Sassen L M, Soei L K, Heere T J, van Woerkens L J, Saxena P R, Verdouw P D
Laboratory for Experimental Cardiology, (Thoraxcenter), Rotterdam, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 1989 Dec;340(6 Pt 2):733-9. doi: 10.1007/BF00169682.
The present investigation compares the systemic and regional haemodynamics in nicorandil-treated and solvent-treated pigs with a concentric stenosis around the left anterior descending coronary artery. The stenosis per se led to a decrease in mean arterial blood pressure, cardiac output, stroke volume, maximum rate of rise in left ventricular pressure and transmural (more marked in the endocardium than in the epicardium) blood flow to and myocardial wall motion in the post-stenotic segment. Infusions of nicorandil (15 and 30 micrograms.kg-1.min-1, intravenously) decreased arterial blood pressure, cardiac output and the maximum rate of rise in left ventricular blood pressure. There was a tendency for epicardial blood flow in the non-stenotic segment to increase but blood flow to the ischaemic myocardium (epicardium as well as endocardium) was further compromised. Using the postsystolic wall thickening as an index for the viability of the myocardium and the Bretschneider formula for myocardial oxygen demand and the calculated myocardial oxygen consumption, we found that nicorandil further compromised the oxygen balance but did not jeopardize the viability of the myocardium. Regionally, nicorandil decreased renal blood flows but enhanced blood flows to the brains and adrenals. It is concluded that nicorandil lacks beneficial effects on the ischaemic myocardium in pigs with a concentric coronary artery stenosis. Apparently, the potential adverse effect (decrease in coronary perfusion pressure) of nicorandil outweighs its potential salutary effects (coronary vasodilatation and decrease in myocardial oxygen consumption due to peripheral vasodilatation.
本研究比较了尼可地尔治疗组和溶剂治疗组猪在左前降支冠状动脉周围存在同心狭窄情况下的全身和局部血流动力学。狭窄本身导致平均动脉血压、心输出量、每搏输出量、左心室压力最大上升速率以及狭窄后节段的跨壁血流(心内膜比心外膜更明显)和心肌壁运动减少。静脉输注尼可地尔(15和30微克·千克⁻¹·分钟⁻¹)可降低动脉血压、心输出量和左心室血压最大上升速率。非狭窄节段的心外膜血流有增加趋势,但缺血心肌(心外膜和心内膜)的血流进一步受损。以收缩期后壁增厚作为心肌存活能力的指标,采用布雷tschneider公式计算心肌需氧量和心肌耗氧量,我们发现尼可地尔进一步损害了氧平衡,但未危及心肌的存活能力。局部而言,尼可地尔减少肾血流量,但增加脑和肾上腺的血流量。结论是,尼可地尔对患有同心冠状动脉狭窄的猪的缺血心肌无有益作用。显然,尼可地尔的潜在不利影响(冠状动脉灌注压降低)超过了其潜在有益作用(冠状动脉扩张和外周血管扩张导致心肌耗氧量降低)。