beta-endorphin and Shock--Septic

Topics: Adrenalectomy; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Drug Evaluation; Drug Evaluation, Preclinical; Endorphins; Humans; Naloxone; Shock, Hemorrhagic; Shock, Septic

Little is known about interactions between immune and neuro-endocrine systems in patients with septic shock. We therefore evaluated whether the corticotropin-releasing hormone (CRH) and/or proopiomelanocortin (POMC) derivatives [ACTH, β-endorphin (β-END), β-lipotropin (β-LPH), α-melanocyte stimulating hormone (α-MSH) or N-acetyl-β-END (Nac-β-END)] have any influences on monocyte deactivation as a major factor of immunosuppression under septic shock conditions. Sixteen patients with septic shock were enrolled in a double-blind, cross-over and placebo controlled clinical study; 0.5μg/(kgbodyweighth) CRH (or placebo) were intravenously administered for 24h. Using flow cytometry we investigated the immunosuppression in patients as far as related to the loss of leukocyte surface antigen-DR expression on circulating monocytes (mHLA-DR). ACTH, β-END immunoreacive material (IRM), β-LPH IRM, α-MSH and Nac-β-END IRM as well as TNF-α and mHLA-DR expression were determined before, during and after treatment with CRH (or placebo). A significant correlation between plasma concentration of α-MSH and mHLA-DR expression and an inverse correlation between mHLA-DR expression and TNF-α plasma level were found. Additionally, a significant increase of mHLA-DR expression was observed 16h after starting the CRH infusion; 8h later, the mHLA-DR expression had decreased again. Our results indicate that the up-regulation of mHLA-DR expression after CRH infusion is not dependent on the release of POMC derivatives. From the correlation between plasma concentration of α-MSH and mHLA-DR expression, we conclude that in patients with septic shock the down-regulation of mHAL-DR expression is accompanied by the loss of monocytic release of α-MSH into the cardiovascular compartment.

Topics: Adrenocorticotropic Hormone; Aged; alpha-MSH; beta-Endorphin; beta-Lipotropin; Corticotropin-Releasing Hormone; Cross-Over Studies; Double-Blind Method; Female; Gene Expression; HLA-DR Antigens; Hospitals, University; Humans; Infusions, Intravenous; Intensive Care Units; Male; Middle Aged; Monocytes; Prospective Studies; Shock, Septic

Endogenous β-endorphin is delivered exclusively from the pituitary gland in various stressful conditions and plays an essential role in the nervous system. Recently, a few studies demonstrated peripheral endogenous opioid secretion from immune cells at inflammatory sites. Here, we investigated the expression of β-endorphin, the most powerful endogenous opioid peptide, in peripheral tissues in response to systemic administration of lipopolysaccharide in mice.. Male C57BL/6N mice received intravenously administered lipopolysaccharide to induce an endotoxic shock-like condition. mRNA for proopiomelanocortin, a precursor of β-endorphin, was quantified in peripheral blood cells, liver and spleen. β-endorphin peptide was measured in the liver and spleen.. Expression of proopiomelanocortin mRNA was detected in peripheral tissues after systemic administration of lipopolysaccharide. Lipopolysaccharide also induced β-endorphin expression in the liver and spleen.. Expression of proopiomelanocortin mRNA and β-endorphin was detected in peripheral tissues after systemic administration of lipopolysaccharide. These results provide new evidence that peripheral endogenous opioids can be produced not only as a result of local inflammation but also by severe systemic stress such as endotoxic shock. Further study is required to clarify the role of peripheral β-endorphin during endotoxic shock.

