Dimmeler S, Kum C K, Troost C, Auweiler M, Lechleuthner A, Nagelschmidt M, Neugebauer E
Medical Clinic IV, University of Frankfurt, Germany.
Shock. 1996 Mar;5(3):213-6. doi: 10.1097/00024382-199603000-00008.
Porcine hypodynamic shock was induced by continuous infusion of 5 micrograms lipopolysaccharide/kg per hour. This resulted in a decrease of cardiac output from baseline values of 3.5 +/- .9 L/min to 1.5 +/- .8 L/min and a reduced left ventricular stroke work index in the endotoxin-group (n = 6 animals). Pretreatment with the H1-antagonist dimethindene (2 mg/kg) in a second group (n = 6) significantly prevented these effects. Furthermore animals pretreated with the H1-antagonist showed a stable mean arterial blood pressure, whereas the control endotoxin-treated group revealed a drastic reduction in mean arterial blood pressure (99 +/- 4.7 mmHg versus 65.8 +/- 10 mmHg after 240 min, respectively). Pulmonary function and systemic vascular resistance were not ameliorated by the H1-antagonist in hypodynamic shock. Gastrointestinal mucosal pH (pHi), which indicates oxygenation of the mucosa, was decreased by endotoxin-infusion (7.45 +/- .32 baseline value to 6.92 +/- .24 after 120 min). This parameter as well as base excess values and lactate levels were significantly improved by dimethindene-pretreatment (p < .05). These results may indicate a beneficial effect of H1-antagonist-pretreatment on endotoxin-induced deterioration of the microcirculation. Furthermore our results clearly demonstrated that only pretreatment before endotoxemia with H1-antagonism is effective, since infusion of H1-antagonist in hypodynamic shock 45 min after addition of endotoxin (n = 6 animals) did not improve the cardiovascular system or the microcirculation.
通过以每小时5微克脂多糖/千克的速度持续输注来诱导猪低动力性休克。这导致心输出量从基线值3.5±0.9升/分钟降至1.5±0.8升/分钟，并且在内毒素组（n = 6只动物）中左心室每搏功指数降低。在第二组（n = 6）中用H1拮抗剂二甲茚定（2毫克/千克）进行预处理可显著预防这些效应。此外，用H1拮抗剂预处理的动物平均动脉血压稳定，而对照内毒素处理组的平均动脉血压则急剧下降（分别在240分钟后为99±4.7毫米汞柱与65.8±10毫米汞柱）。在低动力性休克中，H1拮抗剂并未改善肺功能和全身血管阻力。指示黏膜氧合的胃肠黏膜pH（pHi）因内毒素输注而降低（基线值7.45±0.32降至120分钟后的6.92±0.24）。通过二甲茚定预处理，该参数以及碱剩余值和乳酸水平均得到显著改善（p <0.05）。这些结果可能表明H1拮抗剂预处理对内毒素诱导的微循环恶化具有有益作用。此外，我们的结果清楚地表明，只有在内毒素血症之前用H1拮抗剂进行预处理才有效，因为在内毒素加入后45分钟的低动力性休克中输注H1拮抗剂（n = 6只动物）并不能改善心血管系统或微循环。
