Zhang H, Benlabed M, Spapen H, Nguyen D N, Vincent J L
Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium.
J Surg Res. 1994 Oct;57(4):470-9. doi: 10.1006/jsre.1994.1172.
By its microvascular and anti-inflammatory actions, prostaglandin E1 (PGE1) has been suggested both in animal models and in humans to have a therapeutic value in sepsis. To investigate whether PGE1 could improve the oxygen extraction capabilities in severe sepsis, our study focused on the relationship between oxygen uptake (VO2) and oxygen delivery (DO2) during an acute reduction in blood flow induced by cardiac tamponade in endotoxic dogs. Thirty anesthetized, ventilated dogs were divided into three groups. A first group (N = 10) served as a control receiving 20 ml/kg/hr of saline intravenously. A second group (N = 10) received PGE1 at 100 ng/kg/min along with the same saline infusion. A third group (N = 10) received the same dose of PGE1 with only 1 ml/kg/hr of saline. Thirty minutes after the initiation of this therapy, Escherichia coli endotoxin (2 mg/kg) was injected in each dog. In each group, the administration of PGE1, fluids, or both was continued throughout the study. Tamponade was then induced by repeated bolus injections of warm saline into the pericardial space. Steady-state measurements of VO2 (derived from the expired gases) and DO2 (the product of cardiac index and oxygen content) were obtained sequentially after each saline injection. The administration of PGE1 + fluids resulted in significant increases in stroke volume, cardiac index, and DO2 and reductions in systemic and pulmonary vascular resistance. Stroke volume and cardiac index were lower in the PGE1 alone than in the PGE1 + fluids group. The VO2 levels at critical DO2 (DO2crit) were identical. However, DO2crit, which was 12.2 +/- 2.8 ml/kg/min in the control group, was significantly decreased to 9.8 +/- 2.0 ml/kg/min in the PGE1 + fluids and to 9.3 +/- 2.7 ml/kg/min in the PGE1 alone group (both P < 0.05). Critical oxygen extraction ratio (O2ERcrit) which was 47 +/- 14% in the control group, was increased to 63 +/- 16% in the PGE1 + fluids group and to 61 +/- 17% in the PGE1 alone group (both P < 0.05). To investigate whether PGE1 also improves oxygen extraction capabilities in the absence of endotoxin, a second series of experiments was performed in 14 dogs, receiving saline alone (Control, N = 7) or plus PGE1 at 100 ng/kg/min (PGE1, N = 7). DO2crit was 10.7 +/- 2.9 ml/kg/min in the PGE1 group vs 10.1 +/- 1.8 ml/kg/min in the control group (NS). O2ERcrit tended to be higher in the PGE1 group than that in the control group (68 +/- 13% vs 60 +/- 15%, P = 0.054).(ABSTRACT TRUNCATED AT 400 WORDS)
通过其微血管和抗炎作用,前列腺素E1(PGE1)在动物模型和人类中均被认为在脓毒症中具有治疗价值。为了研究PGE1是否能改善严重脓毒症患者的氧摄取能力,我们的研究聚焦于内毒素血症犬心包填塞导致急性血流减少期间氧摄取(VO2)与氧输送(DO2)之间的关系。30只麻醉通气犬被分为三组。第一组(N = 10)作为对照组,静脉注射20 ml/kg/hr的生理盐水。第二组(N = 10)接受100 ng/kg/min的PGE1并同时输注相同的生理盐水。第三组(N = 10)接受相同剂量的PGE1,但仅输注1 ml/kg/hr的生理盐水。该治疗开始30分钟后,每只犬注射大肠杆菌内毒素(2 mg/kg)。在每组中,整个研究过程持续给予PGE1、液体或两者。然后通过向心包腔反复推注温盐水诱导心包填塞。每次注射盐水后依次获得VO2(源自呼出气体)和DO2(心指数与氧含量的乘积)的稳态测量值。给予PGE1 + 液体导致每搏量、心指数和DO2显著增加,全身和肺血管阻力降低。单独使用PGE1组的每搏量和心指数低于PGE1 + 液体组。临界DO2(DO2crit)时的VO2水平相同。然而,对照组的DO2crit为12.2±2.8 ml/kg/min,PGE1 + 液体组显著降至9.8±2.0 ml/kg/min,单独使用PGE1组降至9.3±2.7 ml/kg/min(两者P < 0.05)。对照组的临界氧摄取率(O2ERcrit)为47±14%,PGE1 + 液体组增至63±16%,单独使用PGE1组增至61±17%(两者P < 0.05)。为了研究PGE1在无内毒素情况下是否也能改善氧摄取能力,对14只犬进行了第二项系列实验,这些犬单独接受生理盐水(对照组,N = 7)或加用100 ng/kg/min的PGE1(PGE1组,N = 7)。PGE1组的DO2crit为10.7±2.9 ml/kg/min,对照组为10.1±1.8 ml/kg/min(无显著性差异)。PGE1组的O2ERcrit倾向于高于对照组(68±13%对60±15%,P = 0.054)。(摘要截断于400字)