naloxone and Shock

There is pre-clinical evidence, involving several animal species, suggesting that opioid peptides play a role in the physiopathology of shock (endotoxic, hypovolemic, cardiogenic, spinal, anaphylactic). Many case reports have suggested that naloxone (an opiate antagonist) might be an effective treatment for shock in humans, but others have not supported such a point of view. This controversy led us to undertake a meta-analysis of the available evidence on the efficacy of naloxone as a treatment measure of shock in humans.. To evaluate the effectiveness and safety of naloxone in human shock and to estimate the methodological quality of the clinical trials.. Computerized bibliographic search up to December 2002, review of references of all papers found on the subject and contact with primary investigators of eligible studies.. Randomized controlled trials evaluating naloxone in human shock, regardless of the patient's age (adult, child or neonate).. Three independent reviewers extracted data on study design, intervention, outcome and methodological quality.. Three independent readers reviewed 80 human publications and selected six clinical trials. Overall agreement on study selection was perfect (concordance: 100%). This meta-analysis includes six studies involving 126 patients with septic, cardiogenic, hemorrhagic or spinal shock. Naloxone therapy was associated with statistically significant hemodynamic improvement (odds ratio 0.24; 95% confidence interval [95%CI] 0.09-0.68). The mean arterial pressure was significantly higher in the naloxone groups than in the placebo groups (weighted mean difference: +9.33 mmHg; 95%CI 7.07-11.59). No heterogeneity was found for this outcome. The death rate was lower in the naloxone group (odds ratio 0.59; 95%CI 0.21-1.67) but this was consistent with the play of chance. A significant heterogeneity for the latter outcome was detected (p<0.05).. Naloxone improves blood pressure, especially mean arterial blood pressure. However, the clinical usefulness of naloxone to treat shock remains to be determined, and additional randomized controlled trials are needed to assess its usefulness.

Topics: Adult; Child; Humans; Infant, Newborn; Naloxone; Narcotic Antagonists; Randomized Controlled Trials as Topic; Shock

To evaluate the effectiveness of naloxone in human shock; and to estimate the methodologic quality of the clinical trials.. Computerized bibliographic search on MEDLINE covering the period from January 1979 to July 1996, review of references of all papers found on the subject, and contact with primary investigators of eligible studies.. To be included in this study, a paper should be a randomized, clinical trial published in a peer-reviewed journal evaluating naloxone in human shock, regardless of the patient's age (adult, child, neonate). Three independent readers reviewed 61 human publications and selected five clinical trials. Overall agreement on study selection was perfect (concordance: 100%). We excluded a posteriori two studies whose authors were unable to provide us with the raw data to complete contingency tables. This meta-analysis deals with three studies including 61 patients with septic shock.. Three independent reviewers extracted data on study design, intervention, outcome, and methodologic quality. The intraclass correlation coefficient was 0.7. The quality score of each study was 48, 60, and 61, on a scale of 104.. Naloxone therapy was associated with statistically significant hemodynamic improvement (typical odds ratio: 0.241; 95% confidence interval: 0.08 to 0.68). The overall effect size was 0.89. However, a publication bias was possible. The case fatality rate was not decreased by naloxone (typical odds ratio: 0.60; 95% confidence interval: 0.21 to 1.67); a chi-square analysis detected significant heterogeneity for the latter outcome (p < .05).. Naloxone improves blood pressure. However, the clinical usefulness of naloxone to treat shock remains to be determined and additional randomized clinical trials are needed to assess its usefulness.

Topics: Clinical Trials as Topic; Hemodynamics; Humans; Naloxone; Narcotic Antagonists; Shock

Naloxone has enjoyed long-standing success as a safe and effective opioid antagonist and has been invaluable in defining the role of endogenous opioid pathways in the response to pathological states such as sepsis and hypovolemia. We look forward to exciting research to further elucidate these pathways and to improve outcome by modulating the patient's physiological response to these stresses.

Topics: Acute Disease; Adult; Animals; Asphyxia Neonatorum; Cerebrovascular Disorders; Child; Emergency Medicine; Humans; Infant, Newborn; Naloxone; Poisoning; Shock; Spinal Cord Injuries; Treatment Outcome

Topics: Animals; Humans; Naloxone; Receptors, Opioid; Shock

Opiates are now known to be important modulators of cardiovascular function in both the normotensive and hypertensive states. There is accumulating evidence that endogenous opiates are elevated in models of hypertension of various etiologies including genetic and renovascular hypertension. Early evidence for elevated opiates in hypertension arose from observations that hypertensive humans and rats with genetic or experimental hypertension exhibited hypoalgesia in various tests of pain sensitivity. Because pain and cardiovascular regulatory systems have in common a number of brain loci, cardiovascular effects of opiates and opiate blockade were studied. These studies have shown that opiate blockade can attenuate the development of hypertension and reduce blood pressure in chronic hypertension possibly via actions on the baroreflexes and/or by modulating the centrally mediated pressor actions of angiotensin II.

Topics: Angiotensin II; Animals; Blood Pressure; Cardiovascular System; Endorphins; Hypertension; Hypertension, Renovascular; Models, Cardiovascular; Naloxone; Narcotics; Pain; Pressoreceptors; Shock

Topics: Animals; Humans; Naloxone; Shock

Topics: Adrenal Cortex Hormones; Animals; Cats; Endorphins; Humans; Mice; Naloxone; Rats; Receptors, Opioid; Shock; Sympathetic Nervous System

Despite the fact that many new exciting prospects are on the horizon, volume support remains the cornerstone of resuscitation of the critically ill surgical patient. Their limitations not withstanding, balanced electrolyte solutions, properly used, are the most efficacious choice in the majority of patients. The patient's eventual survival depends not only on skillful resuscitation but on the ability to identify and correct the underlying cause.

Topics: Adenosine Triphosphate; Albumins; Blood Substitutes; Blood Volume; Dextrans; Fluid Therapy; Fluorocarbons; Humans; Hydroxyethyl Starch Derivatives; Isotonic Solutions; Magnesium; Magnesium Chloride; Naloxone; Plasma Substitutes; Resuscitation; Saline Solution, Hypertonic; Shock; Sodium Chloride; Surgical Procedures, Operative

An improved understanding of the patho-physiological and biochemical changes that occur in shock states has led to new and innovative pharmacologic approaches to shock reversal. In this article, we review the actions of several pharmaceutical agents on the peripheral vasculature in shock states. Agents with known efficacy, probable utility, and possible usefulness are each discussed. A model of factors modulating alpha-1 adrenergic receptor action is presented.

Topics: Adrenal Cortex Hormones; Animals; Catecholamines; Dopamine; Eicosanoic Acids; Humans; Muscle, Smooth, Vascular; Naloxone; Receptors, Adrenergic, alpha; Serotonin; Shock; Thyrotropin-Releasing Hormone; Vascular Resistance

Topics: Acute Disease; Anesthesia; Animals; Blood Circulation; Chronic Disease; Endorphins; Halothane; Humans; Ketamine; Naloxone; Pain; Receptors, Opioid; Shock; Sleep; Thiopental

Topics: Adrenal Gland Neoplasms; Animals; Cardiovascular Physiological Phenomena; Endorphins; Humans; Naloxone; Pheochromocytoma; Receptors, Opioid; Shock

Naloxone and related opioid antagonists have been shown to have therapeutic utility in a variety of conditions. The effects of opioid antagonists in either physiological or pathological processes are most clearly seen when there is excessive occupancy of opioid receptors, as in opiate overdose. Opioid antagonists are also able to reverse several types of cardiovascular shock, conditions in which endogenous opioids appear to be mobilised, resulting in increased opioid receptor occupation. There are also more controversial circumstances in which excessive occupation of opioid receptors may assume pathological significance, such as hypercapnia. Opioid antagonists could be useful in such a situation by re-sensitising the respiratory centres to carbon dioxide. There is some evidence that opioid antagonists may benefit some schizophrenic and manic-depressive patients, suggesting that an endogenous opioid ligand might cause disturbances in mental functioning. The diversity and complexity of opioid mechanisms in the central nervous system suggest that more specific opioid antagonists could be more selective in altering physiological or pathological functioning.

