The effect of diltiazem on coronary flow reserve in humans.

Calcium channel antagonists have been shown to blunt maximal coronary flow after brief coronary occlusion and during pharmacologic coronary dilation in animals. This property, if present in humans, would result in a reduction in coronary flow reserve in the absence of intrinsic abnormalities of the coronary circulation. A reduction of maximal vasodilator capacity by calcium channel antagonists could also constitute an important anti-ischemic mechanism of action of these agents. To evaluate the effect of calcium channel antagonists on coronary flow reserve in awake humans, we measured coronary flow reserve using the coronary Doppler catheter and intracoronary papaverine at baseline and after diltiazem administered by intravenous (125 or 250 micrograms/kg bolus, 5 micrograms/kg/min infusion, n = 8) or intracoronary (150-600 micrograms bolus, n = 10) routes. Intravenous diltiazem reduced heart rate from 77 +/- 18 to 72 +/- 17 beats/min (mean +/- SD, p less than 0.005) and reduced mean arterial pressure from 96 +/- 11 to 86 +/- 15 mm Hg (p less than 0.005). Intravenous diltiazem resulted in a small decrease in coronary flow reserve (peak-to-resting flow velocity ratio) from 3.9 +/- 1.2 to 3.6 +/- 1.1 (p less than 0.01). After intracoronary diltiazem, mean arterial pressure was unchanged (control 99 +/- 12 mm Hg, diltiazem 97 +/- 13 mm Hg), and heart rate was maintained constant by atrial pacing. Coronary flow reserve was unchanged at 3.8 +/- 0.9 at baseline and after intracoronary diltiazem. Thus, treatment with diltiazem does not invalidate the measurement of coronary flow reserve for diagnostic purposes. Furthermore, these results suggest that attenuation of maximal coronary dilation by diltiazem is not a mechanism responsible for its antianginal effects.