Kitakaze M, Node K, Minamino T, Kosaka H, Shinozaki Y, Mori H, Inoue M, Hori M, Kamada T
First Department of Medicine, Osaka University School of Medicine, Japan.
J Am Coll Cardiol. 1996 Jun;27(7):1804-12. doi: 10.1016/0735-1097(96)00064-2.
This study was undertaken to examine whether nitric oxide released in ischemic myocardium decreases the coronary vascular resistance and attenuates the severity of contractile and metabolic dysfunction.
Endothelium-derived relaxing factor, recently identified as nitric oxide, is a potent relaxant of coronary smooth muscle.
The left anterior descending coronary artery was perfused through an extracorporeal bypass tube placed in the carotid artery in 56 open chest dogs. After hemodynamic stabilization, we occluded this bypass tube to decrease coronary blood flow to one third of the control flow. Thereafter, we maintained a constant coronary perfusion pressure (40.9 +/- 3.1 mm Hg).
Under ischemic conditions, the coronary arteriovenous differences in nitrate and nitrite (end products of nitric oxide) increased (from 3.5 +/- 0.4 [mean +/- SEM] to 12.9 +/- 2.1 mumol/liter, p < 0.01). NG-Monomethyl L-arginine (3 micrograms/kg body weight per min, intracoronary) decreased the coronary arteriovenous differences in nitrate and nitrite (5.0 +/- 0.9 mumol/liter, p < 0.05) and coronary blood flow (from 29.8 +/- 0.5 to 18.1 +/- 1.1 ml/100 g per min, p < 0.001). Fractional shortening (from 3.7 +/- 1.0 to -1.3 +/- 0.7%, p < 0.001) and lactate extraction ratio (from -44.0 +/- 4.1 to -59.2 +/- 4.9%, p < 0.005) of the perfused area also decreased. These values were restored by the concomitant administration of L-arginine. Blood flow to the endomyocardium was decreased relative to the epimyocardium. A reduction in coronary blood flow and worsening of myocardial contractile and metabolic functions due to the administration of NG-monomethyl L-arginine during ischemia were observed in denervated hearts. A reduction in coronary blood flow in ischemic myocardium was observed with the administration of NW-nitro-L-arginine methyl ester as well, although neither NW-nitro-L-arginine methyl ester nor NG-monomethyl L-arginine changed coronary blood flow and myocardial contractile and metabolic functions in the nonischemic myocardium. The cyclic guanosine monophosphate content of epicardial coronary artery increased due to myocardial ischemia; this increase was attenuated with NG-monomethyl L-arginine treatment.
We conclude that endogenous nitric oxide predominantly decreases the coronary vascular resistance of ischemic endomyocardium, thereby improving myocardial contractility and metabolic function.
本研究旨在探讨缺血心肌中释放的一氧化氮是否能降低冠状动脉血管阻力，并减轻收缩和代谢功能障碍的严重程度。
内皮源性舒张因子，最近被鉴定为一氧化氮，是冠状动脉平滑肌的一种强效舒张剂。
通过置于56只开胸犬颈动脉的体外循环管灌注左前降支冠状动脉。在血流动力学稳定后，我们阻断该循环管以将冠状动脉血流量减少至对照流量的三分之一。此后，我们维持恒定的冠状动脉灌注压（40.9±3.1 mmHg）。
在缺血条件下，硝酸盐和亚硝酸盐（一氧化氮的终产物）的冠状动脉动静脉差值增加（从3.5±0.4[平均值±标准误]增至12.9±2.1 μmol/升，p<0.01）。NG-单甲基L-精氨酸（3微克/千克体重每分钟，冠状动脉内给药）降低了硝酸盐和亚硝酸盐的冠状动脉动静脉差值（5.0±0.9 μmol/升，p<0.05）以及冠状动脉血流量（从29.8±0.5降至18.1±1.1毫升/100克每分钟，p<0.001）。灌注区域的缩短分数（从3.7±1.0降至-1.3±0.7%，p<0.001）和乳酸摄取率（从-44.0±4.1降至-59.2±4.9%，p<0.005）也降低。这些值通过同时给予L-精氨酸得以恢复。心内膜血流相对于心外膜血流减少。在去神经心脏中，观察到缺血期间因给予NG-单甲基L-精氨酸导致冠状动脉血流量减少以及心肌收缩和代谢功能恶化。给予Nω-硝基-L-精氨酸甲酯时，缺血心肌中的冠状动脉血流量也减少，尽管Nω-硝基-L-精氨酸甲酯和NG-单甲基L-精氨酸均未改变非缺血心肌中的冠状动脉血流量以及心肌收缩和代谢功能。心肌缺血导致心外膜冠状动脉的环磷酸鸟苷含量增加；NG-单甲基L-精氨酸处理可减弱这种增加。
我们得出结论，内源性一氧化氮主要降低缺血心内膜的冠状动脉血管阻力，从而改善心肌收缩力和代谢功能。
