Effects Of Acute Ethanol Intoxication Research Articles

Effects of Acute Ethanol Intoxication on Spinal Cord Injury Outcomes in Female Mice.

Abstract Approximately one in three traumatic spinal cord injuries (SCIs) occurs during or shortly after the consumption of alcohol. A small number of retrospective clinical studies report variable effects of alcohol intoxication on mortality, neurological recovery, and complications after SCI. Some of these studies demonstrate a protective effect of alcohol intoxication on SCI outcomes, whereas others show an increased complication risk. Pre-clinical studies in rat, ferret, and feline SCI models report a detrimental effect of ethanol intoxication on hemorrhage, motor recovery, and biochemical markers of tissue injury. However, no studies to date have investigated the neuropathological consequences of ethanol intoxication at the time of SCI or the reciprocal effect of SCI on ethanol metabolism. Therefore, we combined a pre-clinical mouse model of acute ethanol intoxication and experimental vertebral level T9 contusion SCI to investigate their interactive effects in female mice. We first investigated the effect of SCI on ethanol metabolism and found that T9 SCI does not alter ethanol metabolism. However, we did find that isoflurane anesthesia significantly slowed ethanol metabolism independent of SCI. We also determined how acute ethanol intoxication at the time of SCI alters locomotor recovery and lesion pathology. Using the Basso Mouse Scale (BMS) and CatWalk XT Gait Analysis System, we assessed locomotor recovery for 6 weeks after injury and observed that acute ethanol intoxication at the time of injury did not alter locomotor recovery. We also found no effect of ethanol intoxication on heat hyperalgesia development. There was, however, a detrimental effect of ethanol on tissue sparing after SCI. Therefore, we conclude that acute alcohol intoxication at the time of injury may contribute to the neuropathological consequences of SCI.

Effects of Acute Ethanol Intoxication on Local Field Potentials in the Rat Lateral Septum

Effects of Acute Ethanol Intoxication on Local Field Potentials in the Rat Lateral Septum

Effects of acute ethanol intoxication in an ovine peritonitis model

BackgroundAcute ethanol intoxication has been shown to have contrasting effects on outcomes in sepsis. The aim of this study was to explore the effects of acute ethanol intoxication on hemodynamics, renal function, brain perfusion and lactate/pyruvate in an ovine sepsis model.MethodsAnesthetized, mechanically ventilated female sheep were randomized to an ethanol group (n = 7), which received 1 g/kg ethanol diluted in intravenous (i.v.) saline infusion or a control group (n = 7), which received the same volume of i.v. saline. Both groups received the treatment for a period of 2 h prior to induction of sepsis by intraperitoneal injection of feces. Other treatment included fluid resuscitation but no vasopressors or antibiotics. Global hemodynamics, renal blood flow, brain cortex laser Doppler flowmetry and microdialysis analyses were recorded hourly.ResultsIn the ethanol group, blood ethanol concentrations were 137 ± 29 mg/dL at the time of feces injection and decreased to become undetectable by 12 h. Arterial hypotension occurred earlier in the ethanol than in the control group (8 [7–12] vs. 14 [11–20] hours, p = 0.03). Lactate levels increased to > 2 mmol/L earlier in the ethanol group. Renal dysfunction (9 [6–13] vs. 13 [12–15] hours, p = 0.05) and oliguria (urine output < 0.5 mL/kg/h; 10 [7–12] vs. 13 [12, 13] hours, p = 0.01) developed earlier in the ethanol than in the control group. Brain blood flow and lactate/pyruvate were unaffected. There was no significant difference in survival time.ConclusionsAcute ethanol intoxication in this model of peritonitis resulted in earlier development of shock and renal dysfunction but did not alter brain perfusion and metabolism or short-term survival.

