ObjectiveTo evaluate the in vivo effects of hypertonic saline (HTS) resuscitation on the interactions of endothelial cells (ECs) and polymorphonuclear neutrophils (PMNs) and vascular permeability after hemorrhagic shock.
Summary Background DataThe PMN has been implicated in the pathogenesis of EC damage and organ injury following hemorrhagic shock. Compared to Ringer's lactate (RL), HTS resuscitation diminishes PMN and EC adhesion molecule expression and organ sequestration of PMNs.
MethodsIn a murine model of hemorrhagic shock (50 mmHg for 45 minutes followed by resuscitation) using intravital microscopy on cremaster muscle, the authors studied PMN-EC interactions and vascular leakage (epifluorescence after 50 mg/kg fluorescent albumin) in three resuscitation groups: HTS (shed blood ϩ 4 cc/kg 7.5% HTS, n ϭ 12), RL (shed blood ϩ RL [2ϫ shed blood volume], n ϭ 12), and sham (no hemorrhage or resuscitation, n ϭ 9). EC ICAM-1 expression was evaluated by immunohistochemistry. Data, presented as mean Ϯ SEM, were evaluated by analysis of variance with Bonferroni correction.
ResultsThere were no differences between groups in flow mechanics. Compared to RL, HTS animals (t ϭ 90 minutes) displayed diminished PMN rolling and PMN adhesion to EC at time intervals beyond t ϭ 0. There were no differences between the sham and HTS groups. Vascular leakage was 45% lower in HTS than in RL-resuscitated animals. Cremaster EC ICAM-1 expression was similar in the two groups.
ConclusionsUsing HTS instead of RL to resuscitate hemorrhagic shock diminishes vascular permeability in vivo by altering PMN-EC interactions. HTS could serve as a novel means of immunomodulation in hemorrhagic shock victims, potentially reducing PMN-mediated tissue injury.Over 30 years ago, the Vietnam War established the current standard use of isotonic crystalloid fluids (normal saline [NS] and Ringer's lactate [RL]) for the resuscitation of hemorrhagic shock. Subsequent studies have demonstrated that crystalloids represent an effective and inexpensive means to restore intravascular volume and additionally offer a survival advantage over colloids in the resuscitation of traumatic hemorrhagic shock.
1More recently, "small volume resuscitation" 2 with 4 mL of 7.5% NaCl per kilogram of body weight of hypertonic saline (HTS) has been proposed in the treatment of hemorrhagic shock. Whereas isotonic fluid administration requires large volumes, hypertonic resuscitation offers the advantages of ease of transport, speed of administration, and