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CARDIOVASCULAR ANESTHESIOLOGY

The Comparative Abilities of Propofol and Sevoflurane to Modulate Inflammation and Oxidative Stress in the Kidney After Aortic Cross-Clamping

Pilar Sánchez-Conde, MD^*, José M. Rodríguez-López, MD^*, Juan L. Nicolás, MBBS, Francisco S. Lozano, MD, Francisco J. García-Criado, MD, Carlos Cascajo, MD, Rogelio González-Sarmiento, MD, and Clemente Muriel, MD^*

From the *Department of Anesthesiology, University Hospital of Salamanca, Salamanca, Spain; Department of Anesthesiology, Rodríguez-Chamorro Hospital, Zamora, Spain; Departments of Surgery, and Medicine, University Hospital of Salamanca, Salamanca, Spain.

Address correspondence and reprint requests to José María Rodríguez-López, MD, Servicio de Anestesiología, Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain. Address e-mail to jmrodlop{at}terra.es.

Abstract

BACKGROUND: Propofol has been reported to provide protection against ischemia–reperfusion injury. Nuclear transcription factor kappa B (NFB) plays a key role in oxidative stress and the inflammatory response during ischemia–reperfusion. We compared the effect of propofol with sevoflurane on kidney NFB expression and systemic inflammatory responses induced by aortic clamping.

METHODS: Twenty piglets were divided into four groups: sham surgery group with propofol (group SP, n = 5); sham group with sevoflurane (group SS, n = 5); and suprarenal clamping for 30 min with aorta–aortic bypass under propofol (group CP, n = 5) or sevoflurane (group CS, n = 5) anesthesia. Propofol was administered at 4 mg · kg^–1 · h^–1 IV and sevoflurane given at 1.5% inspiratory concentration. Peripheral blood and kidney biopsies were taken before the start of surgery, 15 min after unclamping the aorta, 24, 48, 72 h, and 7 days after surgery. Plasma creatinine, myeloperoxidase, tumor necrosis factor-, interleukin 1-β; and kidney superoxide anion and superoxidase dismutase were measured. The expression of inducible nitric oxide synthase and renal tissue NFB was measured using Western blotting.

RESULTS: Compared with the CS group, animals in the CP group had lower concentrations of myeloperoxidase, tumor necrosis factor-, interleukin 1β, superoxide anion, superoxidase dismutase (P < 0.05) from 24 to 72 h after surgery and diminished NFB expression and inducible nitric oxide synthase activity (P < 0.05) at 48 and 72 h after surgery, respectively.

CONCLUSIONS: Compared with sevoflurane, propofol administration during suprarenal aortic clamping and unclamping led to modulation of markers of inflammation and decreased NFB expression.

Renal failure is a major source of morbidity and mortality after abdominal aortic surgery when supra- or infrarenal aortic clamping1 issued. Reintroduction of oxygenated blood after organ ischemia results in the activation of multiple cell injury pathways that contribute to organ dysfunction, including those resulting in the production of oxygen-derived free radicals (OFRs).2,3 Propofol and volatile anesthetics have been reported to modulate ischemia–reperfusion (I/R) injury suggesting their potential for organ protection during surgery involving abdominal aortic clamping and possibly a means for improving patient outcome.4 Propofol is a lipophilic hypnotic drug with proven antioxidant activity in both in vitro and in vivo studies resulting in part from its chemical structure, which is similar to the natural antioxidant vitamin E.5,6 Several studies have demonstrated that propofol acts as a scavenger of OFRs, decreasing lipid peroxidation in the liver, kidney, heart, and lung.7 We recently reported that in an in vivo experimental model of reversible renal I/R, propofol anesthesia is associated with diminished neutrophil infiltration, lower plasma proinflammatory cytokine levels, less production of OFRs, less lipid peroxidation, and reduced inducible nitric oxide synthase (iNOS) activity compared with sevoflurane anesthesia.8 Nuclear transcription factor kappa B (NFB) is a pivotal transcription factor that plays a key role in oxidative stress and inflammatory responses activated during IR. Activation of NFB induces expression of a variety of gene products, including cytokines and proinflammatory enzymes, that lead to I/R injury. A study by Zhong et al.9 suggests that sevoflurane attenuates the activation of NFB and subsequently suppresses the expression of NFB-regulated inflammatory genes during reperfusion.

