beta-endorphin and Escherichia-coli-Infections

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

The effects upon survival of large doses of steroid administered to dogs prior to challenging them with lethal sepsis was evaluated in this study. Dogs were given 30 milligrams per kilogram of body weight per day of methylprednisolone sodium succinate for one, two or eight days and then were infused with 9.72 +/- 0.35 X 10(9) Escherichia coli per kilogram of body weight. All dogs in group 1 (n equals six) not given steroid died within 25 hours. Of the dogs in group 2 (n equals 12) given one or two doses of steroid previously, 42 per cent permanently survived (more than seven days). All dogs in group 3 (n equals five) given eight daily doses of steroid prior to infusion of Escherichia coli died within 17 hours. Dogs in group 4 (n equals six) were given eight daily doses of steroid prior to infusion of Escherichia coli and treated on the day of infusion of Escherichia coli with a regimen of methylprednisolone and gentamicin sulfate which results in a 100 per cent survival rate when given to dogs that have not received prior treatment with steroid. Thirty-three per cent of the dogs in group 4 permanently survived. One or two daily large doses of steroid did not detrimentally affect survival of the dogs. Eight days of steroid administration suppressed endogenous cortisol production. When the dogs were treated with six hours of steroid-antibiotic therapy, survival benefits were limited.

Topics: Adrenal Cortex Hormones; Animals; Bacterial Infections; beta-Endorphin; Blood Glucose; Dogs; Endorphins; Escherichia coli Infections; Female; Gentamicins; Hydrocortisone; Male; Methylprednisolone; Neutrophils; Time Factors

Blood was collected at 20-second intervals from the external carotid artery and from the dorsal longitudinal sagittal sinus (sagittal sinus, SS) of ovariectomized sheep. The point of SS catheterization was very near the point at which diencephalic effluent entered the SS. Concentrations of beta-endorphin (beta-EP) immunoreactivity were quantified by radioimmunoassay procedures in blood plasma and in cerebrospinal fluid (CSF) from the cisterna magna. Increases in plasma beta-EP concentration were provoked by intracarotid injection of naloxone and by experimental production of bacteremia (i.e., intravascular bacteria), but these procedures failed to increase beta-EP in CSF. Quantities of beta-EP in plasma samples from the SS were assumed to represent arterial contribution (minus tissue uptake), diencephalic secretion, and retrograde delivery of pituitary beta-EP to the diencephalic effluent. The arterial contribution was removed mathematically by subtracting the arterial plasma beta-EP concentration from the concurrent SS plasma concentration of beta-EP to yield a paired arteriovenous (AV) difference. When this AV difference was consistently positive and satisfied our statistical criterion for being greater than zero, we concluded that either pituitary beta-EP was delivered in a retrograde manner to diencephalon or the diencephalon secreted beta-EP. However, this situation occurred in only 5 of 31 periods examined. Furthermore, only 2 of these 5 periods occurred during times of increasing arterial concentrations of beta-EP. Such concurrence would be expected if both changes were caused by a major discharge of beta-EP from the pituitary gland. Therefore, the present results provide little evidence for retrograde delivery of pituitary beta-EP to the brain without systemic dilution.

Topics: Animals; beta-Endorphin; Brain; Carotid Artery, External; Cranial Sinuses; Endorphins; Escherichia coli Infections; Female; Monitoring, Physiologic; Sheep

Acute bacteremia in sheep caused a surge of plasma beta-endorphin/beta-lipotropin (beta-EP/beta-LPH) associated with shivering behavior, tachycardia, hyperthermia, hemoconcentration, and decreased respiration rate. The surge of plasma beta-EP/beta-LPH was immediately followed by increases (P less than 0.05) in plasma prolactin and growth hormone (GH) concentrations and a depression (P less than 0.05) of plasma luteinizing hormone. These changes in pituitary hormone release were consistent with opioid-induced changes described in the literature. To examine possible opioid mediation, naloxone (2.5 mg X kg-1 X h-1) was continuously infused intravenously from 3 h before to 3 h after induction of an E. coli bacteremia. With the exception of plasma GH, naloxone failed to alter any of the hormonal or clinical parameters associated with bacteremia. For plasma GH, naloxone delayed (P less than 0.01) the increase but did not attenuate its magnitude, suggesting that an opioid mechanism may influence the timing of the pituitary GH release resulting from bacteremia. In general, opioid mechanisms sensitive to the present dosage of naloxone do not appear to mediate bacteremia-induced changes in hormonal or clinical parameters.

Topics: Animals; beta-Endorphin; beta-Lipotropin; Endorphins; Escherichia coli Infections; Female; Growth Hormone; Heart Rate; Hematocrit; Luteinizing Hormone; Naloxone; Pituitary Hormones; Prolactin; Radioimmunoassay; Receptors, Opioid; Respiration; Sepsis; Sheep; Shivering; Time Factors