ENDOTHELIUM-DERIVED RELAXING FACTOR IS IMPORTANT IN MEDIATING THE HIGH-OUTPUT STATE IN CHRONIC SEVERE ANEMIA
ENDOTHELIUM-DERIVED RELAXING FACTOR IS IMPORTANT IN MEDIATING THE HIGH-OUTPUT STATE IN CHRONIC SEVERE ANEMIA
复制标题
DOI：
10.1016/0735-1097(95)00007-q
复制
发表时间：
1995-05-01
影响因子：
24
通讯作者：
CHAWLA, LS
中科院分区：
文献类型：
--
作者：
ANAND, IS;CHANDRASHEKHAR, Y;CHAWLA, LS
目标.我们评估了慢性重度贫血患者的内皮和血管平滑肌功能，以确定基础一氧化氮水平升高是否会导致这些患者的全身血管舒张和高心输出量。背景。慢性重度贫血患者由于全身血管阻力低而处于高输出状态，但血管阻力低的原因尚不清楚。由于血红蛋白是内皮源性舒张因子的有效抑制剂，我们推测在慢性重度贫血中，低循环血红蛋白导致内皮源性舒张因子抑制作用降低。因此，基底内皮源性松弛因子活性增加，这显着导致了这种情况下出现的低全身血管阻力和高动力状态。方法。对8例慢性重度贫血患者在红细胞输注前（红细胞压积16 +/- 2% [平均值+/- SD]）和输注后24小时内（n = 6，红细胞压积30 +/- 1%）以及对照组进行了血液动力学变量和前臂血流量（使用体积描记法）测量。研究了用N-G-单甲基-L-精氨酸阻断内皮源性舒张因子活性对基线血液流变学的影响。此外，还检测了内皮依赖性和非内皮依赖性血管舒张剂对前臂血流的影响。与对照组受试者（2.8 +/- 0.7 ml/min/100 ml，p < 0.0001，95%置信区间[CI]，差值为-5至-2.5）相比，未治疗患者基线前臂血弓显著增加（6.5 +/- 1.2 ml/min/100 ml）。红细胞输注显著降低了贫血患者的血液流速，为每100 ml 3.5 +/- 1.1 ml/min（p < 0.001，95% CI差异为-4.9至-1.9），与对照组无显著差异;增加了全身血管阻力（796 +/- 141至1，230 +/- 151达因）。S . cm（-5），p < 0.001）;心输出量减少（4.9 +/-0.6至3.5 +/-0.5升/分钟每平方米，p < 0.001）。N-G-单甲基-L-精氨酸（16 μ mol/min），一种内皮衍生舒张因子的特异性抑制剂，减少前臂血流量等量（p = 0.9，对照受试者差异的95% CI为-0.7至0.8）（0.98 +/- 0.39 ml/min）和治疗患者（1.03 +/- 0.8 ml/min），但导致流量下降3倍（2.9 +/- 0.9 ml/min）（p = 0.0003，未治疗患者与对照受试者之间差异的95% CI为1.1 - 2.7）。这些发现表明贫血患者基础内皮源性舒张因子活性增加。刺激前臂，血流（内皮依赖性和内皮非依赖性）在所有组中相似，证实正常的内皮和平滑肌功能。这些发现支持了这样的假设，即增强的基底内皮源性舒张因子活性对慢性重度贫血的低全身血管阻力有重要贡献。
Objectives. We evaluated the endothelial and vascular smooth muscle function in patients with chronic severe anemia to determine whether increased basal nitric oxide levels contribute to the systemic vasodilation and high cardiac output seen in these patients.Background. Patients with chronic severe anemia have a high output state due to a low systemic vascular resistance, However, the cause of the low vascular resistance is unclear. Because hemoglobin is a potent inhibitor of endothelium-derived relaxing factor, we postulated that in chronic severe anemia, low circulating hemoglobin results in reduced inhibition of endothelium derived relaxing factor. The basal endothelium derived relaxing factor activity therefore increases, and this contributes significantly to the low systemic vascular resistance and the hyperdynamic state seen in this condition.Methods. Hemodynamic variables and forearm blood flow (using plethysmography) were measured in eight patients with chronic severe anemia before (hematocrit 16 +/- 2% [mean +/- SD]) and within 24 h of red blood cell transfusion (n = 6, hematocrit 30 +/- 1%) and in sis control subjects. The effect on baseline blood how of blocking endothelium-derived relaxing factor activity with N-G-monomethyl-L-arginine was investigated. In addition, the effects of both endothelium-dependent and endothelium-independent vasodilators on forearm blood flow were tested.Results. Baseline forearm blood bow was markedly increased in untreated patients (6.5 +/- 1.2 ml/min per 100 ml) compared with that in control subjects (2.8 +/- 0.7 ml/min per 100 ml, p < 0.0001, 95% confidence interval [CI] for difference -5 to -2.5). Red blood cell transfusion significantly reduced blood how in the anemic patients to 3.5 +/- 1.1 ml/min per 100 ml (p < 0.001, 95% CI for difference -4.9 to -1.9), which was not significantly different from that in control subjects; increased systemic vascular resistance (796 +/- 141 to 1,230 +/- 151 dynes . s . cm(-5), p < 0.001); and decreased cardiac output (4.9 +/- 0.6 to 3.5 +/- 0.5 liters/min per m(2), p < 0.001). N-G-monomethyl-L-arginine (16 mu mol/min), a specific inhibitor of endothelium-derived relaxing factor, reduced forearm blood flow by an equal amount (p = 0.9, 95% CI for difference -0.7 to 0.8) in control subjects (0.98 +/- 0.39 ml/min) and treated patients (1.03 +/- 0.8 ml/min) but caused a threefold greater decrease in flow (2.9 +/- 0.9 ml/min) in untreated patients (p = 0.0003, 95% CI for difference between untreated patients and control subjects 1.1 to 2.7). These findings suggest increased basal endothelium-derived relaxing factor activity in patients with anemia. Stimulated forearm, blood flows (both endothelium dependent and endothelium independent) were similar in all groups, confirming normal endothelial and smooth muscle function.Conclusions. These findings support the hypothesis that enhanced basal endothelium derived relaxing factor activity makes an important contribution to the low systemic vascular resistance in chronic severe anemia.