Combination of Isoflurane and Propofol as General Anesthesia During Orthopedic Surgery of Perioperative Cerebral Hypoperfusion Rats to Avoid Cognitive Impairment.

Xinyue Bu,Chenyi Yang,Guolin Wang,Guoqiang Liu,Di Guo,Zhengyuan Xia,Yi Sun,Tang Li,Haiyun Wang,Ji Ma,Jinxin Wang,Zhuo Yang

doi:10.3389/fmed.2020.549081

Abstract

Background: Perioperative cerebral hypoperfusion (CH) is common, although the underlying mechanism of cognitive impairment that results due to perioperative cerebral hypoperfusion remains to be determined. Isoflurane anesthesia induces neuronal injury via endoplasmic reticulum (ER) stress, whereas a sub-anesthetic dose of propofol improves postoperative cognitive function. However, the effects of the combination of isoflurane plus propofol, which is a common aesthetic combination administered to patients, on ER stress and cognition remain unknown.Methods: We sought to determine the effects of isoflurane plus propofol on ER stress and cognitive function in rats insulted by cerebral hypoperfusion. Ligation of the bilateral common carotid arteries (CCA) was adopted to develop the cerebral hypoperfusion rat model. A second surgery, open reduction and internal fixation (ORIF), requiring general anesthesia, was performed 30 days later so that the effects of anesthetics on the cognitive function of CH rats could be assessed. 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). Behavioral studies (contextual fear conditioning [FC] test), histological analyses (Nissl staining) and biochemical analyses (western blotting of the harvested rat brain tissues) were employed.Results: Hippocampus-dependent memory of rats in group IP1 (1% isoflurane plus 20 mg·kg−1·h−1 propofol) was not impaired, and expression level of γ-aminobutyric acid A type receptor α1 subunit, a key cognition-related protein, remained normal. ER stress alleviator, binding immunoglobulin protein, increased extremely while ER stress transcription factor, C/EBP homologous protein, showed no statistical difference compared with the control group. Numbers of surviving neurons confirmed the substantial neuronal damage caused by propofol or isoflurane alone.Conclusions: These data suggest that ER stress contributes to the underlying mechanism of cognitive impairment and that the combination of isoflurane and propofol did not aggravate cognitive impairment and ER stress in aging rats with CH that were further subjected to ORIF surgery.

Highlights

Perioperative neurocognitive disorders (PND) have become the most common complications after routine surgical procedures, in the elderly [1, 2]
The results suggest that the combination of 1% isoflurane and 20 mg·kg−1·h−1 propofol could protect cognitive function, while other dosages could not
Hippocampal slices were stained with cresyl violet (Nissl staining) to investigate potential neuronal damage caused by anesthetics on days 1 and 7 after open reduction and internal fixation (ORIF)

Summary

Introduction

Perioperative neurocognitive disorders (PND) have become the most common complications after routine surgical procedures, in the elderly [1, 2]. CAS is an independent risk factor for chronic cerebral hypoperfusion (CH) [5], which reduces tissue oxygen levels and leads to oxidative stress and endothelial injury [6]. Oxidative injury to vascular endothelial cells, glia, and neurons impair vascular function and neurovascular coupling, which may result in a vicious cycle that further reduces cerebral perfusion [7]. Taking all these factors into account, aging orthopedic patients with preoperative carotid stenosis make up a population that needs to be treated carefully. The effects of the combination of isoflurane plus propofol, which is a common aesthetic combination administered to patients, on ER stress and cognition remain unknown

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