Combination of isoflurane and propofol, a means for general anesthesia in the orthopedic surgery of perioperative cerebral hypoperfusion rats to avoid cognitive impairment Anesthesia of perioperative cerebral hypoperfusion

Abstract

Background: Perioperative cerebral hypoperfusion often occurs. However, the underlying mechanism of cognitive impairment resulting when perioperative cerebral hypoperfusion occurs remain mostly to be determined. Anesthetic isoflurane induces neuronal injury via endoplasmic reticulum (ER) stress, whereas sub-anesthetic dose of propofol improves postoperative cognitive function. However, the effects of the combination of isoflurane plus propofol, which is a common combination of anesthesia for patient, on ER stress and the associated cognitive function remain unknown. Methods: We therefore set out to determine the effects of isoflurane plus propofol on the ER stress and cognitive function in the rats insulted by cerebral hypoperfusion. A ligation of bilateral common carotid arteries (CCA) surgery was adopted to prepare rats as cerebral hypoperfusion (CH) animal model. A second surgery, open reduction and internal fixation (ORIF), requiring general anesthesia, was operated 30 days later so that the effects of anesthetics on cognitive function of these CH rats could be assessed.The rats received isoflurane alone (1.9%), propofol alone (40 mg·kg -1 ·h -1 ) or a combination of isoflurane and propofol (1% and 20 mg·kg -1 ·h -1 or 1.4% and 10 mg·kg -1 ·h -1 ). Behavior studies (Fear Conditioning test), histological analyses (Nissl staining) and biochemical analyses (western blotting for the harvested rat brain tissues) were employed in the studies. Results: We found that the combination of 1% isoflurane plus 20 mg·kg -1 ·h -1 propol did not aggravate the cognitive impairment and the ER stress in aging rats with cerebral hypoperusion and being subjected to an ORIF surgery. Conclusions: These data suggest that ER stress contributes to the underlying mechanism of cognitive impairment and the combination of isoflurane and propofol did not aggravate the cognitive impairment and the ER stress in aging rats with cerebral hypoperfusion and being subjected to an ORIF surgery. BackgroundPerioperative neurocognitive disorders (PND) have become the most common complications after routine surgical procedures, particularly in the elderly [1, 2]. Following surgery (e.g., common orthopedic procedures), up to 50% of patients experience cognitive disturbances that can lead to serious complications, including poorer prognosis and a higher 1-year mortality rate in subjects with 4 pre-existing neurodegeneration [3]. Carotid artery stenosis (CAS) can be detected in 75% of men and 62% of women aged ≥65, with a stenosis extent of ≥50% occurring in 7% of men and 5% of women in this age group [4]. CAS is an independent risk factor for chronic cerebral hypoperfusion (CCH) [5], which reduces tissue oxygen levels leading to oxidative stress and endothelial injury [6]. In rodents, experimental CCH can be initiated by occlusion of the major arterial supply. This way CCH brings about mitochondrial dysfunction and protein synthesis inhibition. These effects may destroy the balance of anti-oxidases and reactive oxygen species (ROS) and produce oxidative ...