Bone H G, Schenarts P J, Booke M, McGuire R, Harper D, Traber L D, Traber D L
Department of Anesthesiology, University of Texas Medical Branch, Galveston 77555-0833, USA.
Crit Care Med. 1997 Jun;25(6):1010-8. doi: 10.1097/00003246-199706000-00019.
Excessive production of nitric oxide significantly contributes to the hyperdynamic state associated with sepsis. The ability of hemoglobin to scavenge nitric oxide may therefore be beneficial in the treatment of sepsis. In this study, we determined the effects of different doses of the modified human pyridoxalated hemoglobin polyoxyethylene conjugate in an ovine model of hyperdynamic sepsis.
Prospective, experimental study.
Large animal research laboratory at a university medical center.
Sheep (n = 23) were surgically prepared for chronic study. After a 5-day recovery period, all animals received a continuous infusion of live Pseudomonas aeruginosa (2.5 x 10(6) colony-forming units/min) for the next 48 hrs. After 24 hrs of sepsis, the animals were divided into four groups: a) six sheep were used as controls and received a bolus of 200-mL vehicle; b) three sheep received a bolus of 50 mg/kg hemoglobin; c) six sheep received 100 mg/kg of hemoglobin; d) six sheep received 200 mg/kg of hemoglobin.
All animals that survived the first 24 hrs of sepsis (n = 21) developed a hyperdynamic circulation. All three doses of hemoglobin reversed this hyperdynamic state by increasing mean arterial pressure and systemic vascular resistance while decreasing cardiac index. Pulmonary arterial pressure increased after hemoglobin infusion. Increased pulmonary arterial pressure did not affect arterial oxygen saturation nor result in the development of pulmonary edema. Infusion of hemoglobin also caused a 30-fold increase in endothelin-1 plasma concentrations and significantly decreased nitrate and nitrite plasma concentrations.
The infusion of low doses of pyridoxalated hemoglobin polyoxyethylene conjugate in septic sheep reverses the hyperdynamic circulatory state. An increase in pulmonary arterial pressure was the only observed hemodynamic side effect; changes in the structure or function of other organ systems, or their biochemical correlates were not investigated in this study. In addition to a possible nitric oxide scavenging effect, pyridoxalated hemoglobin polyoxyethylene may affect the nitric oxide synthase and endothelin systems.
一氧化氮的过量产生显著促成了与脓毒症相关的高动力状态。因此，血红蛋白清除一氧化氮的能力可能对脓毒症的治疗有益。在本研究中，我们在高动力脓毒症的绵羊模型中确定了不同剂量的改良人吡哆醛化血红蛋白聚氧乙烯结合物的作用。
前瞻性实验研究。
大学医学中心的大型动物研究实验室。
绵羊（n = 23）接受手术准备以进行长期研究。经过5天的恢复期后，所有动物在接下来的48小时内接受持续输注活的铜绿假单胞菌（2.5×10⁶ 菌落形成单位/分钟）。脓毒症24小时后，将动物分为四组：a）六只绵羊作为对照组，接受200毫升载体的推注；b）三只绵羊接受50毫克/千克血红蛋白的推注；c）六只绵羊接受100毫克/千克血红蛋白；d）六只绵羊接受200毫克/千克血红蛋白。
所有在脓毒症最初24小时内存活的动物（n = 21）均出现高动力循环。所有三个剂量的血红蛋白通过增加平均动脉压和全身血管阻力，同时降低心脏指数，逆转了这种高动力状态。输注血红蛋白后肺动脉压升高。肺动脉压升高并未影响动脉血氧饱和度，也未导致肺水肿的发生。输注血红蛋白还使血浆内皮素-1浓度增加了30倍，并显著降低了血浆硝酸盐和亚硝酸盐浓度。
在脓毒症绵羊中输注低剂量的吡哆醛化血红蛋白聚氧乙烯结合物可逆转高动力循环状态。肺动脉压升高是唯一观察到的血流动力学副作用；本研究未调查其他器官系统的结构或功能变化及其生化相关性。除了可能的一氧化氮清除作用外，吡哆醛化血红蛋白聚氧乙烯可能会影响一氧化氮合酶和内皮素系统。
