Therapeutic effects of hypertonic saline on peritonitis-induced septic shock with multiple organ dysfunction syndrome in rats

Significant mortality in patients with sepsis results from the development of multiple organ dysfunction syndrome (MODS). More recently, small-volume resuscitation with 4 ml of 7.5% NaCl per kilogram of body weight of hypertonic saline (HS) has been proposed to restore physiological hemodynamics in hypotensive conditions such as hemorrhagic shock. We therefore hypothesized that HS resuscitation may alleviate the development of MODS in sepsis. In order to test this possibility, we evaluated effects of hypertonic saline in a rat sepsis model induced by cecal ligation and puncture (CLP). Our results demonstrated that CLP for 18 hours was associated with circulatory failure (i.e., hypotension and vascular hyporeactivity to norepinephrine), MODS (examined by biochemical parameters and histological studies) and severe 18-hour mortality. Animals treated with HS (7.5% NaCl, 4 ml/kg; at 3 hours after CLP surgery) not only ameliorated the deterioration of hemodynamic changes but also attenuated polymorphonuclear neutrophil (PMN) infiltration in the lung and the liver. In addition, HS increased the survival rate at 9 and 18 hours when compared with the CLP group. Moreover, HS reduced plasma nitric oxide (NO) and IL-1 and organ O₂^- levels in CLP-treated rats. In conclusion, HS prevented circulatory failure and alleviated MODS as well as decreasing the mortality rate in CLP-treated animals. These beneficial effects of HS may be attributed to reducing the plasma concentration of NO and IL-1β as well as the organ O₂^- level and decreasing lung PMN infiltration and liver necrosis, and thus decreasing the mortality rate in peritonitis-induced septic animals. Our study suggests that HS could be a cheap and novel therapeutic agent in the early sepsis animals or patients.