Isoflurane/nitrous oxide anesthesia and stress-induced procedures enhance neuroapoptosis in intrauterine growth-restricted piglets

• Published in: Intensive care medicine 2012-07, Vol.38 (7), p.1205-1214
• Main Authors: Schubert, Harald, Eiselt, Michael, Walter, Bernd, Fritz, Harald, Brodhun, Michael, Bauer, Reinhard
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthesia: equipment, devices; Anesthesiology; Anesthetics; Anesthetics, Inhalation - toxicity; Animals; Animals, Newborn - physiology; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Brain - drug effects; Brain - growth & development; Cell death; Critical Care Medicine; Disease Models, Animal; Emergency Medicine; Experimental; Fetal Growth Retardation - physiopathology; Fetus; General anesthesia; Growth; Hospitals; Hypotheses; Intensive; Intensive care; Intensive care medicine; Isoflurane - administration & dosage; Isoflurane - toxicity; Laboratory animals; Medical sciences; Medicine; Medicine & Public Health; Metabolism; Neurons; Neurons - drug effects; Neurophysiology; Neurotoxicity; Newborn babies; Nitrous oxide; Nitrous Oxide - administration & dosage; Nitrous Oxide - toxicity; Pain Medicine; Pediatrics; Physiological aspects; Physiology; Pneumology/Respiratory System; Prospective Studies; Stress, Physiological - drug effects; Swine; Synaptic Transmission - drug effects
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s00134-012-2576-2

Purpose There is compelling evidence that interference of various anesthetics with synaptic functions and stress-provoking procedures during critical periods of brain maturation results in increased neuroapoptotic cell death. The hypothesis is that adverse intrauterine environmental conditions leading to intrauterine growth restriction (IUGR) with altered brain development may result in enhanced susceptibility to developmental anesthetic neurotoxicity. Methods This was a prospective, randomized, blinded animal study performed in a university laboratory involving 20 normal-weight (NW) and 19 IUGR newborn piglets. General inhalation anesthesia with isoflurane and nitrous oxide at clinically comparable dosages were administered for about 10 h. Surgical and monitoring procedures were accompanied by appropriate stage of general anesthesia. Resulting effects on developmental anesthetic and stress-induced neurotoxicity were assessed by estimation of apoptotic rates in untreated piglets and piglets after 10-h general anesthesia with MAC 1.0 isoflurane in 70 % nitrous oxide and 30 % oxygen. Results IUGR piglets exposed to different levels of isoflurane inhalation exhibited a significant increased apoptosis rate (TUNEL-positive neuronal cells) compared to NW animals of similar condition ( P