Engelman D T, Watanabe M, Engelman R M, Rousou J A, Flack J E, Deaton D W, Das D K
Department of Surgery, University of Connecticut School of Medicine, Farmington, USA.
J Thorac Cardiovasc Surg. 1995 Oct;110(4 Pt 1):1047-53. doi: 10.1016/s0022-5223(05)80173-4.
Myocardial ischemia and reperfusion may result in endothelial dysfunction and reduced release of nitric oxide. With the use of an amperometric sensor, the first direct measurements of constitutive nitric oxide release from a beating heart were measured from the coronary effluent of isolated working rat hearts subjected to ischemia and reperfusion. Rats, six to eight per group, were randomly studied as follows: control (no pretreatment) and pretreatment with the nitric oxide donor L-arginine (3 mmol/L), its enantiomer D-arginine (3 mmol/L), nitric oxide inhibitor N omega-nitro-L-arginine methyl ester (100 mumol/L), and combined N omega-nitro-L-arginine methyl ester/L-arginine. Isolated hearts were pretreated for 10 minutes before 30 minutes of global ischemia and 30 minutes of reperfusion. A nonischemic control group (n = 4) was continuously perfused with oxygenated unsupplemented buffer. After ischemia/reperfusion, hearts supplemented with L-arginine recovered significantly (p < 0.05) increased developed pressure, first derivative of the aortic pressure (dP/dtmax), and aortic flow compared with all other hearts that underwent ischemia/reperfusion. In addition, nitric oxide release was significantly (p < 0.05) increased during reperfusion in the L-arginine group. During reperfusion, the recovery of aortic flow correlated with nitric oxide release (r = 0.81, p < 0.0001). We conclude that after ischemia/reperfusion, endothelial dysfunction results in decreased nitric oxide release, which can be ameliorated with L-arginine pretreatment. The direct cytoprotective properties of nitric oxide may contribute to improved functional recovery in hearts pretreated with L-arginine. Augmentation of the L-arginine/nitric oxide pathway may provide a new approach for improved recovery after cardiovascular operations.
心肌缺血再灌注可能导致内皮功能障碍和一氧化氮释放减少。使用安培传感器，首次直接测量了经历缺血再灌注的离体工作大鼠心脏冠脉流出液中内源性一氧化氮的释放。每组6至8只大鼠，随机进行如下研究：对照组（无预处理）、一氧化氮供体L-精氨酸（3 mmol/L）预处理组、其对映体D-精氨酸（3 mmol/L）预处理组、一氧化氮抑制剂Nω-硝基-L-精氨酸甲酯（100 μmol/L）预处理组以及Nω-硝基-L-精氨酸甲酯/L-精氨酸联合预处理组。离体心脏在经历30分钟全心缺血和30分钟再灌注前先预处理10分钟。一个非缺血对照组（n = 4）持续用未添加其他成分的含氧缓冲液灌注。缺血/再灌注后，与所有其他经历缺血/再灌注的心脏相比，补充L-精氨酸的心脏在左心室发展压、主动脉压一阶导数（dP/dtmax）和主动脉流量方面显著（p < 0.05）增加。此外，L-精氨酸组在再灌注期间一氧化氮释放显著（p < 0.05）增加。再灌注期间，主动脉流量的恢复与一氧化氮释放相关（r = 0.81，p < 0.0001）。我们得出结论，缺血/再灌注后，内皮功能障碍导致一氧化氮释放减少，L-精氨酸预处理可改善这一情况。一氧化氮的直接细胞保护特性可能有助于改善L-精氨酸预处理心脏的功能恢复。增强L-精氨酸/一氧化氮途径可能为改善心血管手术后的恢复提供一种新方法。
