Inflammation

, Volume 36, Issue 3, pp 680–688

Propofol Attenuates Pulmonary Injury Induced by Collapse and Reventilation of Lung in Rabbits

Authors

  • Hong-Beom Bae
    • Department of Anesthesiology and Pain MedicineChonnam National University, Medical School
  • Mei Li
    • Department of AnesthesiologyThe First Affiliated Hospital, Zhejiang University School of Medicine
  • Seong-Heon Lee
    • Department of Anesthesiology and Pain MedicineChonnam National University, Medical School
  • Cheol-Won Jeong
    • Department of AnesthesiologyChonnam National University School of Dentistry
  • Seok-Jai Kim
    • Department of Anesthesiology and Pain MedicineChonnam National University, Medical School
  • Heong-Seok Kim
    • Department of Anesthesiology and Pain MedicineChonnam National University, Medical School
  • Sung-Su Chung
    • Department of AnesthesiologyChonnam National University School of Dentistry
    • Department of Anesthesiology and Pain MedicineChonnam National University, Medical School
Article

DOI: 10.1007/s10753-012-9592-9

Cite this article as:
Bae, H., Li, M., Lee, S. et al. Inflammation (2013) 36: 680. doi:10.1007/s10753-012-9592-9

Abstract

Propofol is an anesthetic drug with antioxidant and anti-inflammatory properties. We previously found that propofol attenuated lipopolysaccharide-induced acute lung injury in rabbits. This study was performed to evaluate the effects of propofol on lung injury caused by collapse and reventilation in rabbits. The wet/dry weight ratio of the lung, lung injury scores, percentage of polymorphonuclear leukocytes, albumin concentration, malondialdehyde, and interleukin-8 levels in bronchoalveolar lavage fluid were significantly increased in both lungs of the reventilation group. The degree of increase in these parameters was more significant in the right (reventilated) than in the left (non-reventilated) lung. Propofol attenuated these changes. These findings suggest that reventilation of a collapsed lung can cause injury in the contralateral non-reventilated lung as well as the reventilated lung. Propofol may provide a beneficial effect on lung injury induced by collapse and reventilation of the lung.

KEY WORDS

reventilationlung injurypropofolischemia–reperfusioninflammation

INTRODUCTION

Pulmonary edema induced by lung reexpansion is generally believed to develop when a chronically collapsed lung is rapidly reexpanded. However, pulmonary edema can also develop after one-lung ventilation for surgical procedures or may occur in the contralateral lung once reexpansion pulmonary edema develops [13]. Reexpansion pulmonary edema is considered to show a low incidence rate clinically and has diverse clinical features from mild to severe. The mortality rate can reach 20 % in some cases [2, 4, 5].

Although the precise pathophysiology of lung injury by reexpansion is not yet fully elucidated, ischemia–reperfusion (I/R) injury and mechanical stress related to lung inflation have been suggested as possible factors underlying lung injury related to collapse and reexpansion [6]. Perturbation of alveolar surfactant in collapsed and reexpanded lungs has also been suggested to be a factor resulting in lung damage [7]. Several previous studies have suggested that hypoxic pulmonary vasoconstriction followed by reoxygenation may lead to recruitment of neutrophils into the lung and an increase in capillary permeability by release of lipid mediators and immune complexes [4, 8].

Propofol (2,6-diisopropylphenol) has been well established in general anesthesia and sedation for critical care unit and ambulatory surgery. Previous studies have shown that propofol has an ability to scavenge free radical [911]. In addition to its antioxidant effects, propofol has demonstrated immunomodulatory properties, including decreases in the production of inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-6, and decreases in nuclear factor-κB or extracellular signal-regulated kinases activity in various experimental models following exposure to lipopolysaccharide (LPS) [1214]. Propofol also attenuated ALI induced by diverse stimuli, such as intestinal I/R injury, endotoxin, or oleic acid [1518].

In the present study, we examined the effects of propofol on lung injury induced by collapse and reventilation. We also compared the effects between propofol and midazolam because the protective effects of propofol might come from its anesthetic effect [19, 20], rather than its biological effect.