Using a pig experimental model, we hypothesized that propofol anesthesia during suprarenal aortic clamping would lead to a reduction in the expression of NFB by the kidney and, thus, modulation of systemic inflammation resulting from organ I/R compared with sevoflurane anesthesia.

METHODS

This study was approved by the Committee for Animal Research of the Hospital Universitario de Salamanca, Spain. We studied 20 male pigs (3–4 mo old; 20–25 kg body weight), after they were stabilized for at least 1 wk at the Biohealth Centre of Animal Research at the University of Salamanca. The animals were subjected to light/dark cycles of 12 h, a constant temperature (21°C), and controlled ingestion of food and water. Twelve hours before the start of the experiments, the animals were fasted, providing only water ad libitum.

Study Protocol
The animals were divided into four groups: sham surgery group with propofol (n = 5); sham group with sevoflurane (n = 5); and suprarenal clamping with aorta–aortic bypass under propofol (group CP, n = 5) or sevoflurane (group CS, n = 5) anesthesia. All animals were premedicated with IM ketamine hydrochloride (20 mg/kg), diazepam (0.5 mg/kg), and atropine (0.05 mg/kg). A dorsal ear vein was then cannulated with a 20-guage IV catheter, and the animals received propofol 1.5 mg/kg IV until hypnosis was achieved. Orotracheal intubation was then performed and the animals’ lungs ventilated (Boyle 2000 anesthesia station, Datex-Ohmeda, Essex, UK) with a tidal volume of 10 mL/kg, respiratory rate of 15 resp/min, inspiration/expiration rate 1:2, and a 50% oxygen with air mixture. The animals received an IV infusion of lactated Ringer’s solution (10 mL · kg^–1 · h^–1) and 1 g of cefazolin IV via a double-lumen polyethylene catheter inserted in the internal jugular vein. Anesthesia was maintained with propofol 4 mg · kg^–1 · h^–1 IV or sevoflurane 1.5% inspiratory concentration. All animals received mivacurium chloride 0.2 mg/kg IV followed by an infusion of 1 mg · kg^–1 · h^–1 and fentanyl chloride at 2 µg · kg^–1 · h^–1 IV. Hemodynamic monitoring consisted of direct arterial blood pressure via a 20-guage catheter in the carotid artery (Monitor Dash 3000, Marquette Medical Systems, Freiburg, Germany) and an electrocardiogram. Depth of anesthesia was determined by performing palpebral and corneal reflexes before mivacurium administration.10 Adequacy of anesthesia during maintenance was assessed based on hemodynamic responses and additional fentanyl (50 µg) given if the animals were judged to be inadequately anesthetized.

In the sham groups, the surgical technique consisted of a median laparotomy with retroperitoneal dissection to expose the abdominal aorta from the renal arteries to the aortic bifurcation. The same surgical technique was used in the aortic clamping groups. In the latter animals, after administration of sodium heparin 1 mg/kg IV, aortic cross-clamps were applied to the aorta above the renal arteries but below the superior mesenteric artery and to the distal aorta above the iliac arteries. Immediately after cross-clamping, two 1-cm aortotomies were performed for aorto–aortic bypass from the infrarenal aorta (lateroterminal) to the distal aorta and preiliac arteries (terminolateral). A 6-mm diameter collagen-lined Dacron graft (previously submerged for 15 min in a solution of rifampicin) was sutured in an end-to-side fashion. After 30 min of cross-clamping, the aortic clamps were removed and sodium bicarbonate 1 mEq/kg was administered IV. Hemostasis was restored and the laparotomy was closed. Mivacurium infusion was stopped and propofol or sevoflurane administration also terminated. When the animals recovered spontaneous breathing, the tracheal tube was removed, and they were taken to the animal care facility. Metamizol (1.2 g IV) was administered as a postoperative analgesic.

