Therapeutic effects of hypertonic saline on peritonitis-induced septic shock with multiple organ dysfunction syndrome in rats.
OBJECTIVE
Significant mortality in patients with sepsis results from the development of multiple organ dysfunction syndrome. Small-volume resuscitation with 7.5% NaCl hypertonic saline has been proposed to restore physiologic hemodynamics in hemorrhagic shock. Therefore, we hypothesized that hypertonic saline resuscitation could alleviate the development of multiple organ dysfunction syndrome in sepsis induced by cecal ligation and puncture.


METHODS
Randomized, prospective animal experiment.


METHODS
Academic research laboratory.


METHODS
Male Wistar rats.


METHODS
The animals were randomly allocated to one of four groups: 1) sham operation (0.9% NaCl, 4 mL/kg intravenously, at 3 hrs after laparotomy); 2) sham operation plus hypertonic saline (7.5% NaCl, 4 mL/kg intravenously, at 3 hrs after laparotomy); 3) cecal ligation and puncture (0.9% NaCl, 4 mL/kg intravenously, at 3 hrs after cecal ligation and puncture); and 4) cecal ligation and puncture plus hypertonic saline (7.5% NaCl, 4 mL/kg intravenously, at 3 hrs after cecal ligation and puncture).


RESULTS
Cecal ligation and puncture for 18 hrs was associated with circulatory failure (i.e., hypotension and vascular hyporeactivity to norepinephrine), multiple organ dysfunction syndrome (examined by biochemical variables and histologic studies), and 18-hr mortality. Hypertonic saline not only ameliorated the deterioration of hemodynamic changes but also attenuated neutrophil infiltration in the lung and the liver of septic animals. Hypertonic saline increased the survival rate at 9 and 18 hrs compared with the cecal ligation and puncture group. Moreover, hypertonic saline reduced plasma nitric oxide and interleukin-1beta and organ O2-* levels in rats that underwent cecal ligation and puncture.


CONCLUSIONS
Hypertonic saline prevented circulatory failure, alleviated multiple organ dysfunction syndrome, and decreased the mortality rate in animals receiving cecal ligation and puncture. These beneficial effects of hypertonic saline may be attributed to reducing the plasma concentration of nitric oxide and interleukin-1beta as well as the organ O2-* level and decreasing lung neutrophil infiltration and liver necrosis. Our study suggests that hypertonic saline could be a potential and inexpensive therapeutic agent in the early sepsis of animals or patients.
Shih
Chih-Chin
CC
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
Chen
Shiu-Jen
SJ
Chen
Ann
A
Wu
Jeng-Yuan
JY
Liaw
Wen-Jinn
WJ
Wu
Chin-Chen
CC
D000818:Animals; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D053583:Interleukin-1beta / Q000097:blood; D007678:Kidney Glomerulus / Q000473:pathology; D007958:Leukocyte Count; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D009102:Multiple Organ Failure / Q000473:pathology / Q000628:therapy*; D009504:Neutrophils; D009569:Nitric Oxide / Q000097:blood; D010537:Peritoneum / Q000473:pathology; D010538:Peritonitis / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage*; D012772:Shock, Septic / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate
D053583:Interleukin-1beta; D012462:Saline Solution, Hypertonic; D009569:Nitric Oxide