Topics: Alcohol Deterrents; Animals; Bipolar Disorder; Blood Pressure; Brain Ischemia; Clinical Trials as Topic; Humans; Lung Diseases, Obstructive; Naloxone; Naltrexone; Narcotic Antagonists; Receptors, Opioid; Respiration; Schizophrenia; Shock; Spinal Injuries

Topics: Adrenal Medulla; Analgesia; Animals; Behavior; Blood Pressure; Brain; Cardiovascular Physiological Phenomena; Drug Tolerance; Endocrine Glands; Endorphins; Enkephalins; Female; Humans; Morphine; Naloxone; Pain; Pituitary Gland; Pituitary Hormones, Anterior; Pregnancy; Pro-Opiomelanocortin; Protein Precursors; Protein Processing, Post-Translational; Receptors, Opioid; Shock; Spinal Cord; Stress, Physiological; Tissue Distribution

Topics: Animals; Blood Pressure; Brain Stem; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Dogs; Endorphins; Humans; Hypotension; Morphine; Naloxone; Nitroprusside; Rabbits; Receptors, Opioid; Shock; Sleep

In summary, naloxone has proved to be effective and safe during its years of use for narcotic antagonism. Its usefulness in non-narcotic coma and shock remains controversial, although some encouraging but inconclusive evidence exists. The final answer lies on the horizon of medicine; it awaits further delineation of the role of endogenous opioids in health and disease and clear statistical verification of naloxone's efficacy in such disease states.

Topics: Animals; Arousal; Coma; Humans; Naloxone; Shock; Shock, Cardiogenic; Shock, Hemorrhagic; Shock, Septic

Topics: Action Potentials; Animals; Blood Pressure; Brain Stem; Carotid Arteries; Cats; Chemoreceptor Cells; Endorphins; Morphine; Naloxone; Neurotransmitter Agents; Rats; Receptors, Opioid; Respiration; Shock

Topics: Animals; Binding Sites; Cardiovascular System; Cerebrovascular Disorders; Endorphins; Humans; Hypertension; Naloxone; Narcotic Antagonists; Pressoreceptors; Shock; Shock, Septic; Spinal Cord Injuries; Thyrotropin-Releasing Hormone; Wounds and Injuries

Topics: Animals; Brain; Brain Ischemia; Cardiovascular Physiological Phenomena; Cardiovascular System; Endorphins; Enkephalins; Humans; Hypertension; Hypotension; Morphine; Naloxone; Pressoreceptors; Receptors, Opioid; Reflex; Shock; Shock, Hemorrhagic; Shock, Septic; Spinal Cord Injuries; Thyrotropin-Releasing Hormone

Topics: Animals; Cats; Hemodynamics; Intestines; Kidney; Liver; Myocardial Depressant Factor; Naloxone; Narcotic Antagonists; Receptors, Opioid; Shock; Shock, Hemorrhagic

Topics: Animals; beta-Endorphin; Cardiovascular System; Drug Synergism; Endorphins; Guinea Pigs; Humans; Methylprednisolone; Myocardial Contraction; Naloxone; Narcotic Antagonists; Shock; Swine

Topics: Adrenal Cortex Hormones; Animals; Cardiovascular System; Dogs; Dose-Response Relationship, Drug; Drug Interactions; Endorphins; Hypophysectomy; Naloxone; Pituitary-Adrenal System; Rats; Shock; Swine

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Agonists; Dexamethasone; Epoprostenol; Humans; Methylprednisolone; Naloxone; Nitroprusside; Prostaglandins E, Synthetic; Shock

Topics: Humans; Naloxone; Shock

Topics: Acid-Base Imbalance; Arrhythmias, Cardiac; Blood Circulation; Blood Pressure; Child; Digestive System Diseases; Fluid Therapy; Glucocorticoids; Heart Rate; Heparin; Humans; Infection Control; Kidney Diseases; Naloxone; Nutrition Disorders; Respiratory Therapy; Shock

Topics: Acupuncture Therapy; Analgesia; Anesthesia; Anesthetics; Endorphins; Humans; Naloxone; Neurotransmitter Agents; Nociceptors; Opioid-Related Disorders; Receptors, Opioid; Shock

Naloxone hydrochloride (N) 0.4-1.2 mg i.v. was administered during 10 episodes of shock (8 septic and 2 cardiogenic) in 9 adult patients. Shock was defined as systolic blood pressure (SBP) less than or equal to 90 mmHg and urine output less than 0.5 ml/h and signs and symptoms of hypoperfusion lasting for greater than or equal to 30 min, despite fluid loading to a CVP 5 cmH2O above baseline. N was given as early as 30 min after onset of shock and resulted in an increase of SBP from a mean of 75 +/- 10 to a mean of 130 +/- 25 mmHg maximum (P less than 0.01). Within 10-60 min urine output increased from 16 +/- 12 to 122 +/- 56 ml/h, heart rate, CVP and arterial blood gas tensions remained unchanged. No side effects were observed. Naloxone, even in small doses, may improve hemodynamic parameters in human shock, provided it is administered very early.

Topics: Adult; Aged; Blood Pressure; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Naloxone; Prospective Studies; Shock; Time Factors

Naloxone and related opioid antagonists have been shown to have therapeutic utility in a variety of conditions. The effects of opioid antagonists in either physiological or pathological processes are most clearly seen when there is excessive occupancy of opioid receptors, as in opiate overdose. Opioid antagonists are also able to reverse several types of cardiovascular shock, conditions in which endogenous opioids appear to be mobilised, resulting in increased opioid receptor occupation. There are also more controversial circumstances in which excessive occupation of opioid receptors may assume pathological significance, such as hypercapnia. Opioid antagonists could be useful in such a situation by re-sensitising the respiratory centres to carbon dioxide. There is some evidence that opioid antagonists may benefit some schizophrenic and manic-depressive patients, suggesting that an endogenous opioid ligand might cause disturbances in mental functioning. The diversity and complexity of opioid mechanisms in the central nervous system suggest that more specific opioid antagonists could be more selective in altering physiological or pathological functioning.

Topics: Alcohol Deterrents; Animals; Bipolar Disorder; Blood Pressure; Brain Ischemia; Clinical Trials as Topic; Humans; Lung Diseases, Obstructive; Naloxone; Naltrexone; Narcotic Antagonists; Receptors, Opioid; Respiration; Schizophrenia; Shock; Spinal Injuries

Topics: Adrenergic Agonists; Advanced Cardiac Life Support; Animals; Clinical Trials as Topic; Drug Therapy, Combination; Epinephrine; Heart Arrest; Humans; Naloxone; Shock

To evaluate the acute hemodynamic and acid-base balance effects of hypertonic-hyperoncotic solution (HHS) combined with naloxone in the treatment of hemorrhagic shock in 45 male splenectomized adult mongrel dogs, a severe controlled hemorrhagic shock (20 mmHg mean arterial pressure during 30 min) was established in the groups (n=6) no treatment, shed blood reinfusion, hypertonic-hyperoncotic (saline-dextran) solution alone, naloxone alone (NX), or combination. Interventions included propiopromazine-pentobarbital anesthesia and installation of Swan-Ganz, femoral arterial, and urethral catheters, and exsanguination at 20 mmHg mean arterial pressure during 30 min followed by treatment and observation for 160 min. Fifteen (33%) dogs died before completing the 30-min shock period. Another 33% from the no-treatment group died during the following 90 min. Shed blood improved the cardiac index, arterial pressure, and acid-base balance. NX restored the cardiac index to less than 60% of baseline and reduced vascular resistance. Additionally, NX produced no improvement in acidosis, with 1 dog dead at 95 min posttreatment. HHS restored the cardiac index for 45 min and increased vascular resistance and arterial pressure. Acidosis was not improved. Single-dose HHS combined with naloxone resulted in a high cardiac index, oxygen consumption, and urine output with low peripheral vascular resistance (and no acute mortality) compared with untreated or single-dose groups.

