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Anesthetic propofol overdose causes vascular hyperpermeability by reducing endothelial glycocalyx and ATP production.

Lin MC, Lin CF, Li CF, Sun DP, Wang LY, Hsing CH - Int J Mol Sci (2015)

Bottom Line: In vivo, we intraperitoneally injected ICR mice with overdosed propofol, and the results showed that a propofol overdose significantly induced systemic vascular hyperpermeability and reduced the expression of endothelial glycocalyx, syndecan-1, syndecan-4, perlecan mRNA and heparan sulfate (HS) in the vessels of multiple organs.In vitro, a propofol overdose reduced the expression of syndecan-1, syndecan-4, perlecan, glypican-1 mRNA and HS and induced significant decreases in the nicotinamide adenine dinucleotide (NAD+)/NADH ratio and ATP concentrations in human microvascular endothelial cells (HMEC-1).Oligomycin treatment also induced significant decreases in the NAD+/NADH ratio, in ATP concentrations and in syndecan-4, perlecan and glypican-1 mRNA expression in HMEC-1 cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Chi Mei Medical Center, Liouying, 201, Taikang, Taikang Village, Liuying District, Tainan 736, Taiwan. mygegon@gmail.com.

ABSTRACT
Prolonged treatment with a large dose of propofol may cause diffuse cellular cytotoxicity; however, the detailed underlying mechanism remains unclear, particularly in vascular endothelial cells. Previous studies showed that a propofol overdose induces endothelial injury and vascular barrier dysfunction. Regarding the important role of endothelial glycocalyx on the maintenance of vascular barrier integrity, we therefore hypothesized that a propofol overdose-induced endothelial barrier dysfunction is caused by impaired endothelial glycocalyx. In vivo, we intraperitoneally injected ICR mice with overdosed propofol, and the results showed that a propofol overdose significantly induced systemic vascular hyperpermeability and reduced the expression of endothelial glycocalyx, syndecan-1, syndecan-4, perlecan mRNA and heparan sulfate (HS) in the vessels of multiple organs. In vitro, a propofol overdose reduced the expression of syndecan-1, syndecan-4, perlecan, glypican-1 mRNA and HS and induced significant decreases in the nicotinamide adenine dinucleotide (NAD+)/NADH ratio and ATP concentrations in human microvascular endothelial cells (HMEC-1). Oligomycin treatment also induced significant decreases in the NAD+/NADH ratio, in ATP concentrations and in syndecan-4, perlecan and glypican-1 mRNA expression in HMEC-1 cells. These results demonstrate that a propofol overdose induces a partially ATP-dependent reduction of endothelial glycocalyx expression and consequently leads to vascular hyperpermeability due to the loss of endothelial barrier functions.

No MeSH data available.


Related in: MedlinePlus

Propofol overdose effect on systemic vascular permeability in ICR mice. Each mouse (n = 6 for each group) was intraperitoneally injected with 10 mg of PBS-diluted propofol in the propofol group or with PBS only in the control group within 5 h. (A) The optical density (OD) values of peritoneal Evans blue and (B) the concentrations of serum albumin in the collected lavaged ascites were analyzed. The values are shown (means ± standard deviation of six mice). * p < 0.05, compared with the control group; (C) Photographs of mouse snouts and inguinal areas show the degree of Evans blue staining in both groups.
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ijms-16-12092-f001: Propofol overdose effect on systemic vascular permeability in ICR mice. Each mouse (n = 6 for each group) was intraperitoneally injected with 10 mg of PBS-diluted propofol in the propofol group or with PBS only in the control group within 5 h. (A) The optical density (OD) values of peritoneal Evans blue and (B) the concentrations of serum albumin in the collected lavaged ascites were analyzed. The values are shown (means ± standard deviation of six mice). * p < 0.05, compared with the control group; (C) Photographs of mouse snouts and inguinal areas show the degree of Evans blue staining in both groups.

Mentions: To examine the effects of a propofol overdose in vascular injury, we used the animal model described in Paragraph 2 of the Animal Experiments subsection of the Experimental Section. The vigor of the mice was only mildly depressed throughout the course of propofol injections. Intravenously-injected Evans blue dye, which binds to serum proteins, was used to determine alterations in vascular permeability. Five hours after the initiation of propofol injection, the OD values of Evans blue (Figure 1A) and albumin levels (Figure 1B) in the lavaged ascites of the propofol mice were significantly (p < 0.05) higher than those in control mice. In addition, because of the vascular leakage of Evans blue stain, the propofol group mice, but not control group mice, had a significant blue gross appearance, especially in the snout, inguinal area and retroperitoneal wall (Figure 1C). Moreover, mice in the propofol group showed vascular endothelial cells undergoing necrosis-like cell death in transmission electron micrographs (Supplementary Data, Figure S1).