Neuroprotective effect of acute ethanol intoxication in TBI is associated to the hierarchical modulation of early transcriptional responses

Ethanol intoxication is a risk factor for traumatic brain injury (TBI) but clinical evidence suggests that it may actually improve the prognosis of intoxicated TBI patients.We have employed a closed, weight-drop TBI model of different severity (2cm or 3cm falling height), preceded (−30min) or followed (+20min) by ethanol administration (5g/Kg). This protocol allows us to study the interaction of binge ethanol intoxication in TBI, monitoring behavioral changes, histological responses and the transcriptional regulation of a series of activity-regulated genes (immediate early genes, IEGs). We demonstrate that ethanol pretreatment before moderate TBI (2cm) significantly reduces neurological impairment and accelerates recovery. In addition, better preservation of neuronal numbers and cFos+cells was observed 7days after TBI. At transcriptional level, ethanol reduced the upregulation of a subset of IEGs encoding for transcription factors such as Atf3, c-Fos, FosB, Egr1, Egr3 and Npas4 but did not affect the upregulation of others (e.g. Gadd45b and Gadd45c). While a subset of IEGs encoding for effector proteins (such as Bdnf, InhbA and Dusp5) were downregulated by ethanol, others (such as Il-6) were unaffected. Notably, the majority of genes were sensitive to ethanol only when administered before TBI and not afterwards (the exceptions being c-Fos, Egr1 and Dusp5). Furthermore, while severe TBI (3cm) induced a qualitatively similar (but quantitatively larger) transcriptional response to moderate TBI, it was no longer sensitive to ethanol pretreatment. Thus, we have shown that a subset of the TBI-induced transcriptional responses were sensitive to ethanol intoxication at the instance of trauma (ultimately resulting in beneficial outcomes) and that the effect of ethanol was restricted to a certain time window (pre TBI treatment) and to TBI severity (moderate). This information could be critical for the translational value of ethanol in TBI and for the design of clinical studies aimed at disentangling the role of ethanol intoxication in TBI.

The Effect of Acute Ethanol Intoxication on Salivary Proteins of Innate and Adaptive Immunity

Human salivary proteins: peroxidase, lysozyme, lactoferrin, and IgA, participate in the protection of oral tissues, as well as upper digestive and respiratory tracts, against a number of microbial pathogens. In the current study, we investigated the effect of acute consumption of a large dose of ethanol on representative human salivary proteins of the innate and adaptive immune systems. Eight healthy male volunteers drank an average of 2.0 g (1.4 to 2.5 g/kg) body weight of ethanol, in the form of vodka, in the 6-hour period. Samples of resting whole saliva were collected 12 hours before, then 36 and 108 hours after, the alcohol consumption. The levels of total protein, immunoglobulin A, lysozyme and lactoferrin as well as peroxidase activity were determined in saliva. At 36 hours after alcohol consumption, salivary protein and lysozyme concentrations as well as peroxidase activity were significantly decreased (p = 0.002, p = 0.043, and p = 0.003, respectively), in comparison to the values obtained at 12 hours before drinking. Between 36 and 108 hours after alcohol consumption, the salivary protein and lysozyme concentrations, as well as peroxidase activity showed a tendency to increase, although at 108 hours after the drinking session, the concentration of protein and peroxidase activity were still significantly lower than before drinking. There was no significant change in the level of lactoferrin, after the drinking session. The salivary concentration of IgA tended to increase at 36 hours after alcohol consumption, and at 108 hours it was significantly higher (p = 0.028), when compared to IgA concentration in the saliva collected before drinking (from 8% to 26% and 32% of total protein content, respectively). Our report is the first to show that acute ingestion of relatively large, yet tolerable dose of alcohol, significantly disturbs salivary antimicrobial defense system. Reduced lysozyme level and decreased peroxidase activity may contribute to increased susceptibility to infections, when acute alcohol intake coincides with exposure to pathogens.

Effect of exogenous melatonin on ethanol-induced changes in Na(+),K(+)- and Ca(2+)-ATPase activities in rat synaptosomes.

In the present study, the effects of acute ethanol (EtOH) toxicity and of exogenous melatonin (MLT) on this toxicity were examined by measuring membrane-bound ATPases and acetylcholinesterase activities in rat synaptosomal membranes. The concentrations of plasma alpha-tocopherol and adrenal ascorbic acid (AA) were also measured. Synaptosomal Na(+),K(+)-ATPase and Ca(2+)-ATPase activities were significantly depressed in acute EtOH-intoxicated rats compared with controls, while acetylcholinesterase activity remained unaltered. Pretreatment with MLT (10 mg/kg) prior to acute EtOH administration prevented EtOH-induced inhibition of ATPases. Adrenal AA and plasma alpha-tocopherol levels were also depressed regardless of MLT pretreatment. MLT treatment alone affected neither membrane-bound enzyme activities nor tissue and blood levels of vitamins C and E. It is concluded that acute EtOH intoxication disturbs neural transport functions through the membrane-bound ATPase activity depression. Reduced AA and alpha-tocopherol levels may contribute to the neurodegenerative effects of EtOH. However, pretreatment with a high dose of MLT before EtOH administration may be beneficial to prevent EtOH-induced toxicity on ATPase-mediated neural transport functions.

