beta-endorphin and Apnea

The activation of the laryngeal chemoreflex may be a pathogenic mechanism in apnoea, apparent life threatening events, and SIDS. Infants with apnoea and increased levels of beta-endorphin immunoreactivity in CSF have been successfully treated with naloxone. Beta-endorphin may induce respiratory depression, and naloxone is a beta-endorphin antagonist. We therefore wanted to measure beta-endorphin levels in CSF before and after the chemoreflex induced apnoea. This study includes 13 piglets, 5-10 days of age, treated with and without naloxone. Respiration, blood pressure, and heart rate were monitored. CSF was sampled before and after the laryngeal chemoreflex induced apnoea. We found a shorter duration of apnoea in the piglets which had received naloxone than in those which did not (p = 0.02). The beta-endorphin immunoreactivity levels in CSF increased after apnoea, and the increased levels correlated positively with the duration of the apnoea in the piglets which had not received naloxone (r = 0.94, p = 0.02), but not in those pretreated with naloxone (r = 0.1, p = 0.8). The median amount of beta-endorphin immunoreactivity in CSF after apnoea in the naloxone-treated piglets was not significantly different from that in the non-treated piglets: 615 +/- 589 (n = 7) fmol/ml CSF and 984 +/- 851 (n = 6) fmol/ml CSF, respectively. The beta-endorphin immunoreactivity levels measured before the apnoea were less than 4.3 fmol/ml CSF.. The laryngeal chemoreflex induced apnoea may possible be partly mediated by beta-endorphin.

Topics: Animals; Animals, Newborn; Apnea; beta-Endorphin; Blood Pressure; Bradycardia; Female; Humans; Larynx; Male; Naloxone; Narcotic Antagonists; Radioimmunoassay; Random Allocation; Reflex; Swine; Time Factors

To determine whether beta-endorphin is involved in the laryngeal chemoreflex, we initially injected 0.01-1 mg of beta-endorphin into the cisterna magna (i.c.m.) and registered the respiratory and cardiovascular patterns in 5-10-d-old piglets. From 0.1 to 1 mg of beta-endorphin i.c.m. induced a decrease in the minute volume, heart rate, and blood pressure within 15 min. Within the next 30 min respiratory pauses accompanied by blood pressure increases and reductions in heart rate developed, similar to the respiratory and cardiovascular pattern of the induced laryngeal chemoreflex. Based on these initial data, we decided to induce a laryngeal chemoreflex in piglets pretreated with 0.1 mg of beta-endorphin i.c.m (n = 6), 0.2 mg of beta-endorphin i.c.m. (n = 6), 0.1 mg of beta-endorphin i.c.m. and 100 micrograms/kg naloxone i.v. (n = 6), 100 micrograms/kg naloxone i.v. (n = 6), or water i.c.m. (n = 6). Because elevated levels of hypoxanthine in the vitreous humor may indicate hypoxia before death, we therefore measured the postmortem hypoxanthine levels in the vitreous humor. The laryngeal chemoreflex-induced apnea was shortened in the piglet group pretreated with water i.c.m and naloxone i.v. (p < 0.01) and in the piglet group pretreated with 0.1 mg of beta-endorphin i.c.m and naloxone i.v. (p < 0.05), but not significantly prolonged in the piglet groups pretreated with 0.1 or 0.2 mg of beta-endorphin i.c.m. when compared with the piglets pretreated with water i.c.m.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Animals; Apnea; beta-Endorphin; Blood Glucose; Body Weight; Cisterna Magna; Female; Hematocrit; Hemoglobins; Hypoxanthine; Hypoxanthines; Injections; Larynx; Male; Pilot Projects; Reflex; Swine; Vitreous Body