MATERIALS AND METHODS

Animals and Surgical Procedure

Male albino rabbits, 2.0–2.5 kg in weight, were purchased from Damul Science (Daejeon, Korea). The rabbits were kept on a 12-h light/dark cycle with free access to food and water. All experiments were conducted in accordance with Institutional Review Board-approved protocols. Rabbits were allocated to each experimental group (each group n = 14, 7 for analysis of broncholaveolar fluid and 7 for lung histology and wet/dry ratio of lung). Rabbits were initially anesthetized with ketamine hydrochloride [30 mg/kg, intramuscular (IM) injection] and xylazine hydrochloride (3 mg/kg, IM injection). An intravenous angiocatheter was inserted into an ear vein as an administration route for fluids and drugs. Lactated Ringer’s solution was infused at a rate of 8 ml/h until the end of the study. After infiltration of lidocaine, a tracheostomy was performed aseptically, and a 3.5-mm uncuffed endotracheal tube was inserted into the trachea under spontaneous ventilation. After the start of continuous intravenous infusion of ketamine (3 mg/kg/h) and vecuronium bromide (0.05 mg/kg/h) for maintenance of anesthesia and muscle paralysis, rabbits were mechanically ventilated with 50 % oxygen using a pressure-controlled ventilator (IV100B; Sechrist, Anaheim, CA). Inspiratory pressure and positive end-expiratory pressure (PEEP) were set to 18 cmH2O and 3 cmH2O, respectively. The respiratory rate was controlled to produce an initial arterial carbon dioxide tension (PaCO2) of 35–50 mmHg. The arterial catheter was placed in the right carotid artery to monitor the arterial pressure and heart rate, and to harvest blood samples for blood gas analysis and assay. In all groups, after confirming the surgical anesthetic state, a right posterolateral thoracotomy was performed after infiltration with lidocaine, and the right main bronchus was dissected from the surrounding tissue. The rabbits were placed on a heating pad under a radiant heating lamp to maintain the body temperature between 36.5 °C and 37.5 °C at the esophagus.

Experimental Protocols

After the baseline measurements, animals were randomly assigned to one of six groups as follows: The sham group underwent two-lung ventilation for 6 h (Sham); the collapse group underwent collapse of the right lung for 6 h (Collapse); the reventilation group underwent collapse of the right lung for 3 h followed by reventilation of the collapsed right lung for 3 h (Revent); the midazolam-treated group underwent intravenous infusion of a 0.2 mg/kg bolus of midazolam followed by 1 mg/kg/h and collapse of the right lung for 3 h followed by reventilation of the collapsed right lung for 3 h (M-Revent); the low-dose propofol-treated group received an intravenous infusion of a 1 mg/kg bolus of propofol followed by 5 mg/kg/h and collapse of the right lung for 3 h followed by reventilation of the collapsed right lung for 3 h (P5-Revent), and the high-dose propofol-treated group received an intravenous infusion of a 5 mg/kg bolus of propofol followed by 20 mg/kg/h and collapse of the right lung for 3 h followed by reventilation of the collapsed right lung for 3 h (P20-Revent). The propofol dose was selected according to reports of the dose used for sedation in experimental surgery of the rabbit [21, 22].

The collapse and reventilation of the right lung were performed as previously described with modification [23]. Briefly, the right lung was collapsed by right main bronchial clipping about 5 s after disconnecting the endotracheal tube from the ventilator circuit to ensure lung collapse. The rabbits were then mechanically ventilated immediately after right main bronchial clipping. Reventilation was performed by release of the clipping and ventilation with a mechanical ventilator. All groups were infused with an equivalent volume of saline, midazolam, or propofol. The infusion of saline, midazolam, or propofol was started 0.5 h before a thoracotomy and was continued during the experiment.

The mean arterial pressure, heart rate, arterial blood sample for blood cell counts, and blood gas analysis were obtained at −0.5, 0, 1, 2, 3, 4, 5, and 6 h after right main bronchial clipping. The thorax was opened immediately after the rabbits were killed by injection of an overdose of thiamylal, and the lungs were removed en bloc by observers unaware of the nature of the experiment. Seven rabbits in each group were randomly allocated for analysis of bronchoalveolar lavage (BAL) fluid, and examination of lung histology and the W/D weight ratio were performed using the remaining rabbits in each group.

Arterial Blood Gas Analysis and Cell Counts

Arterial blood specimens were analyzed for pulmonary arterial oxygen tension (PaO2) using a blood gas analyzer (GEM Premier Plus; Instrumentation Laboratory, Bedford, MA, USA). The number of peripheral leukocytes was measured using a cell counter (XE 2100; Sysmex, Kobe, Japan).