Topics: Albumins; Animals; Dogs; Hypertonic Solutions; Male; Naloxone; Narcotic Antagonists; Shock

This study tested the possibility of adrenal autotransplantation in rats. Since the cortex and the medulla of the adrenal gland were from different origin embryologically, either whole adrenal glands (ADR), or capsule and cortex (CAP) or medulla (MED) were autotransplanted in the subcutaneous tissue. The functions of regenerated adrenal nodules were tested by measuring plasma corticosterone levels every fortnight. At the end of 9 weeks the rats were exposed to hypovolemic shock followed by naloxone injection to reverse the shock response. Results showed that rats transplanted with either cortex or whole adrenal started secreting corticosterone at 5 weeks post-transplantation (107.73 +/- 21.98 ng/ml, 126.04 +/- 48.41 ng/ml, respectively). Corticosterone levels increased to the value which were not significantly different from control by 9 weeks post-transplantation. However, rats transplanted with adrenal medulla showed very low corticosterone levels. Nine weeks post-transplantation, the mean blood pressure (MBP) of the CAP group was 135 +/- 13 mmHg and was not significantly different from sham-operated controls, whereas MBP of MED group was significantly lower than sham-operated animals (99 +/- 11 mmHg versus 141 +/- 9 mmHg). The MBP of the ADR group was also lower compared to sham-operated controls (112 +/- 17 mmHg P < 0.05). The MBP of the adrenal group was not statistically significant compared to the CAP group. After 1% body weight haemorrhage, the MBP decreased significantly in ADR (45 +/- 5 mmHg, P < 0.05) and MED group (36 +/- 9 mmHg, P < 0.001) compared to sham-operated rats (78 +/- 11 mmHg) but not in the CAP (56 +/- 9 mmHg). It was concluded that autotransplanted whole adrenal or adrenocortical tissues survived subcutaneously and produced sufficient corticosterone to alleviate haemorrhagic shock. Adrenal medullary tissue failed to regenerate subcutaneously and the presence of adrenal medullary tissue may suppressed the growth of transplanted adrenal gland.

Topics: Adrenal Cortex; Adrenal Glands; Adrenal Medulla; Animals; Blood Pressure; Corticosterone; Male; Naloxone; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Regeneration; Shock; Transplantation, Autologous

A double-blind paired protocol was used to evaluate, in eight male volunteers, the effects of the endogenous opiate antagonist naloxone (NAL; 0.05 mg.kg-1) on cardiovascular responses to 50 degrees head-up tilt-induced central hypovolaemia. Progressive central hypovolaemia was characterized by a phase of normotensive-tachycardia followed by an episode of hypotensive-bradycardia. The NAL shortened the former from 20 (8-40) to 5 (3-10) min (median and range; P < 0.02). Control head-up tilt increased the means of thoracic electrical impedance [from 35.8 (SEM 2.1) to 40.0 (SEM 1.8) omega; P < 0.01] of heart rate [HR; from 67 (SEM 5) to 96 (SEM 8) beats.min-1, P < 0.02], of total peripheral resistance [TPR; from 25.5 (SEM 3.2) to 50.4 (SEM 10.5)mmHg.min.1-1, P < 0.05] and of mean arterial pressure [MAP; from 96 (SEM 2) to 101 (SEM 2)mmHg, P < 0.02]. Decreases were observed in stroke volume [from 65 (SEM 12) to 38 (SEM 9) ml, P < 0.01], in cardiac output [from 3.7 (SEM 0.7) to 2.5 (SEM 0.5) 1.min-1, P < 0.01], in pulse pressure [from 55 (SEM 4) to 37 (SEM 3)mmHg, P < 0.01] and in central venous oxygen saturation [from 73 (SEM 2) to 59 (SEM 4)%, P < 0.01]. During NAL, mean HR increased from 70 (SEM 3); n.s. compared to control) to only 86 (SEM 9) beats.min-1 (P < 0.02 compared to control) and MAP remained stable.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Baroreflex; Blood Pressure; Bradycardia; Cardiac Output; Double-Blind Method; Endorphins; Head; Heart Rate; Humans; Male; Naloxone; Posture; Sex Factors; Shock; Tachycardia; Time Factors; Vagus Nerve

Modulation of learning and memory acquisition, retention and retrieval in the one trial passive avoidance learning task in mice by three inescapable stresses, i.e., footshock (FS), psychological (PSY) and forced swimming (SW) were investigated. Pre-, post-training and pre-test FS-stress (2 mA, 0.2 Hz, 1 sec for 30 min) and pre-training PSY-stress (communication box, 5 min) resulted in enhanced test latencies. On the contrary, SW-stress (20 degrees C, 5 min) immediately or 1 hr after training impaired retention latencies that tended to recover after 2 hr post-training SW-stress, suggesting that at least 2 hr are required to consolidate newly acquired information. In contrast, pre-stress naloxone (Nx), which did not affect FS- and PSY-stress induced facilitatory effects, returned to control levels the impaired retention latencies induced by SW-stress. Taken collectively, these results imply the involvement of an opioid-dependent mechanism in the modulation of memory by SW-stress and non-opioid in the case of FS- and PSY-stress. Furthermore, they suggest that different mechanisms are involved in stress-induced memory modifications and the production of stress-induced analgesia (SIA) since in the latter, FS and PSY but not SW stress produce Nx-sensitive antinociception.

Topics: Animals; Avoidance Learning; Behavior, Animal; Electric Stimulation; Foot; Learning; Male; Memory; Mice; Naloxone; Shock; Stress, Physiological; Swimming

Subcutaneous injection of the potent, nonselective opioid antagonist diprenorphine inhibits the vasopressin response to acute hypovolemia. To determine if this inhibition is due to antagonism of opioid receptors in brain pathways that mediate volume control, we determined the vasopressin response to different stimuli when diprenorphine or other opiates were injected into the cerebral ventricles, the nucleus tractus solitarius (NTS), or the lateral parabrachial nucleus (PBN) of rats. We found that the vasopressin response to hypovolemia was inhibited by injection of diprenorphine into the cerebral ventricles at a dose too low to be effective when given subcutaneously. This response also was inhibited when a 20-fold lower dose of diprenorphine was injected into the PBN but not when it was injected into the NTS. The inhibitory effect of diprenorphine in the PBN was not attributable to a decrease in osmotic or hypovolemic stimulation and did not occur with osmotic or hypotensive stimuli. Injecting the PBN with equimolar doses of the mu antagonist naloxone, the delta antagonist ICI-154,129 or the kappa-1 agonist U-50,488H had no effect on basal or volume-stimulated vasopressin. We conclude that the inhibition of vasopressin by diprenorphine is due partially to action at a novel class of opioid receptors that transmit volume stimuli through the PBN.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Acute Disease; Animals; Antihypertensive Agents; Brain; Cerebral Ventricles; Diprenorphine; Enkephalin, Leucine; Hemodynamics; Male; Naloxone; Narcotic Antagonists; Pyrrolidines; Rats; Rats, Sprague-Dawley; Shock; Solitary Nucleus; Stimulation, Chemical; Vasopressins

The effects of continuous naloxone infusion on the response to intestinal ischemia-reperfusion were studied in a rat model. Naloxone was given as a bolus injection (2 mg/kg bw) followed by a continuous infusion (4 mg/kg bw/h) starting before (-10 min) intestinal ischemia was applied (0-60 min) and continuing 2 h after reperfusion of the intestine. Blood pressure, acidosis and survival were determined. Saline-infused shocked rats and untreated shocked rats served as comparisons and non-shocked animals as controls. Blood pressure was slightly higher before and during the continuous naloxone infusion but did not differ after reperfusion in the three shock groups. Acidosis was less pronounced in naloxone compared to untreated shocked rats. Survival rates were significantly higher in naloxone-treated shocked rats compared to untreated shock and significantly lower in saline treated shocked rats compared to non-shocked controls. In conclusion a naloxone effect on acidosis and survival in shock after intestinal ischemia and reperfusion is possible.