Piglets were given IL-1 beta intravenously (Index I, n = 8) or intrathecally (Index II, n = 9) prior to apnea to test the hypothesis that IL-1 beta may prolong periods of apnea during sleep and infection. Apnea variables and the quality of autoresuscitation were recorded and compared to an apnea control group (Ctr. I, n = 7, apnea without injection of IL-1 beta) and a procedure control group (Ctr. II, n = 6, apnea after intratecally injected sterile water). Hypoxanthine (Hx) and xanthine (X) were analyzed in plasma, CSF and vitreous humor. The duration of apnea was significantly longer in the Index I - mean: 38, intraquartile range: 27-52 sec and Index II-group 26 (24-36) sec than in the Ctr. 1-12 (10-13) sec (p < 0.01) and the Ctr. II-group 14 (6-18) sec (p < 0.01). The number of respirations per 2 min following apnea in the Index I-group mean: 21, intraquartile range: 7-40 and was significantly less than in the Ctr. I-group 109 (39-150) (p < 0.01), while a similar tendency was found in the Index II-group 42 (27-55) (p = 0.06).. Intravenous and intrathecal injection of IL-1 beta prolong the duration of apnea and modifies autoresuscitation.

Topics: Animals; Animals, Newborn; Apnea; beta-Endorphin; Female; Heart Rate; Hypoxanthine; Hypoxanthines; Injections, Intravenous; Injections, Spinal; Interleukin-1; Male; Random Allocation; Respiratory Mechanics; Swine; Vitreous Body; Xanthine; Xanthines

Apnea of prematurity is a common problem in neonatal intensive care nurseries. Xanthines are used to treat apnea, but their mechanism of action is not clearly understood. To determine whether xanthines stimulated beta-endorphin (beta-ED) release in preterm infants, plasma beta-ED concentrations were measured in 27 infants with apnea of prematurity. These infants had a mean (+/- SD) birthweight of 1560 +/- 487 g, gestational age 31 +/- 2.5 weeks, and a postnatal age of 7.3 +/- 4.6 d. Twenty-five of the infants were treated with I.V. aminophylline 2.5 mg/kg/dose 4 times daily and 2 were treated orally with caffeine (10 mg/kg). Blood samples were collected prior to and 30 min after treatment with xanthines. Apneic spells greater than 15 sec were recorded and reviewed every 24 h using a Hewlett-Packard Merlin Monitor (Waltham, MA.) system. Infants were then stratified into responders (Group 1, n = 14) and nonresponders (Group 2, n = 13), with responders defined as showing more than 50% decrease in the frequency of apneic spells in the first 24 h of treatment. beta-ED were measured as previously described using a radioimmunoassay technique. In group 1, plasma beta-ED concentration increased significantly, (p = 0.0496) from pre-xanthine (24.4 +/- 12 pg/ml) to post xanthine (34.6 +/- 24 pg/ml) treatment, whereas in Group 2 the concentrations remained the same (23.3 +/- 5 pg/ml) and (22.6 +/- 4 pg/ml). Birthweight, gestational age, postnatal age, and diagnoses in both groups were compared and no significant differences were observed. Interestingly, xanthine treatment caused increased plasma beta-ED release when apneas decreased.

Topics: Apnea; beta-Endorphin; Caffeine; Humans; Infant, Newborn; Infant, Premature, Diseases; Xanthine; Xanthines

A consecutive cohort of 87 infants (46 infants less than 37 weeks gestational age and 41 term infants greater than or equal to 37 weeks gestation) admitted to the Neonatal Intensive Care Unit (NICU) and a convenience cohort of 27 term well babies at the University of Nebraska Medical Center (Omaha, NE) were evaluated for plasma beta-endorphin (beta E) levels during the first 4 h after birth. Demographic data, maternal history, and respiratory status at the time of sampling as well as development of documented apneic episodes during the initial hospitalization were analyzed for all infants. All NICU infants had higher plasma beta E levels than the control infants. Premature infants had significantly higher neonatal plasma beta E levels than term infants in either the control or NICU groups, but the response was gender specific; premature males had higher plasma beta E than premature females (P = 0.008). Perinatal stress, including respiratory problems, was associated with the increase in plasma beta E, but prematurity and being male were significantly predictors of an elevated plasma beta E level. Immaturity in respiratory control, as evaluated by the development of documented apneic episodes during the infant's initial hospitalization, did not correlate with an elevated perinatal plasma beta E level.

