Transient Central Cholinergic Activation Enhances Sympathetic Nervous System Activity but Does Not Improve Hemorrhage-Induced Hypotension in Alcohol-Intoxicated Rodents

Mathis, Keisa W.; Molina, Patricia E.

doi:10.1097/shk.0b013e31819e2d13

Cited by 8 publications

(10 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This activation was evidenced by increases in circulating levels of counter-regulatory hormones such as AVP and epinephrine as well as enhanced blood pressure following a range of cardiovascular challenges (67, 68). As had been reported in other models, intracerebroventricular (ICV) administration of choline, a pre-cursor of acetylcholine, produced an immediate activation of the SNS as evidenced by an increase in MABP and a rise in plasma epinephrine, norepinephrine, and AVP within five minutes of injection in dextrose control animals (69). While we confirmed that SNS activation could be achieved with this approach, ICV choline did not reverse the hemorrhage-induced hypotension or produce a sustained increase in vasoactive hormone release throughout the duration of hemorrhage in AAI animals.…”

Section: Acute Alcohol Intoxication Disrupts Central Avp Controlling mentioning

confidence: 54%

Alcohol Abuse and the Injured Host

Molina

Whitaker

2013

Shock

Self Cite

View full text Add to dashboard Cite

Traumatic injury ranks as the number one cause of death for the under 44 year old age group and 5th leading cause of death overall (www.nationaltraumainstitute.org/home/trauma_statistics.html). Although improved resuscitation of trauma patients has dramatically reduced immediate mortality from hemorrhagic shock, long-term morbidity and mortality continue to be unacceptably high during the post-resuscitation period, particularly as a result of impaired host immune responses to subsequent challenges such as surgery or infection. Acute alcohol intoxication (AAI) is a significant risk factor for traumatic injury; with intoxicating blood alcohol levels present in more than 40% of injured patients (1–5). Severity of trauma, hemorrhagic shock and injury is higher in intoxicated individuals than that of sober victims, resulting in higher mortality rates in this patient population. Necessary invasive procedures (surgery, anesthesia) and subsequent challenges (infection) that intoxicated trauma victims are frequently subjected to are additional stresses to an already compromised inflammatory and neuroendocrine milieu and further contribute to their morbidity and mortality. Thus, dissecting the dynamic imbalance produced by AAI during trauma is of critical relevance for a significant proportion of injured victims. This review outlines how AAI at the time of hemorrhagic shock not only prevents adequate responses to fluid resuscitation but also impairs the ability of the host to overcome a secondary infection. Moreover, it discusses the neuroendocrine mechanisms underlying alcohol-induced hemodynamic dysregulation and its relevance to host defense restoration of homeostasis following injury.

show abstract

Section: Acute Alcohol Intoxication Disrupts Central Avp Controlling mentioning

confidence: 54%

Alcohol Abuse and the Injured Host

Molina

Whitaker

2013

Shock

Self Cite

View full text Add to dashboard Cite

show abstract

“…The results from recent studies demonstrated that intracerebroventricular (ICV) administration of choline, a precursor of acetylcholine, immediately stimulates sympathetic nervous system (SNS) outflow in control and alcohol-intoxicated animals, reflected in an increase in MABP and plasma epinephrine, norepinephrine, and AVP (26). However, these effects were transient and not prolonged enough to improve hemodynamic stability following hemorrhagic shock in alcohol-intoxicated animals.…”

mentioning

confidence: 93%

“…Alcohol-intoxicated trauma patients enter the emergency department more hypotensive than their sober counterparts (41). Clinical data suggest that mean arterial blood pressure (MABP) at the time of admittance into the emergency department is one of the most critical indicators of a patient's outcome and survival from traumatic injury and blood loss (15); therefore, the greater hypotension noted in alcohol-intoxicated trauma patients is likely to contribute to their increased morbidity and mortality.Previously, we demonstrated that acute intoxication produced by intragastric administration of alcohol decreases baseline MABP, accentuates hypotension throughout hemorrhage, and blunts the pressor response to fluid resuscitation, regardless of the dose (1.75, 5, and 8 g/kg) and frequency (single dose, 3-day binge, and 15-h constant infusion, respectively) of alcohol administration (12,25,26,30,33). This impaired hemodynamic compensatory response to hemorrhage in alcohol-intoxicated rats is associated with suppression of catecholamine (epinephrine and norepinephrine) and AVP responses (30).…”

mentioning

confidence: 98%

“…Previously, we demonstrated that acute intoxication produced by intragastric administration of alcohol decreases baseline MABP, accentuates hypotension throughout hemorrhage, and blunts the pressor response to fluid resuscitation, regardless of the dose (1.75, 5, and 8 g/kg) and frequency (single dose, 3-day binge, and 15-h constant infusion, respectively) of alcohol administration (12,25,26,30,33). This impaired hemodynamic compensatory response to hemorrhage in alcohol-intoxicated rats is associated with suppression of catecholamine (epinephrine and norepinephrine) and AVP responses (30).…”

mentioning

confidence: 98%

See 1 more Smart Citation

Central acetylcholinesterase inhibition improves hemodynamic counterregulation to severe blood loss in alcohol-intoxicated rats

