Engelman D T, Watanabe M, Maulik N, Engelman R M, Rousou J A, Flack J E, Deaton D W, Das D K
Department of Surgery, Baystate Medical Center, Springfield, Mass 01199, USA.
Circulation. 1996 Nov 1;94(9 Suppl):II407-11.
It has been shown that increased nitric oxide (NO) generation is associated with improved myocardial preservation during ischemia/reperfusion. This study sought to determine the optimal timing for NO supplementation in the setting of cardioplegic arrest, regional ischemia, and reperfusion.
Isolated working rat hearts were arrested with normothermic oxygenated potassium cardioplegia for 5 minutes, followed by 60 minutes of normothermic continuous cardioplegic administration with left anterior descending coronary artery (LAD) occlusion. The hearts were divided into four groups. Hearts in group 1 were ischemic/reperfused controls without L-arginine treatment. Hearts in group 2 were perfused with 3 mmol/L L-arginine for 5 minutes before cardioplegic arrest. Hearts in group 3 were perfused with 3 mmol/L L-arginine in the cardioplegia solution. Hearts in group 4 were perfused with 3 mmol/L L-arginine for 5 minutes only during initial reperfusion. Myocardial contractile function after 30 minutes of reperfusion was significantly better in group 2 compared with the other groups and was significantly lower in group 4 than group 1. Coronary flow, although decreased from base line in all groups at 30 minutes of reperfusion, was highest in group 2. The tissue accumulation of cGMP in groups 2 and 3 increased significantly after L-arginine infusion compared with the control group (group 1). In contrast, the LAD regional cGMP after reperfusion in group 4 was comparable to group 1 and significantly lower than groups 2 and 3, whereas the circumflex region cGMP in group 4 was significantly increased over group 1, comparable to groups 2 and 3. LDH release in groups 2 and 3 was significantly lower compared with groups 1 and 4.
As assessed by myocardial function and LDH release, L-arginine is most beneficial when given before cardioplegic arrest, effective during cardioplegic arrest, and detrimental during reperfusion. This suggests that L-arginine given during reperfusion is deleterious to optimal recovery of myocardial function in this ischemic model and that the effect of NO generation in the ischemic/reperfused myocardium may be dependent on the condition of the endothelium.
研究表明，一氧化氮（NO）生成增加与缺血/再灌注期间心肌保护的改善有关。本研究旨在确定在心脏停搏、局部缺血和再灌注情况下补充NO的最佳时机。
将离体工作的大鼠心脏用常温含氧钾停搏液停搏5分钟，然后在左冠状动脉前降支（LAD）闭塞的情况下进行60分钟的常温持续停搏液灌注。心脏分为四组。第1组心脏为缺血/再灌注对照组，未用L-精氨酸处理。第2组心脏在心脏停搏前5分钟用3 mmol/L L-精氨酸灌注。第3组心脏在停搏液中用3 mmol/L L-精氨酸灌注。第4组心脏仅在初始再灌注期间用3 mmol/L L-精氨酸灌注5分钟。再灌注30分钟后，第2组心肌收缩功能明显优于其他组，第4组明显低于第1组。冠状动脉血流量虽然在再灌注30分钟时所有组均较基线下降，但第2组最高。与对照组（第1组）相比，第2组和第3组在输注L-精氨酸后组织中cGMP的积累显著增加。相比之下，第4组再灌注后LAD区域的cGMP与第1组相当，明显低于第2组和第3组，而第4组回旋支区域的cGMP比第1组显著增加，与第2组和第3组相当。第2组和第3组的乳酸脱氢酶释放明显低于第1组和第4组。
通过心肌功能和乳酸脱氢酶释放评估，L-精氨酸在心脏停搏前给予最有益，在心脏停搏期间有效，而在再灌注期间有害。这表明在该缺血模型中，再灌注期间给予L-精氨酸对心肌功能的最佳恢复有害，并且缺血/再灌注心肌中NO生成的作用可能取决于内皮的状况。