Measurements
Peripheral blood and kidney biopsies were taken at the following time points: before the start of surgery; 15 min after reperfusion (in the sham groups the values for baseline and reperfusion were the same because I/R was not performed in these groups); 24, 48, and 72 h after surgery, and on the 7th day after surgery. From 24 h until 72 h after surgery, percutaneous renal biopsies were performed after first giving ketamine hydrochloride (20 mg/kg) IM with diazepam (0.5 mg/kg) and atropine (0.05 mg/kg). A Bard Monopty Biopsy Instrument (Covington, GA) was used and the needle was guided by ultrasonography (Sigma AC Start; Kontron Instruments, Montigny le Bretoneux, France). The following determinations were made: plasma creatinine levels; renal myeloperoxidase (MPO) as a measure of the degree of neutrophil infiltration into tissues; plasma proinflammatory cytokine levels [tumor necrosis factor (TNF-), interleukin (IL)-1β]; renal superoxide anion (SOA) and its detoxifying enzyme superoxide-dismutase (SOD). The expression of NFB and iNOS activity was assessed 48 and 72 h after surgery, respectively, from the renal biopsy material. On the 7th day after surgery, the animals were anesthetized using the techniques described above and, after taking blood and kidney samples, were killed by IV administration of potassium chloride (40 mEq).

Assays
All assays were performed by an investigator blinded to study group assignment. Plasma creatinine concentrations were determined, using a Hitachi 747-200 automatic analyzer (Boerhinger Mannheim, Indianapolis, IN). The presence of MPO, an enzyme specific for neutrophils and used as an index for the assessment of neutrophil accumulation, was determined from the kidney biopsy tissue with the method of Bradley et al.,11 modified by Mullane et al.12 as previously reported.13 After collection, the samples were immediately placed on ice, homogenized in phosphate buffer, frozen in liquid nitrogen, and stored at –80°C for batch analysis. A double-beam spectrophotometer was used for MPO assay. The lower limit of detection of the assay for MPO was 5 UI/g tis. Intra- and interassay coefficients of variation were below 9%.

Commercial kits were used for the determination of TNF- and IL-1β (Test-Pig ELISA Kit; Biomed, Diepenbeek, Belgium) based on enzyme-linked immunosorbent assay (ELISA). Recordings were done on a plate reader (GEST, General Elisa System Technology, Menarini Labs, Badalona, Spain) for the automatic ELISA technique in triplicate. The blood samples were immediately centrifuged and the serum separated, divided into aliquots, and placed in Eppendorf tubes and frozen at –80°C until assay. The ELISA assay was performed in a 96-well plate with respective anticytokine monoclonal antibody adhered to each well. Serum samples or cytokine standard solutions were added in duplicate per well together with the corresponding blanks. After washing the plates with Wash Buffer to remove nonadhering material, polyclonal anticytokine-conjugated peroxidase was added, the plates washed again, and the substrate solution was added, thus initiating the peroxidase catalysis. The color change was achieved by acidification. Absorbance was measured on a plate reader (GEST: General Elisa System Technology, Menarini Labs, Badalona, Spain) at a wavelength of 450 nm. The lower limit of detection of the assay for TNF- and IL-1β were 11.2 and 4.4 pg/mL, respectively. Intra- and interassay coefficients of variation for TNF- and IL-1β were below 10%.

Kidney biopsy tissue was placed in a 0.05 M monobasic potassium phosphate buffer at a temperature between 0°C and 4°C to minimize oxidative processes. They were then weighed and homogenized by adding 10 mL of the buffer described per each gram of tissue. The homogenates were centrifuged at 100,000g for 60 min at 4°C. The soluble fraction obtained was divided into aliquots and placed in Eppendorf tubes and stored at –80°C until sample processing. Determination of the rate of SOA production was accomplished with a modification of the technique described by Forman and Boveris.14 Protein concentrations were measured spectrophotometrically, using the Bradford method.15 The enzyme activity of SOD was measured following the technique described by Misra and Fridovich16 as previously reported.13 The lower limit of detection of the assays for SOA and SOD was 3.2 nmol/mg protein/mn and 24.4 U/mg protein, respectively. Intra- and interassay coefficients of variation for SOA and SOD were below 9%.