Topics: Animals; beta-Endorphin; Blood Cells; Disease Models, Animal; Gene Expression; Inflammation; Lipopolysaccharides; Liver; Male; Mice; Mice, Inbred C57BL; Pro-Opiomelanocortin; Shock, Septic; Spleen; Tissue Distribution

The aim of the study was to assess the adequacy of pituitary function by determining the plasma concentrations of corticotroph-type (corticotropin, beta-endorphin immunoreactive material [beta-END IRM], authentic beta-END, and beta-lipotropin IRM) as well as melanotroph-type (alpha-melanocyte-stimulating hormone [alpha-MSH] and N-acetyl-beta-END [Nac-beta-END] IRM) proopiomelanocortin (POMC) derivatives in patients under septic shock upon administration of corticotropin-releasing hormone (CRH). The objectives were to assess whether an insufficient release of corticotroph- or melanotroph-type POMC derivatives from the pituitary into the cardiovascular compartment correlates with the 28-day mortality rate. Seventeen patients with septic shock but without adrenocortical insufficiency and 16 healthy volunteers were enrolled in the study, and CRH stimulation tests were performed with an i.v. bolus injection of 100 microg human CRH. After treatment with CRH, plasma concentrations of corticotroph-type POMC derivatives increased in survivors and nonsurvivors, melanotroph-type POMC derivatives such as alpha-MSH or Nac-beta-END IRM increased only in survivors in contrast to nonsurvivors. The release of alpha-MSH and Nac-beta-END IRM was suppressed by dexamethasone in survivors but not in nonsurvivors. In patients with septic shock, the response of the pituitary to CRH stimulation in terms of alpha-MSH or Nac-beta-END IRM release was impaired in nonsurvivors compared with survivors or controls. Reduced responses of alpha-MSH or Nac-beta-END IRM to CRH and the invalid suppression by dexamethasone reflect a state of dysfunction of the melanotroph-type POMC system in nonsurvivors. Considering anticytokine and anti-inflammatory effects of alpha-MSH, this dysfunction may increase the risk of death in patients with septic shock.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Aged, 80 and over; alpha-MSH; beta-Endorphin; Corticotropin-Releasing Hormone; Dexamethasone; Female; Glucocorticoids; Humans; Male; Middle Aged; Pituitary Gland; Pro-Opiomelanocortin; Prospective Studies; Shock, Septic

The function of the hypothalamic-pituitary-adrenal axis as related to the degree of severity of a septic process was assessed by measuring plasma levels of beta-endorphin, ACTH and cortisol. Sixty-one cases of postoperative patients treated at the intensive care unit were classified into four groups according to the severity of infection: Group 1 (control) included patients who did not show any sign of infection, group 2 patients with sepsis, group 3 patients with septic syndrome and group 4 patients with septic shock. Compared to G1 patients' ACTH values (4.16+/-2.6pg/ml), a statistically significant increase in ACTH values in various stages of septicemia (p < 0.005) with a noticeable difference also between G3 (7.11 +/-3.7pg/ml) and G4 (11.5+/-6.6pg/ml) (p<0.05) was found. Differences were also observed in beta-endorphin (with a level of significance between the several groups of p = 0.0001). Also, beta-endorphin values in G4 (40.6+/-30.3 pg/ml) differed significantly from each of G1 (17.5 +/-6.6 pg/ml), G2 (21.1+/-11.3 pg/ml) and G3 (23.5+/-12 pg/ ml) (p<0.05). A progressive hypercortisolemia was obvious, with values of G4 (37.2+/-15.6 microg/dl) differing significantly from those of G1 (18+/-4.6microg/dl) and G2 (24-/+8.4microg/dl) (p<0.05) and of G3 (28.5+/-12.3 microg/dl) from that of G1 (p < 0.05). Interestingly, a dissociation of ACTH, beta-endorphin and cortisol was observed, in that the increased values of beta-endorphin and cortisol, detected in the G3 were not associated with a parallel increase in ACTH. These findings might be interpreted in the sense of an impairment of the stress stimulation of the hypothalamic pituitary adrenal axis. Provided that such a situation can be lethal, our results further confirm the idea that a low-dose, steroid replacement might be beneficial to critical illness.

