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

Abstract

Acute alcohol intoxication (AAI) impairs the hemodynamic and arginine vasopressin (AVP) counter-regulation to hemorrhagic shock (HS) and lactated Ringer's solution (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 periventricular nucleus NO inhibitory tone, subsequently improving mean arterial blood pressure (MABP) and organ perfusion. Male Sprague-Dawley rats received a 15-hour alcohol infusion (2.5 g/kg + 0.3 g/kg/h) or dextrose (DEX) before HS (40 mm Hg × 60 minutes) and FR with HTS (7.5%, 4 ml/kg) or LR (2.4 × blood volume removed). Organ blood flow was determined, and brains were collected for NO content at 2 hours after FR. HTS improved MABP recovery in AAI (109 vs. 80 mm Hg) and DEX (114 vs. 83 mm Hg) animals compared with LR. This was associated with higher (>60%) circulating AVP levels at 2 hours after FR compared with 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 the liver (72%), small intestine (65%), and large intestine (67%) compared with shams. FR with HTS improved liver (threefold) and small intestine (twofold) blood flow compared with LR in AAI-HS animals. The enhanced MABP response to HTS was prevented by pretreatment with a systemic AVP V1a receptor antagonist. HTS decreased periventricular nucleus NO content in both groups 2 hours after FR. These results suggest that FR with HTS in AAI results in the removal of central NO inhibition of AVP, restoring AVP levels and improving MABP and organ perfusion in AAI-HS.