Acute Ethanol Effects on Focal Cerebral Ischemia in Fasted Rats

The effects of acute ethanol intoxication were investigated in a rat model of unilateral middle cerebral artery occlusion. Groups of 5 to 8 male Sprague-Dawley rats were subjected to 4 hr of left middle cerebral artery occlusion. All groups were deprived of food overnight and were pretreated intraperitoneally with 5% dextrose solution (10 ml/kg), 20% ethyl alcohol in 5% dextrose solution (2 g/kg), or 30% ethyl alcohol in a 5% dextrose solution (3 g/kg) 1 hr before middle cerebral artery occlusion. Regional cerebral blood flow during ipsilateral occlusion was approximately 9.1 to 10% of baseline in all groups. The mean % brain water content in control, 2 g/kg ethanol-treated groups, and 3 g/kg ethanol-treated groups were: in the ischemic core--81.6, 81.2, and 82.4; intermediate zone--80.5, 80.6, and 81.7; and outer zone--79.7, 79.7, and 80.8, respectively. Brain Na+ and K+ content in the three groups was related to water content, but much greater with ethanol pretreatment. The water content of the intermediate zones in the 3 g/kg ethanol-treated animals was significantly greater than in the control (p < 0.01 and 0.001) and the 2 g/kg ethanol-treated groups. One-way analysis of variance indicated a significant dose-effect relationship in which the lower dose of ethanol tended to reduce ischemic core water content, and the larger dose increased ischemic core water, compared with the control. None of the overnight fasted groups had any significant hyperglycemia. The group given 3 g/kg i.p. ethanol 1 hr before had exacerbated edema formation with a mean whole blood level of ethanol of approximately 230 mg/dl. The neurotoxic effects of high concentrations of ethanol were unrelated to any change in plasma glucose concentrations.

Acute Ethanol Intoxication Inhibits Neutrophil β2‐Integrin Expression in Rats During Endotoxemia

The effects of acute ethanol intoxication on neutrophil [polymorphonuclear leukocyte (PMN)] adhesion molecule expression and certain other functional properties during endotoxemia were studied in rats to elucidate the mechanisms underlying the immunosuppressive effects of ethanol. Acute ethanol intoxication was induced by an intraperitoneal injection of 20% ethanol at a dose of 5.5 g of ethanol/kg. Control animals received an intraperitoneal injection of saline. Thirty minutes after intraperitoneal injection, animals were given a 90-min intravenous infusion of Escherichia coli endotoxin (total dose of 112.5 microg/rat in 2.5 ml of saline) or saline. Certain rats received granulocyte colony-stimulating factor (G-CSF; 50 microg/kg in 5% dextrose, subcutaneous injection twice daily) or vehicle pretreatment for 2 days before intravenous endotoxin infusion. Endotoxemia significantly upregulated CD11b/c and CD18 expression on PMNs when compared with those of saline-infused rats. Acute ethanol intoxication inhibited this endotoxin-induced upregulation of CD11b/c and CD18 expression on PMNs. Ethanol intoxication also suppressed the phagocytic activities of PMNs in saline-infused rats, but this suppression failed to reach statistical significance in endotoxin-infused rats. Hydrogen peroxide generation by PMNs in saline- or endotoxin-infused rats was not affected by ethanol intoxication. Histological examination showed extensive PMN sequestration in the liver after endotoxin infusion, and ethanol intoxication significantly attenuated this hepatic sequestration of PMNs. G-CSF pretreatment enhanced neutrophil phagocytosis, CD11b/c and CD18 expression in endotoxin-infused rats, and prevented the ethanol-induced inhibition of neutrophil CD18 expression and phagocytosis. The impairment of beta2-integrin expression on PMNs may be one mechanism underlying ethanol-induced defects of neutrophil delivery into tissue sites of infection. G-CSF may be of benefit to the infected alcoholic host by enhancing leukocyte defense functions.