Preparation of Bronchoalveolar Lavage Fluid

BAL fluid was harvested from both lungs. Through each mainstem bronchus, 30 ml of saline was infused slowly and withdrawn four times. The saline contained ethylene diamine tetraacetic acid-Na and was cooled to 4 °C to prevent metabolism of leukocytes. Indomethacin was added to the BAL fluid to further inhibit metabolism of arachidonic acid to prostaglandins during the analysis. The BAL fluid was analyzed for cell counts and cell differentiation. A cytocentrifuged spin (CF-RD; Sakura, Tokyo, Japan) preparation of the BAL fluid was stained with Wright-Giemsa for cell differentiation. The number of leukocytes in the BAL fluid was counted using a cell counter (XE2100; Sysmex). The fluid was then centrifuged at 250×g at 4 °C for 20 min to remove cells. The cell-free supernatant was divided into several aliquots and stored at −80 °C for measurements of various mediators.

Measurements of Albumin, Malondialdehyde (MDA), and Interleukin (IL)-8 Concentrations in the Bronchoalveolar Lavage Fluid

Albumin concentrations were determined by nephrometry using the immunogloblin G fraction of goat anti-rabbit albumin (Cappel, Durham, NC, USA). IL-8 concentrations were measured using commercially available enzyme-linked immunosorbent assay kits (R&D Systems, Minneapolis, MN, USA), according to the manufacturer’s instructions. The assay kit cross-reacts with rabbit IL-8, and human recombinant IL-8 was used as the standard [24]. Malondialdehyde (MDA) was measured with a BIOXYTECH LPO-586 kit (Oxis International, Portland, OR, USA) using the method of Gerard-Monnier et al. [25]. Briefly, N-methyl-2-phenylindole was added to the BAL fluid, followed by the addition of 12 N HCl and incubation at 45 °C for 60 min. After centrifugation at 2,500×g at 4 °C for 10 min, the absorbance of the clear supernatant was measured at 586 nm. A standard curve was constructed with an MDA standard, and the MDA concentration was expressed in micromoles per liter.

Histopathological Examination

The lower lobes of both lungs were fixed by instillation of 10 % formaldehyde solution through the main bronchus at 20 cmH2O. The lungs were embedded in paraffin, and the sections were stained with hematoxylin and eosin. Lung injury was scored as follows by a pathologist (who was unaware of the nature of the experiment) under light microscopy as previously described [26]—0 (no reaction in alveolar walls), 1 (diffuse reaction in alveolar walls, primarily neutrophilic, no thickening of alveolar walls), 2 (diffuse presence of inflammatory cells [neutrophilic and mononuclear] in alveolar walls and slight thickening), 3 (distinct thickening [two or three times] of the alveolar walls due to the presence of inflammatory cells), 4 (alveolar wall thickening with up to 25 % of the lung consolidated), 5 (alveolar wall thickening with more than 50 % of the lung consolidated).

Wet Weight/Dry Weight Ratio of Lung

The upper lobes of both lungs were weighed and then dried to a constant weight at 60 °C over 48 h in an oven. To assess tissue edema, the W/D ratio was calculated.

Statistical Analysis

Data from experiments are expressed as the mean ± standard deviation (SD) except for the lung injury score, which is represented as a median. SPSS (version 15.0; SPSS Inc, Chicago, USA) was used for all statistical analyses. Data were statistically analyzed using the following tests for multiple comparisons: repeated measures analysis of variance (ANOVA) followed by Dunnett’s test for multiple time point observation within groups, one-way ANOVA with Tukey’s post hoc test for multigroup comparisons, and Wilcoxon’s U test for histological data. A value of p < 0.05 was deemed to be statistically significant.

