Koifman Bella, Topilski Ian, Megidish Ricki, Zelmanovich Laslo, Chernihovsky Tamara, Bykhovsy Elda, Keren Gad
Department of Cardiology, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Am J Cardiol. 2006 Jul 15;98(2):172-7. doi: 10.1016/j.amjcard.2006.01.085. Epub 2006 May 12.
The purpose of the present study was to evaluate the effects of losartan and the combination of losartan and L-arginine on endothelial function and hemodynamic variables in patients with heart failure (HF). Endothelium-dependent vasodilation is impaired in patients with HF. It was hypothesized that the administration of losartan and the combination of losartan and L-arginine might increase nitric oxide production and have a beneficial additive effect on endothelial function and hemodynamic variables in patients with HF. Nine patients with HF (ejection fraction<35%) were given losartan 50 mg orally on 2 consecutive days. On the second day, 1 hour after losartan 50 mg administration, L-arginine 20 g was given by intravenous infusion. Endothelial function in the form of endothelium-dependent brachial artery flow-mediated vasodilation (FMV) was measured by ultrasound. Hemodynamic variables were estimated using Doppler echocardiography at baseline and at 2 and 4 hours after losartan alone and after combination therapy. Urinary levels of nitrite (NO2) or nitrate (NO3) were measured. Four hours after losartan administration, significant reductions in systemic vascular resistance and estimated end-systolic elastase were observed. On the second day, 1 hour after L-arginine infusion, an additive hemodynamic effect was observed, with significant increases in the cardiac index and stroke volume and significant reductions in systemic vascular resistance and calculated left ventricular end-diastolic pressure. A trend toward improved FMV was observed with losartan alone, but without statistical significance. Combination therapy significantly improved postintervention FMV compared with baseline. The increase in urinary nitric oxide excretion after losartan treatment and combination therapy was significantly correlated with improved hemodynamic variables and improved FMV. In conclusion, losartan induces significant afterload reduction, reduced contractility, and increased nitric oxide urinary excretion. The combination of L-arginine and losartan seems to have superior effects on hemodynamic variables and endothelium-dependent vasodilation compared with losartan alone.
本研究的目的是评估氯沙坦以及氯沙坦与L-精氨酸联合用药对心力衰竭（HF）患者内皮功能和血流动力学变量的影响。HF患者存在内皮依赖性血管舒张功能受损的情况。研究假设，给予氯沙坦以及氯沙坦与L-精氨酸联合用药可能会增加一氧化氮生成，并对HF患者的内皮功能和血流动力学变量产生有益的相加作用。9例HF患者（射血分数<35%）连续2天口服50mg氯沙坦。在第二天，给予50mg氯沙坦1小时后，静脉输注20g L-精氨酸。通过超声测量以内皮依赖性肱动脉血流介导的血管舒张（FMV）形式的内皮功能。在基线以及单独使用氯沙坦后和联合治疗后2小时及4小时，使用多普勒超声心动图评估血流动力学变量。测量尿中亚硝酸盐（NO2）或硝酸盐（NO3）水平。给予氯沙坦4小时后，观察到全身血管阻力和估计的收缩末期弹性显著降低。在第二天，给予L-精氨酸输注1小时后，观察到相加的血流动力学效应，心指数和每搏量显著增加，全身血管阻力和计算的左心室舒张末期压力显著降低。单独使用氯沙坦时观察到FMV有改善趋势，但无统计学意义。与基线相比，联合治疗显著改善了干预后的FMV。氯沙坦治疗和联合治疗后尿中一氧化氮排泄增加与血流动力学变量改善和FMV改善显著相关。总之，氯沙坦可显著降低后负荷、降低收缩力并增加尿中一氧化氮排泄。与单独使用氯沙坦相比，L-精氨酸与氯沙坦联合用药似乎对血流动力学变量和内皮依赖性血管舒张具有更优的效果。