Acute Ethanol Administration Modulates Leukocyte Actin Polymerization in Endotoxic Rats

The effects of acute ethanol intoxication with or without endotoxemia were studied on chemoattractant-initiated actin polymerization in circulating and liver-recruited neutrophils [polymorphonuclear leukocytes (PMNs)] and Kupffer cells of age-matched male and female rats. In female rats, F-actin content in response to f-Met-Leu-Phe in circulating PMNs was significantly upregulated by ethanol+endotoxin (ET) treatment relative to saline+ET-treated animals. Male rats did not show this upregulated response. In liver-recruited PMNs, the F-actin response did not change significantly due to ethanol + ET treatment in cells of either gender. The actin polymerization response in Kupffer cells was smaller than in liver sequestered PMNs and also exhibited a gender difference. In Kupffer cells of female rats, only ethanol+ET treatment elicited an F-actin response to f-Met-Leu-Phe, whereas in cells of male rats similar increases in F-actin content were observed in both saline+ET and ethanol+ET groups. We conclude that ethanol-enhanced actin polymerization in rats is associated with gender differences. This may be one of the underlying mechanisms resulting in upregulated leukocyte activation in acutely ethanol-intoxicated endotoxic animals.

Acute Ethanol Intoxication Suppresses the Pulmonary Inflammatory Response in Rats Challenged with Intrapulmonary Endotoxin

The effects of acute ethanol intoxication on the functional activities of circulating and lung-recruited polymorphonuclear leukocytes (PMNs) and alveolar macrophages (AMs) were determined in rats challenged with intratracheal endotoxin to elucidate the mechanisms underlying the defects of pulmonary host defenses caused by acute ethanol intoxication. Acute ethanol Intoxication was induced by an intraperitoneal injection of 20% ethanol at a dose of 5.5 g of ethanol/kg. The control animals were injected with an equal amount of saline. Thirty min after intraperitoneal injection, rats were challenged with intratracheal endotoxin (300 micrograms/kg in 0.5 ml of saline) or saline. The rats were killed 3 h after intratracheal injection. CD11b/c expression on PMNs and phagocytosis and hydrogen peroxide generation of PMNs and AMs were determined by flow cytometry. Cytokine-Induced neutrophil chemoattractant (CINC) level in bronchoalveolar lavage fluid was measured with a specific ELISA. Intratracheal endotoxin caused a significant PMN recruitment into the lung in control animals. Acute ethanol intoxication completely suppressed the endotoxin-induced pulmonary recruitment of PMNs. Pulmonary-recruited PMNs exhibited a significant upregulation (8-fold) of CD11b/c expression when compared with circulating PMNs. This upregulation of CD11b/c expression was abolished by ethanol intoxication. Ethanol intoxication suppressed hydrogen peroxide generation by AMs and lung-recruited PMNs, and the phagocytosis of circulating PMNs. In contrast, acute ethanol intoxication did not affect pulmonary CINC production. These data indicate that the antiinflammatory effects of alcohol seem to be primarily based on the effects of ethanol on the PMNs themselves and not on the generation of certain chemotactic stimuli. In addition to the impairment of PMN recruitment, the suppression of AM and PMN activities also contributes to the mechanisms underlying ethanol-induced defects of pulmonary host defenses.

Acute effects of ethanol on mineral metabolism and trabecular bone in Sprague-Dawley rats.