Topics: Acid-Base Equilibrium; Acidosis; Animals; Blood Pressure; Hematocrit; Infusions, Intravenous; Intestines; Ischemia; Naloxone; Rats; Rats, Wistar; Reperfusion; Shock

Topics: Hemorrhagic Fever with Renal Syndrome; Humans; Naloxone; Shock

In this trial, the effect of supplementary administration of the opioid antagonist Naloxone was tested, in comparison to infusion of Ringer's-solution only, in the treatment of hypovolemic shock in cows suffering from right-sided abomasal displacement. Twenty cows were selected by several criteria (pulse rate greater than 95/min; plasma chloride content less than 90 mmol/l; body temperature less than 39.5 degrees C) and alternatively assigned to the Naloxone group and the control group. All animals were treated surgically by the usual clinical method. After opening the abdominal cavity paralumbally from the right, intravenous administration of 13 l of Ringer's-solution was started and continued for about 5 hours. In addition, the cows of the experimental group received 0.75 g Naloxone as an intravenous bolus before, and 1 g Naloxone dissolved in 7 l fluid during the first hour of the permanent drip infusion. Further treatments (additional fluid therapy or administration of purgatives and ruminomotorics on the following days) were given according to the condition of the animal. The evaluation of efficacy was done in regard to the clinical (course of disease), and clinicochemical (e.g. hemogram, blood gas analysis, plasma chloride, plasma lactate) parameters as well as to blood pressure. No statistically significant differences were found between both groups. Only nine of the twenty cows were sent home cured, one patient of each group died one day after surgery, and the remaining 9 animals had to be sent to the slaughterhouse within 3 to 22 days after surgery after only transient improvement. These results suggest, that under the conditions described, conventional fluid therapy is equivalent to fluid therapy with addition of Naloxone. Hypoxic damage of the abomasum caused by its displacement and the subsequent hypovolemic shock are discussed as main causes for the poor postsurgical prognosis of right-sided abomasal displacement.

Topics: Abomasum; Animals; Cattle; Cattle Diseases; Female; Naloxone; Shock; Stomach Volvulus

The case of a 6-year-old female who developed hypovolemic shock from mushroom poisoning is discussed. The mushroom ingested, Chlorophyllum molybdites, is considered to be a benign gastrointestinal irritant. This case emphasizes that the gastrointestinal irritant mushrooms can produce severe toxicity and that pediatric patients have a limited capacity for fluid loss before becoming hypovolemic.

Topics: Charcoal; Child; Female; Fluid Therapy; Humans; Mushroom Poisoning; Naloxone; Parenteral Nutrition, Total; Penicillin G; Ranitidine; Shock

Adrenal vein (AD), portal vein (PV), and femoral artery (FA) plasma levels of immunoreactive (IR) Met-enkephalin pentapeptide (ME) and extended ME-IR forms, obtained after sequential incubation of plasma with trypsin and carboxypeptidase B, were examined in 4 cats during splanchnic artery occlusion shock at baseline (S1), during early shock (S2), late shock (S3), and after naloxone (1 mg/kg, i.v.) administration (S4). Early shock (S2) led to a significant increase in levels of extended and fully processed Met-enkephalin IR at all 3 collection sites (AD, PV, FA) without a change in proportional levels of extended Met-enkephalin IR to the pentapeptide IR (ME). Naloxone administration during late shock (S4), however, resulted in a disproportionate increase (150-fold from baseline) in adrenal vein plasma levels of extended Met-enkephalin IR forms, as compared to ME IR (23-fold). In contrast, no changes in plasma levels occurred in PV and FA.

Topics: Adrenal Glands; Animals; Arteries; Cats; Enkephalin, Methionine; Ligation; Naloxone; Portal Vein; Radioimmunoassay; Shock; Splanchnic Circulation; Time Factors; Veins

It has been reported that naloxone may be useful in the treatment of hypovolemic shock. However, the effects of naloxone on cardiac energy metabolism in hemorrhagic shock have not been investigated. The effects of naloxone on myocardial metabolism were evaluated in the rats which were bled to a systolic pressure of 40 mmHg and maintained at that pressure for 30 min. Naloxone (10 mg/kg) was administered intravenously 5 min before the heart was removed. Then the intramyocardial high energy phosphates, pyruvate, lactate, and glycogen were measured. Naloxone increased systolic blood pressure and decreased heart rate significantly. However, there were no significant differences in high energy phosphates, energy charge, pyruvate, lactate and glycogen between the control and naloxone groups. These data suggest that naloxone may have no direct effect on the cardiac energy metabolism in a 30-min hypovolemic shock.

Topics: Animals; Blood Pressure; Energy Metabolism; Heart Rate; Male; Myocardium; Naloxone; Rats; Rats, Inbred Strains; Shock

A variety of neurotransmitters and neuropeptides appear to participate in the central control mechanisms of arterial blood pressure. Our knowledge of these mechanisms is limited as yet. In the present study the involvement of the opioid peptide beta-endorphin in circulatory homeostasis was studied. Under conditions in which beta-endorphin does not affect basal blood pressure and heart rate this peptide had a pronounced prohypotensive influence in normotensive rats. This was found for two conditions during which circulatory homeostasis was challenged. Firstly, during blood letting in a rat model employed to test blood pressure regulation during hemorrhage, and secondly, for the central hypotensive action of alpha-methyldopa. In the first model hypotension was produced by stepwise bleeding to respectively 80, 60 and 40 mmHg mean arterial pressure. Intracerebroventricular (i.c.v.) administration of an antiserum raised against beta-endorphin or of naloxone (s.c. or i.c.v.) caused a significant increase in the required bleeding volume, whereas an opposite action was observed after the injection of morphine (s.c.) or of beta-endorphin (i.c.v.). The role of beta-endorphin in the hypotensive action of alpha-methyldopa, given intracisternally (i.c.) was evaluated in conscious rats equipped with chronic cannulas. Pretreatment with the opiate antagonist naltrexone (i.c.) caused an inhibition of the hypotension and bradycardia induced by alpha-methyldopa. This effect of the receptor antagonist was mimicked by i.c. administration of a beta-endorphin antiserum. Taken together, these data point to a hypotensive influence exerted by endogenous beta-endorphin under conditions during which circulatory homeostasis are challenged.

Topics: Animals; beta-Endorphin; Blood Pressure; Blood Volume; Bloodletting; Dose-Response Relationship, Drug; Endorphins; Homeostasis; Male; Methyldopa; Morphine; Naloxone; Rats; Rats, Inbred Strains; Shock

The effects of subcutaneous (s.c.) administration of compound 48/80 (a well known histamine liberator) on latency to thermoalgesic stimulus, hematocrit (Hct) and plasma levels of beta-endorphin-like immunoreactivity (beta-END-LI) were investigated in male rats. The s.c. administration of compound 48/80 in doses ranging from 0.5 to 5.0 mg/kg into the rats produced significant analgesia in the hot plate test and increased Hct in a dose-dependent manner. Concomitant variation was observed between the analgesia and the increase of Hct. This analgesic effect, but not the increase of Hct, was diminished by pretreatment with the opiate receptor antagonist, naloxone (5 mg/kg, s.c.). A significant increase of plasma beta-END-LI was observed by s.c. injection of compound 48/80. Together with a previous finding that compound 48/80 induced-hypovolemia increases the renin release from kidney and then causes water intake in the rats, it is suggested that s.c. administration of compound 48/80 induced analgesia mediated through stimulation of an opioid system, may be closely related to stimulation of the renin-angiotensin system.

