Hypertonic saline resuscitation enhances blood pressure recovery and decreases organ injury following hemorrhage in acute alcohol intoxicated rodents

Abstract

Background Acute alcohol intoxication (AAI) impairs the hemodynamic and arginine vasopressin (AVP) counter-regulation to hemorrhagic shock (HS) and lactated Ringer’s (LR) fluid resuscitation (FR). The mechanism of AAI-induced suppression of AVP release in response to HS involves accentuated nitric oxide (NO) inhibitory tone. In contrast, AAI does not prevent AVP response to increased osmolarity produced by hypertonic saline (HTS) infusion. We hypothesized that FR with HTS during AAI would enhance AVP release by decreasing PVN NO inhibitory tone subsequently improving mean arterial blood pressure (MABP) and organ perfusion. Methods Male Sprague Dawley rats received a 15h alcohol infusion (2.5g/kg + 0.3 g/kg/h) or dextrose (DEX) prior to HS (40mmHg × 60 min) and FR with HTS (7.5%; 4ml/kg) or LR (2.4 × blood volume removed). Organ blood flow was determined and brains collected for NO content at 2h post-FR. Results HTS improved MABP recovery in AAI (109 vs 80mmHg) and DEX (114 vs 83mmHg) animals compared to LR. This was associated with higher (>60%) circulating AVP levels at 2h post-FR than those detected in LR animals in both groups. Neither AAI alone nor HS in DEX animals resuscitated with LR altered organ blood flow. In AAI animals, HS and FR with LR reduced blood flow to liver (72%), small intestine (65%), and large intestine (67%) compared to shams. FR with HTS improved liver (3-fold) and small intestine (2-fold) blood flow compared to LR in AAI-HS animals. The enhanced MABP response to HTS was prevented by pretreatment with a systemic AVP V1a receptor antagonist. HTS decreased PVN NO content in both groups 2h post-FR. Conclusions These results suggest that FR with HTS in AAI results in removal of central NO inhibition of AVP, restoring AVP levels and improving MABP and organ perfusion in AAI-HS.

Alcohol Abuse and the Injured Host

“…The impact of AAI on end-organ blood flow has been studied using fluorescent microspheres to determine tissue perfusion 2 hours post-resuscitation (Figure 2). We demonstrated that hemorrhagic shock in AAI animals results in greater reduction of blood flow to the liver, kidney, small and large intestines than that seen in non-intoxicated animals (25). These studies confirmed marked decreases in end-organ blood flow despite fluid resuscitation.…”

“…The intoxicated trauma patient may be particularly vulnerable to organ injury following traumatic injury and resulting hemorrhage and resuscitation (25). A large proportion of acutely intoxicated trauma victims are also chronic alcohol abusers (26).…”

“…A large proportion of acutely intoxicated trauma victims are also chronic alcohol abusers (26). Therefore, preexisting and ongoing injury resulting chronic alcohol abuse may compound with the effects of hypotension predisposing them to an even worsened outcome (25, 27). These clinical findings have been confirmed in animal models which have begun to investigate the complex mechanisms of liver injury following hypotension during alcohol intoxication (28).…”

“…Administration of an AVP V 1 receptor antagonist during hemorrhage significantly attenuates the restoration of blood pressure during the resuscitation period (73). Studies from our laboratory have demonstrated the importance of AVP in blood pressure recovery during fluid resuscitation with hypertonic saline (25). The immediate pressor effect of hypertonic saline resuscitation was demonstrated to be mediated by an increase in circulating concentration of AVP.…”

“…Indeed, subsequent studies examining resuscitation with HTS demonstrated enhanced MABP recovery and elevated circulating levels of AVP in AAI animals (25). The pressor response to HTS was found to be the result of circulating AVP, and specifically through AVP’s actions at the V1 receptor.…”