Hypertonic Saline Resuscitation of Hemorrhagic Shock Diminishes Neutrophil Rolling and Adherence to Endothelium and Reduces In Vivo Vascular Leakage

Abstract

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

Small Volume Hypertonic Resuscitation of Circulatory Shock

“…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.…”

“…51 More recently it has been shown that polymorph nuclear rolling and sticking, as well as lung expression of ICAM 1, and leakage are inhibited by treating severe hemorrhage with HS. 52,53 It has also be shown that hypertonic saline inhibits neutrophile priming via attenuation of p38 MAPK signaling. 54 Inhibition of alveolar macrophage activation by prevention of the systemic oxidative stress due to gut ischemia/reperfusion has also been claimed.…”

Primeiro escore de risco inflamatório das endopróteses de aorta

“…A number of authors have postulated that, the more crystalloid solution utilized, the greater the transcription of pro-inflammatory genes, the greater the expression of cellular adhesion molecules, such as E-selectin and Pselectin, the greater the neutrophil activation and the greater the release of cytokines and hydrogenated metabolites will be [11][12][13][14][15]. Pascual et al [16,17] demonstrated that the infusion of hypertonic solutions might reduce the adhesion and transmigration of inflammatory cells.…”

Volume replacement and microhemodynamic changes in polytrauma

“…Inappropriate cellular activation and their vigorous interaction with the endothelial lining are responsible for local and systemic release of toxic mediators, in particular reactive oxygen species (ROS) that cause vessel injury and leakage. When different methods to determine permeability changes and estimate fluid sequestration and organ edema were used, the application of hypertonic saline in various models of organ damage revealed less extravasation and leakage than did normotonic crystalloids [44][45][46][47]. Newer crystalloids, such as ethyl pyruvate solution, might even be superior to hypertonic saline because of their unique ROS scavenging action [48] and anti-inflammatory property [49].…”