Topics: Animals; beta-Endorphin; Dose-Response Relationship, Drug; Injections, Subcutaneous; Male; Naloxone; Nociceptors; p-Methoxy-N-methylphenethylamine; Radioimmunoassay; Rats; Rats, Inbred Strains; Renin-Angiotensin System; Shock

The liver metabolic response of rats following a standardized intestinal shock, induced by applying a pressure of 120 cm water on the mesenteric vessels for 60 min, was studied. Immediately prior to the release of the pressure on the vessels saline or naloxone was given either as a single injection or as a continuous infusion. After the reperfusion of the intestine no early disturbances in liver metabolism were found as evidenced from the ATP, glucose and lactate levels in liver biopsies taken 15 min following reflow. Within 60 min of reflow reduction of ATP and increases of glucose and lactate levels occurred. There were no major hemodynamic or liver metabolic differences between saline- and naloxone-treated shocked rats. When saline or naloxone was given as a continuous infusion, the changes in liver metabolism were, however, less severe than those observed in the single injection situation pointing toward a non-specific effect of volume replacement rather than a blockade of opioid receptors. Hepatic hypoxia and/or cellular effects of "shock factors" could be mechanisms of pathophysiologic importance for the disturbed liver metabolism in this shock model.

Topics: Acid-Base Equilibrium; Adenosine Triphosphate; Animals; Blood Glucose; Blood Pressure; Carbon Dioxide; Female; Hematocrit; Hydrogen-Ion Concentration; Intestinal Diseases; Intestinal Mucosa; Lactates; Liver; Male; Naloxone; Rats; Rats, Inbred Strains; Shock

Topics: Animals; Endorphins; Humans; Naloxone; Shock; Shock, Septic

Recent studies have been conducted to evaluate the relationship between plasma beta-endorphin (END) levels and the hemodynamic changes that occur in severely stressed animals. Using our canine hypovolemic shock model, END levels were analyzed during the baseline period, at the beginning of treatment (after a period of fixed-pressure hypovolemic shock), and at the end of treatment. Mean arterial pressure (MAP) and cardiac output were also measured at these intervals. Animals were given iv 5 ml of 0.9% NaCl, 4 mg/kg of naloxone (NAL), 30 mg/kg of methylprednisolone (MP), or 4 mg/kg of NAL and 30 mg/kg of MP. A fifth group was composed of nonsteroid-treated animals. Scatterplots were generated and linear regression lines were drawn comparing END with cardiac output and MAP. In the nonsteroid-treated animals, a significant correlation was found between decreases in both MAP and cardiac output and increasing levels of END. The addition of MP did not seem to alter the relationship, suggesting that MP did not affect END release.

Topics: Animals; beta-Endorphin; Blood Pressure; Cardiac Output; Dogs; Endorphins; Methylprednisolone; Naloxone; Shock

The effect of naloxone (4.4-5.9 mg i.v.) was evaluated in 10 patients with circulatory shock (sepsis, n = 7; intoxication, n = 1; cardiogenic shock, n = 2) not responding to full conventional therapy. In addition, we measured plasma ACTH and immunoreactive beta-endorphin before and 60 min after administration of naloxone and compared the results with hormone concentrations in 10 intensive care patients without shock. Only in two patient with septic shock a transient increase (duration 15 min and 60 min, respectively) of systolic blood pressure was observed, while naloxone was ineffective in the remaining eight patients. No adverse effects of naloxone were found. Plasma ACTH and immunoreactive beta-endorphin concentrations in patients with shock were not different from those in controls (ACTH, 79 +/- 28 vs 120 +/- 60 pg/ml; immunoreactive beta-endorphin, 952 +/- 262 vs 1,070 +/- 378 pg/ml). Our findings suggest that naloxone in a single dose of 4.4-5.9 mg i.v. does not improve the management of circulatory shock unresponsive to conventional treatment. beta-endorphin seems to play no major role in the hypotension of shock.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Endorphins; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Naloxone; Shock; Shock, Cardiogenic; Shock, Septic

The hemodynamic effects of pentobarbital were tested in an experimental model used for cardiovascular research. Anesthesia was induced with an i.v. bolus and maintained with a continuous infusion of pentobarbital. The cardiovascular performance was then evaluated at various pentobarbital plasma concentrations ranging from 25 to 100 mg X l-1. Optimal experimental conditions were found at plasma pentobarbital concentrations within the range 40-60 mg X l-1, as the animals were well anesthetized with intact hemodynamics or ECG. The method of continuous pentobarbital administration seems advantageous for experimental research. Circulatory impairment following pentobarbital overdose was not affected by naloxone.

Topics: Animals; Carbon Dioxide; Cardiovascular System; Hemodynamics; Naloxone; Osmolar Concentration; Pentobarbital; Shock; Swine; Tidal Volume

Topics: Blood Pressure; Dose-Response Relationship, Drug; Humans; Naloxone; Shock

The roles of, and interactions between, steroids and naloxone, an opioid antagonist, in the reversal of experimental hypotensive shock were studied in normal and adrenalectomized rats. In normal rats treated with dexamethasone or deoxycorticosterone or 17-hydroxyprogesterone the hypotension and shock caused by 1% bodyweight and 2% bodyweight haemorrhage could be substantially reversed by naloxone in a dose-related manner. In contrast, the reversal of hypotension by naloxone was markedly less in adrenalectomized rats. It is concluded that there is a co-ordinate release of pressor catecholamines and depressor enkephalins from adrenal glands in hypovolaemic shock. Eventually, the use of naloxone would be of much less value in the treatment of hypotension or shock in patients with Addison's disease.

Topics: 17-alpha-Hydroxyprogesterone; Adrenalectomy; Animals; Blood Pressure; Desoxycorticosterone; Dexamethasone; Drug Interactions; Hydroxyprogesterones; Male; Morphine; Naloxone; Rats; Rats, Inbred Strains; Shock; Steroids

Topics: Animals; beta-Endorphin; Dogs; Endorphins; Heart; Heat Exhaustion; Hemodynamics; Hot Temperature; Naloxone; Potassium; Shock

Topics: Analgesia; Animals; Avoidance Learning; Behavior, Animal; Conditioning, Classical; Endorphins; Fear; Formaldehyde; Models, Biological; Motor Activity; Naloxone; Naltrexone; Nociceptors; Sensory Thresholds; Shock; Stress, Physiological

The late addition of methylprednisolone (MP) in our canine hypovolemic shock protocol was evaluated to determine whether any hemodynamic enhancement of the naloxone (NAL) effect might be present. Thirty-four dogs were bled to a mean arterial pressure (MAP) of 40-45 mm Hg and held there for 45 minutes. All animals were then treated (T = 0) with 0.9% NaCl (NS) or NAL. In two groups of animals, MP (30 mg/kg) was given as an IV bolus 30 minutes after initiating NS or NAL therapy. At 60 minutes, the infusions were stopped and the shed blood was returned. Animals treated with NAL with or without MP showed improvement in MAP, maximal left ventricular contractility (LVdP/dt max), and cardiac output (CO) compared to NS. We found little hemodynamic improvement with the addition of MP at T = 30 for either the NAL or NS. Plasma endorphinlike activity (PELA) values decreased during treatment in the groups receiving NAL. Survival was improved in all groups except those receiving NS, but survival was statistically better only in the group that received NAL.