Kidney tissue obtained by percutaneous biopsy were analyzed for iNOS and NFkB expression using Western blotting. The samples were immediately frozen in liquid nitrogen and stored in sealed tubes at –80°C. After this, the frozen material was sliced and added to a cell lysis solution at 4°C according to the samples—3 mL/g—(140 mmol/L NaCl, 15 mmol/L EDTA, 10% glycerol, 20 mmol/L Tris base [pH 8]). Two protease inhibitors were added to this buffer solution: 2 mmol/L phenylmethylsulfonylfluoride and 50 µg/mL of trypsin inhibitor. Samples were then homogenized at 4°C and the lysed samples introduced through a 21-gauge needle into an Eppendorf tube. Samples were kept on ice for 30–60 min and then centrifuged at 4°C and 15,000g for 20 min (Mikro 12–24 centrifuge, Hettich, Germany). The supernatant was conserved at –20°C in aliquots for the determination of protein concentrations with the method of Bradford15 and for Western blotting. Primary antibodies for iNOS and for the NFB P65 subunit were used for each sample respectively (Santa Cruz Biotechnology, Santa Cruz, CA). After digitization of the radioautographs (Scanner® Model VM 6552 Trust, Dordrecht, the Netherlands, and the Adobe Photoshop^TM 3.0 program, Uxbridge, UK), optical densities were read with the MacBAS V2.2 program (Fuji Medical Systems Inc., Stamdford, CT).

Statistical Analysis
The results are expressed as means ± se of the mean. Data were analyzed by ANOVA, using the Fisher’s exact test and analysis of variance (Student– Newman–Keuls or Scheffé test for normally distributed data and the Kruskall–Wallis Z test for data not normally distributed). Statistical significance was for values of P < 0.05. Sample size was determined by using data from our earlier study.8 We estimated that for detection of 100% difference in the most important markers of inflammation (MPO, TNF-, IL-1β, SOA, and SOD) between the mean for the surgical groups and the mean for sham groups, a maximum of five animals per group would provide a power of 0.8.

RESULTS

Survival and Hemodynamic Data
All animals survived without complications until the 7th postoperative day. There were no significant differences in hemodynamic measurements between the two clamping groups of animals (data not shown).

Kidney Function
Serum creatinine data are shown in Figure 1. Compared with sham operated animals, there was an increase (P < 0.01) in plasma creatinine after surgery for both cross-clamping groups at all times after surgery until the measurements on the 7th postoperative day. The increase in creatinine was less (P < 0.05) in group CP compared with group CS between 24 and 72 h after surgery.

View larger version (8K): [in this window] [in a new window]   Figure 1. Serum creatinine levels by groups and study time period. SP: sham-propofol; SS: sham-sevoflurane; CP: clamping-propofol; CS: clamping-sevoflurane. Data are presented as mean ± sem. *P < 0.01 versus SP and SS groups. #P < 0.05 versus CP group.

MPO Activity in Kidney Tissue
The results for the MPO assay are shown in Figure 2. Compared with the sham operated groups, there was an increase in MPO at all time points after surgery in groups CP and CS (P < 0.01). The maximal values were observed 72 h after surgery. Levels of MPO were higher in group CS compared with group CP 24, 48, and 72 h after surgery (P < 0.05).

View larger version (8K): [in this window] [in a new window]   Figure 2. Myeloperoxidase (MPO) activity in renal tissue, by groups and study time period. SP: sham-propofol; SS: sham-sevoflurane; CP: clamping-propofol; CS: clamping-sevoflurane. Data are presented as mean ± sem. *P < 0.01 versus SP and SS groups. #P < 0.05 versus CP group.

Plasma Proinflammatory Cytokine Levels
Plasma proinflammatory cytokine levels are shown in Figures 3 and 4. Compared with the sham groups, plasma TNF- and IL-1β levels were higher in both cross-clamping groups at all study time points after surgery (P < 0.05). Compared with group CS, plasma cytokine levels were lower in group CP 24, 48, and 72 h after surgery (P < 0.05). The maximal plasma proinflammatory cytokines levels were observed 72 h after surgery.

View larger version (11K): [in this window] [in a new window]   Figure 3. Plasma tumor necrosis factor- (TNF–) by groups and study time period. SP: sham-propofol; SS: sham-sevoflurane; CP: clamping-propofol; CS: clamping-sevoflurane. Data are presented as mean ± sem. *P < 0.01 versus SP and SS groups. #P < 0.05 versus CP group.

