Differential effects of verapamil and diltiazem on regional blood flow and function in the canine normal and ischemic myocardium.
We studied the effects of verapamil and diltiazem on regional myocardial blood flow (RMBF, tracer microspheres) and function during ischemia in 18 open-chest dogs. Instrumentation included left ventricular and aortic pressure transducers, an electromagnetic flowmeter, and a hydraulic occluder on the circumflex coronary artery; sonocardiometry measured shortening of severely ischemic, moderately ischemic, and nonischemic subendocardial segments (% delta L). Measurements were made in the control state, 10 min after subtotal coronary stenosis, and 10 min later in control (n = 6, group I), verapamil-treated (0.3 mg/kg i.v.) (n = 6, group II), and diltiazem-treated (0.3 mg/kg i.v.) (n = 6, group III) dogs. The effects of coronary stenosis were similar in all three groups and after 20 min of coronary stenosis there were no further modifications of any parameter in group I. Verapamil and diltiazem produced similar reductions in heart rate and mean aortic pressure. In severely ischemic zones, RMBF was similarly decreased [0.22 +/- 0.03-0.12 +/- 0.04 ml/min/g, p less than 0.01 (verapamil) and 0.21 +/- 0.02-0.12 +/- 0.02 ml/min/g, p less than 0.01 (diltiazem)] without any change in function. In moderately ischemic zones, verapamil did not modify RMBF and function while diltiazem increased RMBF from 0.43 +/- 0.05 to 0.96 +/- 0.18 ml/min/g (p less than 0.05) and % delta L from 3.5 +/- 1.2 to 6.2 +/- 1.2 (p less than 0.05). In nonischemic zones, although RMBF was increased by 42.9 +/- 13.6% (p less than 0.05) with verapamil and 156.9 +/- 33.8% (p less than 0.01) with diltiazem, % delta L remained unchanged. Thus, (a) diltiazem and verapamil, although increasing flow, do not affect function in nonischemic areas; (b) diltiazem and verapamil exert almost no effects either on flow or on function in severely ischemic areas; and (c) while verapamil shows no effects on flow and function, diltiazem increases both parameters in marginal areas demonstrating its ability to preserve the viability of this zone.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D014700:Verapamil / Q000494:pharmacology*
D001552:Benzazepines; D014700:Verapamil; D004110:Diltiazem