Topics: Adrenocorticotropic Hormone; Analysis of Variance; beta-Endorphin; Female; Humans; Hydrocortisone; Male; Shock, Septic; Systemic Inflammatory Response Syndrome

Current research suggests that the secretion of beta-endorphin from the pituitary gland may be associated with the refractory hypotension seen in patients with septic shock. Extensive animal research and a few clinical studies have demonstrated that naloxone, a narcotic antagonist, can increase MAP, cardiac output, and cardiac contractility and improve survival in victims of endotoxic shock. The ability of naloxone to improve MAP, however, appears to decrease with prolonged persistent hypotension (greater than eight hours). Studies also suggest that a synergistic effect exists between naloxone and the steroid methylprednisolone in improving the hemodynamics of these patients. In the future, naloxone may prove to be essential in the management of patients in the early stages of septic shock, but more complete clinical trials are warranted. It is imperative that nurses be involved in this type of clinical research.

Topics: beta-Endorphin; Education, Nursing, Continuing; Female; Humans; Infant, Newborn; Naloxone; Shock, Septic

Two groups of awake dogs were given an iv bolus of endotoxin (3.0 mg/kg from Salmonella typhimurium); one group (n = 9) was pretreated with either naloxone (2.0 mg/kg iv bolus with 1.7 mg/kg.h; n = 6) or naltrexone (2.0 mg/kg iv bolus with repeat bolus of 1.0 mg/kg at 1, 3 and 5 h; n = 3) and the second group (n = 10) received no opiate antagonist. All of nine dogs that were pretreated with an antagonist survived for 24 h, compared to only five of ten dogs that were not pretreated. Survival correlated with improved BP (mean of 91 vs. 61 mm Hg) and cardiac output (3.9 vs. 2.45 L/min) measured during the first 3 h after the infliction of shock. However, both antagonist-treated and nonantagonist-treated survivors had BP and cardiac output which were statistically lower than their baseline values or saline-treated controls at comparable times. Nonsurvivors had significantly higher levels of norepinephrine (peak level: 1149 ng/ml) and epinephrine (peak level: 31.29 ng/ml) than survivors. Opiate antagonists thus appeared to increase survival in a subgroup of dogs that might not otherwise have survived if they had not been so treated; this survival was associated with improved hemodynamics, but not with increased adrenergic activity.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Blood Pressure; Cardiac Output; Dogs; Endotoxins; Epinephrine; Male; Naloxone; Naltrexone; Norepinephrine; Receptors, Opioid; Salmonella typhimurium; Shock, Septic

The nature of circulating pro-opiomelanocortin (POMC)-related peptides was investigated in patients with a diagnosis of septic shock. Also, changes following administration of methylprednisolone were monitored using established chromatographic techniques and three radioimmunoassays directed towards the N-terminal, mid-portion and C-terminal regions of the precursor. Adrenocorticotrophin and beta-endorphin-like peptides were identified in the circulation. By 60 min after a pharmacological dose of methylprednisolone (30 mg/kg) concentrations of these peptides were reduced and continued to fall up to 180 min. beta-Lipotrophin and N-terminal POMC(1-76) were also detected by the beta-endorphin and gamma 3-MSH assays respectively. The concentrations of these peptides were noticeably reduced only after 180 min. The 31,000 Da MSH/ACTH/beta-endorphin (POMC) and the 22,000 Da MSH/ACTH precursors were also present in the circulation in septic shock and their concentrations increased following steroid treatment.

