Fluvastatin attenuates severe hemorrhagic shock-induced organ damage in rats.
OBJECTIVE
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 (1mg/kg) before HS. HS was produced by bleeding from a femoral arterial catheter to remove 60% of total blood volume (6ml/100g BW) over 30min. The mean arterial pressure (MAP) and heart rate (HR) were monitored continuously for 12h 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 30min before induction of HS and at 0, 1, 3, 6, 9 and 12h 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 1h after HS. Kidney, liver, lung and small intestine were removed for pathology examination at 48h 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.


CONCLUSIONS
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.
Lee
Chia-Chi
CC
Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
Lee
Ru-Ping
RP
Subeq
Yi-Maun
YM
Lee
Chung-Jen
CJ
Chen
Tse-Min
TM
Hsu
Bang-Gee
BG
D000818:Animals; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000975:Antioxidants; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000627:therapeutic use*; D000077340:Fluvastatin; D006339:Heart Rate / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D011921:Rats, Inbred WKY; D012771:Shock, Hemorrhagic / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014812:Vitamin K / Q000008:administration & dosage / Q000627:therapeutic use
D000933:Antifibrinolytic Agents; D000975:Antioxidants; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D014409:Tumor Necrosis Factor-alpha; D014812:Vitamin K; D016753:Interleukin-10; D000077340:Fluvastatin