RESULTS

Propofol Restores the Decrease of Arterial Blood Oxygenation Induced by Collapse and Reexpansion

The mean arterial pressure and heart rate were stable during experimental period, without statistical differences (data not shown). The mean PaO2 was decreased during one-lung ventilation in each group except for the sham operation group. The value of PaO2 did not reach that of the baseline after reventilation, but pretreatment with propofol restored arterial blood oxygenation. However, midazolam, another sedative agent, did not prevent the decrease in arterial oxygenation induced by reventilation (Table 1). Peripheral blood leukocyte counts were increased 2 h after the start of the experiment in all groups, but no difference was found among the groups (Table 1).
Table 1

Changes in arterial oxygenation and peripheral blood leukocyte

Variables

Time after start of one or two lung ventilations

0 h

1 h

2 h

3 h

4 h

5 h

6 h

PaO2 (mmHg)

 Sham

229 ± 12

235 ± 17***

224 ± 32***

216 ± 27***

217 ± 23***

234 ± 15***

233 ± 15***

 Collapse

236 ± 24

98 ± 39*, **

98 ± 41*, **

98 ± 39*, **

99 ± 44*, **

103 ± 41*, **

101 ± 40*, **

 Revent

259 ± 28

89 ± 39*, **

86 ± 34*, **

91 ± 39*, **

211 ± 26*, ***

204 ± 34*, ***

189 ± 26*, **, ***

 M-Revent

245 ± 27

87 ± 41*, **

83 ± 35*, **

87 ± 41*, **

207 ± 22*, ***

200 ± 17*, **, ***

192 ± 26*, **, ***

 P5-Revent

244 ± 39

84 ± 21*, **

90 ± 29*, **

93 ± 27*, **

201 ± 33*, ***

223 ± 44***

230 ± 59***

 P20-Revent

255 ± 27

91 ± 15*, **

90 ± 20*, **

98 ± 26*, **

235 ± 33***

238 ± 28***

248 ± 23***

Leukocyte (×102/mm3)

 Sham

57 ± 12

72 ± 13

91 ± 17*

93 ± 16*

93 ± 20*

96 ± 21*

97 ± 21*

 Collapse

67 ± 17

68 ± 21

97 ± 26*

101 ± 22*

112 ± 19*

113 ± 26*

105 ± 26*

 Revent

66 ± 34

68 ± 31

97 ± 45*

124 ± 57*

123 ± 56*

112 ± 51*

102 ± 40*

 M-Revent

60 ± 25

62 ± 27

96 ± 35*

121 ± 22*

122 ± 17*

117 ± 32*

115 ± 32*

 P5-Revent

54 ± 15

43 ± 11

98 ± 26*

113 ± 29*

82 ± 29*

85 ± 26*

78 ± 16*

 P20-Revent

58 ± 12

51 ± 11

93 ± 22*

121 ± 33*

94 ± 37*

88 ± 31*

83 ± 29*

Values are mean±SD

MAP mean arterial pressure, HR heart rate

*P < 0.05 versus value of the time 0 h in each group. **P < 0.05 versus value of the sham group in each time point. ***P < 0.05 versus value of the collapse group in each time point

Propofol Attenuated the Increase of Neutrophil Recruitment, and IL-8 and MDA Concentration in BAL Fluid Induced by Reventilation Injury

The total cell number in BAL fluid did not change in any of the groups as compared with the sham operation group, and no difference was observed between the right and left lung [right versus left, 0.45 ± 0.05 versus 0.48 ± 0.04 (×103/ml)]. However, pretreatment of propofol attenuated the increase in neutrophil accumulation as well as IL-8 and MDA concentrations in the right reventilated lung in a dose-dependent fashion (Fig. 1). Propofol also attenuated the increase of these mediators in the contralateral left lung (non-reventilated lung) in reventilation group. Interestingly, lung collapse itself (collapse group) did not increase neutrophil accumulation or IL-8 or MDA concentration in BAL fluid as compared with the sham operation group. Midazolam did not attenuate the increase of these mediators induced by reventilation of the lung (Fig. 1).
https://static-content.springer.com/image/art%3A10.1007%2Fs10753-012-9592-9/MediaObjects/10753_2012_9592_Fig1_HTML.gif
Fig. 1

