beta-endorphin and Respiratory-Insufficiency

Glycyl-L-glutamine (Gly-Gln; beta-endorphin 30-31) is an endogenous dipeptide that is synthesized through the post-translational processing of beta-endorphin. Previously, we showed that Gly-Gln inhibits the hypotension and respiratory depression produced by central beta-endorphin administration. In this study, we tested whether cyclo(Gly-Gln), a non-polar, cyclic Gly-Gln derivative, was similarly effective following intracerebro-ventricular (i.c.v.) or intra-arterial (i.a.) administration to pentobarbital-anesthetized rats pretreated with beta-endorphin (0.5 nmol i.c.v.). Intracerebroventricular cyclo(Gly-Gln) (0.3, 0.6 or 1.0 nmol) injection produced a dose-dependent inhibition of beta-endorphin-induced hypotension, but not bradycardia, with a potency similar to that of Gly-Gln. Cyclo(Gly-Gln) (5 mg/kg) was also effective following i.a. injection and significantly attenuated the fall in arterial pressure elicited by i.c.v. beta-endorphin, consistent with evidence that cyclic dipeptides permeate the blood-brain barrier; i.a. Gly-Gln was ineffective. Intra-arterial cyclo(Gly-Gln) (5 mg/kg) and i.c.v. Gly-Gln (10 nmol) also attenuated the hypotension and respiratory depression induced by morphine (50 or 100 nmol i.c.v.). Cyclo(Gly-Gln) (0.5, 5.0 or 50.0 mg/kg i.a.) had no effect on arterial pressure or heart rate when given alone. These findings indicate that cyclo(Gly-Gln) is a biologically active peptide capable of reversing the cardiorespiratory depression produced by beta-endorphin or morphine.

Topics: Animals; beta-Endorphin; Blood Pressure; Depression, Chemical; Dose-Response Relationship, Drug; Heart Rate; Hemodynamics; Injections, Intra-Arterial; Injections, Intraventricular; Male; Morphine; Narcotic Antagonists; Narcotics; Rats; Rats, Sprague-Dawley; Respiratory Insufficiency; Respiratory Mechanics

Only little information is available on the effects of acute and chronic stress on the opioid and adrenergic systems in patients at intensive care units. Animal models showed a stimulation of beta-endorphin and catecholamines.. In the present study, in 12 patients who were intubated and were receiving artificial respiration because of cardiopulmonary resuscitation or primary respiratory failure, venous plasma concentrations of adrenaline, noradrenaline and beta-endorphin immuno-reactive material (IRM) were determined by a radioimmunoassay. In these patients, regular endobronchial suctioning was necessary. For inducing acute stress patients underwent three different methods of endobronchial suctioning or lavage.. In all patients concentrations of both adrenaline (529 +/- 117 pg/ml) and noradrenaline (2694 +/- 262 pg/ml) were increased above normal resting values. In 5 patients plasma beta-endorphin IRM concentration was below the detection limit, the other patients had beta-endorphin IRM concentrations above normal (26.65 +/- 3.80 pg/ml). Epinephrine (227 +/- 33 vs. 743 +/- 189 pg/ml; p < 0.01) and norepinephrine (1673 +/- 161 vs. 3423 +/- 368 pg/ml; p < 0.001) were significantly lower in the group with undetectable beta-endorphin IRM concentrations than in the group with detectable beta-endorphin IRM whereas heart rate was significantly higher (120/min vs. 99/min; p < 0.0003). beta-endorphin IRM concentrations were correlated negatively to heart rate (-0.55; p < 0.0005) and positively to the noradrenaline concentration (0.56; p < 0.0004). Artificially ventilated patients showed increased levels of beta-endorphin (19.27 +/- 3.16 pg/ml) as compared to the spontaneously breathing patients (13.29 +/- 4.34 pg/ml). Following acute stress due to endobronchial suctioning or lavage, blood pressure (150/70 mmHg vs. 172/81 mmHg; p < 0.01) and heart rate (107/min vs. 119/min; p < 0.005) increased in all patients, the other parameters did not.. It is concluded that beta-endorphin IRM concentration in the plasma is linked to epinephrine and norepinephrine concentrations under intensive care conditions. Endobronchial lavage or suctioning does not influence beta-endorphin IRM levels in plasma.

Topics: Acute Disease; Adolescent; Aged; beta-Endorphin; Blood Pressure; Bronchoalveolar Lavage; Cardiopulmonary Resuscitation; Chronic Disease; Consciousness; Critical Care; Epinephrine; Heart Rate; Humans; Middle Aged; Norepinephrine; Oxygen; Pulse; Respiration, Artificial; Respiratory Insufficiency; Sensitivity and Specificity; Stress, Physiological

Using male and female Wistar rats, pituitary response to cardiac and respiratory failure type (CFT and RFT) sudden death caused by the intravenous administration of KC1 and SCC, respectively, was examined by analyzing variation in pituitary immunoreactive beta-endorphin (IR-beta-EP) levels determined by radioimmunoassay after death and in circulating IR-beta-EP levels during periods of agony. In the pituitary gland of both sexes which differed significantly in ratio of the organ weight to body weight for CFT and RFT (CFT greater than RFT), IR-beta-EP was significantly less in RFT than in CFT (p less than 0.05). No variation in plasma IR-beta-EP was noted during short periods of agony in CFT, but it markedly increased during long periods of agony in RFT. The highest elevation at 2 or 4 minutes after SCC administration was about 3 times the preadministration value for IR-beta-EP in males (p less than 0.01). But elevation in females was lower than in males. Rise plasma IR-beta-EP during agony of RFT is regarded to be of pituitary origin due to dexamethasone treatment. The pituitary was thus concluded to respond more to the fatal agony in RFT than in CFT.

Topics: Animals; beta-Endorphin; Death, Sudden; Death, Sudden, Cardiac; Female; Male; Pituitary Gland; Rats; Rats, Wistar; Respiratory Insufficiency

A child with respiratory failure and cor pulmonale secondary to the obesity hypoventilation syndrome (OHS) was found to have abnormal beta-endorphin levels in cerebrospinal fluid (CSF) and serum. A single iv dose of 10 microgram/kg of naloxone early in the course of respiratory failure resulted in dramatic improvement which lasted approximately 3 to 4 h. The patient failed to response to progesterone, and because of deteriorating respiratory status a low-dose continuous infusion of naloxone, 2 microgram/kg.h, was begun and gradually increased to 10 microgram/kg.h, during which time there was a dramatic improvement in respiratory status and clinical condition. After 5 days, naloxone infusion was discontinued and progressive respiratory deterioration recurred. The child died of over-whelming sepsis and disseminated intravascular coagulation.

Topics: Adolescent; beta-Endorphin; Carbon Dioxide; Endorphins; Female; Humans; Infant; Male; Naloxone; Obesity Hypoventilation Syndrome; Pulmonary Heart Disease; Respiratory Insufficiency