View larger version (11K): [in this window] [in a new window]   Figure 4. Plasma Interleukin 1 β (IL-1β) by groups and study time period. SP: sham-propofol; SS: sham-sevoflurane; CP: clamping-propofol; CS: clamping-sevoflurane. Data are presented as mean ± sem. *P < 0.01 versus SP and SS groups. #P < 0.05 versus CP group.

View larger version (10K): [in this window] [in a new window]   Figure 5. Superoxide anion (SOA) levels in renal tissue, by groups and study time period. SP: sham-propofol; SS: sham-sevoflurane; CP: clamping-propofol; CS: clamping-sevoflurane. Data are presented as mean ± sem. *P < 0.01 versus SP and SS groups. #P < 0.05 versus CP group.

View larger version (13K): [in this window] [in a new window]   Figure 6. Superoxide dismutase (SOD) levels in renal tissue, by groups and study time period. SP: sham-propofol; SS: sham-sevoflurane; CP: clamping-propofol; CS: clamping-sevoflurane. Data are presented as mean ± sem *P < 0.01 versus SP and SS groups. #P < 0.05 versus CP group.

NFB Expression in Kidney Tissue

View larger version (10K): [in this window] [in a new window]   Figure 7. Nuclear transcriptional factor kappa B (NFB) expression in the kidney 48 h after surgery. Top: a representative Western blot for NFB. Bottom: mean ± sem of four different blots. *P < 0.01 versus SP and SS groups. #P < 0.05 versus CP group. SP: Sham-Propofol; SS: sham-sevoflurane; CP: clamping-propofol; CS: clamping-sevoflurane.

iNOS Expression in Kidney Tissue
Western blot results for iNOS expression assay are shown in Figure 8. There was an increase in the expression of iNOS in kidney tissue in the aorta clamping groups compared with the sham groups (P < 0.01) 72 h after surgery. Kidney iNOS levels 72 h after surgery were higher in group CS compared with group CS (P < 0.05).

View larger version (11K): [in this window] [in a new window]   Figure 8. Inducible nitric oxide synthase (iNOS) expression in the kidney 72 h after surgery. Top: a representative Western blot for iNOS. Bottom: mean ± sem of four different blots. *P < 0.01 versus SP and SS groups. #P < 0.05 versus CP group. SP: sham-propofol; SS: sham-sevoflurane; CP: clamping-propofol; CS: clamping-sevoflurane.

DISCUSSION

Abdominal aortic surgery with aortic cross-clamping is associated with significant morbidity that may result partially from an I/R induced inflammatory response.1 Aortic clamping elicits the release of cytokines that exert a systemic effect that lasts as long as 1 wk. Increased cytokine levels are correlated with organ failure and mortality (e.g., TNF-).17 Further, complications secondary to aortic clamping seem to be neutrophil-dependent,18 mainly mediated by the activation of resident neutrophils. Our findings show that renal ischemia after suprarenal aortic clamping induces kidney damage, characterized by an increase in plasma creatinine levels, neutrophil infiltration (as assessed by the increased MPO activity), an increase in OFR production (SOA and SOD), an increase in plasma cytokine levels, and an increase in the expression of NFB and iNOS. These results further show that anesthesia with propofol, modulated after I/R injury, compared with sevoflurane anesthesia, as demonstrated by lower levels of proinflammatory cytokines, decreased neutrophil infiltration and OFR production in kidney tissue, and decreased kidney NFB and iNOS expression in the propofol treated animals. These finding were associated with lower plasma creatinine levels after surgery for animals given propofol versus sevoflurane.

