beta-endorphin and Shock

Animal experiments have shown that severe haemorrhage often is characterized by an initial general increase in sympathetic activity leading to an increase in heart rate and a subsequent vagally mediated, reversible decrease in heart rate. It is likely that the decrease in heart rate is triggered by mechanoreceptors situated in the left ventricle. The receptors are supposed to be activated by a reduction in end-systolic volume occurring as a result of a decrease in venous return concomitant with the initial increase in heart rate. SA vago-vagal reflex elicited from and returning to the heart is thereby activated, resulting in a slowing of the heart. It has been hypothesized that the left ventricular receptors are activated when the ventricle contracts around an almost bloodless chamber. The decrease in heart rate may allow for an increased filling of the heart and an improved coronary perfusion. However, these experimental observations are in clear contradiction to the general description of the regulatory mechanisms operating during haemorrhagic shock in man as presented by authoritative medical, surgical and anesthesiological textbooks. Until now the (over-simplified) notion has been, that progressive haemorrhage results in an increased activation of the sympathetic nervous system leading to an increase in heart rate and that the occurrence of bradycardia was a sign of irreversible shock. The present systematic measurements in patients in haemorrhagic shock showed that the heart rate during severe haemorrhage often was normal (mean value 73 beats/min, range 46-98 beats/min). Simultaneous measurements of plasma concentrations of pancreatic polypeptide (an index of vagal activity) indicated that organs other than the heart also were exposed to increased vagal activity. A marked increase in the plasma concentration of vasopressin was not a constant finding as it was during the experimental-induced hypotensive central hypovolemia. This difference may be due to a decline in the release of vasopressin during prolonged haemorrhage. In order to elucidate essential regulatory mechanisms behind the clinical observations, central hypovolemia was induced experimentally by "head-up tilt", "lower-body negative pressure", "venous tourniquets of the thighs plus haemorrhage", and by epidural anesthesia. The initial stage of central hypovolemia was characterized by an increase in sympathetic nervous activity resulting in an increase in heart rate. Activation of the renin-

Topics: Aldosterone; Angiotensin II; Animals; Atropine; beta-Endorphin; Blood Pressure; Blood Volume; Endocrine Glands; Heart Rate; Humans; Myocardium; Pressoreceptors; Renin; Shock; Shock, Hemorrhagic; Vasopressins

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; beta-Endorphin; Circadian Rhythm; Dynorphins; Endocrine Glands; Endorphins; Enkephalins; Female; Humans; Hypothalamo-Hypophyseal System; Islets of Langerhans; Melanocyte-Stimulating Hormones; Oxytocin; Pain; Pituitary Gland, Anterior; Pituitary Gland, Posterior; Pregnancy; Rats; Receptors, Opioid; Shock; Stress, Physiological

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

Topics: Animals; beta-Endorphin; Calcitonin; Calcium; Guinea Pigs; Histamine; Immunoenzyme Techniques; Male; Neuropeptide Y; Neurotensin; Shock; Substance P; Thyroid Gland; Vasoactive Intestinal Peptide

beta-endorphin and cortisol were measured in cerebrospinal fluid (CSF) and plasma by radioimmunological method (RIA) in two groups of rabbits with spinal cord traumatic injuries at cervical and lumbar levels, respectively with and without concomitant spinal shock and arterial hypotension, and in a group of sham operated animals as controls. The two groups with spinal lesions displayed a significant beta-endorphin increase in CSF, whereas the cortisol level remained unchanged both in the spinal traumatized rabbits and in controls. Both the opioid and the cortisol concentration rose significantly in plasma in all three groups and in particular resulted significantly higher in the cervical traumatized group where spinal trauma was associated with spinal shock and hypotension. However, no significant difference was found when beta-endorphin concentrations in plasma were compared between the sham operated animals and the spinal lumbar traumatized animals without concomitant spinal shock. The results seem to suggest that the beta-endorphin increase in CSF is related to the nervous tissue lesion, while its increase in plasma, like that of cortisol, is due to surgery or other stress factors inherent in the experiment. This independent behaviour of beta-endorphin in plasma and in CSF suggests its different origin in these two compartments.

Topics: Animals; Arousal; beta-Endorphin; Female; Hydrocortisone; Hypotension; Male; Rabbits; Radioimmunoassay; Shock; Spinal Cord; Spinal Cord Injuries

This paper observed the effect of Dexamethasone (Dex) on the levels of plasma Beta-endorphin-like-immunoreactivity (ir-beta-EP) and its correlation with hemodynamics during the shock. Ten adult mongrel dogs were randomized into two groups. Intestinal shock was created by occluding both superior mesenteric artery and vein in the two groups. After two hours of occlusion, the dogs in treated group were given Dex (5 mg/kg) and the dogs in control group were given normal saline. The intestinal vascular obstruction was released four hours later. It was shown that plasma levels of ir-beta-EP in control group were increased significantly during the shock and correlated significantly with deteriorated hemodynamics. In Dex treated group, the levels of plasma ir-beta-EP and ACTH were significantly lower than that in control group, hemodynamics were improved, and the survival times were much longer. Our results suggest that endogenous opiate beta-EP is involved in the cardiovascular pathophysiology of intestinal shock, and the beneficial effects of steroids (Dex) in the treatment of shock are correlated with its suppressing endogenous beta-EP secretion and release.

Topics: Animals; beta-Endorphin; Dexamethasone; Dogs; Female; Hemodynamics; Intestines; Ischemia; Male; 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

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

Beta-endorphin has been implicated in the cardiovascular depression that occurs in shock. While pharmacologic doses of beta-endorphin cause hypotension, physiologic doses of beta-endorphin have not been studied. In this study, six dogs (group I) were given IV beta-endorphin (peak concentrations previously determined in canine shock, 3,200 pg/ml); 5 minutes prior to beta-endorphin infusion, four dogs (group II) were given naloxone, 2 mg/kg bolus, and continuous infusion, 2 mg/kg/hr. In group I, beta-endorphin decreased stroke volume (from 0.99 +/- .12 to 0.57 +/- .08 ml/kg), dP/dt (from 3,167 +/- 140 to 2,875 +/- 412 mmHg X sec), and coronary blood flow (from 2.5 +/- .47 to .68 +/- .11 ml/min/gm), while heart rate rose significantly. Naloxone pretreatment maintained dP/dt, stroke volume, and coronary blood flow with no change in heart rate or mean arterial pressure. This study confirms that beta-endorphin depresses contractility and coronary blood flow in normovolemic nonstressed dogs, suggesting that beta-endorphin is in part responsible for cardiovascular depression in shock.

Topics: Animals; beta-Endorphin; Blood Pressure; Cardiovascular System; Coronary Circulation; Dogs; Endorphins; Heart Rate; Myocardial Contraction; Shock

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

In ten shock patients studied, there was a significant positive correlation between beta-ELIR blood plasma levels and the ratio of pulse rate of radial artery to systolic blood pressure.

Topics: beta-Endorphin; Blood Pressure; Endorphins; Female; Humans; Male; Pulse; Shock

Topics: Adrenal Glands; Animals; beta-Endorphin; Blood Pressure; Brain; Digestive System; Endorphins; Humans; Hypertension; Morphine; Pain; Pituitary Gland; Receptors, Opioid; Shock