Percentage of polymorphonuclear leukocytes (PMNL) and concentration of IL-8 and MDA in BAL fluid of right (Rt) and left (Lt) lung. BAL fluid was collected 6 h after the start of each experiment. Percentage of PMNL and concentration of IL-8 and MDA in BAL fluid were determined as described in “Materials and Methods.” Sham, sham operation group; Collapse, collapse group underwent collapse of right lung for 6 h; Revent, reventilation group underwent collapse of right lung for 3 h followed by reventilation of collapsed right lung for 3 h; M-Revent, midazolam-treated group underwent collapse of right lung for 3 h followed by reventilation of collapsed right lung for 3 h and midazolam (0.2 mg/kg bolus, then 1 mg/kg/h); P5-Revent, low-dose propofol-treated group underwent collapse of right lung for 3 h followed by reventilation of collapsed right lung for 3 h and propofol (1 mg/kg bolus, then 5 mg/kg/h); P20-Revent, high-dose propofol-treated group underwent collapse of right lung for 3 h followed by reventilation of collapsed right lung for 3 h and propofol (4 mg/kg bolus, then 20 mg/kg/h). Each value represents mean ± SD from seven rabbits. *P < 0.05 versus Sham group, †P < 0.05 versus Revent group, #P < 0.05 versus value of right lung. ‡P < 0.05 versus P5-Revent group.

Propofol Diminished the Increase of Albumin Concentration in BAL Fluid and Wet/Dry Weight Ratio

In the right (reventilated) lung, the albumin concentration and W/D ratio were much than the sham and collapse groups. Pretreatment of propofol diminished the increase in the albumin concentration and W/D ratio in the right (reventilated) lung (Fig. 2). Propofol also attenuated the increase in the albumin concentration and W/D ratio in the contralateral left lung in reventilation group. However, midazolam showed no effect on these changes induced by collapse and reventilation.
https://static-content.springer.com/image/art%3A10.1007%2Fs10753-012-9592-9/MediaObjects/10753_2012_9592_Fig2_HTML.gif
Fig. 2

Concentration of albumin in the BAL fluid and wet to dry weight (W/D) ratio of right (Rt) and left (Lt) lung. BAL fluid was collected at 6 h after the start of each experiment. W/D ratio and albumin concentration in BAL fluid were determined as described in “Materials and Methods.” Each values represent mean ± SD from seven rabbits. *P < 0.05 versus Sham group, †P < 0.05 versus Revent group, #P < 0.05 versus value of right lung.

Histopathologic Grading and Lung Injury Scores

Light microscopic findings in the reventilation group included edema, hemorrhage, thickening of the alveolar wall, and infiltration of inflammatory cells into alveolar spaces (Fig. 3). Propofol attenuated histopathologic changes in the left lung as well as reventilated right lung (Figs. 3 and 4). Assessment of lung injury scores demonstrated that propofol reduced the histopathologic severity of lung injury (Table 2).
https://static-content.springer.com/image/art%3A10.1007%2Fs10753-012-9592-9/MediaObjects/10753_2012_9592_Fig3_HTML.gif
Fig. 3

Representative photomicrographs of the right lung in rabbits showing a Sham, b Collapse, c Revent, d M-Revent, e P5-Revent, and f P20-Revent. Original print magnifications ×400. Arrows indicate thickening of the alveolar walls with presence of neutrophils.

https://static-content.springer.com/image/art%3A10.1007%2Fs10753-012-9592-9/MediaObjects/10753_2012_9592_Fig4_HTML.gif
Fig. 4

Representative photomicrographs of the left lung in rabbits showing a Sham, b Collapse, c Revent, d M-Revent, e P5-Revent, and f P20-Revent. Original print magnifications ×400. Arrows indicated thickening of the alveolar walls with presence of neutrophils.

Table 2

Lung injury score (LIS)

 

Sham

Collapse

Revent

M-Revent

P5-Revent

P20-Revent

LIS

 Left

1(1–2)

1(1–2)

2(1–3)*

2(1–3)*

2(1–2)

1(1–2)**, ***

Right

1(1–2)

1(1–2)

3(2–4)*

3(2–4)*

2(1–3)*, **

2(1–3)*, **

Lung injury was scored 0+ (no damage) to 5+ (maximal damage) according to the criteria described in “Materials and Methods.” Each value represents median (range) from seven rabbits

*P < 0.05 versus value of Sham group, **P < 0.05 versus value of Revent group, ***P < 0.05 versus value of right lung

DISCUSSION

In the present study, we demonstrated that propofol attenuated lung injury induced by collapse and reventilation of the lung. Specifically, propofol pretreatment decreased IL-8 and MDA production and neutrophil accumulation in BAL fluid of the reventilated lung, which are thought to be associated with the protective effects of propofol. Several studies have shown that propofol scavenges free radicals and modulates inflammatory responses in various experimental models [10, 1215, 27].