In order to assess the effects of acute ethanol intoxication on bone, 45 female Sprague-Dawley rats were studied. Five rats were sacrificed at baseline. The remainder received either ethanol (2 g/kg of body weight) intraperitoneally or isotonic saline. Rats were sacrificed in groups of 10 (5 intoxicated and 5 placebo) at 1, 4, 8, and 24 hours after injection. At the time of sacrifice, a blood sample was obtained and the 4th vertebra was excised for histomorphometric analysis of undecalcified bone. Effect of ethanol was assessed by an analysis of variance test using a Scheffé procedure. In ethanol-treated rats we observed (mean +/- SD, ethanol versus controls, maximum difference point, P value) a significant decrease in osteiod surface with osteoblasts (42.86 +/- 15.61% versus 64.57 +/- 6.24%, P < 0.05); osteoclast number (0.05 +/- 0.02 n/mm2 versus 0.17 +/- 0.09 n/nm2, P < 0.05), and osteocalcin (36.9 +/- 2.21 ng/ml versus 45.8 +/- 5.1 ng/ml, P < 0.05). Osteoclast surface was initially reduced (0.129 +/- 0.09% versus 0.425 +/- 0. 26%, P < 0.01) but showed a subsequent increase (0.765 +/- 0.24% versus 0.226 +/- 0.17%, P < 0.01) attributable to alcohol. There was also a significant decrease in serum Ca (8.51 +/- 0.23 mg/dl versus 9.10 +/- 0.29 mg/dl, P < 0.01) and parathyroid hormone values (23.51 +/- 5.72 pg/ml versus 76.39 +/- 11.66 pg/ml, P < 0.001). We conclude that acute alcohol intoxication in rats induces early striking changes in bone histology and analytical parameters, not completely reversed after 24 hours. These data are consistent with a toxic effect induced by alcohol on bone.

Effects of acute ethanol intoxication on experimental brain injury in the rat: neurobehavioral and phosphorus-31 nuclear magnetic resonance spectroscopy studies

Using the lateral fluid-percussion model of experimental brain injury in the rat, the authors investigated the effect of acute ethanol (EtOH) intoxication on cardiovascular changes, neurological motor deficits, brain bioenergetics, and mortality associated with traumatic brain injury. Two hours after gastric administration of EtOH (low dose in 20 animals, 1.5 g/kg; high dose in 28, 3.0 g/kg) or saline (equal volume), animals were subjected to a fluid-percussion brain injury centered over the left parietal cortex. These injuries were of either moderate (X = 2.2 atm; 10 animals/treatment) or high severity (X = 3.0 atm; 18 animals/saline, 10 animals/low-dose EtOH, and 18 animals/high-dose EtOH). Neurological motor function was evaluated daily over a 1-week period, while a subset of eight animals receiving high-dose EtOH and subjected to brain injury of high severity were monitored for 4 hours using phosphorus-31 nuclear magnetic resonance spectroscopy to determine intracellular pH, free magnesium, and brain cytosolic phosphorylation potential. A significant (p < 0.05) and prolonged (up to 1 hour) hypotension was observed in animals pretreated with either low- or high-dose EtOH. Neither low-dose (blood-EtOH concentration = 110 +/- 40 mg/dl) nor high-dose (blood-EtOH = 340 +/- 70 mg/dl) EtOH had any effect on survival or neurological motor function after moderate brain injury. Following severe brain injury, animals pretreated with high-dose (blood-EtOH concentration = 352 +/- 65 mg/dl) EtOH showed a significantly increased mortality and markedly worsened neurological deficits at 24 hours postinjury. Following injury, free magnesium and cytosolic phosphorylation potential declined in both groups by approximately 50% to 60%, with no significant differences between groups with respect to these variables. In contrast, brain intracellular pH in the EtOH-treated animals was consistently higher than in the control group after injury. These data suggest that prior exposure to EtOH, particularly at high concentrations, may have detrimental effects on neurobehavioral function and survival in the acute period (up to 24 hours) after severe brain injury, and may be associated with posttraumatic cerebral alkalosis.