Mathis¹,

Molina²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

View full text Add to dashboard Cite

Acute alcohol intoxication results in impaired hemodynamic counterregulation to blood loss and is associated with an attenuated hemorrhage-induced release of catecholamines and AVP. We speculated that restoration of the neuroendocrine response to hemorrhage would improve mean arterial blood pressure (MABP) recovery during acute alcohol intoxication. Previously, we demonstrated that intracerebroventricular (i.c.v.) choline, a precursor of acetylcholine, transiently increases sympathetic nervous system (SNS) outflow but is not capable of improving neuroendocrine and hemodynamic compensation to hemorrhage in alcohol-treated rats. We hypothesized that prolongation of the observed effect via i.c.v. neostigmine, an acetylcholinesterase inhibitor, would enhance SNS outflow, restore the neuroendocrine response, and in turn improve hemodynamic responses to hemorrhage during acute alcohol intoxication. I.c.v. neostigmine (1 microg) increased MABP, catecholamines, and AVP within 5 min and reversed hypotension due to 40% hemorrhage and intragastric alcohol (30% wt/vol, 2.5 g/kg) administration in chronically catheterized male Sprague-Dawley rats (225-250 g body wt). Acute alcohol intoxication before 50% hemorrhage decreased basal MABP, accentuated hypotension midhemorrhage, suppressed the hemorrhage-induced release of norepinephrine and AVP, and prevented restoration of MABP to basal levels after fluid resuscitation with lactated Ringer solution. I.c.v. neostigmine (0.5 microg) produced a sustained increase in MABP beginning at 30 min of hemorrhage that persisted throughout fluid resuscitation in control and alcohol-treated animals. I.c.v. neostigmine enhanced epinephrine responses and restored the hemorrhage-induced release of norepinephrine and AVP in alcohol-treated rats. These results demonstrate that inhibition of acetylcholinesterase in the central nervous system enhances SNS outflow, restores the neuroendocrine response to severe blood loss, and thereby improves hemodynamic counterregulation during acute alcohol intoxication. This study provides evidence for a central (and not peripheral) role of alcohol in impairing hemodynamic stability during hemorrhagic shock.

show abstract

“…Investigations into the mechanism of this impaired counterregulatory response have ruled out impaired vascular pressor response as a primary mechanism for the greater hypotension following blood loss observed in the intoxicated host (7). In contrast, studies examining the role of the blunted sympathetic response to hemorrhage have provided strong support for the hypothesis that the impaired response to blood loss during AAI is due to central alterations in sympathetic outflow (8, 9). Central administration of acetylcholinesterase inhibitors increases sympathetic outflow, significantly improves the blunted counterregulatory hormone response associated with AAI, and contributes to an enhanced blood pressure recovery following hemorrhage (8).…”

Section: Introductionmentioning

confidence: 99%

Delayed Resuscitation with Physostigmine Increases End Organ Damage in Alcohol Intoxicated Rats

Molina²

2011

Shock

Self Cite

View full text Add to dashboard Cite

Previous studies from our laboratory have identified a role for blunted central sympathetic activation in the acute alcohol intoxication (AAI)-induced impairment of the counterregulatory response to hemorrhagic shock (HS). Immediate fluid resuscitation (FR) with acetylcholinesterase-inhibitors restores the neuroendocrine and pressor responses to FR in AAI+HS. We hypothesized this intervention would remain beneficial following delay and that restoration of MABP during FR would attenuate organ damage. Male Sprague-Dawley rats received a primed constant alcohol infusion (2.5 g/kg + 0.3 g/kg/h for 15h) or isocaloric dextrose (DEX) prior to HS (40 mmHg for 60 min) and FR with lactated Ringer’s (LR) ± physostigmine (PHYS; 100 ug/kg) immediately or following a 60 min delay post-HS. Immediate LR elevated MABP in DEX+HS. AAI delayed the initial MABP recovery. Delayed LR did not further increase MABP in DEX- or AAI+HS. LR+PHYS increased MABP in DEX- and AAI+HS following immediate and delayed FR. No differences were noted in markers of organ dysfunction (ALT, AST, BUN, creatinine) following DEX+HS and this was unaltered by immediate or delayed LR+PHYS. AAI+HS increased ALT, which was attenuated by immediate LR+PHYS. In contrast, delayed LR+PHYS exacerbated tissue injury in AAI+HS, as reflected by increased ALT, AST, BUN, creatinine, and liver protein carbonylation over time-matched LR. In conclusion, PHYS enhanced blood pressure recovery independent of time of FR and presence of AAI. However, in AAI+HS, delayed LR+PHYS accentuated organ damage and dysfunction. These findings suggest that while enhancing the sympathetic response can improve hemodynamic recovery during AAI, it may compromise tissue perfusion and enhance tissue injury.

show abstract

Transient Central Cholinergic Activation Enhances Sympathetic Nervous System Activity but Does Not Improve Hemorrhage-Induced Hypotension in Alcohol-Intoxicated Rodents

Cited by 8 publications

References 37 publications

Alcohol Abuse and the Injured Host

Alcohol Abuse and the Injured Host

Central acetylcholinesterase inhibition improves hemodynamic counterregulation to severe blood loss in alcohol-intoxicated rats

Delayed Resuscitation with Physostigmine Increases End Organ Damage in Alcohol Intoxicated Rats

Contact Info

Product

Resources

About