Topics: Animals; Dogs; Endorphins; Hemodynamics; Methylprednisolone; Naloxone; Shock

The contribution of endogenous opioid peptides to the development of circulatory derangement in severe shock was studied using naloxone. A standardized intestinal shock was induced in rats by applying a pressure of 120 cm water on the mesenteric vessels for 60 min. The rats were then given either saline or naloxone. Mean arterial blood pressure improved and a less severe acidosis resulted in naloxone-treated animals compared to saline-treated. No differences were found in hematocrit, the degree of small intestinal mucosal lesions, or survival rates after 7 days comparing naloxone and saline treatment. Survival time increased after naloxone but not after saline treatment. The results support the hypothesis that endogenous opioid peptides contribute to cardiovascular collapse in intestinal shock.

Topics: Acid-Base Equilibrium; Animals; Blood Pressure; Female; Hematocrit; Hemoglobins; Intestinal Mucosa; Intestines; Ischemia; Male; Naloxone; Rats; Rats, Inbred Strains; Shock

The effect of naloxone on a number of experimental shock models, using the anaesthetized rat, was studied with special emphasis on mean arterial blood pressure (MABP) and chance of survival. Only a slight increase in MABP was noted in haemorrhagic shock models whereas survival was not affected. Naloxone was without effect in endotoxin shock (i.p. administration of endotoxin). In endotoxin shock (i.v. administration) naloxone increased MABP especially at a high dose of endotoxin. Although survival time was prolonged, the chance of permanent survival was not improved. Naloxone had practically no effect in anaphylactic shock and intestinal ischaemia shock. It is concluded that if naloxone has any effect it is relatively slight. However, this does not exclude the possibility that naloxone might still be considered as an adjunct to other forms of shock treatment at least in certain types of shock.

Topics: Anaphylaxis; Animals; Blood Pressure; Female; Intestines; Ischemia; Male; Naloxone; Rats; Rats, Inbred Strains; Shock; Shock, Hemorrhagic; Shock, Septic; Time Factors

Previous studies have suggested that methylprednisolone (MP) pretreatment attenuates the usual hemodynamic response to naloxone (NAL) treatment of hypovolemic shock. In this study, both drugs were given concurrently during shock to evaluate hemodynamic changes, plasma endorphin-like activity (PELA), and survival. Twenty-six dogs were bled to a mean arterial pressure (MAP) of 40 to 45 mm Hg, which was maintained for 45 min. Animals were then treated with iv 0.9% NaCl (NS), 5 ml; NAL, 4 mg/kg; MP, 30 mg/kg; or NAL, 4 mg/kg, plus MP, 30 mg/kg. Animals treated with NAL and/or MP had significantly (p less than .05) improved MAP, cardiac output, and myocardial contractility compared with NS-treated animals. NAL and MP each significantly lowered PELA levels and both NAL and NAL plus MP significantly improved survival.

Topics: Animals; Critical Care; Dogs; Drug Therapy, Combination; Hemodynamics; Methylprednisolone; Naloxone; Shock

A study was done to measure beta-endorphin immunoreactivity (beta-EI) in swine subjected to cardiopulmonary bypass at normal aortic perfusion pressures and during low-flow states such as can occur with shock. Fifteen pigs, divided into three groups of five each, were placed on total and right heart bypass and perfused as follows: group I, normal blood pressure (80 mmHg); group II, low blood pressure (45 mmHg); and group III, low flows (25 ml/kg/hr). beta-endorphin immunoreactivity was assayed six times during the procedure. Ventricular performance was evaluated by measuring stroke volume (SV) while controlling preload, afterload, and heart rate. Determinations of SV were made at the beginning of bypass, after a 1-hr pump run, and after administration of naloxone (1.1 mg/kg). There were no significant changes in beta-EI in any of the groups during the study. The initial SV in group III (23 +/- 6 ml) decreased significantly (p less than 0.05) after 1 hr of decreased cardiac perfusion (8.0 +/- 7 ml) and was not improved by naloxone (5.0 +/- 7 ml). Ventricular performance was not improved in any group following naloxone administration. In our study, naloxone administered to swine following inadequate myocardial perfusion did not effect a significant cardiac hemodynamic response.

Topics: Animals; beta-Endorphin; Cardiopulmonary Bypass; Coronary Circulation; Endorphins; Hemodynamics; Lactates; Lactic Acid; Naloxone; Oxygen Consumption; Shock; Stroke Volume; Swine

The contribution of endorphins (endogenous opiates) to the pathophysiology of shock was evaluated by the administration of naloxone (NAL) at different time intervals after inducing hypovolemia. Forty-four dogs were bled into a reservoir to a mean arterial pressure (MAP) of 40-45 mmHg and maintained at this pressure for 30, 45, or 60 minutes. The animals were then given either intravenous 0.9% NaCl (S) or NAL. Animals treated after 30 minutes of hypovolemia at a fixed MAP had similar hemodynamic responses to both NAL or S. After 45 minutes, the NAL-treated animals showed significant improvement in MAP, cardiac output (CO), and survival (P less than 0.05) when compared with S-treated animals. Animals treated with NAL after 60 minutes showed little significant hemodynamic difference from animals treated with S but all S-treated animals died during the 60-minute treatment period. Plasma endorphinlike activity (PELA) rose with hypovolemia and then returned toward control levels in all NAL treated animals before reinfusion of shed blood while it remained elevated in S-treated animals until after reinfusion.

Topics: Animals; Blood Pressure; Cardiac Output; Dogs; Endorphins; Hemodynamics; Naloxone; Receptors, Opioid; Shock; Stroke Volume; Time Factors; Vascular Resistance

The courses of the hemodynamic and cardiometabolic effects of naloxone were evaluated in propoxyphene-induced shock in eight pentobarbital-anesthetized pigs. Circulatory shock was induced by an infusion of propoxyphene chloride 15 mg . min-1 i.v. At shock, i.e. MAP less than 60 mmHg and/or CI less than 2.0 l . min-1 . m-2, naloxone was administered at 0.75, 1.5 and 3.0 mg . kg-1 with an interval between increments of 8 min. The propoxyphene infusion of 15 mg . min-1 was continued throughout the study. Following the injection of naloxone 0.75 mg . kg-1, increases were observed (% of baseline value) in MAP (41%), i.e. deficit to baseline 59%, HR (66%), CI (67%) and SVI (108%), whereas MPAP and MPAOP were unchanged. dP/dt increased (34%). In the coronary circulation naloxone initiated the following changes: CSF increased (69%) as did MVO2 (48%) with unchanged MO2-extraction, but CVR decreased further (36%). The maximum effects of naloxone were registered 2-3 min after 0.75 mg . kg-1. Following 1.5 and 3.0 mg . kg-1, no changes in hemodynamics were observed other than those caused by progressing propoxyphene intoxication.

Topics: Animals; Dextropropoxyphene; Heart; Hemodynamics; Myocardium; Naloxone; Pentobarbital; Receptors, Opioid; Shock; Swine

Topics: Animals; Diprenorphine; Hematocrit; Hypotension; Male; Morphinans; Naloxone; Nitroprusside; Rats; Rats, Inbred Strains; Saline Solution, Hypertonic; Shock; Vasopressins

Despite the array of hemorrhage models, animal species and experimental designs, it seems clear that naloxone with or without volume replacement has no place in the treatment of rapidly exsanguinating traumatized patients. In this situation, the adrenergic hemodynamic effects, indirectly due to naloxone, further decrease tissue perfusion leading to a deleterious outcome. We suggest that the membrane stabilizing effects rather than the hemodynamic effects of naloxone should be pursued in the treatment of low perfusion states with longer survival times than rapid hemorrhage, such as septic and cardiogenic shock.

