Verdouw P D, Sassen L M, Duncker D J, Schmeets I O, Rensen R J, Saxena P R
Laboratory for Experimental Cardiology, Erasmus University Rotterdam, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 1987 Sep;336(3):352-8. doi: 10.1007/BF00172690.
The present investigation was conducted to study systemic and regional haemodynamic effects of nicorandil, a potent coronary vasodilator, after intravenous or local intracoronary administration in anaesthetized or conscious pigs. Intravenous infusions of nicorandil for 10 min in both anaesthetized (15, 30, 75 and 150 micrograms.kg-1.min-1) and conscious (20, 40 and 80 micrograms.kg-1.min-1) pigs reduced arterial blood pressure, stroke volume, left ventricular end-diastolic pressure (LVEDP) and systemic vascular resistance, but increased heart rate and maxLVdP/dt. Since nicorandil decreased LVEDP at doses which did not affect arterial blood pressure, the drug may be considered as a more potent venodilator than arterial dilator. Nicorandil increased cardiac output only in conscious animals due to a more marked tachycardia (85% after 80 micrograms.kg-1.min-1) than in anaesthetized animals (30% after 75 micrograms.kg-1.min-1). The nicorandil-induced increase in heart rate and maxLVdP/dt, being substantially attenuated in conscious pigs after treatment with propranolol, can be ascribed to a reflex activation of the sympathetic nervous system following the fall in arterial pressure. Although cardiac output did not change in anaesthetized animals, intravenous infusions of nicorandil did cause a redistribution of blood flow in favour of organs such as the heart, adrenals, spleen, small intestine and brain at the expense of that to the stomach and kidneys; hepatic artery and skeletal muscle blood flow did not change. The increase in myocardial blood flow, primarily to the subepicardial layers, was associated with an enhancement in coronary venous oxygen content and was also notices after intracoronary infusions of nicorandil (0.6, 1.5, 3 and 6 micrograms.kg-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
本研究旨在探讨强效冠状动脉扩张剂尼可地尔在麻醉或清醒猪体内静脉注射或冠状动脉内局部给药后的全身和局部血流动力学效应。在麻醉猪（剂量为15、30、75和150微克·千克⁻¹·分钟⁻¹）和清醒猪（剂量为20、40和80微克·千克⁻¹·分钟⁻¹）中静脉输注尼可地尔10分钟，可降低动脉血压、每搏输出量、左心室舒张末期压力（LVEDP）和全身血管阻力，但会增加心率和最大左心室dp/dt。由于尼可地尔在不影响动脉血压的剂量下可降低LVEDP，因此该药物可被认为是一种比动脉扩张剂更强效的静脉扩张剂。尼可地尔仅在清醒动物中增加心输出量，这是因为其心动过速比麻醉动物更明显（80微克·千克⁻¹·分钟⁻¹后增加85%）（75微克·千克⁻¹·分钟⁻¹后增加30%）。尼可地尔引起的心率和最大左心室dp/dt增加在普萘洛尔治疗后的清醒猪中显著减弱，这可归因于动脉压下降后交感神经系统的反射性激活。尽管麻醉动物的心输出量没有变化，但静脉输注尼可地尔确实导致了血流重新分布，有利于心脏、肾上腺、脾脏、小肠和大脑等器官，而以胃和肾脏的血流为代价；肝动脉和骨骼肌血流没有变化。心肌血流量增加，主要是心外膜下层，与冠状静脉氧含量增加有关，冠状动脉内输注尼可地尔（0.6、1.5、3和6微克·千克⁻¹·分钟⁻¹）后也观察到这种情况。（摘要截取自250字）
