Responses of coronary collateral flow and dependent myocardial mechanical function to the calcium antagonist, diltiazem.

We sought to determine whether the calcium antagonist, diltiazem, increased regional myocardial collateral blood flow in a dog model in which the physiologic conditions thought to be associated with angina pectoris had been induced, and to determine if such changes would be reflected in alterations in function of the collateral-dependent myocardium. Regional myocardial function and blood flow were measured with instruments in dogs for weeks as the left circumflex artery was progressively stenosed to occlusion by an implanted ameroid constrictor. The extent of collateral development was determined in terms of the reduction in regional function induced by brief, total test occlusions. When collaterals had developed adequate for the metabolic requirements at rest, pacing tachycardia stress test produced ischemia-related hypofunction. Under these conditions, diltiazem, 20 mirogram/min/kg, increased blood flow via collateral channels from approximately 140 to 190 ml/min/100 g tissue (epicardium) and from 80 to 140 ml/min/100 g tissue (endocardium) in the colateral-dependent area without significant modification in hypofunction. Similar results were obtained in dogs with greater collateral flow reserve later in the collateral development process when the ameroid constrictor had completely occluded the vessel and stress testing did not produce hypofunction. Thus, diltiazem increased collateral flow to collateral-dependent myocardium under conditions simulating unstable angina pectoris.