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通过检测支气管肺泡灌洗液中的消化活性来检测动物模型中胃内容物的肺误吸。

Detection of pulmonary aspiration of gastric contents in an animal model by assay of peptic activity in bronchoalveolar fluid.

作者信息

Badellino M M, Buckman R F, Malaspina P J, Eynon C A, O'Brien G M, Kueppers F

机构信息

Department of Surgery, Temple University School of Medicine, Philadelphia, PA, USA.

出版信息

Crit Care Med. 1996 Nov;24(11):1881-5. doi: 10.1097/00003246-199611000-00019.

Abstract

OBJECTIVE

To determine whether peptic activity in bronchoalveolar fluid, due to the presence of the gastric proteolytic enzyme pepsin, could serve as a biochemical marker for pulmonary aspiration of gastric contents.

DESIGN

Prospective, experimental trial.

SETTING

A university animal research laboratory.

SUBJECTS

Thirty-six New Zealand rabbits, weighing 2 to 4 kg.

INTERVENTIONS

New Zealand rabbits were anesthetized, intubated via tracheostomy, and mechanically ventilated. Pulmonary aspiration was induced by the intratracheal instillation of 2 mL/kg human gastric juice (pH 1.2 +/- 0.2; pepsin activity 0.02 +/- 0.006 microgram/mL; human gastric juice group, n = 24) or normal saline solution (pH 5.2 +/- 0.2; normal saline solution group; n = 12). Mechanical ventilation was continued. Bronchoalveolar lavage was performed at 15 mins (human gastric juice group, n = 8; normal saline solution group, n = 4), 30 mins (human gastric juice group, n = 8; normal saline solution group, n = 4), or 60 mins (human gastric juice group, n = 8; normal saline solution group, n = 4) postaspiration.

MEASUREMENTS AND MAIN RESULTS

Peak airway pressure and PaO2 values were measured at baseline and 15 and 30 mins after aspiration. The pH of retrieved bronchoalveolar lavage fluid was measured and pepsin activity in sample fluid was determined. Changes from baseline in peak airway pressure and PaO2 were significant in human gastric juice animals at 15 and 30 mins when compared with normal saline solution animals (PaO2 -4% vs. -44%, peak airway pressure 20% vs. 36% at 15 mins; PaO2 -16% vs. -79%, peak airway pressure 28% vs. 69% at 30 mins; normal saline solution group vs. human gastric juice group, p < .02). Bronchoalveolar lavage fluid pH was not significantly different between groups at any time postaspiration (6.6 +/- 0.7 vs. 6.0 +/- 0.4 at 15 mins; 7.4 +/- 0.9 vs. 6.5 +/- 0.4 at 30 mins; 7.2 +/- 0.5 vs. 6.4 +/- 0.4 at 60 mins, normal saline solution group vs. human gastric juice group, p = NS). No peptic activity was present in bronchoalveolar lavage fluid from normal saline solution animals at any time. In the human gastric juice group, peptic activity was detected in postaspiration bronchoalveolar lavage fluid in eight of eight animals at 15 mins, six of eight animals at 30 mins, and five of eight animals at 60 mins (normal saline solution group vs. human gastric juice group; p < .001 at 15 mins, p < .01 at 30 mins, p = NS at 60 mins). Peptic activity of bronchoalveolar lavage fluid varied; mean values were greater at 15 mins than at 30 or 60 mins (pepsin activity: 0.004 +/- 0.002 microgram/mL vs. 0.002 +/- 0.001 microgram/mL vs. 0.0006 +/- 0.0001 microgram/mL, respectively, p < .05).

CONCLUSIONS

The results of this study suggest that peptic activity in bronchoalveolar lavage fluid can be detected up to 60 mins after induced, experimental gastric juice aspiration and may prove a clinically useful biochemical marker for episodes of occult pulmonary aspiration of gastric contents.

摘要

目的

确定由于胃蛋白水解酶胃蛋白酶的存在,支气管肺泡液中的消化活性是否可作为胃内容物肺吸入的生化标志物。

设计

前瞻性实验性试验。

地点

一所大学动物研究实验室。

对象

36只体重2至4千克的新西兰兔。

干预措施

将新西兰兔麻醉,经气管切开插管并进行机械通气。通过气管内滴注2 mL/kg人胃液(pH 1.2±0.2;胃蛋白酶活性0.02±0.006微克/毫升;人胃液组,n = 24)或生理盐水溶液(pH 5.2±0.2;生理盐水溶液组;n = 12)诱导肺吸入。继续进行机械通气。在吸入后15分钟(人胃液组,n = 8;生理盐水溶液组,n = 4)、30分钟(人胃液组,n = 8;生理盐水溶液组,n = 4)或60分钟(人胃液组,n = 8;生理盐水溶液组,n = 4)进行支气管肺泡灌洗。

测量指标及主要结果

在基线以及吸入后15分钟和30分钟测量气道峰压和PaO2值。测量回收的支气管肺泡灌洗液的pH,并测定样本液中的胃蛋白酶活性。与生理盐水溶液组动物相比,人胃液组动物在吸入后15分钟和30分钟时气道峰压和PaO2相对于基线的变化显著(15分钟时PaO2 -4%对-44%,气道峰压20%对36%;30分钟时PaO2 -16%对-79%,气道峰压28%对69%;生理盐水溶液组对人胃液组,p <.02)。在吸入后的任何时间,两组之间支气管肺泡灌洗液的pH均无显著差异(15分钟时6.6±0.7对6.0±0.4;30分钟时7.4±0.9对6.5±0.4;60分钟时7.2±0.5对6.4±0.4,生理盐水溶液组对人胃液组,p =无显著差异)。生理盐水溶液组动物的支气管肺泡灌洗液在任何时间均未出现消化活性。在人胃液组中,吸入后支气管肺泡灌洗液在15分钟时8只动物中的8只、30分钟时8只动物中的6只以及60分钟时8只动物中的5只检测到胃蛋白酶活性(生理盐水溶液组对人胃液组;15分钟时p <.001,30分钟时p <.01,60分钟时p =无显著差异)。支气管肺泡灌洗液的胃蛋白酶活性各不相同;平均值在15分钟时高于30分钟或60分钟时(胃蛋白酶活性分别为:0.004±0.002微克/毫升对0.002±0.001微克/毫升对0.0006±0.0001微克/毫升,p <.05)。

结论

本研究结果表明,在诱导性实验性胃液吸入后长达60分钟可检测到支气管肺泡灌洗液中的消化活性,这可能证明是胃内容物隐匿性肺吸入发作的一种临床上有用的生化标志物。

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