NFB is a transcription factor that plays a key role in oxidative stress and inflammatory responses during I/R. NFB activation requires either the degradation of its cytoplasmic inhibitor IB or proteolytic cleavage of the NFB protein inhibitor p105. Free NFB dimers then translocate to the nucleus and activate target genes such as cytokines (e.g., TNF-, IL-1), adhesion molecules (e.g., ICAM-1), and proinflammatory enzymes (e.g., iNOS). This transcriptional pathway activation (NFB/IB) is now known to be directly involved in most inflammatory processes, and is responsible for signal transduction to the nucleus for the expression of many cytokines (TNF-, IL-1β) and enzymes (iNOS).19 Indeed, NFB has been purported to be the most important transcriptional factor in the regulation of iNOS transcription in several cell types. Activation of iNOS is associated with an excessive production of nitric oxide (NO). The role of NO in I/R is controversial but its cytotoxic effect is believed to be due to the formation of peroxynitrites.20 NO derived from iNOS activation during reperfusion seems to play a deleterious role in renal damage after I/R, since specific iNOS inhibition reduces the renal injury induced by I/R.21 In many tissues, I/R results in neutrophil recruitment/adhesion to the endothelium surface, leading to production of cytokines, such as TNF-, and OFRs, such as SOA. Both TNF- and SOA induce a transcriptional signaling pathway in the endothelium and in neutrophils, resulting in NFB activation.19

As shown by both in vitro and in vivo studies, the antioxidant activity of propofol results in part from its phenolic chemical structure, which is similar to the natural antioxidant, vitamin E.5,6 Immunomodulatory effects of propofol, such as suppression of respiratory burst of neutrophils, may be caused by the intralipid carrier of the drug, whereas other actions, such its ability to scavenge free radicals, seems to be a property of the propofol molecule itself.6,7 In vitro studies using cell cultures of macrophages in a medium with lipopolysaccharide (an inducer of iNOS) report that propofol in clinical therapeutic concentrations inhibit iNOS mRNA transcription and iNOS activity. All this suggests a possible direct action of propofol at transcription factor level that would modulate iNOS activity.22 Studies by De la Cruz et al.23,24 suggest that propofol is associated with less lipid peroxidation and reduced iNOS activity.

Two limitations of this study should be mentioned. First, we did not perform all the determinations at the same time. The NFB assay, for example, was only determined at 48-h postsurgery. This limitation was due to technical and economic reasons. Second, NFB analysis is incomplete because we measured p65 levels in total kidney homogenate, and the measurement of p65 by Western blot in total kidney protein does not provide an accurate indication of NFB transcriptional activity. p65 must translocate to the nucleus, and we have considered that the increase in p65 in whole kidney protein reflects an increase in the nucleus.

In conclusion, the results of the present study indicate that propofol may favorably modulate the inflammatory consequences of I/R that follow aortic clamping compared with sevoflurane. These effects might result in renal protection as measured by changes in serum creatinine after surgery. The possible mechanisms involved with this favorable effect of propofol appear, in part, to be an attenuated expression of NFB induced by I/R, leading to less production of proinflammatory cytokines, neutrophil infiltration, and OFR production. Whether this protective action exerts a beneficial clinical effect in patients requiring general anesthesia during major aortic surgery requires further investigation.

ACKNOWLEDGMENTS

We thank Mark Anderson and Nicholas Skinner from the University Transfer Office for technical assistance.

Footnotes

Accepted for publication October 8, 2007.

Supported by the Instituto de Salud Carlos III and grant FISS 00/1093 from the Ministerio de Sanidad, Spain.

There is no relationship between the authors and any associated company or organization.