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Chromatography, Gel; Female; Humans; Male; Melanocyte-Stimulating Hormones; Methylprednisolone; Peptides; Pro-Opiomelanocortin; Shock, Septic

A relationship between increased peripheral resistance (TPRI) and decreased cardiac index (CI) and mortality from sepsis has been suggested. The relationship between endogenous opiates and this response was evaluated.. Chronically instrumented sheep were given E. coli endotoxin (LPS, 1.5 mcg/kg x 30 minutes). In one study, survivors (n = 9) and nonsurvivors (n = 11) of LPS were compared along with survivors (n = 8) of half the dose of LPS. In a second study, two groups of animals received naloxone: one (n = 11) had a bolus of 2 mg/kg followed by a 2 mg/kg/hr continuous infusion started 30 minutes before LPS while the other had the bolus and infusion started 1 hour after LPS was begun.. Both vasoconstrictive and vasodilative phases were seen. Vasoconstriction was associated with elevated beta endorphin levels, a pattern sustained until death in the nonsurvivors. Both pre- and posttreatment with naloxone lessened the maximum increase in total peripheral resistance index compared with untreated sheep.. The vasoconstrictive aspects of the response to LPS correlated with elevated beta endorphin levels and with mortality. This vascular response is attenuated with naloxone blockade.

Topics: Animals; beta-Endorphin; Escherichia coli; Female; Hemodynamics; Lipopolysaccharides; Naloxone; Pulmonary Circulation; Sheep; Shock, Septic; Vasoconstriction; Vasodilation

This study evaluated the effects of naloxone hydrochloride in the treatment of Escherichia coli-induced shock in baboons. The baboons were studied for 12 hours and monitored for survival times. All baboons were intravenously infused for two hours with E coli and treated as follows: group 1, E coli (control); group 2, E coli plus naloxone hydrochloride, 0.5 mg/kg bolus plus 0.5 mg/kg/h for 9.5 hours; and group 3, E coli plus naloxone hydrochloride, 2.0 mg/kg bolus plus 2.0 mg/kg/h for 3.8 hours. Naloxone was administered after arterial pressure had reached the nadir (more than two hours following initiation of E coli infusion). Mean arterial pressure was supported by the lower dose of naloxone; however, sustained leukopenia and neutropenia were not reversed by its infusion. Naloxone prevented the increase in plasma beta-endorphin level and blunted the increase in plasma cortisol level. Despite these effects, naloxone did not prevent multiple-organ disease and did not decrease mortality.

Topics: Animals; beta-Endorphin; Blood Pressure; Blood Urea Nitrogen; Creatinine; Disease Models, Animal; Drug Evaluation, Preclinical; Escherichia coli Infections; Female; Heart Rate; Hydrocortisone; Injections, Intravenous; Male; Monitoring, Physiologic; Naloxone; Papio; Sepsis; Shock, Septic; Time Factors

Hyperinsulinism has been associated with infection and endotoxin shock in rodents, dogs, and humans. In dogs with Escherichia coli-induced endotoxin shock, this hyperinsulinism was in response to glucose administration. To determine the role of endogenous opiates in endotoxin-induced glucose-stimulated hyperinsulinism, plasma beta-endorphin, Met-enkephalin, Leu-enkephalin, insulin, and glucose concentrations were measured for 6 h in fasted, anesthetized dogs given LD70 of E. coli endotoxin; endotoxin and glucose; endotoxin, glucose, and naloxone (an opiate antagonist); glucose and naloxone; or glucose alone. Plasma endogenous opiate immunoreactivity was elevated in dogs that received endotoxin, regardless of the presence of glucose or naloxone. The elevation of plasma Met-enkephalin and beta-endorphin preceded the onset of hyperinsulinism, but the elevation of plasma Leu-enkephalin did not. Plasma insulin was elevated 100-fold by 360 min in dogs given endotoxin and glucose. The magnitude of this hyperinsulinism was markedly reduced by naloxone, supporting the hypothesis that endogenous opiates are involved in the development of the glucose-stimulated hyperinsulinism associated with endotoxin shock. Interestingly, naloxone, given in conjunction with glucose, appeared to have a stimulatory effect on insulin secretion.

