Propofol attenuates endotoxin-induced endothelial cell injury, angiotensin-converting enzyme shedding, and lung edema

E. Gina Votta-Velis, Richard D. Minshall, David J. Visintine, Maricela Castellon, Irina V. Balyasnikova*

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

BACKGROUND: Acute lung injury (ALI) is a frequent complication in septic patients. Previously, we found that propofol, a highly lipid-soluble anesthetic, attenuates ischemia-reperfusion and oxidative lung injury in the isolated perfused rat lung. In the present study, we evaluated the effect of propofol on endotoxin-induced ALI and endothelial dysfunction. METHODS: The effect of propofol on endotoxin-induced lung endothelial injury was evaluated by plasma and lung tissue homogenate angiotensin I converting enzyme (ACE) activity, pulmonary vascular anti-ACE monoclonal antibody binding, and lung wet weight to body weight ratio (LW/BW). RESULTS: When injected IV into rats, endotoxin produced endothelial cell injury and lung edema, as indicated by: 1) an increase in plasma ACE activity, 2) a decrease in lung ACE activity and anti-ACE monoclonal antibody binding, and 3) an increase in LW/BW. Monoclonal antibody 1A2 was up to 1.8 times more sensitive than other anti-ACE monoclonal antibodies in detecting the decrease in ACE in lungs of endotoxin-treated rats. Pretreatment of rats with a bolus of propofol before endotoxin injection significantly inhibited the increase in ACE activity in the blood, the decrease in ACE activity in the lung, the decrease in anti-ACE monoclonal antibody binding in the lung, and the increase in LW/BW ratio. Importantly, propofol also significantly increased the survival rate of endotoxin-treated animals. The protective effect of propofol in endotoxin-treated animals in vivo was confirmed in vitro, i.e., propofol decreased endothelial cell injury and ACE shedding from endothelial cells in culture. CONCLUSIONS: These results suggest that propofol offers significant protection against endotoxin-induced pulmonary microvessel endothelial cell injury and that anti-ACE monoclonal antibody 1A2 is a sensitive probe for monitoring endothelial dysfunction and ALI during sepsis.

Original languageEnglish (US)
Pages (from-to)1363-1370
Number of pages8
JournalAnesthesia and Analgesia
Volume105
Issue number5
DOIs
StatePublished - Jan 1 2007

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Propofol
Peptidyl-Dipeptidase A
Endotoxins
Edema
Endothelial Cells
Lung
Wounds and Injuries
Monoclonal Antibodies
Acute Lung Injury
Lung Injury
Pulmonary Edema
Microvessels
Reperfusion
Blood Vessels
Anesthetics
Sepsis
Ischemia
Survival Rate
Cell Culture Techniques
Body Weight

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Votta-Velis, E. Gina ; Minshall, Richard D. ; Visintine, David J. ; Castellon, Maricela ; Balyasnikova, Irina V. / Propofol attenuates endotoxin-induced endothelial cell injury, angiotensin-converting enzyme shedding, and lung edema. In: Anesthesia and Analgesia. 2007 ; Vol. 105, No. 5. pp. 1363-1370.
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abstract = "BACKGROUND: Acute lung injury (ALI) is a frequent complication in septic patients. Previously, we found that propofol, a highly lipid-soluble anesthetic, attenuates ischemia-reperfusion and oxidative lung injury in the isolated perfused rat lung. In the present study, we evaluated the effect of propofol on endotoxin-induced ALI and endothelial dysfunction. METHODS: The effect of propofol on endotoxin-induced lung endothelial injury was evaluated by plasma and lung tissue homogenate angiotensin I converting enzyme (ACE) activity, pulmonary vascular anti-ACE monoclonal antibody binding, and lung wet weight to body weight ratio (LW/BW). RESULTS: When injected IV into rats, endotoxin produced endothelial cell injury and lung edema, as indicated by: 1) an increase in plasma ACE activity, 2) a decrease in lung ACE activity and anti-ACE monoclonal antibody binding, and 3) an increase in LW/BW. Monoclonal antibody 1A2 was up to 1.8 times more sensitive than other anti-ACE monoclonal antibodies in detecting the decrease in ACE in lungs of endotoxin-treated rats. Pretreatment of rats with a bolus of propofol before endotoxin injection significantly inhibited the increase in ACE activity in the blood, the decrease in ACE activity in the lung, the decrease in anti-ACE monoclonal antibody binding in the lung, and the increase in LW/BW ratio. Importantly, propofol also significantly increased the survival rate of endotoxin-treated animals. The protective effect of propofol in endotoxin-treated animals in vivo was confirmed in vitro, i.e., propofol decreased endothelial cell injury and ACE shedding from endothelial cells in culture. CONCLUSIONS: These results suggest that propofol offers significant protection against endotoxin-induced pulmonary microvessel endothelial cell injury and that anti-ACE monoclonal antibody 1A2 is a sensitive probe for monitoring endothelial dysfunction and ALI during sepsis.",
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Propofol attenuates endotoxin-induced endothelial cell injury, angiotensin-converting enzyme shedding, and lung edema. / Votta-Velis, E. Gina; Minshall, Richard D.; Visintine, David J.; Castellon, Maricela; Balyasnikova, Irina V.

In: Anesthesia and Analgesia, Vol. 105, No. 5, 01.01.2007, p. 1363-1370.

Research output: Contribution to journalArticle

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AU - Votta-Velis, E. Gina

AU - Minshall, Richard D.

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AB - BACKGROUND: Acute lung injury (ALI) is a frequent complication in septic patients. Previously, we found that propofol, a highly lipid-soluble anesthetic, attenuates ischemia-reperfusion and oxidative lung injury in the isolated perfused rat lung. In the present study, we evaluated the effect of propofol on endotoxin-induced ALI and endothelial dysfunction. METHODS: The effect of propofol on endotoxin-induced lung endothelial injury was evaluated by plasma and lung tissue homogenate angiotensin I converting enzyme (ACE) activity, pulmonary vascular anti-ACE monoclonal antibody binding, and lung wet weight to body weight ratio (LW/BW). RESULTS: When injected IV into rats, endotoxin produced endothelial cell injury and lung edema, as indicated by: 1) an increase in plasma ACE activity, 2) a decrease in lung ACE activity and anti-ACE monoclonal antibody binding, and 3) an increase in LW/BW. Monoclonal antibody 1A2 was up to 1.8 times more sensitive than other anti-ACE monoclonal antibodies in detecting the decrease in ACE in lungs of endotoxin-treated rats. Pretreatment of rats with a bolus of propofol before endotoxin injection significantly inhibited the increase in ACE activity in the blood, the decrease in ACE activity in the lung, the decrease in anti-ACE monoclonal antibody binding in the lung, and the increase in LW/BW ratio. Importantly, propofol also significantly increased the survival rate of endotoxin-treated animals. The protective effect of propofol in endotoxin-treated animals in vivo was confirmed in vitro, i.e., propofol decreased endothelial cell injury and ACE shedding from endothelial cells in culture. CONCLUSIONS: These results suggest that propofol offers significant protection against endotoxin-induced pulmonary microvessel endothelial cell injury and that anti-ACE monoclonal antibody 1A2 is a sensitive probe for monitoring endothelial dysfunction and ALI during sepsis.

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