Booke M, Meyer J, Lingnau W, Hinder F, Traber L D, Traber D L
Department of Anesthesiology, University of Texas Medical Branch, Galveston 77555-1091, USA.
New Horiz. 1995 Feb;3(1):123-38.
Sepsis, as a general inflammatory process, affects the whole organism, mainly because of the intense vasodilation and reduced perfusion pressures associated with it. The high mortality rates seen with sepsis are correlated with a reduction in mean arterial pressure. Therefore, the restoration of adequate arterial pressures is imperative. Nitric oxide (NO.) is at least partly responsible for the vasodilation. Inhibition of nitric oxide synthase (NOS) is, therefore, a logical approach for the treatment of sepsis. As with any other vasoconstrictive drug, NOS inhibitors are clinically indicated only in hyperdynamic sepsis. In animal models, their administration leads to an immediate restoration of blood pressure, accompanied by improved myocardial, pulmonary, and renal function. An increase in oxygen extraction prevents oxygen consumption from decreasing, despite a marked reduction in cardiac output to normal concentrations. In sepsis, virtually all regional blood flows are increased. In our experiments, no organ systems showed a reduction below preseptic baseline values when NOS inhibitors were administered. Furthermore, NOS inhibition did not cause an increase in lactate concentrations, indicating adequate nutritive organ blood flow. Consequently, NOS inhibitors seem to be beneficial and safe when administered under the right circumstances and in a controlled fashion.
脓毒症作为一种全身性炎症过程，会影响整个机体，主要是因为与之相关的强烈血管舒张和灌注压力降低。脓毒症患者的高死亡率与平均动脉压降低有关。因此，恢复足够的动脉压势在必行。一氧化氮（NO.）至少部分导致了血管舒张。因此，抑制一氧化氮合酶（NOS）是治疗脓毒症的合理方法。与任何其他血管收缩药物一样，NOS抑制剂仅在高动力型脓毒症中有临床应用指征。在动物模型中，给予NOS抑制剂可使血压立即恢复，并伴有心肌、肺和肾功能改善。尽管心输出量显著降低至正常浓度，但氧摄取增加可防止氧消耗减少。在脓毒症中，几乎所有局部血流都会增加。在我们的实验中，给予NOS抑制剂时，没有任何器官系统显示低于脓毒症前基线值。此外，抑制NOS并未导致乳酸浓度升高，表明营养器官血流充足。因此，在适当情况下以可控方式给予NOS抑制剂似乎是有益且安全的。
