HSPTX可预防失血性休克复苏诱导的组织损伤：一种比乳酸林格氏液更具吸引力的替代方案。

HSPTX protects against hemorrhagic shock resuscitation-induced tissue injury: an attractive alternative to Ringer's lactate.

作者信息

Coimbra Raul, Porcides Rafael, Loomis William, Melbostad Heidi, Lall Rohan, Deree Jessica, Wolf Paul, Hoyt David B

机构信息

Department of Surgery, Division of Trauma and Surgical Critical Care, University of California San Diego School of Medicine, 200 W. Arbor Drive, San Diego, CA 92103, USA.

出版信息

J Trauma. 2006 Jan;60(1):41-51. doi: 10.1097/01.ta.0000197417.03460.0a.

DOI:10.1097/01.ta.0000197417.03460.0a

PMID:16456435

Abstract

BACKGROUND

Conventional fluid resuscitation with Ringer's lactated (RL) activates neutrophils and causes end-organ damage. We have previously shown that HSPTX, a combination of small volume hypertonic saline (HS) and pentoxifylline (PTX), a phosphodiesterase-inhibitor, downregulates in vitro neutrophil activation and proinflammatory mediator synthesis. Herein, we hypothesized that HSPTX decreases end-organ injury when compared with RL in an animal model of hemorrhagic shock.

METHODS

Sprague-Dawley rats were bled to a mean arterial pressure of 35 mm Hg for 1 hour. Animals were divided into 3 groups: sham (no shock, no resuscitation, n = 7), RL (32 mL/kg, n = 7), and HSPTX (7.5% NaCl 4 mL/kg + PTX 25 mg/kg; n = 7). Shed blood was infused after fluid resuscitation. Blood pressure was monitored until the end of resuscitation. Animals were sacrificed at 24 hour after resuscitation. Bronchoalveolar lavage fluid (BALF) was obtained for white cell count (total and differential) and TNF-alpha and IL-1beta levels were measured by ELISA. Lung and intestinal injury at 24 hour were evaluated by histopathology. Organ damage was graded by a pathologist and a score was created (0 = no injury; 3 = severe). Lung neutrophil infiltration was evaluated by MPO immune staining.

RESULTS

There were no differences in mean arterial pressure between groups. At 24 hours, BALF leukocyte count was decreased by 30% in HSPTX animals (p < 0.01). TNF-alpha and IL-1beta levels were markedly decreased in HSPTX-resuscitated animals compared with their RL counterparts (p < 0.01). HSPTX-resuscitated animals (lung injury score = 1.0 +/- 0.4) had markedly decreased acute lung injury compared with RL-treated animals (2.5 +/- 0.3) (p < 0.01). RL resuscitation led to a two-fold increase in lung neutrophil infiltration whereas in HSPTX-treated animals, the number of MPO + cells was similar to sham animals (p < 0.001). Intestinal injury was markedly attenuated by HSPTX (1.1 +/- 0.3) compared with RL animals (2.6 +/- 0.4) (p < 0.001).

CONCLUSIONS

HSPTX, a small volume resuscitation strategy with marked immunomodulatory potential led to a marked decrease in end-organ damage. HSPTX is an attractive alternative to RL in hemorrhagic shock resuscitation.

摘要

背景

使用乳酸林格氏液（RL）进行传统的液体复苏会激活中性粒细胞并导致终末器官损伤。我们之前已经表明，HSPTX，即小剂量高渗盐水（HS）与磷酸二酯酶抑制剂己酮可可碱（PTX）的组合，可在体外下调中性粒细胞活化和促炎介质合成。在此，我们假设在失血性休克动物模型中，与RL相比，HSPTX可减少终末器官损伤。

方法

将Sprague-Dawley大鼠放血至平均动脉压为35 mmHg，持续1小时。动物分为3组：假手术组（无休克，未复苏，n = 7）、RL组（32 mL/kg，n = 7）和HSPTX组（7.5% NaCl 4 mL/kg + PTX 25 mg/kg；n = 7）。液体复苏后回输 shed blood。监测血压直至复苏结束。复苏后24小时处死动物。获取支气管肺泡灌洗液（BALF）进行白细胞计数（总数和分类），并通过ELISA法检测TNF-α和IL-1β水平。通过组织病理学评估复苏后24小时的肺和肠道损伤。由病理学家对器官损伤进行分级并创建评分（0 = 无损伤；3 = 严重）。通过MPO免疫染色评估肺中性粒细胞浸润。

结果

各组间平均动脉压无差异。在24小时时，HSPTX组动物的BALF白细胞计数降低了30%（p < 0.01）。与接受RL复苏的动物相比，接受HSPTX复苏的动物的TNF-α和IL-1β水平显著降低（p < 0.01）。与接受RL治疗的动物（2.5 +/- 0.3）相比，接受HSPTX复苏的动物（肺损伤评分 = 1.0 +/- 0.4）的急性肺损伤明显减轻（p < 0.01）。RL复苏导致肺中性粒细胞浸润增加两倍，而在接受HSPTX治疗的动物中，MPO + 细胞数量与假手术组动物相似（p < 0.001）。与RL组动物（2.6 +/- 0.4）相比，HSPTX组（1.1 +/- 0.3）的肠道损伤明显减轻（p < 0.001）。