Propofol exerts protective effects on the acute lung injury induced by endotoxin in rats.
Acute lung injury (ALI) is a major culprit of mortality in endotoxemia. Propofol has been commonly used in critical ill patients for sedation. This experiment attempted to elucidate the effects and possible mechanisms of propofol on the ALI induced by endotoxin. Experimentations were carried out using anesthetized, ventilated rats and isolated perfused rat lungs. Endotoxemia was induced by intravenous lipopolysaccharide (LPS, 10 mg kg(-1)). Various groups of rats received infusion of physiological saline solution (PSS) and LPS. Five min after LPS, propofol at low dose (5 mg kg(-1)h(-1)) or high dose (10 mg kg(-1)h(-1)) was infused for 6h. In isolated perfused rat lungs, PSS, LPS, and propofol (30 or 60 mg kg(-1)) were added into the perfusion circuit. During or after 6h observation, we determined the lung weight (LW)/body weight ratio, LW gain, exhaled nitric oxide (NO) and protein concentration in broncheoalveolar lavage. Lung pathology was evaluated to quantify the lung injury score. Plasma nitrate/nitrite, methyl guanidine (MG), tumor necrosis factor(alpha), and interleukin-1(beta) were examined. Blood leukocytes were counted. Capillary filtration coefficient (K(fc)) was obtained in isolated perfused lungs. Posttreatment of propofol at low or high dose attenuated or prevented the extent of ALI. It also reduced the plasma nitrate/nitrite, MG, and pro-inflammatory cytokines including tumor necrosis factor(alpha) (TNF(alpha)) and interleukin-1(beta) (IL-1(beta)). In the isolated perfused rat lungs, propofol significantly reduced the LPS-induced increase in K(fc). This agent did not affect the leukocytopenia caused by LPS. Accordingly, the effects of propofol on the ALI were not related to leukocyte activation or sequestration. Our results suggest that propofol exerts protective effect on the endotoxin-induced ALI. The mechanisms of actions may be mediated through inhibition on the release of pro-inflammatory cytokines, free radicals and NO. In addition, propofol abrogates the microvascular leakage of water and protein in the lungs. The results imply that the use of propofol in critically ill is not only for sedation, but also useful for the prevention of inflammatory progression and lung damage.
Chu
Chia-Hsiang
CH
Department of Pediatrics, Tzu Chi Hospital, Hualien, Taiwan.
David Liu
Demeral
D
Hsu
Yung-Hsiang
YH
Lee
Kuan-Chiao
KC
Chen
Hsing I
HI
D000208:Acute Disease; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004731:Endotoxins; D005609:Free Radicals / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000187:drug effects / Q000378:metabolism; D007970:Leukopenia / Q000503:physiopathology; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008760:Methylguanidine / Q000097:blood; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D004731:Endotoxins; D005609:Free Radicals; D006993:Hypnotics and Sedatives; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D008760:Methylguanidine; D015742:Propofol