Differential Effects of Verapamil and Diltiazem on Regional Blood Flow and Function in the Canine Normal and Ischemic Myocardium

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Abstract
The effects of verapamil and diltiazem on regional myocardial blood flow (RMBF, tracer microspheres) and function during ischemia in 18 open-chest dogs were studied. 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 [no.] = 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 3 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 per g, P < 0.01 (verapamil) and 0.21 .+-. 0.02-0.12 .+-. 0.02 ml/min per g, P < 0.01 (diltiazem)] without any change in function. In moderately ischemic zones, verapamil did mot modify RMBF and function while diltiazem increased RMBF from 0.43 .+-. 0.05 6o 0.96 .+-. 0.18 ml/min per g (P < 0.05) and %.DELTA.L from 3.5 .+-. 1.2 to 6.2 .+-. 1.2 (P < 0.05). In nonischemic zones, although RMBF was increased by 42.9 .+-. 13.6% (P < 0.05) with verapamil and 156.9 .+-. 33.8% (P < 0.01) with diltiazem, %.DELTA.L remained unchanged. Evidently, diltiazem and verapamil, although increasing flow, do not affect function in nonischemic areas; diltiazem and verapamil exert almost no effects either on flow or on function in severely ischemic areas, and, 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.