title: Effects of pentobarbital on proopiomelanocortin opioid products of neonatal piglets during normoxia and hypoxia.
abstract: Abstract Endogenous opioids have been shown to suppress physiological functions in the neonate. It has been suggested that anesthesia with barbiturates might enhance this suppression by influencing opioid systems directly. To explore this possibility, naive piglets, 2.2+/-0.8 (X+/-SD) days old, underwent one of five protocols: 1) normoxia (control); 2) 10% 0(2)/90% N(2) (hypoxia); 3) saline injection ip during normoxia (sham anesthesia); 4) pentobarbital sodium, 25 mg/kg ip, during normoxia (barbiturate anesthesia); and 5) pentobarbital sodium, 25 mg/kg ip, during hypoxia (combined hypoxia and barbiturate anesthesia). Following the inhalation of either gas mixture for at least 30 min, and precisely 30 min after an injection, blood, cerebrospinal fluid and a dorsal medullary slice containing the nucleus tractus solitarii were collected and processed for measurement by radioimmunoassay of opioid proopiomelanocortin products. These comprised beta-lipotropin (the precursor), beta-endorphin-like immunoreactivity (containing the active peptide beta-endorphin) and N-acetyl beta-endorphin (a deactivated peptide). The most striking result was seen in the cerebrospinal fluid: As compared to barbiturate anesthesia, peptide levels with all other treatments, including combined hypoxia and barbiturate anesthesia, were consistently higher. In the plasma, peptide levels after either combined hypoxia and barbiturate anesthesia or hypoxia alone were generally higher than those of their respective controls (sham anesthesia, control). Plasma levels of beta-endorphin-like immunoreactivity and estimated beta-endorphin with combined hypoxia and barbiturate anesthesia were also higher than those with barbiturate anesthesia. The latter pattern was reversed in the nucleus tractus solitarii, in which beta-endorphin-like immunoreactivity and estimated beta-endorphin levels were lower with combined hypoxia and barbiturate anesthesia than with barbiturate anesthesia alone, although no significant differences were achieved. These results suggest that pentobarbital may decrease the central neuronal release of active endorphins, and thus decrease the quantity of these ligands available for interaction with opioid receptors. Hypoxia, on the other hand, appears to increase such release even in the presence of pentobarbital. Thus, during a hypoxic insult, the suppressive influence of opioids on physiological functions would be enhanced regardless of the presence of barbiturate anesthesia.
authors.affiliation: Departments of Pediatrics and Physiology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9063, USA.
authors.forename: I R
authors.initials: IR
authors.lastname: Moss
authors.forename: J D
authors.initials: JD
authors.lastname: Inman