Dose related coronary and systemic haemodynamic effects of intravenous bepridil in patients with coronary artery disease.
The acute coronary and systemic haemodynamic effects of intravenous bepridil were investigated in 27 patients with coronary artery disease; 13 (group 1) received 2 mg kg-1 and 14 (group 2) 4 mg kg-1 over 5 min. An immediate systemic and coronary vasodilation occurred in both groups during and immediately after the infusion. Changes were dose-related with a maximal decrease in left ventricular (LV) systolic pressure of 11% (group 1) and 18% (group 2), in mean aortic pressure of 11% (group 1) and 19% (group 2), and in coronary resistance of 23% (group 1) and 41% (group 2). Coronary flow increased by 17% (group 1) and 47% (group 2) (all changes significantly different from control (C) values and between groups). Cardiac output, measured immediately after bepridil, was unaltered, although in group 2 stroke volume index increased (14%) and systemic resistance decreased (16%), both P less than 0.05 vs C. In group 2, heart rate (HR) and contractility initially increased (8% and 10%, respectively, P less than 0.05 vs C), secondary to the greater fall in afterload, followed by a significant reduction at 5 and 10 min after bepridil (9% and 10%, respectively), accompanied by a 36% increase in LV enddiastolic pressure (P less than 0.05 vs C). No such changes were observed in group 1, apart from a simultaneous decrease in HR (9%, P less than 0.05 vs C). Thus, in humans, a dose-related, biphasic haemodynamic pattern is observed with intravenous bepridil, consisting of an acute, short-lasting vasodilation, followed by late negative chronotropic and inotropic effects, which, with longterm bepridil administration, may be beneficial during myocardial ischaemic.
D000328:Adult; D000787:Angina Pectoris / Q000188:drug therapy; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D015764:Bepridil; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D011759:Pyrrolidines; D015764:Bepridil