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

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 IP 1 (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 Bu et al. Anesthesia During Perioperative Cerebral Hypoperfusion 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.

1% Isoflurane and 1.2 μg/ml of Propofol: A Combination of Anesthetics That Causes the Least Damage to Hypoxic Neurons

“…Previous studies showed that isoflurane minimum alveolar concentration (MAC) value was 1.45 ± 0.17%; 1.9% isoflurane, equivalent to 1.3 MAC, was sufficient to induce general anesthesia in rats (Boruta et al, 2012 ), while a minimal infusion rate at 40 mg·kg −1 ·h −1 was required using propofol alone to induce general anesthesia in rats (Logginidou et al, 2003 ). Our previous study confirmed that a single use of anesthetic dose propofol (40 mg·kg −1 ·h −1 ) or isoflurane (1.9%) aggravated cognitive impairment of aging rats with cerebral hypoperfusion, while a combination of sub-anesthesia dose propofol and isoflurane (1% isoflurane plus 20 mg·kg −1 ·h −1 propofol) did not (Bu et al, 2020 ). However, the effects of different combinations of propofol and isoflurane on hippocampal neurons remain to be explored.…”

“…All this evidences could prove that a single high dose of propofol or isoflurane may cause neuron damage and cognitive impairment, which aroused our interest in studying low-dose combination applications. Our previous in vivo study revealed that combination of sub-anesthetic dose isoflurane and propofol (1% isoflurane plus 20 mg·kg −1 ·h −1 propofol) did not cause cognitive impairment of aged rats with cerebral hypoperfusion as compared with single-use of propofol (20 mg·kg −1 ·h −1 ) or isoflurane (1.9%; Bu et al, 2020 ). In the present study, we compared the effects of three different dosages of isoflurane and propofol (1% and 1.2 μg/ml, 1.4% and 0.6 μg/ml, or 0.5% and 1.8 μg/ml) on primary hypoxic hippocampal neurons with the aim of finding the way to minimize the damage caused by anesthetic to vulnerable neurons.…”

“…•h −1 propofol) did not (Bu et al, 2020). However, the effects of different combinations of propofol and isoflurane on hippocampal neurons remain to be explored.…”

Sub‐dose anesthetics combined with chloride regulators protect the brain against chronic ischemia–hypoxia injury

“…All the rats were randomly assigned to the following five groups ( n = 22/group): (1) sham surgery (Sham), (2) CCH, (3) CCH + sub‐anesthetic dose combining propofol and sevoflurane (PS‐low), (4) CCH + PS‐low + BTN (MCE), and (5) CCH + PS‐low + NEM (MCE). The sample size is set based on our previous experience 13,24 . All the outcome assessments were performed by investigators blinded to the group assignments.…”

Table_1.DOCX

“…•h −1 propofol) did not cause cognitive impairment of aged rats with cerebral hypoperfusion as compared with single-use of propofol (20 mg•kg −1 •h −1 ) or isoflurane (1.9%; Bu et al, 2020). In the present study, we compared the effects of three different dosages of isoflurane and propofol (1% and 1.2 µg/ml, 1.4% and 0.6 µg/ml, or 0.5% and 1.8 µg/ml) on primary hypoxic hippocampal neurons with the aim of finding the way to minimize the damage caused by anesthetic to vulnerable neurons.…”