Topics: Animals; beta-Endorphin; Blood Glucose; Dogs; Endorphins; Endotoxins; Enkephalin, Leucine; Enkephalin, Methionine; Escherichia coli; Glucose; Hyperinsulinism; Insulin; Kinetics; Male; Naloxone; Shock, Septic

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

Opiopeptides may contribute to the pathophysiology of both endotoxic and hemorrhagic shock. To determine if endorphin secretion is similar in both types of shock, we divided 25 sheep into three groups: a saline control group (n = 10), an endotoxin-treated group (n = 9), and a hemorrhage group (n = 6). Each sheep had baseline determinations of mean arterial pressure (MAP) and plasma levels of beta-endorphin-like immunoreactivity (iB-EP). Experimental animals either received endotoxin (450 ng/kg intravenous) or underwent withdrawal of blood volume sufficient to diminish MAP by approximately one-third of baseline values. MAP and iB-EP levels were determined every 15 minutes thereafter for 5 hours. Individual data were averaged within each group and then compared between groups using analysis of variance. Both the endotoxin- and hemorrhage-treated groups showed a significant fall in MAP, which was significantly lower in the hemorrhage group than the endotoxin group. Endotoxin-treated animals displayed a mean peak iB-EP level 1,550% above baseline as compared to a mean peak iB-EP level of only 201% above baseline in the hemorrhage-treated group, despite a significantly greater degree of hypotension in the latter group; this difference in peak iB-EP response was significant. Mean peak iB-EP levels coincided with mean trough MAP values in the endotoxin-treated group while the mean peak iB-EP lagged the onset of mean trough MAP in the hemorrhage group. These results demonstrate that iB-EP secretory patterns differ in endotoxic versus hemorrhagic shock and suggest that distinct mechanisms of opiopeptide secretion accompany the two shock states.

Topics: Animals; beta-Endorphin; Blood Pressure; Endorphins; Endotoxins; Sheep; Shock, Hemorrhagic; Shock, Septic

Chemical antagonists were used to assess the role of beta-endorphin and arginine-vasopressin (AVP) in canine endotoxin shock. Fifteen awake dogs were given Escherichia coli endotoxin IV. Within 5 min, CO decreased to 28%, LV dP/dt to 46%, and MAP to 52% baseline. Fifteen minutes after endotoxin, five dogs each received naloxone, AVP antagonist, or no treatment. Control (untreated) animals exhibited persistent cardiovascular depression, with CO 49%, LV dP/dt 69%, and MAP 91% of baseline after 45 min. Naloxone improved CO to 69%, LV dP/dt to 94%, and MAP to 91% by 30 min after treatment. AVP blockade improved CO to 105%, LV dP/dt to 107%, and MAP to 95% of baseline by 30 min after treatment, and caused significant tachycardia. Plasma cortisol and AVP increased markedly in all groups after endotoxin administration. AVP antagonist treatment increased mean survival from 1.4 to 4 days. These data suggest that abnormally elevated AVP contributes to cardiovascular depression in canine endotoxin shock and that AVP blockade is therapeutic in the animal model studied.

Topics: Animals; Arginine Vasopressin; beta-Endorphin; Blood Pressure; Cardiac Output; Cardiovascular Diseases; Dogs; Endorphins; Endotoxins; Escherichia coli; Female; Heart Rate; Hydrocortisone; Kinetics; Male; Naloxone; Shock, Septic

There is recent evidence that circulating opioid peptides, or 'endorphins', act as chemical messengers responsible for the induction of the complex cardiovascular changes leading to hypotension in septicaemic shock. The pilot study of an investigation of opioid peptides in septicaemia in burned patients is presented. Serial measurements of plasma beta-endorphin and metenkephalin were performed throughout the recovery of six patients with large burns (20-70 per cent BSA). Our preliminary findings concur with previous evidence that opioid peptides may play a role in the hypotension of septicaemic shock.