Effect of Acute Ethanol Ingestion on Orthostatic Vital Signs

Study objective: To determine the effect of acute ethanol intoxication on the results of orthostatic tilt testing. Design: Prospective, randomized crossover study. Subjects received ethanol (1.1 gm/kg) or an equal volume of water added to nonalcoholic beer. Orthostatic vital signs, ethanol concentration, and relative volume status were checked initially and hourly for 8 hours. Participants: Twenty healthy human volunteers, 10 men, and 10 women. Results: Peak ethanol concentration was 116±18 mg/dL (mean± SD) 1 hour after ingestion. ANOVA for repeated measures revealed a significant difference in orthostatic pulse changeand relative volume deficit between the ethanol and placebo groups ( P<.05). Post hoc testing revealed significant differences between the two groups at two, five, seven and eight hours post ingestion for pulse change, and two to eight hours for volume status (Bonferroni's corrected t test, P<.0055). At 2 and 5 to 8 hours, there were significantly more positive tilt tests (±30 beat/minute increase) in the ethanol group than in the placebo group ( P<.05). Starting at 2 hours, the ethanol group had a statistically significant relative fluid deficit averaging .5 L by 3 hours. There was no difference in postural blood pressure changes between the two groups. Conclusion: In healthy volunteers, ethanol intoxication resulted in exaggerated postural pulse changes and in a greater proportion of positive orthostatic tilt test results than in a placebo group. These changes were accompanied by significant relative fluid deficits. [Tomaszewski C, Cline DM, Whitley TW, Grant T: Effect of acute ethanol ingestion on orthostatic vital signs. Ann Emerg Med May 1995;25:636-641.]

Effect of acute ethanol intoxication on glucoregulation during prolonged insulin-induced hypoglycemia.

This study examined the interaction of acute ethanol administration on glucose homeostasis during insulin-induced hypoglycemia (IIH). Glucose kinetics and net hepatic balances of alanine, glycerol, and lactate were estimated in three groups of dogs: group I underwent 3 h of IIH; group II received a continuous ethanol infusion in addition to IIH; group III received ethanol for 3 h. In group I, IIH resulted in a sustained twofold increase in glucose rate of appearance (Ra) and net hepatic uptake (NHU) of glycerol and lactate but no change in NHU of alanine. In group II, glucose Ra rose transiently, NHU of alanine and glycerol increased two- and fivefold, respectively, whereas NHU of lactate dropped 60%. In group III, no alterations in plasma glucose levels, glucose Ra, and NHU of alanine and glycerol were observed, but NHU of lactate switched to a net output. These results demonstrate that ethanol alone or with IIH exclusively inhibited NHU of lactate, and this was responsible, in a stoichiometric fashion, for the failure of the delayed increase in glucose Ra during IIH.

Effects of acute ethanol intoxication during pregnancy on central dopaminergic system in male rats

Pregnant albino rats received 2 IP injections, spaced by 4 h, of either ethanol (2.9 g/kg in 24% v/v saline solution) or saline, on gestational day (GD) 8. During adulthood, male rats prenatally exposed to alcohol exhibited an increased stereotyped behavioral response to 12 mg/kg of amphetamine (AMPH) or 1 mg/kg of apomorphine (APO), whereas the stereotypy induced by 6 mg/kg of AMPH showed no difference between control and experimental animals. Also, the hypoactivity response elicited by small doses of APO was not significantly affected by the prenatal treatment with alcohol. Analysis of dopaminergic function in the striatum and nucleus accumbens demonstrated no change on dopamine (DA) levels in both structures in alcohol pre-exposed 55- and 180-day-old rats. A reduction in striatum 3–4 dihydroxyphenylacetic acid levels was observed at both ages. These results indicate that an acute intoxication with alcohol on GD 8 induces a long-lasting decrease in striatal but not in nucleus accumbens DA metabolism. As a consequence, a lower striatal DA release might produce a compensatory supersensivity of postsynaptic DA sites. This interpretation is consistent and correlates with behavioral results.

The effect of acute ethanol intoxication to rats on the reduced glutathione content and lipid hydroperoxides production in liver mitochondria

The effect of acute ethanol intoxication to rats on the reduced glutathione content and lipid hydroperoxides production in liver mitochondria

Voluntary wheel running reduced the effects of acute ethanol on activity and avoidance in C57BL/6J mice

C57BL/6J mice were given five weeks of voluntary wheel running and then studied for behavioral impairment after an intoxicating dose of ethanol. Forty-four mice, 22 males and 22 females, were assigned to Wheel (free access to a running wheel in the home cage) or No Wheel conditions. At the end of the training period, animals were removed from the exercise cages and tested for noise avoidance after 2.4 g/kg ethanol (EtOH) or physiological saline (Sal). Mice could avoid 87.5-dB noise by entering and remaining in a randomly designated “safe corner.” In unexercised animals, EtOH caused a strong suppression on locomotor activity and avoidance behavior: No Wheel EtOH mice differed significantly from No Wheel Sal mice on both measures. In exercised animals, EtOH failed to cause significant suppression: Wheel EtOH animals did not differ significantly from Wheel Sal animals on either measure. The present results suggest that prior exercise training may be effective in offsetting the effects of acute ethanol intoxication.