Anesthetic propofol overdose causes vascular hyperpermeability by reducing endothelial glycocalyx and ATP production.

Lin MC, Lin CF, Li CF, Sun DP, Wang LY, Hsing CH - Int J Mol Sci (2015)

Propofol overdose effect on systemic vascular permeability in ICR mice. Each mouse (n = 6 for each group) was intraperitoneally injected with 10 mg of PBS-diluted propofol in the propofol group or with PBS only in the control group within 5 h. (A) The optical density (OD) values of peritoneal Evans blue and (B) the concentrations of serum albumin in the collected lavaged ascites were analyzed. The values are shown (means ± standard deviation of six mice). * p < 0.05, compared with the control group; (C) Photographs of mouse snouts and inguinal areas show the degree of Evans blue staining in both groups.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490431&req=5

ijms-16-12092-f001: Propofol overdose effect on systemic vascular permeability in ICR mice. Each mouse (n = 6 for each group) was intraperitoneally injected with 10 mg of PBS-diluted propofol in the propofol group or with PBS only in the control group within 5 h. (A) The optical density (OD) values of peritoneal Evans blue and (B) the concentrations of serum albumin in the collected lavaged ascites were analyzed. The values are shown (means ± standard deviation of six mice). * p < 0.05, compared with the control group; (C) Photographs of mouse snouts and inguinal areas show the degree of Evans blue staining in both groups.
Mentions: To examine the effects of a propofol overdose in vascular injury, we used the animal model described in Paragraph 2 of the Animal Experiments subsection of the Experimental Section. The vigor of the mice was only mildly depressed throughout the course of propofol injections. Intravenously-injected Evans blue dye, which binds to serum proteins, was used to determine alterations in vascular permeability. Five hours after the initiation of propofol injection, the OD values of Evans blue (Figure 1A) and albumin levels (Figure 1B) in the lavaged ascites of the propofol mice were significantly (p < 0.05) higher than those in control mice. In addition, because of the vascular leakage of Evans blue stain, the propofol group mice, but not control group mice, had a significant blue gross appearance, especially in the snout, inguinal area and retroperitoneal wall (Figure 1C). Moreover, mice in the propofol group showed vascular endothelial cells undergoing necrosis-like cell death in transmission electron micrographs (Supplementary Data, Figure S1).

Bottom Line: In vivo, we intraperitoneally injected ICR mice with overdosed propofol, and the results showed that a propofol overdose significantly induced systemic vascular hyperpermeability and reduced the expression of endothelial glycocalyx, syndecan-1, syndecan-4, perlecan mRNA and heparan sulfate (HS) in the vessels of multiple organs.In vitro, a propofol overdose reduced the expression of syndecan-1, syndecan-4, perlecan, glypican-1 mRNA and HS and induced significant decreases in the nicotinamide adenine dinucleotide (NAD+)/NADH ratio and ATP concentrations in human microvascular endothelial cells (HMEC-1).Oligomycin treatment also induced significant decreases in the NAD+/NADH ratio, in ATP concentrations and in syndecan-4, perlecan and glypican-1 mRNA expression in HMEC-1 cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Chi Mei Medical Center, Liouying, 201, Taikang, Taikang Village, Liuying District, Tainan 736, Taiwan. mygegon@gmail.com.

ABSTRACT
Prolonged treatment with a large dose of propofol may cause diffuse cellular cytotoxicity; however, the detailed underlying mechanism remains unclear, particularly in vascular endothelial cells. Previous studies showed that a propofol overdose induces endothelial injury and vascular barrier dysfunction. Regarding the important role of endothelial glycocalyx on the maintenance of vascular barrier integrity, we therefore hypothesized that a propofol overdose-induced endothelial barrier dysfunction is caused by impaired endothelial glycocalyx. In vivo, we intraperitoneally injected ICR mice with overdosed propofol, and the results showed that a propofol overdose significantly induced systemic vascular hyperpermeability and reduced the expression of endothelial glycocalyx, syndecan-1, syndecan-4, perlecan mRNA and heparan sulfate (HS) in the vessels of multiple organs. In vitro, a propofol overdose reduced the expression of syndecan-1, syndecan-4, perlecan, glypican-1 mRNA and HS and induced significant decreases in the nicotinamide adenine dinucleotide (NAD+)/NADH ratio and ATP concentrations in human microvascular endothelial cells (HMEC-1). Oligomycin treatment also induced significant decreases in the NAD+/NADH ratio, in ATP concentrations and in syndecan-4, perlecan and glypican-1 mRNA expression in HMEC-1 cells. These results demonstrate that a propofol overdose induces a partially ATP-dependent reduction of endothelial glycocalyx expression and consequently leads to vascular hyperpermeability due to the loss of endothelial barrier functions.

No MeSH data available.


Related in: MedlinePlus