Topics: Adolescent; Adult; beta-Endorphin; Burns; Endorphins; Enkephalin, Methionine; Female; Humans; Male; Middle Aged; Radioimmunoassay; Shock, Septic

A 0.01 and 0.1-mg/kg dose of iv naloxone was administered to seven patients in septic shock, in order to evaluate naloxone's hemodynamic effect and possible relation to changes in plasma beta-endorphin and catecholamine levels. Naloxone failed to modify cardiac index, blood pressure, heart rate, and systemic vascular resistance. Plasma beta-endorphin, norepinephrine, and epinephrine were elevated but did not change after naloxone administration. These results suggest that beta-endorphin release is a consequence but not a cause of shock, and that the beneficial hemodynamic effects of naloxone in animal studies could be related to species differences or nociceptive stimulations.

Topics: Adult; Aged; Bacterial Infections; beta-Endorphin; Endorphins; Epinephrine; Female; Hemodynamics; Humans; Male; Middle Aged; Naloxone; Norepinephrine; Shock, Septic

Plasma levels of beta-endorphin-like immunoreactivity (BLI) were similarly elevated in patients with septic shock (group A) and in normotensive subjects recovering from cardiac surgery (group B) (1231 +/- 483 pg ml-1 and 1,240 +/- 355 pg ml-1, respectively). In neither group was cardiac output reduced, but total peripheral resistance index (TPRI) was low in group A and low or normal in group B. Intravenous methylprednisolone (MP) 30 mg kg-1 variably suppressed BLI by a mean of only 30% in group A, while in group B, BLI usually rose and then fell following MP. In group A percentage changes in BLI were positively correlated with percentage changes in cardiac index (CI) and mean arterial pressure (MAP) (r = .83, P less than .01, r = .59, P less than .05 respectively). No such correlations were found in group B. These findings suggest that increases in circulating beta-endorphin are unlikely to be responsible for myocardial depression or hypotension in septic shock. ACTH levels were in general normal in group A but were consistently elevated in group B, although plasma cortisol was similarly elevated in both groups. Furthermore there was a good correlation between percentage changes in ACTH and BLI following MP in group B (r = .87, P less than .01) but not in group A. Possible explanations for these findings are discussed.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Blood Pressure; Cardiac Output; Combined Modality Therapy; Coronary Artery Bypass; Endorphins; Hemodynamics; Humans; Male; Methylprednisolone; Middle Aged; Postoperative Complications; Shock, Septic

Plasma beta-endorphin-like immunoreactivity (beta-ELIR) levels were measured during hyper and hypodynamic phases of septic shock in patients (n = 36) due to a variety of microorganisms. Plasma beta-ELIR levels were elevated in all groups, but were most marked in patients with hyperdynamic circulation due to gram-positive and gram-negative organisms, followed by hypodynamic circulation due to gram-negative organisms and were least elevated in hypodynamic shock due to gram-positive organisms. There was strong correlation between plasma beta-ELIR levels and cardiac index in patients with a hyperdynamic circulation (gram-negative organisms, rs = 0.79, p less than 0.01; gram-positive, rs = 0.85, p less than 0.01) but little to no correlation in patients with hypodynamic circulation (gram-negative, rs = 0.32, p = NS; gram-positive organisms rs = 0.04, p = NS). These results imply that plasma beta-ELIR levels may be involved in the early phases of septic shock and may contribute to a hyperdynamic circulation, whereas plasma beta-ELIR levels may be normal or may not be related to hypodynamic circulation as seen in later phases of shock.

Topics: Bacteria; beta-Endorphin; Endorphins; Female; Hemodynamics; Humans; Male; Middle Aged; Naloxone; Shock, Septic

The effect of beta-endorphin injected into either the lateral ventricle or the cisterna magna on blood pressure, heart rate, peripheral platelet and leukocyte counts, hematocrit levels, catecholamines, and pulmonary platelet trapping was studied. The effect of endotoxin on the endogenous opiocortin system was also investigated. Injection of beta-endorphin caused a significant decrease in blood pressure, bradycardia, and pulmonary platelet trapping. beta-Endorphin had no effect on peripheral platelet and leukocyte counts, catecholamines, or hematocrit levels. Endotoxin shock caused a marked rise in circulating beta-endorphin and a decrease in cerebrospinal fluid beta-endorphin. Our results confirm that endotoxin shock activates the opiocortin system, and we suggest that the endorphins may participate in the evolution of the lung injury seen in septic shock.

