Rossen J D, Simonetti I, Marcus M L, Braun P, Winniford M D
Cardiovascular Division, University of Iowa College of Medicine, Iowa City.
Circulation. 1989 Nov;80(5):1240-6. doi: 10.1161/01.cir.80.5.1240.
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.
钙通道拮抗剂已被证明在动物短暂冠状动脉闭塞后及药物性冠状动脉扩张期间会削弱最大冠状动脉血流量。如果人类也存在这种特性，那么在冠状动脉循环无内在异常的情况下，将会导致冠状动脉血流储备减少。钙通道拮抗剂降低最大血管扩张能力也可能构成这些药物重要的抗缺血作用机制。为评估钙通道拮抗剂对清醒人类冠状动脉血流储备的影响，我们在基线时以及静脉注射地尔硫䓬（125或250微克/千克推注，5微克/千克/分钟输注，n = 8）或冠状动脉内注射（150 - 600微克推注，n = 10）后，使用冠状动脉多普勒导管和冠状动脉内注射罂粟碱测量冠状动脉血流储备。静脉注射地尔硫䓬使心率从77±18次/分钟降至72±17次/分钟（平均值±标准差，p < 0.005），平均动脉压从96±11毫米汞柱降至86±15毫米汞柱（p < 0.005）。静脉注射地尔硫䓬导致冠状动脉血流储备（峰值与静息血流速度比值）略有下降，从3.9±1.2降至3.6±1.1（p < 0.01）。冠状动脉内注射地尔硫䓬后，平均动脉压未改变（对照组99±12毫米汞柱，地尔硫䓬组97±13毫米汞柱），通过心房起搏使心率保持恒定。冠状动脉血流储备在基线时及冠状动脉内注射地尔硫䓬后均未改变，为3.8±0.9。因此，地尔硫䓬治疗不会使用于诊断目的的冠状动脉血流储备测量无效。此外，这些结果表明，地尔硫䓬对最大冠状动脉扩张的减弱不是其抗心绞痛作用的机制。