Topics: Apgar Score; Apnea; beta-Endorphin; Cohort Studies; Delivery, Obstetric; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Male; Pregnancy; Reference Values; Respiration; Sex Characteristics

Beta-endorphin-like immunoreactivity (B-ELI) was measured in cerebrospinal fluid (CSF) and plasma from infants of postnatal age 24 h to 70 days. Three groups were examined: 17 were of postconceptual age greater than or equal to 37 weeks, 16 were postconceptual age less than or equal to 35 weeks without apnea and 10 were of postconceptual age less than or equal to 35 weeks with apnea. All infants were clinically stable. Two-way analysis of variance between groups showed no difference in the concentration of B-ELI in CSF or plasma, or in the CSF/plasma B-ELI ratio. Concentrations of B-ELI in plasma were significantly higher in infants of postnatal age 1-3 weeks and greater than or equal to 4 weeks, than in infants of postnatal age less than 1 week. We conclude that, in nonstressed infants, there is no relationship between the concentration of B-ELI in CSF or plasma and a concurrent diagnosis of apnea of prematurity. Our data indicate that a significant developmental increase occurs in the plasma concentration of B-ELI after the first week of life.

Topics: Aging; Apnea; beta-Endorphin; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Male; Radioimmunoassay

Topics: Apnea; beta-Endorphin; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Naltrexone; Respiratory Distress Syndrome, Newborn; Sudden Infant Death

Twenty-nine premature infants were studied to determine whether neonatal asphyxia, apnea, and low blood pressure in the first day of life are associated with elevated plasma beta-endorphin concentrations. Plasma beta-endorphin levels were determined at 0.5 to 2, 4 to 6, and 18 to 24 hours of life, using radioimmunoassay. Premature infants with moderate or severe asphyxia (n = 19) had higher levels at 0.5 to 2 hours of age (32.1 +/- 6.7 vs 16.4 +/- 7.4 pmol/L) and significantly higher levels at 4 to 6 hours of age (50.4 +/- 10.0 vs 22.9 +/- 9.2 pmol/L) compared with the ten nonasphyxiated premature infants. A significant elevation in levels at age 0.5 to 2 hours (39.4 +/- 9.9 vs 17.7 +/- 4.4 pmol/L) and age 4 to 6 hours (59.3 +/- 13.8 vs 27.1 +/- 17.1 pmol/L) was observed in premature infants with low blood pressure or impaired perfusion (n = 12) who required the administration of volume expanders. No differences were observed in premature infants with and without apnea. It may be speculated that the increased endogenous release of beta-endorphins in response to perinatal asphyxia may play a role in the pathogenesis of shock observed in the first day of life.

Topics: Apnea; Asphyxia Neonatorum; beta-Endorphin; Endorphins; Humans; Hypotension; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Radioimmunoassay

To gain further insight into the possible role of endogenous opioid peptides in the respiratory difficulties associated with the apnea of infancy and other disorders possibly related to apnea, the levels of beta-endorphin immunoreactivity were measured in the cerebrospinal fluid (CSF) of five groups of infants: (1) infants with proved apnea, (2) infants with histories of an apparent life-threatening event (ALTE), (3) siblings of victims of the sudden infant death syndrome (SIDS), (4) infants with suspected but unproved apnea, and (5) infants undergoing investigation for other acute illnesses. Twenty-two infants considered at risk for an ALTE (groups 1 to 3) had significantly higher CSF beta-endorphin equivalents (88 +/- 7 pg/mL) than did the 22 control patients in groups 4 and 5 (31 +/- 3 pg/mL). Plasma beta-endorphin immunoreactivity, which was also measured in some of the infants, did not correlate with levels in CSF and, in fact, was significantly lower in the groups at risk for an ALTE (50 +/- 9 pg/mL; n = 14) than in the control subjects (80 +/- 6 pg/mL; n = 11). These studies indicate that elevated beta-endorphin immunoreactivity in CSF may be a marker in infants who have apnea and who may be considered at risk for an ALTE.