REFERENCES

1. Weight SC, Bell PRF, Nicholson ML. Renal ischaemia-reperfusion injury. Br J Surg 1996;83:162–70[Web of Science][Medline]
2. Runzer TD, Ansley DM, Godin DV, Chambers GK. Tissue antioxidant capacity during anesthesia: propofol enhances in vivo red cell and tissue antioxidant capacity in a rat model. Anesth Analg 2002;94:89–93[Abstract/Free Full Text]
3. Huang CJ, Slovin PN, Nielsen RB, Skimming JW. Diprivan attenuates the cytotoxicity of nitric oxide in cultured human bronchial epithelial cells. Intensive Care Med 2002;28:1145–50[Web of Science][Medline]
4. Kato R, Foex P. Myocardial protection by anesthetic agents against ischemia-reperfusion injury: an updater for anaesthesiologist. Can J Anaesth 2002;49:777–91[Web of Science][Medline]
5. Ansley DM, Lee JU, Godin VD, Garnett ME, Qayumi AK. Propofol enhances red cell antioxidant capacity in swine and humans. Can J Anaesth 1998;45:233–9[Web of Science][Medline]
6. Murphy PG, Myers DS, Davies MJ, Webster NR, Jones JG. The antioxidant potential of propofol (2,6-diisopropylphenol). Br J Anaesth 1992;68:613–8[Abstract/Free Full Text]
7. Kahraman S, Demiryürek AT. Propofol is a peroxynitrite scavenger. Anesth Analg 1997;84:1127–9[Web of Science][Medline]
8. Rodriguez-Lopez JM, Sanchez-Conde P, Lozano FS, Nicolas JL, García-Criado FJ, Cascajo C, Muriel C. Laboratory investigation: effects of propofol on the systemic inflammatory response during aortic surgery. Can J Anaesth 2006;53:701–10[Web of Science][Medline]
9. Zhong C, Zhou Y, Liu H. Nuclear factor B and anesthetic preconditioning during myocardial ischemia-reperfusion. Anesthesiology 2004;100:540–6[Web of Science][Medline]
10. Hall LW, Clarke KW, Trim CM Anaesthesia of the pig. In: Hall LW, ed. Veterinary anaesthesia. 10th ed. London: Saunders; 2000:367–83
11. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982;78:206–9[Web of Science][Medline]
12. Mullane KM, Kraemer R, Smith B. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J Pharmacol Meth 1985;14:157–67[Web of Science][Medline]
13. García-Criado FJ, Eleno N, Santos-Benito F, Valdunciel JJ, Reverte M, Lozano-Sánchez FS, Ludeña MD, Gómez-Alonso A, López-Novoa JM. Protective effect of exogenous nitric oxide on the renal function and inflammatory response in a model of ischemia-reperfusion. Transplantation 1998;66:982–90[Web of Science][Medline]
14. Forman HJ, Boveris A Superoxide radical and hydrogen peroxide in mitochondria. In: Pryor WA, ed. Free radicals in biology. Vol. 5. New York: Academic Press; 1982:65–90
15. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantites of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–54[Web of Science][Medline]
16. Misra HP, Fridovich Y. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972;247:3170–5[Abstract/Free Full Text]
17. Adam D, Lee AJ, Bradbury AW, Ross J. Elevated levels of soluble tumor necrosis factor receptors are associated with increased mortality rates in patients who undergo operation for ruptured abdominal aortic aneurysm. J Vasc Surg 2000;31:514–9[Web of Science][Medline]
18. Barry MC, Kelly C, Burke P, Sheehan SJ, Redmond HP, Bouchier-Hayes D. Immunological and physiological responses to aortic surgery: effect of reperfusion on neutrophil and monocyte activation and pulmonary function. Br J Surg 1997;84:513–9[Web of Science][Medline]
19. Lozano FS, Barros MB, García-Criado FJ, Gomez-Alonso A. Exogenous nitric oxide can control SIRS and downregulate NFB. J Surg Res 2005;124:52–8[Web of Science][Medline]
20. Xie QW, Kashiwabara Y, Nathan C. Role of transcription factor NF-B/Rel in induction of nitric oxide synthase. J Biol Chem 1994;269:4705–8[Abstract/Free Full Text]
21. Chatterjee PK, Patel NS, Kvale EO, Cuzzocrea S, Brown PA, Stewart KN, Mota-Filipe H, Thiemermann C. Inhibition of inducible nitric oxide synthase reduces renal ischemia/ reperfusion injury. Kidney Int 2002;61:862–71[Web of Science][Medline]
22. Chen RM, Wu GJ, Tai YT, Sun WZ, Lin YL, Jean WC, Chen TL. Propofol reduces nitric oxide biosynthesis in lipopolysaccharide-activated macrophages by downregulating the expression of inducible nitric oxide synthase. Arch Toxicol 2003;77:418–23[Web of Science][Medline]
23. De La Cruz JP, Villalobos MA, Sedeño G, Sánchez de la Cuesta F. Effect of propofol on oxidative stress in an in vitro model of anoxia-reoxigenation in the rat brain. Brain Res 1998;800:136–44[Web of Science][Medline]
24. De la Cruz JP, Sedeño G, Carmona JA, Sánchez de la Cuesta F. The in vitro effects of propofol on tisular oxidative stress in the rat. Anesth Analg 1998;87:1141–6[Abstract/Free Full Text]

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