Topics: Animals; Blood Pressure; Cardiac Output; Female; Fluid Therapy; Heart Rate; Male; Naloxone; Shock; Swine; Time Factors; Vascular Resistance

Topics: Humans; Naloxone; Shock

In 1978 Holaday and Faden reported that naloxone prevented and reversed endotoxin-induced hypotension in rats. Since then, the potential of endogenous opioid peptides in the treatment of shock has come under scrutiny. This brief review puts the work of the last 8 years in perspective.

Topics: Animals; Autonomic Nervous System; Hemodynamics; Humans; Naloxone; Narcotic Antagonists; Shock; Shock, Septic

Topics: Animals; Cats; Dogs; Endorphins; Humans; Naloxone; Narcotic Antagonists; Receptors, Opioid; Shock; Thyrotropin-Releasing Hormone

Topics: Adult; Humans; Male; Methotrimeprazine; Naloxone; Receptors, Opioid; Shock; Suicide, Attempted

Circulatory shock and pain were associated as frequent consequences of surgery and trauma prior to the development of anesthetics. The recent discovery of the endogenous opioid systems affords the opportunity to link the occurrence of pain and circulatory shock at a functional level. The involvement of opioid systems in endogenously and exogenously induced analgesia is well established. In this review, evidence is presented indicating that endogenously activated opioid systems contribute to the pathophysiology of circulatory shock following such diverse causes as endotoxemia, hemorrhage, and spinal cord trauma. The opiate antagonist naloxone (Narcan), acting to oppose endogenous opiates, rapidly reverses the hemodynamic, metabolic, and biochemical sequelae of shock in experimental animal models. Additionally, naloxone has been shown to prevent paralysis following acute cervical spinal cord injury. As with all drugs, several physiologic and pathophysiologic circumstances limit the usefulness of naloxone in reversing shock and improving tissue perfusion. They include acidosis, hypothermia, interactions with administered steroids, and the potential for antagonizing opioid-induced analgesia, which may exacerbate pain in the traumatized patient. Two approaches have yielded potential ways to circumvent these limitations: first, the development of specific opioid-receptor antagonists, which reverse shock without affecting opioid analgesia, and second, the pharmacologic use of thyrotropin releasing hormone (TRH), which acts through its own effector system, independent of endogenous opioid receptors, to produce autonomic effects that reverse shock in experimental animals without affecting analgesia.

Topics: Animals; Humans; Naloxone; Narcotic Antagonists; Rodentia; Shock; Shock, Hemorrhagic; Shock, Septic; Spinal Cord Injuries; Thyrotropin-Releasing Hormone; Wounds and Injuries

Topics: Adult; Female; Humans; Mesenteric Vascular Occlusion; Naloxone; Postoperative Complications; Shock

The possible beneficial actions of naloxone (NAL) were evaluated in canine splanchnic arterial occlusion (SAO). MEan arterial pressure (MAP), cardiac output (CO) and left ventricular contractility (LV dP/dt max) were measured in pentobarbital anesthetized dogs. Animals received intravenously NAL (8 mg/kg) or an equivalent volume of 0.9% saline prior to occlusion or sham occlusion, followed by infusion of 8 mg/kg/hr. The occlusion was released after 2 hr and the dogs monitored for an additional 3 hr or until MAP fell to 40 mmHg. Blood was drawn during the experiments for analysis of dopamine (DA), norepinephrine (NE) and epinephrine (E). SAO and SAO + NAL dogs had decreased MAP and CO after release. However, SAO + NAL animals had a higher LV dP/dt max. NAL in sham and SAO dogs produced significantly higher plasma DA and E levels than in their respective control groups. 67% of SAO + NAL survived 3 hr post release, compared to 43% of SAO dogs. Although the mechanism of NAL protection remains undefined, it may relate to altered vascular response to endogenous opiates or catecholamines.

Topics: Animals; Dogs; Dopamine; Endorphins; Epinephrine; Female; Hemodynamics; Male; Naloxone; Norepinephrine; Shock; Splanchnic Circulation

In mice, fatal shock induced by release of endogenous histamine by compound 48/80 was reversed by the intracerebroventricular (i.c.v.) administration of the opiate antagonist naloxone (10-25 micrograms) but not by the systemic administration of the selective peripherally acting antagonist, naltrexone methyl bromide (1-5 mg/kg). Moreover, systemic or i.c.v. administration of morphine (25 mg/kg and 25 micrograms, respectively) exacerbated shock induced by compound 40/80. This effect was blocked by i.c.v. naloxone (10 micrograms) or naltrexone methyl bromide (10 micrograms) but not by systemic naltrexone methyl bromide (5 mg/kg). The pathogenic effect of i.c.v. morphine was blocked by the systemic administration of the opiate antagonist Win 44,441-3 (5 mg/kg) but not by its inactive (+) isomer, Win 44,441-2. The results suggest possible involvement of central opiate (endorphin) mechanisms in the pathophysiology of fatal histamine shock in mice.

Topics: Animals; Central Nervous System; Endorphins; Histamine; Male; Mice; Mice, Inbred ICR; Morphine; Naloxone; Naltrexone; p-Methoxy-N-methylphenethylamine; Shock

Topics: Animals; Cats; Endorphins; Humans; Naloxone; Rats; Receptors, Opioid; Shock; Shock, Hemorrhagic; Shock, Septic; Spinal Cord Injuries; Thyrotropin-Releasing Hormone

Topics: Absorption; Atropine; Diazepam; Drug Therapy; Emergencies; Epinephrine; History, 18th Century; History, 19th Century; Humans; Lidocaine; Naloxone; Resuscitation; Shock

This study examined the effects of bolus injections of naloxone hydrochloride, a specific narcotic antagonist, on systemic cardiovascular function, intracranial and cerebral perfusion pressures, blood gas status, and cortical encephalograms (EEG's) in 38 cats after two different grades of experimental brain injury. Naloxone had no prolonged effects on uninjured control animals. However, as compared to a saline-injected control group, naloxone significantly reversed the hypotension and reduction in pulse pressure seen after higher grades of injury. These changes persisted for at least 60 minutes after injection and were accompanied by increased intracranial and perfusion pressures. More severely injured hypotensive cats injected with naloxone also had higher values of arterial pO2 and pH, lower pCO2, as well as higher EEG amplitudes. In less severely injured normotensive cats, naloxone produced greater effects on cardiovascular variables and intracranial pressure when injected 15 minutes rather than 45 minutes after injury. These data suggest that endogenous opiates may contribute to some instances of hypotension seen after concussive brain injury. Levels of endogenous opiates may also increase transiently even with lesser degrees of injury not associated with hypotension. The possible clinical application of narcotic antagonists to the treatment of head injury is discussed.

Topics: Animals; Blood Gas Analysis; Brain Concussion; Cats; Cerebrovascular Circulation; Endorphins; Female; Hypotension; Male; Naloxone; Shock; Time Factors

Topics: Adult; Female; Humans; Liver Diseases; Naloxone; Necrosis; Shock

B-endorphin, which is released concomitantly with ACTH from the pituitary during stress, may also alter cardiac performance in hemorrhagic shock. In this study of 36 dogs subjected to hemorrhagic shock without resuscitation, we demonstrate the interaction of high doses of dexamethasone (DEX) or methylprednisolone (M) and opiate receptor blockade with naloxone (NAL). NAL, when given alone, resulted in the most hemodynamic improvement and the longest survival time while those animals receiving DEX or M, even in combination with NAL, did not do as well. These data suggest that corticosteroids block the NAL effect following hemorrhagic shock.