Topics: Adult; Apnea; beta-Endorphin; Female; Humans; Infant; Infant, Newborn; Male; Radioimmunoassay; Risk Factors; Sudden Infant Death

Elaboration of beta-endorphins (beta-ED) is implicated in the modulation of respiratory control in infants. Therefore, beta-ED concentrations were measured in paired samples of CSF and plasma in three groups of infants. Group 1 and group 3 were used as controls. Group 2 infants suffered prolonged apnea of infancy (near-miss sudden infant death syndrome) and were successfully resuscitated. Age and weight (mean +/- SEM) in groups 1, 2 and 3 were 8.5 +/- 3 months and 7.2 +/- 1.4 kg, 3.8 +/- 0.7 months and 5.2 +/- 0.6 kg, and 3.4 +/- 0.9 months and 3.4 +/- 0.7 kg, respectively. CSF beta-ED concentrations were found to be significantly elevated in group 2, 67.8 +/- 4.7 pg/ml, when compared to group 1, 29.8 +/- 3.1 pg/ml, and group 3, 46.5 +/- 7.2 pg/ml (p less than 0.01). No correlation was observed with plasma and CSF concentrations in all three groups. beta-ED may play a role in the pathophysiology of prolonged infant apnea (near-miss sudden infant death syndrome).

Topics: Apnea; beta-Endorphin; Endorphins; Humans; Infant; Infant, Newborn; Sudden Infant Death

Plasma levels of beta-endorphin-like immunoreactivity (beta-ELI) were measured in premature infants with apnea (n = 11) and compared to those in nonapneic controls (n = 9). Naltrexone (1-3 mg/kg) was given to the infants with apnea, 6 of whom were also receiving methylxanthines. Chest wall movements, nasal airflow, transcutaneous PO2 and electrocardiogram were recorded for 4-6 h prior to and for 4-6 h after administration of naltrexone. Samples for beta-ELI were taken prior to and 1 h post naltrexone. beta-ELI levels were significantly higher (p less than 0.007) in infants with apnea of prematurity than in control infants. No significant difference was found in beta-ELI levels before and after naltrexone. Naltrexone did not decrease the incidence of apnea.

Topics: Apnea; beta-Endorphin; Endorphins; Humans; Infant; Infant, Newborn; Infant, Premature; Injections, Intravenous; Naltrexone; Respiration; Xanthines

In an attempt to determine whether plasma beta-endorphin (beta-ED) concentrations correlate with occurrence of apnea in preterm infants, measurements were made in three groups of infants. The control group consisted of 11 infants with a mean (+/- SEM) gestational age of 30.5 +/- 0.8 weeks, a mean (+/- SEM) birthweight of 1650 +/- 180 g, and a mean (+/- SEM) postnatal age of 1.3 +/- 0.5 days. Eight infants with apnea, bradycardia, and associated hypotension had a mean (+/- SEM) gestational age, birthweight and postnatal age of 30 +/- 0.9 weeks, 1165 +/- 90 g, and 7.8 +/- 1.9 days, respectively. The third group consisted of eight infants experiencing apnea alone without bradycardia and had a mean (+/- SEM) gestational age, birthweight, and postnatal age of 31 +/- 0.8 weeks, 1380 +/- 125 g, and 2.6 +/- 0.9 days, respectively. The last two groups of infants suffered varying degrees of apnea, but differed in their severity. The plasma endorphin concentrations (+/- SEM) were 26.9 +/- 2, 68.0 +/- 9.0, and 39.6 +/- 2.0 pg/ml, respectively, for the previously described three groups. Significant elevation in beta-ED concentration was observed in the severely apneic infants with bradycardia when compared to the other two groups. The association of increased plasma beta-ED release with severe apneic spells may suggest that these endogenous opiates play a role in the pathophysiology of apnea of prematurity.

Topics: Apnea; beta-Endorphin; Bradycardia; Endorphins; Humans; Hypotension; Infant, Newborn; Infant, Premature, Diseases; Radioimmunoassay; Recurrence

Topics: Apnea; beta-Endorphin; Endorphins; Humans; Infant; Sudden Infant Death

Topics: Apnea; beta-Endorphin; Endorphins; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases