Disproportional response between refractory period and blood flow to alpha 1- and beta-adrenoceptor blockade in canine ischemic myocardium.
We investigated the response of refractory periods and blood flow to blockade of alpha 1- and beta-adrenoceptors alone, or in combination on endocardium and epicardium, during myocardial ischemia. Dogs were anesthetized with alpha-chloralose and divided into bunazosin (an alpha 1-blocking agent)-treated (0.1-0.2 mg/kg, i.v., n = 14), propranolol-treated (0.2 mg/kg, i.v., n = 12), and vehicle-control (n = 10) groups. The diagonal branches of the left anterior descending artery were ligated. The refractory period (ERP) and blood flow (RMBF) were determined by an S1-S2 extrastimulus method and a nonradioactive microsphere technique, respectively. The duration of regional electrograms (DRE) was measured in the endocardial and epicardial sites. Bunazosin alone reversed the ischemia-related shortening of ERPs at both the endocardial and epicardial sites, with a greater effect seen epicardially (P < .05). Subsequent administration of propranolol further prolonged ERPs in both sites, although the effect was greater in the epicardial surface (P < .05). Bunazosin reduced RMBF to a greater degree at the endocardial site than at the epicardial site in the ischemic zone (P < .01 and P < .05, respectively), but the magnitude of the reduction in RMBF and the difference in RMBF between sites were similar to the control group (P < .01). Propranolol alone and subsequent administration of bunazosin prolonged the ERP more at the epicardial site (P < .01) than at the endocardial sites in the ischemic zone. Propranolol produced no significant difference in RMBF between both sites. DREs in animals treated with bunazosin and propranolol alone, or in combination, were similar to those in animals treated with vehicle. These results suggest that differences in ERPs between endocardium and epicardium with blockade of alpha 1- and/or beta-adrenoceptor are not due to concomitant alterations in RMBF, but to differences in electrophysiological properties of the endocardial and epicardial cells during the acute phase of myocardial ischemia.
Department of Cardiovascular Medicine, Tokai University, Kanagawa, Japan.
K
K
Usui
T
T
Tanabe
S
S
Handa
Y
Y
Shinozaki
H
H
Mori
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; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D004699:Endocardium / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010496:Pericardium / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects*; D017180:Tachycardia, Ventricular / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000503:physiopathology
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011799:Quinazolines; C018176:bunazosin; D011433:Propranolol