Although the pathogenic mechanisms underlying reexpanded lung injury are complicated, several factors, including mechanical stress, decreases in surfactants, and I/R injury appear to be involved in reexpanded lung injury. During one-lung ventilation, the collapsed lung may be exposed to sustained hypoxia because of the decrease in the ventilation/perfusion ratio of this lung and subsequent hypoxic pulmonary vasoconstriction. Reventilation of the collapsed lung may result in a sudden increase in oxygen tension that produces lipid peroxidation by ROS and an increase in MDA concentration in BAL fluid, as shown in the present study. A burst of ROS is produced immediately after reperfusion, which may stimulate proinflammatory cytokine release, including IL-8, to promote recruitment of neutrophils to the lung [28]. Additionally, an increase in pulmonary oxygen concentration owing to alveoli reventilation can induce respiratory bursting of primed neutrophils in lung tissue, which further promotes recruitment of neutrophils and increases pulmonary vascular permeability [23, 28]. As another possible factor, collapse and rapid reexpansion can cause nonphysiological stress and strain to pulmonary vessels and alveoli, which may produce inflammatory cytokines and mediators within the lung [29].

IL-8 is one of the most potent neutrophil chemotactic factors and plays a critical role in the development and progression of acute lung injury and I/R injury. Previous studies showed that administration of a neutralizing monoclonal anti-IL-8 antibody decreased the severity of lung injury and lethality by preventing activation and recruitment of neutrophils in in vivo models of exposure to reexpansion, reperfusion, or LPS [3032]. This was evident in this study, with an increase in the IL-8 and percentage of neutrophils in BAL fluid.

In the present study, IL-8 and MDA concentrations and neutrophil accumulation in the BAL fluid of the collapsed lung (collapse group) were not increased as compared with the control group. These results suggest that lung reexpansion significantly augments an increase in these mediators and neutrophil accumulation, although IL-8 production and neutrophil priming may begin in the collapsed lung [23, 32]. An increase in pulmonary oxygen concentration owing to alveoli reventilation can induce respiratory bursting of primed neutrophils in lung tissue, which further promotes recruitment of neutrophils and increases pulmonary vascular permeability [23, 28]. If a more sensitive method had been used in the present study, a modest increase in these mediators and neutrophil accumulation might have been expected in the collapsed lung. Unilateral collapse and reventilation of the lung also resulted in inflammatory responses not only in the reventilated lung but also in the contralateral lung, in which these responses were not as severe as those observed in the reventilated lung, consistent with previous findings [33]. These results are consistent with several studies showing that remote I/R injury, such as in the intestine and liver, may also cause lung and systemic organ injury [15, 27].

The present study has a few limitations. First, the global increase in leukocyte numbers over time in all groups suggests that there was a systemic pro-inflammatory response caused by surgical stress in this model. We cannot exclude the possibility that inflammatory mediators released by surgical stress before reexpansion might amplify reexpansion lung injury. Second, because one-lung ventilation with high tidal volumes and zero PEEP is injurious in the isolated rabbit lung model [34], the peak inspiratory pressure and PEEP were set to avoid lung collapse and overdistension during the experiment. Consequently, arterial carbon dioxide tension significantly increased (data not shown) after single-lung ventilation. Therefore, we could not exclude the effects of hypercapnea on I/R-induced lung injury. Third, we did not compare the effect between propofol and volatile anesthetics in our model. Recent studies have shown that volatile anesthetics including sevoflurane protect the lungs better than propofol during one-lung ventilation [35, 36], although other studies have demonstrated that volatile anesthetics augment the release of alveolar inflammatory cytokines during mechanical ventilation [37, 38]. However, propofol has a higher antioxidant capacity than volatile anesthetics and preserves immune-modulatory function of alveolar macrophages compared with volatile anesthetics during mechanical ventilation [36, 39]. It suggests that propofol as a sedative drug may have a beneficial effect in patients with reduced antioxidant capacity.

In conclusion, although the pathogenesis of lung injury induced by collapse and reexpansion is complicated, activation of neutrophils or macrophages by reventilation of the lung partly contributes to the development of reexpansion lung injury via the release of ROS, various proteases, or inflammatory mediators. It is possible that propofol may affect various steps differently. The present study shows that propofol may have a beneficial effect in patients with reduced antioxidant capacity.

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© Springer Science+Business Media New York 2013