Systemic physiology and neuroapoptotic profiles in young and adult rats exposed to surgery: A randomized controlled study comprising four different anaesthetic techniques.
BACKGROUND
Experimental evidence indicates that general anaesthetics can induce apoptotic neurodegeneration in the developing brain. The majority of these studies have been performed in the absence of surgery and it currently remains unclear how the presence of surgical stimuli would influence neuroapoptosis as well as systemic homeostasis. Here we explored this possibility by performing dorsal skin flap surgery in young and adult rats under four distinct currently used anaesthesia regimens.


METHODS
Young (21-days) and adult (2 months) male Sprague-Dawley rats were randomized to 150 min exposure to one of four anaesthetics regimens: (i) sevoflurane/dexmedetomidine, (ii) sevoflurane/fentanyl; (iii) propofol/dexmedetomidine, and (iv) propofol/fentanyl. Animals underwent a dorsal skin flap procedure while physiologic, metabolic and biochemical parameters were closely monitored. Neuroapoptotic profiles were evaluated in the cortex, thalamus and hippocampus (CA1 and CA3) at the end of the procedure in each experimental group.


RESULTS
Significant perturbations of systemic homeostasis were found under all anaesthetic regimens. Hyperglycemia and decreased heart rate were particularly relevant in experimental groups receiving dexmedetomidine, while propofol administration was associated with increased systemic lactate levels and metabolic acidosis. A substantial difference in anaesthesia/surgery-induced neuroapoptosis was found between young and adult rats in several brain regions. Combination of sevoflurane and dexmedetomidine resulted in the highest number of caspase-3 positive cells, although the extent of cell death remained relatively low in all experimental groups.


CONCLUSIONS
Combination of anaesthesia and surgery induces significant perturbations of physiological parameters in both young and adult spontaneously breathing rats undergoing surgery. These observations further enlighten the need for detailed physiological monitoring under these experimental conditions. Although some statistically significant differences in activated caspase-3 profiles were detected between experimental groups, the overall extent of neuronal cell death remained very low under all conditions questioning, thereby, the physiological significance of apoptotic neurodegeneration in the context of anaesthesia and surgery.
Department of Plastic Surgery, Odense University Hospital, Sdr. Boulevard 29, Odense 5000, Denmark. Electronic address: rami.mossad.ibrahim@hotmail.com.
Rami Mossad
RM
Ibrahim
Department of Plastic Surgery, Odense University Hospital, Sdr. Boulevard 29, Odense 5000, Denmark.
Caspar Weel
CW
Krammer
Institute of Clinical Research, University of Southern Denmark, Winsløvparken 19, Odense 5000 Denmark; Department of Anesthesiology & Intensive Care - Pediatric Section, Odense University Hospital, Sdr. Boulevard 29, Odense 5000 Denmark.
Tom Giedsing
TG
Hansen
Institute of Clinical Research, University of Southern Denmark, Winsløvparken 19, Odense 5000 Denmark; Department of Pathology, Odense University Hospital, Sdr. Boulevard 29, Odense 5000 Denmark.
Bjarne Winther
BW
Kristensen
Department of Anesthesiology, Pharmacology and Intensive Care, University Hospitals of Geneva, 4 rue Gabrielle-Perret-Gentil, Geneva 1205, Switzerland; Department of Fundamental Neuroscience, University of Geneva Medical School, Geneva, Switzerland.
Laszlo
L
Vutskits
Department of Plastic Surgery, Odense University Hospital, Sdr. Boulevard 29, Odense 5000, Denmark; Institute of Clinical Research, University of Southern Denmark, Winsløvparken 19, Odense 5000 Denmark.
Jens Ahm
JA
Sørensen
D000375:Aging / Q000473:pathology; D018681:Anesthetics, General / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000473:pathology*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D011183:Postoperative Complications / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
D018681:Anesthetics, General
Abstract; Anaesthesia; Apoptosis; Brain; Dexmedetomidine; Homeostasis; Surgery