening of the refractory period of ischemic epicardial tissue (p < 0.05) but only minimal shortening of ischemic endocardial refractory periods, resulting in an increased difference in repolarization time between the endo- and epicardial sites. Treatment with bunazosin ameliorated this ischemia-related shortening of refractory periods at both the endo- and epicardial sites, with a greater effect seen epicardially (p < 0.05), resulting in values similar to those in the nonischemic tissue. Treatment with propranolol prolonged refractory periods more in the epicardial (p < 0.01) than in endocardial sites, exacerbating the disparity in the refractory period between the endo- and epicardial sites (p < 0.05). Propranolol also prolonged the refractory period of nonischemic tissue (p < 0.05 and p < 0.01 in endo- and epicardial sites, respectively), resulting in a significant difference between the ischemic and normal myocardium at the endocardial site (p < 0.05). Results suggest that the alpha1-blocker bunazosin reduces the refractory-period disparity between the ischemic and normal myocardium without increasing the disparity between the endo- and epicardial surfaces, whereas propranolol produces a greater disparity.
authors.affiliation: Department of Cardiovascular Medicine, School of Medicine, Tokai University, Isehara, Kanagawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tanabe
authors.forename: K
authors.initials: K
authors.lastname: Usui
authors.forename: S
authors.initials: S
authors.lastname: Kusuzaki
authors.forename: M
authors.initials: M
authors.lastname: Yoshitake
authors.forename: O
authors.initials: O
authors.lastname: Takigawa
authors.forename: T
authors.initials: T
authors.lastname: Iwamoto
authors.forename: S
authors.initials: S
authors.lastname: Handa
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004699:Endocardium / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D010496:Pericardium / Q000187:drug effects* / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D012032:Refractory Period, Electrophysiological / Q000187:drug effects*; D017180:Tachycardia, Ventricular / Q000517:prevention & control; D014693:Ventricular Fibrillation / Q000517:prevention & control; D016276:Ventricular Function
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011799:Quinazolines; D018340:Receptors, Adrenergic, alpha-1; C018176:bunazosin; D011433:Propranolol