Effects of sevoflurane and clonidine on acid base status and long-term emotional and cognitive outcomes in spontaneously breathing rat pups.
BACKGROUND
Numerous experiments in rodents suggest a causative link between exposure to general anaesthetics during brain growth spurt and poor long-lasting neurological outcomes. Many of these studies have been questioned with regard of their translational value, mainly because of extremely long anaesthesia exposure. Therefore, the aim of the present study was to assess the impact of a short sevoflurane anaesthesia, alone or combined with clonidine treatment, on respiratory function in spontaneously breathing rat pups and overall effects on long-lasting emotional and cognitive functions.


METHODS
At postnatal day (PND) 7, male Sprague Dawley rat pups were randomized into four groups and exposed to sevoflurane for one hour, to a single dose of intraperitoneal clonidine or to a combination of both and compared to a control group. Blood gas analysis was performed at the end of sevoflurane anaesthesia and after 60 minutes from clonidine or saline injection. Emotional and cognitive outcomes were evaluated in different group of animals at infancy (PND12), adolescence (PND 30-40) and adulthood (PND 70-90).


RESULTS
Rat pups exposed to either sevoflurane or to a combination of sevoflurane and clonidine developed severe hypercapnic acidosis, but maintained normal arterial oxygenation. Emotional and cognitive outcomes were not found altered in any of the behavioural task used either at infancy, adolescence or adulthood.


CONCLUSIONS
Sixty minutes of sevoflurane anaesthesia in newborn rats, either alone or combined with clonidine, caused severe hypercapnic acidosis in spontaneously breathing rat pups, but was devoid of long-term behavioural dysfunctions in the present setting.
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.|Department of Anaesthesia and Intensive Care, Policlinico Umberto I, Rome, Italy.
Nicole
N
Almenrader
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Paola
P
Colucci
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Valentina
V
De Castro
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Daniela
D
Valeri
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Maura
M
Palmery
Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Rome, Italy.
Viviana
V
Trezza
Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Patrizia
http://orcid.org/0000-0002-2827-8755
P
Campolongo
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001639:Bicarbonates / Q000097:blood; D001784:Blood Gas Analysis; D002245:Carbon Dioxide / Q000097:blood; D003000:Clonidine / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D004644:Emotions / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000097:blood; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D000077149:Sevoflurane; D013997:Time Factors
D001639:Bicarbonates; D008738:Methyl Ethers; D002245:Carbon Dioxide; D019344:Lactic Acid; D000077149:Sevoflurane; D003000:Clonidine