Fluvastatin attenuates severe hemorrhagic shock-induced organ damage in rats

Objectives: Multiple organ dysfunction resulting from hemorrhagic shock (HS) and subsequent resuscitation was mediated by several inflammatory factors such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10). The present study was designed to investigate the protective effects of fluvastatin on these mediators after HS in rats. Methods: The experimental rats were randomly divided into three groups. The vehicle group received only vitamin K without HS, the HS-control group received vitamin K and HS, and the HS-experimental group received both vitamin K and fluvastatin (1 mg/kg) before HS. HS was produced by bleeding from a femoral arterial catheter to remove 60% of total blood volume (6 ml/100 g BW) over 30 min. The mean arterial pressure (MAP) and heart rate (HR) were monitored continuously for 12 h after the start of blood withdrawal. The biochemical parameters, including arterial blood gas, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), and lactate were obtained at 30 min before induction of HS and at 0, 1, 3,6,9 and 12 h after HS. Equal volume of normal saline was given to replace blood volume loss. Cytokine levels including TNF-alpha and IL-10 in serum were measured at 1 h after HS. Kidney, liver, lung and small intestine were removed for pathology examination at 48 h after HS. Results: HS significantly increased HR, blood GOT, GPT, BUN, Cre, LDH, CPK, lactate, TNF-alpha and IL-10 levels, and also induced metabolic acidosis and decreased MAP in rats. Pre-treatment with fluvastatin was found to improve survival rate, preserved MAP, decreased the markers of organ injury, suppressed the release of TNF-alpha and increased IL-10 after HS in rats. Conclusion: Pre-treatment with fluvastatin can suppress the release of serum TNF-alpha and can also increase serum IL-10 level to protect HS-induced multi-organ damage in rats. (C) 2009 Elsevier Ireland Ltd. All rights reserved.