Meadow W, Rudinsky B, Bell A, Hipps R
Department of Pediatrics, University of Chicago, IL, USA.
Crit Care Med. 1995 Apr;23(4):705-14. doi: 10.1097/00003246-199504000-00020.
To determine the effects of the inhibition of endothelium-derived relaxation factor in an animal model of neonatal group B streptococcal sepsis.
Comparison of three experimental protocols: a) N-nitro-L-arginine; b) group B streptococcal; and c) group B streptococcal/N-nitro-L-arginine.
Piglets, 1 to 2 wks old.
Endothelium-derived relaxation factor inhibition was produced in nonseptic piglets by the infusion of a competitive inhibitor of nitric oxide synthase, N-nitro-L-arginine, at 30 mg/kg (N-nitro-L-arginine protocol; n = 6). Human group B streptococcal sepsis was modeled in piglets by the continuous infusion of live group B streptococcal organisms at approximately 5 x 10(9) organisms/kg cumulative dose (group B streptococcal protocol; n = 8). Endothelium-derived relaxation factor inhibition during a group B streptococcal sepsis was produced by N-nitro-L-arginine infusion during continuing group B streptococcal infusion (group B streptococcal/N-nitro-L-arginine protocol; n = 7).
Both N-nitro-L-arginine and group B streptococcal infusion significantly increased systemic and pulmonary vascular resistance and decreased cardiac output and oxygen delivery. N-nitro-L-arginine differed from group B streptococcal infusions in its effects on systemic blood pressure (BP) (N-nitro-L-arginine increased BP while group B streptococcal infusions did not), and pulmonary/systemic vascular resistance ratio (group B streptococcal infusions increased pulmonary/systemic vascular resistance ratio more than N-nitro-L-arginine did). The group B streptococcal/N-nitro-L-arginine group differed significantly from piglets receiving continued group B streptococcal infusion without N-nitro-L-arginine in cardiac output (significantly lower in group B streptococcal/N-nitro-L-arginine), oxygen delivery (significantly lower in group B streptococcal/N-nitro-L-arginine), and pulmonary vascular resistance (significantly higher in group B streptococcal/N-nitro-L-arginine).
Group B streptococcal sepsis in human newborns and in animal models of human newborns is characterized by a hemodynamic constellation of "cold shock"--increased vascular resistance and reduced systemic blood flow. Endothelium-derived relaxation factor inhibition during group B streptococcal sepsis in piglets exacerbated many of the adverse hemodynamic consequences of group B streptococcal infusion. We speculate that endothelium-derived relaxation factor inhibition has no foreseeable therapeutic role in neonatal septic shock.
在新生儿B族链球菌败血症动物模型中确定内皮源性舒张因子抑制的作用。
三种实验方案的比较：a）N-硝基-L-精氨酸；b）B族链球菌；c）B族链球菌/N-硝基-L-精氨酸。
1至2周龄的仔猪。
通过以30mg/kg输注一氧化氮合酶竞争性抑制剂N-硝基-L-精氨酸，在非败血症仔猪中产生内皮源性舒张因子抑制作用（N-硝基-L-精氨酸方案；n = 6）。通过以约5×10⁹个菌/kg的累积剂量持续输注活的B族链球菌，在仔猪中模拟人类B族链球菌败血症（B族链球菌方案；n = 8）。在持续输注B族链球菌期间通过输注N-硝基-L-精氨酸，在B族链球菌败血症期间产生内皮源性舒张因子抑制作用（B族链球菌/N-硝基-L-精氨酸方案；n = 7）。
N-硝基-L-精氨酸和B族链球菌输注均显著增加全身和肺血管阻力，并降低心输出量和氧输送。N-硝基-L-精氨酸与B族链球菌输注在对全身血压（BP）的影响上有所不同（N-硝基-L-精氨酸使BP升高，而B族链球菌输注则不然），以及在肺/全身血管阻力比值方面（B族链球菌输注比N-硝基-L-精氨酸更能增加肺/全身血管阻力比值）。B族链球菌/N-硝基-L-精氨酸组与未使用N-硝基-L-精氨酸而持续接受B族链球菌输注的仔猪相比，在心输出量（B族链球菌/N-硝基-L-精氨酸组显著更低）、氧输送（B族链球菌/N-硝基-L-精氨酸组显著更低）和肺血管阻力（B族链球菌/N-硝基-L-精氨酸组显著更高）方面有显著差异。
人类新生儿及人类新生儿动物模型中的B族链球菌败血症具有“冷休克”的血流动力学特征——血管阻力增加和全身血流减少。仔猪B族链球菌败血症期间内皮源性舒张因子抑制加剧了B族链球菌输注的许多不良血流动力学后果。我们推测内皮源性舒张因子抑制在新生儿感染性休克中没有可预见的治疗作用。
