Lipid metabolism disturbances and AMPK activation in prolonged propofol-sedated rabbits under mechanical ventilation

Abstract

Aim: To explore the mechanisms underlying the propofol infusion syndrome (PRIS), a potentially fatal complication during prolonged propofol infusion. Methods: Male rabbits under mechanical ventilation through endotracheal intubation were divided into 3 groups (n=6 for each) that were sedated with 1% propofol (Group P), isoflurane (Group I) or isoflurane while receiving 10% intralipid (Group II), respectively. Blood biochemical parameters were collected at 0, 6, 12, 18, 24, and 30-36 h after the initiation of treatments. The hearts were removed out immediately after the experiments, and the level of tumor necrosis factor (TNF)-α in the hearts were studied using immunohistochemistry. AMP-activated protein kinase (AMPK) and phospho-AMPK in the hearts were assessed using Western blotting. Results: The mortality rate was 50% in Group P, and 0% in Groups I and II. The serum lipids and liver function indices in Group P were significantly increased, but moderately increased in Group II. Significant decreases in these indices were found in Groups I. All the groups showed dramatically increased release of creatine kinase (CK). Intense positive staining of TNF-α was found in all the heart samples in Group P, but only weak and neglectful staining was found in the hearts from Group II and Group I, respectively. AMPK phosphorylation was significantly increased in the hearts of Group P. Conclusion: Continuous infusion of large dose of propofol in rabbits undergoing prolonged mechanical ventilation causes hyperlipidemia, liver dysfunction, increased CK levels, AMPK activation and myocardial injury. The imbalance between energy demand and utilization may contribute to PRIS.

Anesthetic Propofol Overdose Causes Vascular Hyperpermeability by Reducing Endothelial Glycocalyx and ATP Production

“…This time, rather than investigating how propofol induces the shedding of glycocalyx, we examined how a propofol overdose reduces its biosynthesis. Consistent with previous studies [ 5 , 39 ], we found that a propofol overdose significantly reduced endothelial ATP concentrations. Moreover, we found that a propofol overdose-induced ATP reduction was associated with a decrease in the production of endothelial proteoglycans.…”

Propofol Infusion Syndrome in Adults: A Clinical Update

“…Furthermore, as was described above, propofol has calcium channel blocking properties on the heart, which lead to decreased cardiac performance [ 23 ] and promote inflammation in the cardiac muscle [ 24 ]. It is also possible that some patients who develop PRIS have a subclinical mitochondrial disorder [ 25 , 26 ].…”

Glutamate microinjection into the hypothalamic paraventricular nucleus attenuates ulcerative colitis in rats

“…The frozen samples were weighed and homogenized in ice-cold buffer. The sample protein concentration was determined with a BCA protein assay kit according to a previously described method [32] . The sample proteins were separated by 10% SDSpolyacrylamide gel electrophoresis (SDS-PAGE) and electrophoretically transferred onto a nitrocellulose membrane.…”