Doss D N, Estafanous F G, Ferrario C M, Brum J M, Murray P A
Center for Anesthesiology Research, Cleveland Clinic Foundation, OH 44195, USA.
Anesth Analg. 1995 Jul;81(1):30-4. doi: 10.1097/00000539-199507000-00006.
In the nonfailing heart, normovolemic hemodilution increases cardiac output and decreases total peripheral resistance (TPR). Putative mechanisms mediating the decrease in TPR include reflex vasodilation and changes in the local regulation of blood flow. Our objectives were to determine whether ablation of reflex neural mechanisms or the inhibition of nitric oxide (NO) synthase, the enzyme responsible for the synthesis of the endothelium-derived relaxing factor (EDRF-NO), modulates the systemic vasodilator response to normovolemic hemodilution. Three groups of male Sprague-Dawley rats were subjected to acute normovolemic hemodilution, which was achieved by exchanging a volume of blood equivalent to 3.8% of body weight with hydroxyethyl starch. Hemodilution increased cardiac output and decreased TPR. Subsequent administration of the NO synthase inhibitor, L-nitroarginine (LNA), returned both cardiac output and TPR to control values. Pretreatment with LNA prior to hemodilution increased TPR, an effect that was partially reversed by the NO donor, sodium nitroprusside. In this setting, hemodilution failed to decrease TPR. After spinal cord destruction by "pithing," hemodilution decreased TPR to the same extent as that observed in intact rats. This hemodilution-induced decrease in TPR was abolished by the subsequent administration of LNA. These results indicate that neural reflexes do not modulate the systemic vascular response to hemodilution. Moreover, the systemic vasodilator response to hemodilution is abolished after inhibition of endogenous NO synthesis.
在无心力衰竭的心脏中，正常血容量性血液稀释可增加心输出量并降低总外周阻力（TPR）。介导TPR降低的可能机制包括反射性血管舒张和局部血流调节的变化。我们的目的是确定反射神经机制的消融或一氧化氮（NO）合酶（负责合成内皮源性舒张因子（EDRF-NO）的酶）的抑制是否会调节对正常血容量性血液稀释的全身血管舒张反应。三组雄性Sprague-Dawley大鼠接受急性正常血容量性血液稀释，这是通过用羟乙基淀粉交换相当于体重3.8%的血量来实现的。血液稀释增加了心输出量并降低了TPR。随后给予NO合酶抑制剂L-硝基精氨酸（LNA），使心输出量和TPR均恢复到对照值。在血液稀释前用LNA预处理可增加TPR，这种作用被NO供体硝普钠部分逆转。在这种情况下，血液稀释未能降低TPR。通过“脊髓损毁”破坏脊髓后，血液稀释使TPR降低的程度与在完整大鼠中观察到的相同。随后给予LNA消除了这种血液稀释诱导的TPR降低。这些结果表明，神经反射不调节对血液稀释的全身血管反应。此外，抑制内源性NO合成后，对血液稀释的全身血管舒张反应被消除。