Acute ethanol intoxication decreases the likelihood of resuscitation from cardiac arrest in rats

Acute ethanol intoxication has been shown to depress myocardial performance in both laboratory and clinical studies. The present study was designed to examine the effect of acute ethanol intoxication on resuscitation of rats subjected to cardiac arrest. Rats were given 1.2 g ("moderately intoxicated") or 2.4 g ("highly intoxicated") of ethanol/kg, or distilled water ("nonintoxicated" rats). Using a standardized technique, we induced cardiac arrest. CPR was then attempted using chest compressions interposed with abdominal compressions. Resuscitation was said to be successful if BP returned spontaneously within 6 mins of institution of chest compressions interposed with abdominal compressions, and if systolic BP was 50% of its prearrest level within 10 mins of discontinuation of chest compressions interposed with abdominal compressions. Mean +/- SD serum ethanol levels were 121.3 +/- 12.9 mg/dL (26.3 +/- 2.8 mmol/L) (moderately intoxicated rats) and 254.4 +/- 34.6 mg/dL (55.2 +/- 7.5 mmol/L) (highly intoxicated rats). Resuscitation was successful in 75% (15/20) of nonintoxicated rats, 46.7% (7/15) of moderately intoxicated rats, and 33.3% (5/15) of highly intoxicated rats. The difference in resuscitation rates was significant for nonintoxicated rats compared with either intoxicated rats as a group (p = .021) or highly intoxicated rats (p = .019), but was not significant for nonintoxicated rats compared with moderately intoxicated rats. Acute ethanol intoxication appears to decrease the likelihood of successful resuscitation in a dose-dependent fashion.

Ethanol potentiation of 5-HT 3 receptor-mediated ion current in NCB-20 neuroblastoma cells

The effect of acute ethanol (EtOH) exposure on 5-HT 3 receptor-mediated ion current was examined in whole-cell patch-clamp recordings from NCB-20 neuroblastoma cells. The physiologic and pharmacologic properties of 5-HT-activated ion current in NCB-20 cells indicated that it was mediated by 5-HT 3 receptors. EtOH potentiated 5-HT 3 receptor-mediated current in a concentration-dependent manner at concentrations (25–100 mM) which are achieved during EtOH intoxication in vivo.

Kinetic disposition of ethanol in the neonatal piglet and hemodynamic effects in the presence and absence of 4-methylpyrazole

The hemodynamic effects of acute ethanol intoxication and the kinetic disposition of ethanol are reported for the first time in neonatal piglets under nitrous oxide anesthesia. Two hours after a single dose of ethanol (1.4 g/kg), blood pressure decreased from 76 ± 4 to 71 ± 4 mm Hg (p < 0.05) and heart rate increased from 194 ± 10 to 227 ± 8 beats/min (p < 0.05; means ± SE). By 5 hr, blood pressure dropped to 67.5 ± 4 mm Hg and heart rate increased to 239 ± 8 beats/min. In piglets pretreated with 4-methylpyrazole, an alcohol dehydrogenase inhibitor, there was a transient increase in blood pressure (p < 0.05) and a decrease in heart rate (p < 0.05) immediately after the end of the ethanol infusion. However, the hemodynamic alterations observed 2 hr after ethanol treatment alone were prevented with 4-methylpyrazole. These findings indicate that ethanol metabolites play a significant role in hemodynamic alterations observed after acute ethanol intoxication. The mean ethanol metabolic rate derived from plasma data was 94 ± 9 mg/liter/hr. This corresponded to an apparent K m of 68 ± 3 mg/liter and a V m of 123 ± 11 mg/liter/hr. The V d was 0.966 ± 0.031 liter/kg. The metabolic rate for ethanol, derived from plasma data, correlated with in vitro alcohol dehydrogenase activity at pH 7.4 and 25 and 37°C. The optimum pH for hepatic alcohol dehydrogenase activity was 9.9.