Strand O A, Leone A M, Giercksky K E, Skovlund E, Kirkebøen K A
Department of Infectious Diseases, Institute for Experimental Medical Research, Ullevål University Hospital, Oslo, Norway.
Crit Care Med. 1998 Sep;26(9):1490-9. doi: 10.1097/00003246-199809000-00015.
To test the effect of a continuous infusion of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on survival rate and hemodynamics in a pig model of endogenous peritoneal live bacterial sepsis.
Prospective, randomized trial.
Laboratory at a university medical center.
Thirty-five pigs with an average weight of 26 kg (range 21 to 33).
After surgical preparation, animals (control, n=6) given anesthesia and fluids were observed for 9 hrs. Fifteen experimental animals received 0.5 g of cecal content/kg of body weight intraperitoneally after surgery. Nine of these animals received standard anesthesia and fluids and were observed for 9 hrs or until death. Six animals received a continuous infusion of L-NMMA (10 mg/kg/hr) 3 hrs after sepsis induction. Starting 3 hrs after surgery, five nonrandomized animals were given anesthesia and fluids and received a 6-hr continuous infusion of L-NMMA (10 mg/kg/hr). An additional nine animals were anesthetized and blood samples were taken to determine plasma nitrate concentrations in nonoperated pigs.
L-NMMA treatment increased 9-hr survival in septic animals from 11% to 83% (p < .001), prevented a further decrease in mean arterial pressure and restored mean arterial pressure to control levels (p < .00002 vs. nontreated septic animals). Mean pulmonary arterial pressure increased slightly during L-NMMA infusion (p < .0003). Coronary blood flow was preserved during L-NMMA treatment. Cardiac index and urine production reached and maintained control levels during L-NMMA treatment of septic animals. Mean central venous pH did not deteriorate during L-NMMA treatment. Animals treated with L-NMMA had plasma nitrate concentrations similar to nonseptic control animals. The results from the nonseptic control group receiving L-NMMA suggest that a substantial part of the effect of L-NMMA in this model of septic shock may be due to inhibition of the constitutive nitric oxide production.
In this porcine model of peritoneal sepsis, infusion of L-NMMA increased survival rate and maintained mean arterial pressure without worsening tissue oxygenation. Coronary blood flow, cardiac index, systemic vascular resistance, and urine production were well maintained during L-NMMA treatment.
在内源性腹膜活菌败血症猪模型中，测试持续输注一氧化氮合酶抑制剂N（G）-单甲基-L-精氨酸（L-NMMA）对存活率和血流动力学的影响。
前瞻性随机试验。
大学医学中心实验室。
35头猪，平均体重26千克（范围21至33千克）。
手术准备后，对给予麻醉和液体的动物（对照组，n = 6）观察9小时。15只实验动物在术后经腹腔注射0.5克/千克体重的盲肠内容物。其中9只动物接受标准麻醉和液体治疗，并观察9小时或直至死亡。6只动物在诱导败血症3小时后接受L-NMMA持续输注（10毫克/千克/小时）。术后3小时开始，5只非随机动物接受麻醉和液体治疗，并接受6小时的L-NMMA持续输注（10毫克/千克/小时）。另外9只动物进行麻醉并采集血样以测定未手术猪的血浆硝酸盐浓度。
L-NMMA治疗使败血症动物的9小时存活率从11%提高到83%（p <.001），防止平均动脉压进一步下降，并使平均动脉压恢复到对照水平（与未治疗的败血症动物相比，p <.00002）。在L-NMMA输注期间，平均肺动脉压略有升高（p <.0003）。在L-NMMA治疗期间，冠状动脉血流量得以维持。在对败血症动物进行L-NMMA治疗期间，心脏指数和尿量达到并维持在对照水平。在L-NMMA治疗期间，平均中心静脉pH值没有恶化。接受L-NMMA治疗的动物的血浆硝酸盐浓度与非败血症对照动物相似。接受L-NMMA的非败血症对照组的结果表明，在该败血症休克模型中，L-NMMA的大部分作用可能是由于抑制了组成型一氧化氮的产生。
在该猪腹膜败血症模型中，输注L-NMMA可提高存活率并维持平均动脉压，而不会使组织氧合恶化。在L-NMMA治疗期间，冠状动脉血流量、心脏指数、全身血管阻力和尿量均得到良好维持。
