Meyer J, Cox C S, Herndon D N, Nakazawa H, Lentz C W, Traber L D, Traber D L
Department of Anesthesiology, University of Texas Medical Branch, Galveston 77555-1091.
Crit Care Med. 1993 Jan;21(1):84-9. doi: 10.1097/00003246-199301000-00017.
To evaluate the hypothesis that heparin administration increases cardiac output and improves oxygenation in experimental hyperdynamic sepsis in sheep.
Prospective trial.
Laboratory at a large university-affiliated medical center.
A total of 14 sheep weighing 28 to 44 kg.
All 14 chronically instrumented sheep received a continuous infusion of Escherichia coli endotoxin (10 ng/kg/min) over 24 hrs. Seven sheep received a fixed bolus of beef lung heparin (5000 units) every 4 hrs intravenously. The other seven sheep served as controls.
The heparinized animals showed a triphasic cardiovascular response. Cardiac index increased (p < .05), and systemic vascular resistance index decreased (p < .05) at 2 hrs after the start of the endotoxin infusion (early phase, 0 to 2 hrs). Both variables returned to approximately baseline levels at 4 hrs (second period, 2 to 4 hrs). A hyperdynamic state (in terms of an increased cardiac index), a decreased systemic vascular resistance index, and a decreased mean arterial pressure (MAP) (p < .05 for all) was observed in the third phase (8 to 24 hrs). In the control group, cardiac index, systemic vascular resistance index, and MAP showed no changes in the first period, but a slight decrease in cardiac index and a slight increase in systemic vascular resistance index in the second period. The onset of the hyperdynamic state was less pronounced in the control group and cardiac index was lower (p < .05); likewise, systemic vascular resistance index was increased (p < .05) when compared with heparinized animals. Both groups developed pulmonary hypertension during the endotoxin infusion. The gas exchange in the heparin group was significantly impaired in the first and second periods, but returned to baseline levels in the hyperdynamic phase, whereas the oxygenation of the nonheparinized animals showed only minor changes in the first and second phases, but deteriorated significantly during the third phase of endotoxemia.
In this experimental model of hyperdynamic sepsis, heparin significantly influenced the cardiopulmonary performance. Heparin preserved gas exchange and increased cardiac output but lowered systemic vascular resistance and MAP in the hyperdynamic state.
评估肝素给药可增加心输出量并改善绵羊实验性高动力型脓毒症氧合的假说。
前瞻性试验。
一所大型大学附属医院的实验室。
共14只体重28至44千克的绵羊。
14只长期植入仪器的绵羊在24小时内持续输注大肠杆菌内毒素（10纳克/千克/分钟）。7只绵羊每4小时静脉注射一次固定剂量的牛肺肝素（5000单位）。另外7只绵羊作为对照。
肝素化动物呈现三相心血管反应。内毒素输注开始后2小时（早期，0至2小时），心脏指数增加（p < 0.05），全身血管阻力指数降低（p < 0.05）。这两个变量在4小时时恢复到大致基线水平（第二阶段，2至4小时）。在第三阶段（8至24小时）观察到高动力状态（以心脏指数增加为指标）、全身血管阻力指数降低以及平均动脉压（MAP）降低（所有指标p < 0.05）。在对照组中，心脏指数、全身血管阻力指数和MAP在第一阶段无变化，但在第二阶段心脏指数略有降低，全身血管阻力指数略有增加。对照组高动力状态的出现不太明显，心脏指数较低（p < 0.05）；同样，与肝素化动物相比，全身血管阻力指数增加（p < 0.05）。两组在内毒素输注期间均出现肺动脉高压。肝素组在第一和第二阶段气体交换明显受损，但在高动力阶段恢复到基线水平，而非肝素化动物的氧合在第一和第二阶段仅出现轻微变化，但在内毒素血症的第三阶段显著恶化。
在这个高动力型脓毒症实验模型中，肝素显著影响心肺功能。肝素在高动力状态下保持气体交换、增加心输出量，但降低全身血管阻力和平均动脉压。
