Pyrrolidine dithiocarbamate improves mortality in a rat model of severe hemorrhage

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• 作者：Anna E. Montegudo ; BS^a ; ¹ ; Mary A. Palilonis ; BS^a ; ¹ ; Cathy C. Moore ; PhD^a ; Toan Huynh ; MD^a ; ^b ; Iain H. McKillop ; PhD^a ; Susan L. Evans ; MD^a ; ^b ; ^{susan.evans@carolinashealthcare.org}
• 关键词：Hemorrhagic shock ; Pyrrolidine dithiocarbamate ; Multiple organ failure ; Organ injury
• 刊名：Journal of Surgical Research
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：179
• 期：1
• 页码：e149-e155
• 全文大小：322 K

文摘

Background

Hemorrhagic shock is a life threatening condition characterized by diminishing organ function. The aim of this study was to determine whether an effective pyrrolidine dithiocarbamate (PDTC) treatment protocol could be established to decrease organ dysfunction and mortality in a lethal hemorrhagic shock-resuscitation (HSR) model.

Materials and methods

Sprague-Dawley rats were randomized into three experimental groups; HSR alone (HSR), PDTC (100 mg/kg) administered 12 h pre-HSR (PDTC-12), and PDTC administered 1 h post-shock prior to resuscitation (PDTC+1). Hemorrhage was induced by arterial blood withdrawal to a mean arterial pressure (MAP) of 25 ¡À 5 mmHg for 1 h. Resuscitation was performed until pre-HSR MAP was attained. Blood was collected immediately prior to HSR, 1 h post-shock, and at protocol end. Measurements of base excess, lactate, arterial partial pressure of carbon dioxide (PaCO₂) and oxygen (PaO₂), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, blood urea nitrogen (BUN), and lipase were performed.

Results

In PDTC+1 animals, PDTC was ineffective in improving survival. In contrast, survival was significantly increased in the PDTC-12 animals versus PDTC+1 and HSR groups. Analysis of physiologic parameters demonstrated that elevations in base deficit and lactate levels following hemorrhage were blunted by PDTC administration in the PDTC-12 group. At time of death, creatinine, ALT, and AST levels were significantly higher in HSR versus PDTC-12 animals.

Conclusions

Administration of PDTC 12 h prior to HSR significantly improves survival through preservation of organ function.