Hypertonic Saline Resuscitation Reduces Apoptosis and Tissue Damage of the Small Intestine in a Mouse Model of Hemorrhagic Shock

Abstract

The effect of hypertonic saline resuscitation on intestinal damage and the incidence of apoptosis after hemorrhagic shock were investigated. After anesthesia, male BALB/c mice weighing 24-34 g were hemorrhaged to the mean arterial pressure of 40 +/- 5 mmHg for 90 min. Animals were randomly assigned to four groups: 1) resuscitation with 4 mL/kg of 7.5% NaCl (hypertonic saline; HS) + shed blood (SB); 2) resuscitation with two times the volume of shed blood of lactated Ringer's solution (2LR) + SB; 3) sham (catheter only); or 4) control (no treatment). Intestinal damage was graded based on the extent of the vacuolation at the basal area of the intestinal villi. Apoptosis of the small intestines was examined with the terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling method and with DNA laddering. Caspase-3 activation, heat shock protein (HSP) 70, and HSP40 were assessed by western blotting. Apoptosis of the small intestine and intestinal damage were significantly lower (P < 0.01) in the HS+SB group compared with the 2LR+SB group 2 h and 6 h after hemorrhagic shock and resuscitation, respectively. This corresponded with more DNA fragmentation in the small intestine of the 2LR+SB group compared with the HS+SB group 2 h after hemorrhage and resuscitation. In addition, we observed less caspase-3 activation in the small intestine of the HS+SB group compared with the 2LR+SB group at 2 h after resuscitation. The content of HSP40 and HSP70 in the HS+SB group was similar to that in controls, but slightly decreased in the 2LR+SB group. HS resuscitation reduced intestinal damage and apoptosis after hemorrhagic shock, suggesting that HS resuscitation may improve the outcome after hemorrhagic shock by reducing apoptosis and damage to the small intestine.

Small Volume Hypertonic Resuscitation of Circulatory Shock

“…55 A possible interaction between hypertonic saline for the treatment of hemorrhage, apoptosis, and tissue damage of the small intestine has also been recently suggested. 57 In another study, we have shown that hypertonic saline may exert its long-term benefits after hemorrhagic shock by modulating bone marrow apoptosis. 58 , a mechanism that has been linked to sepsis and multiple organ dysfunctions.…”

“…45 More recently, a series of experiments have shown that hypertonic saline solution, even without dextran, significantly interferes with the immune responses, both in vitro and in vivo. [46][47][48][49][50][51][52][53][54][55][56][57] The addition of hypertonic saline solution to a lymphocyte culture media, in concentrations similar to those obtained with systemic infusion of 4 mL/kg of 7.5% NaCl in humans, determined a significant increase in lymphocyte proliferation. 46 The addition of prostaglandin E 2 (PGE 2 ) to the culture media, in the absence of hypertonic saline, caused a reduction in T-cells proliferation, when compared to control cultures.…”

Comparison of the effects of lactated Ringer solution with and without hydroxyethyl starch fluid resuscitation on gut edema during severe splanchnic ischemia

“…Resuscitation fluids can also influence inflammatory and immune responses. It has been shown that HES effectively decreases leukocyte adherence, improves endothelial integrity, decreases apoptosis and attenuates tissue edema and injury in different animal and human models of fluid resuscitation (19)(20)(21)(22)(23).…”

Efeitos da solução salina hipertônica a 7,5% em glicose a 5% nas concentrações séricas de sódio, cloreto e potássio de eqüinos com hipovolemia induzida

“…Os seus benefícios foram demonstrados em várias espécies, como eqüinos (Schmall et al, 1990a(Schmall et al, e 1990b, caninos (Prough et al, 1991;Schertel et al, 1996), bovinos (Constable, 1999), murinos (Murao, 2003), suínos (Hellyer e Meyer, 1994) e ovinos (Taylor, 1999).…”