Duncker D J, Mizrahi J, Bache R J
Department of Internal Medicine, University of Minnesota Medical School, Minneapolis 00000, USA.
J Cardiovasc Pharmacol. 1995 May;25(5):823-32. doi: 10.1097/00005344-199505000-00020.
We examined the effect of the novel nitrovasodilator ITF 296 and isosorbide dinitrate (ISDN) on myocardial blood flow (BF) distal to a coronary artery stenosis. Eleven dogs with a Doppler velocity probe, hydraulic occluder, and indwelling microcatheter in the left anterior descending coronary artery (LAD) were studied during treadmill exercise in the presence of a coronary artery stenosis. On separate days, the effects of ITF 296 in doses of 4 and 20 micrograms/kg/min i.v. or ISDN 20 micrograms/kg/min i.v. were compared. Coronary pressure distal to the stenosis was maintained constant during the control period and after administration of either nitrovasodilator. Neither ITF 296 nor ISDN significantly altered heart rate (HR), arterial blood pressure (BP), or left ventricular end-diastolic pressure (LVEDP). In the presence of a stenosis that decreased distal coronary pressure to 58 +/- 4 mm Hg, mean myocardial BF measured with microspheres was 0.91 +/- 0.08 ml/min/g in the LAD-dependent region and 2.36 +/- 0.11 ml/min/g in the posterior control region, respectively. With no change in distal coronary pressure, ITF 296 increased mean BF in the LAD region to 1.25 +/- 0.05 ml/min/g (4 micrograms/kg/min i.v.) and 1.40 +/- 0.10 ml/min/g (20 micrograms/kg/min i.v.), whereas ISDN (20 micrograms/kg/min i.v.) increased flow to 1.28 +/- 0.18 ml/min/g (each p < 0.05). The increase in BF occurred exclusively in the deeper layers, with no change in subepicardial BF. Consequently, the endocardial/epicardial (endo/epi) BF ratio increased from 0.33 +/- 0.04 during control stenosis to 0.70 +/- 0.10 after ITF 296 (20 micrograms/kg/min), and to 0.56 +/- 0.08 after ISDN (each p < 0.05). Neither ITF 296 nor ISDN had an effect on myocardial BF in the normally perfused control region. Therefore, both ITF 296 and ISDN improved BF to the deeper myocardial layers distal to a coronary artery stenosis. This effect occurred without alterations in stenosis severity or diastolic intraventricular pressure, suggesting that these agents act by dilating the penetrating arteries which deliver BF to the subendocardium.
我们研究了新型硝基血管扩张剂ITF 296和硝酸异山梨酯（ISDN）对冠状动脉狭窄远端心肌血流（BF）的影响。在冠状动脉狭窄的情况下，对11只在左前降支冠状动脉（LAD）中植入多普勒速度探头、液压闭塞器和留置微导管的犬进行跑步机运动实验研究。在不同日期，比较了静脉注射剂量为4和20微克/千克/分钟的ITF 296或静脉注射20微克/千克/分钟的ISDN的效果。在对照期和给予任何一种硝基血管扩张剂后，狭窄远端的冠状动脉压力保持恒定。ITF 296和ISDN均未显著改变心率（HR）、动脉血压（BP）或左心室舒张末期压力（LVEDP）。在存在使远端冠状动脉压力降至58±4毫米汞柱的狭窄情况下，用微球测量的LAD依赖区域的平均心肌BF分别为0.91±0.08毫升/分钟/克，后对照区域为2.36±0.11毫升/分钟/克。在远端冠状动脉压力无变化的情况下，ITF 296将LAD区域的平均BF增加至1.25±0.05毫升/分钟/克（静脉注射4微克/千克/分钟）和1.40±0.10毫升/分钟/克（静脉注射20微克/千克/分钟），而ISDN（静脉注射20微克/千克/分钟）将血流增加至1.28±0.18毫升/分钟/克（各p<0.05）。BF的增加仅发生在较深层，心外膜下BF无变化。因此，心内膜/心外膜（内膜/外膜）BF比值从对照狭窄时的0.33±0.04增加到ITF 296（20微克/千克/分钟）后的0.70±0.10，以及ISDN后的0.56±0.08（各p<0.05）。ITF 296和ISDN对正常灌注的对照区域的心肌BF均无影响。因此，ITF 296和ISDN均改善了冠状动脉狭窄远端较深层心肌的BF。这种作用在狭窄严重程度或舒张期心室内压力无改变的情况下发生，表明这些药物通过扩张向心内膜下输送BF的穿通动脉起作用。
