静脉注射和吸入左西孟旦对严重啮齿类动物脓毒症的影响。
Effects of intravenous and inhaled levosimendan in severe rodent sepsis.
作者信息
Scheiermann Patrick, Ahluwalia Devan, Hoegl Sandra, Dolfen Andrea, Revermann Marc, Zwissler Bernhard, Muhl Heiko, Boost Kim A, Hofstetter Christian
机构信息
Hospital of the Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
出版信息
Intensive Care Med. 2009 Aug;35(8):1412-9. doi: 10.1007/s00134-009-1481-9. Epub 2009 Apr 15.
PURPOSE
We aimed at comparing the effects of intravenous (i.v.) and inhaled (inh.) levosimendan (LEVO) on survival, inflammatory cytokines and the apoptotic mediator caspase-3 in a rat model of severe sepsis induced by cecal ligation and incision (CLI).
METHODS
Twenty-eight anesthetized/ventilated male Sprague-Dawley rats (body weight 528 +/- 20 g) underwent laparotomy. Cecal mobilisation served as control (SHAM, n = 7). In all other groups, severe sepsis was induced by CLI. No further intervention occurred in the CLI-group (n = 7). 180 min after CLI, 24 microg/kg i.v. LEVO was administered in the CLI + LEVO-IV-group (n = 7), and 24 microg/kg inh. LEVO was administered via jet nebulizer in the CLI + LEVO-INH-group (n = 7).
RESULTS
CLI induced arterial hypotension, with i.v. and inh. LEVO attenuating blood pressure decrease over 390 min [CLI 34(31/50), CLI + LEVO-IV 82(69/131), CLI + LEVO-INH 78(62/85) mmHg; median(25/75% quartile), P < 0.05]. CLI induced metabolic acidosis. I.v. and inh. LEVO avoided arterial pH [CLI 7.18(7.16/7.2), CLI + LEVO-IV 7.27(7.24/7.31), CLI + LEVO-INH 7.26(7.24/7.28)] and base excess deterioration [CLI -19(-21.8/-17.9), CLI + LEVO-IV -13(-14.8/-12), CLI + LEVO-INH -12.7(-14/-12.2)* mmol/l]. Overall mortality in the CLI-group was 57% compared to 0%* in both LEVO-treated groups after 390 min. LEVO administration significantly attenuated the increase in proinflammatory interleukin (IL)-1beta [CLI 896(739/911), CLI + LEVO-IV 302(230/385)*, CLI + LEVO-INH 346(271/548) pg/ml] and IL-6 [CLI 35651(31413/35816), CLI + LEVO-IV 21156(18397/28026), CLI + LEVO-INH 13674(10105/24843) pg/ml] in the plasma and reduced cleaved caspase-3 expression in the spleen.
CONCLUSIONS
In a rat model of severe sepsis induced by CLI, i.v. and inh. LEVO equally attenuated arterial hypotension, metabolic acidosis and prolonged survival. Moreover, i.v. and inh. LEVO inhibited proinflammatory mediator release and reduced splenic caspase-3 expression.
目的
我们旨在比较静脉注射（i.v.）和吸入（inh.）左西孟旦（LEVO）对盲肠结扎和切开（CLI）诱导的大鼠严重脓毒症模型的生存率、炎性细胞因子和凋亡介质半胱天冬酶-3的影响。
方法
28只麻醉/通气的雄性Sprague-Dawley大鼠（体重528±20 g）接受剖腹手术。盲肠松动作为对照（假手术组，n = 7）。在所有其他组中，通过CLI诱导严重脓毒症。CLI组（n = 7）未进行进一步干预。CLI后180分钟，CLI + LEVO-IV组（n = 7）静脉注射24 μg/kg LEVO，CLI + LEVO-INH组（n = 7）通过喷射雾化器吸入24 μg/kg LEVO。
结果
CLI诱导动脉低血压，静脉注射和吸入LEVO在390分钟内减轻血压下降[CLI 34(31/50)，CLI + LEVO-IV 82(69/131)，CLI + LEVO-INH 78(62/85) mmHg；中位数(25/75%四分位数)，P < 0.05]。CLI诱导代谢性酸中毒。静脉注射和吸入LEVO避免了动脉pH值[CLI 7.18(7.16/7.2)，CLI + LEVO-IV 7.27(7.24/7.31)，CLI + LEVO-INH 7.26(7.24/7.28)]和碱剩余恶化[CLI -19(-21.8/-17.9)，CLI + LEVO-IV -13(-14.8/-12)，CLI + LEVO-INH -12.7(-14/-12.2)* mmol/l]。CLI组的总体死亡率为57%，而在390分钟后，两个LEVO治疗组的死亡率均为0%。给予LEVO显著减轻了促炎白细胞介素（IL）-1β[CLI 896(739/911)，CLI + LEVO-IV 302(230/385)，CLI + LEVO-INH 346(271/548) pg/ml]和IL-6[CLI 35651(31413/35816)，CLI + LEVO-IV 21156(18397/28026)，CLI + LEVO-INH 13674(10105/24843) pg/ml]在血浆中的升高，并降低了脾脏中裂解的半胱天冬酶-3表达。
结论
在CLI诱导的大鼠严重脓毒症模型中，静脉注射和吸入LEVO同样减轻了动脉低血压、代谢性酸中毒并延长了生存期。此外，静脉注射和吸入LEVO抑制了促炎介质的释放并降低了脾脏半胱天冬酶-3的表达。
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