Topics: Animals; beta-Endorphin; Blood Platelets; Blood Pressure; Cardiovascular System; Cisterna Magna; Dogs; Endorphins; Female; Heart Rate; Hematocrit; Injections, Intraventricular; Leukocyte Count; Lung; Male; Platelet Count; Shock, Septic

Previous studies established that naloxone reverses hypotension in endotoxin, hemorrhagic, and spinal shock. We studied endotoxin shock in hypophysectomized (Hx) rats, which have little circulating beta-endorphin. Hx or intact rats received surgically implanted jugular catheters for drug injection and aortic catheters for arterial blood pressure (MAP) recording. On the second day after implantation, rats were pretreated with either naloxone or saline. Two minutes later each rat received endotoxin. Following endotoxin, all rats showed a brief biphasic hypertensive-hypotensive response followed by stabilization of MAP near baseline. Within 20 min, all Hx rats, regardless of pretreatment, and the saline-treated intact rats, showed progressive hypotension (P less than 0.005). Only the naloxone-pretreated intact rats maintained a stable MAP. Plasma endorphin measured at 20 min was undetectable in Hx rats in contrast to intact rats (P less than 0.001); plasma corticosterone levels were likewise suppressed in the Hx rats (P less than 0.01). Thus (1) naloxone protected only the rats with an intact pituitary-adrenal-sympathetic system, and (2) pituitary endorphin is not required to generate endotoxin shock in hypophysectomized rats.

Topics: Animals; beta-Endorphin; Blood Pressure; Corticosterone; Endorphins; Hypophysectomy; Hypotension; Male; Naloxone; Pituitary Gland; Rats; Rats, Inbred Strains; Shock, Septic

To improve understanding of the role of endorphins in septic shock, we examined the effects of anesthesia, splenectomy, live Escherichia coli infusion, and treatment with naloxone, respectively, on plasma beta-endorphin immunoreactivity (beta-EI) and plasma cortisol in dogs. Baseline levels of plasma beta-EI and cortisol were established in awake dogs. Pentobarbital anesthesia alone did not affect plasma beta-EI, but splenectomy was followed by a significant (P less than 0.001) rise in both plasma beta-EI and cortisol. Infusion of saline over a 3-hour period following splenectomy induced no further increase in plasma beta-EI, but infusion of live E. coli in splenectomized dogs caused a further rise in plasma beta-EI (P less than 0.02). Following induction of septic shock in a separate group of splenectomized animals, treatment with naloxone (3 mg/kg bolus and 2 mg/kg/hr infusion) did not alter the rise in plasma beta-EI. These results confirm release of beta-endorphin during septic shock and further implicate the hypothalamic-pituitary-adrenal axis in its pathophysiology. Based on the finding that naloxone did not affect the dynamics of plasma beta-EI, mechanisms are postulated to explain the therapeutic value of this drug in septic shock.

Topics: Anesthesia; Animals; beta-Endorphin; Dogs; Endorphins; Escherichia coli; Hydrocortisone; Naloxone; Postoperative Complications; Radioimmunoassay; Sepsis; Shock, Septic; Splenectomy

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; beta-Lipotropin; Catecholamines; Dogs; Endorphins; Female; Hemodynamics; Male; Naloxone; Shock, Hemorrhagic; Shock, Septic

Topics: Animals; beta-Endorphin; Catecholamines; Dogs; Endorphins; Hemodynamics; Naloxone; Shock, Septic