Topics: Adrenal Cortex Hormones; Animals; Dexamethasone; Dogs; Hemodynamics; Methylprednisolone; Naloxone; Shock

Topics: Animals; Endorphins; Naloxone; Shock

Topics: Animals; Cats; Cerebrovascular Circulation; Disease Models, Animal; Myocardial Contraction; Naloxone; Rats; Respiration; Shock; Spinal Cord Injuries

Topics: Diabetes Complications; Diabetic Coma; Drug Combinations; Endocrine System Diseases; Glucose; Humans; Hyperthyroidism; Insulin; Male; Middle Aged; Naloxone; Potassium; Shock; Somatostatin; Thyroid Hormones

Topics: Adrenal Glands; Animals; Autonomic Nervous System; Blood Circulation; Humans; Naloxone; Parasympathetic Nervous System; Shock; Sympathetic Nervous System; Thyrotropin-Releasing Hormone

Topics: Alcoholic Intoxication; Arousal; Coma; Drug Interactions; Humans; Naloxone; Shock

The hypothesis that opiate receptors are involved in the cardiovascular pathophysiology of hypovolemic shock was tested by using the opiate receptor antagonist naloxone. Naloxone increased mean arterial pressure, cardiac output, stroke volume and left ventricular dP/dtmax in a canine hemorrhagic shock model. Naloxone treatment also prolonged survival time. All these responses were dose-dependent and were independent of blood reinfusion. It is concluded that endorphins activated by stress act on opiate receptors to bring about some of the cardiovascular abnormalities in hypovolemic shock.

Topics: Animals; Blood Pressure; Dogs; Dose-Response Relationship, Drug; Female; Heart Rate; Hemodynamics; Male; Myocardial Contraction; Naloxone; Shock; Shock, Hemorrhagic; Time Factors

Topics: Animals; Endorphins; Hemodynamics; Humans; Naloxone; Narcotic Antagonists; Narcotics; Shock; Stress, Physiological

Electrical stimulation of the rabbit sciatic nerve resulted in the development of shock. Injection of physiological saline (1 ml, i. v.) did not change the progressive fall of the blood pressure or depression of palpitation and respiration. The animals died 135--191 min after discontinuance of the stimulation. Injection of nalorphine (0.4 mg/kg, i. v.) or naloxone (0.1 mg/kg i. v.) greatly improved the animals' condition. The blood pressure, palpitation and respiration returned to normal in 90--120 min after the injections. No lethal cases were recorded in this group of animals. It was shown in a supplementary group of animals that naloxone did not change the reserpine-produced hypotension.

Topics: Animals; Drug Evaluation, Preclinical; Electroshock; Nalorphine; Naloxone; Pain; Rabbits; Shock; Time Factors

Topics: Adrenal Glands; Animals; Dogs; Endorphins; Enkephalins; Naloxone; Pituitary Gland; Shock; Shock, Hemorrhagic

Topics: Adolescent; Adult; Coma; Female; First Aid; Heart Failure; Humans; Male; Naloxone; Respiratory Insufficiency; Shock; Wounds and Injuries

Topics: Endorphins; Hemodynamics; Humans; Models, Biological; Naloxone; Shock

Topics: Aged; Humans; Hypnotics and Sedatives; Hypotension; Male; Naloxone; Shock

Topics: Adrenal Glands; Animals; Dogs; Humans; Naloxone; Pituitary Gland; Rats; Shock

Topics: Adrenal Medulla; Animals; Blood Pressure; Catecholamines; Heart Rate; Male; Naloxone; Rats; Rats, Inbred Strains; Receptors, Opioid; Shock; Sympathetic Nervous System

These studies have demonstrated that the opiate-antagonist naloxone improves blood pressure and functional neurologic recovery after spinal injury. From these findings we suggest that endorphins are released in response to spinal injury and contribute to the hypotension and to the ultimate neurologic deficit. Naloxone's ability to reverse the presumed endorphin-mediated hypotension in this model supports the hypothesis that its therapeutic effects may be secondary to its improvement of spinal cord blood flow, thereby reducing the ischemic damage caused by spinal cord trauma.

Topics: Animals; Cats; Endorphins; Female; Hypotension; Male; Naloxone; Rats; Shock; Spinal Cord Injuries

Topics: Animals; Arterial Occlusive Diseases; Blood Pressure; Cats; Myocardial Depressant Factor; Naloxone; Shock; Splanchnic Circulation

The possible involvement of pituitary endorphins in the pathophysiology of shock was evaluated by measuring cardiorespiratory variables after naloxone injection in conscious hypophysectomized and sham-hypophysectomized rats subjected to controlled hemorrhage. Additionally, the role of the central nervous system (CNS) in mediating the cardiodepressant effects of endorphins in shock was studied. After the induction of hypovolemic shock (20 min at below 40 mmHg), hypophysectomized and sham-hypophysectomized rats received intraventricular (ivt) injections of naloxone HCl (10 micrograms) or an equivalent volume of saline (20 microliters over 20 s). In sham-hypophysectomized rats, both injections significantly elevated mean arterial pressure and pulse pressure; however, the increase produced by naloxone was significantly greater than that produced by saline. By contrast, hypophysectomized rats showed no response to naloxone or saline. Intravenous (iv) administration of naloxone HCl (3 mg/kg) or saline to these same hypophysectomized rats 15 min after ivt administration had no additional cardiovascular effects; as before, only animals with intact pituitaries responded to naloxone. Heart rate and respiration rate were unaffected by ivt or iv naloxone. From these data we suggest that pituitary endorphins contribute to the pathophysiology of hypovolemic shock, at least in part through actions within the CNS.

Topics: Animals; Blood Pressure; Central Nervous System; Endorphins; Heart Rate; Male; Naloxone; Pituitary Gland; Rats; Respiration; Shock; Time Factors

The endogenous opiate ligand, beta-endorphin, is released during stress. We tested the hypothesis that endorphins may be involved in the pathophysiology of hemorrhagic shock by using the opiate receptor blocking agent, naloxone. Two groups of five anesthetized dogs were instrumented to monitor cardiovascular performance and subjected to a protocol in which they were bled into a reservoir to lower mean arterial pressure to 45 mmHg and maintained at that pressure for one hour. At that time the reservoir was clamped and on group of dogs received an intravenous bolus of naloxone (2 mg/kg) and an infusion at 2 mg/kg-hr. These dogs demonstrated a prompt increase in arterial pressure, left ventricular dp/dtmax and cardiac output. The shed blood was returned at t = 2 hr and drug infusion continued for 2 hours. The control group of dogs received saline in equivalent volume. The control dogs died within 30 minutes of clamping the reservoir while all five treated dogs survived beyond 72 hours (P less than 0.02). These data suggest the involvement of endorphins acting on opiate receptors as part of the pathophysiology in this shock model.

Topics: Animals; Blood Pressure; Blood Volume; Dogs; Heart Rate; Hypotension; Naloxone; Receptors, Opioid; Shock; Vascular Resistance

Topics: Animals; Cardiac Output; Cardiovascular System; Dogs; Dose-Response Relationship, Drug; Endotoxins; Female; Heart Rate; Hemodynamics; Male; Mesenteric Arteries; Naloxone; Receptors, Opioid; Shock; Vascular Resistance; Venous Pressure

The opiate antagonist naloxone has been used to treat shock following acute blood loss in conscious rats. Naloxone treatment rapidly increased mean arterial pressure and pulse pressure in this new shock model. More importantly, these blood pressure changes were sustained and survival was significantly increased with maloxone as compared with placebo treatment. From these findings, it may be inferred that endorphins may play a role in the pathophysiology of hypovolemic shock. It is suggested that narcotic antagonists may prove to be of therapeutic value in the treatment of shock.

Topics: Animals; Blood Pressure; Hypotension; Male; Naloxone; Rats; Shock