Ann Thorac Surg 2001;71:801-806
© 2001 The Society of Thoracic Surgeons
Original article: cardiovascular
Proinflammatory cytokines in cerebrospinal fluid in repair of thoracoabdominal aorta
Takashi Kunihara, MDa,
Shigeyuki Sasaki, MDa,
Norihiko Shiiya, MDa,
Tsukasa Miyatake, MDa,
Naoki Mafune, PhDb,
Keishu Yasuda, MDa
a Department of Cardiovascular Surgery, Hokkaido University School of Medicine, Sapporo, Japan
b Department of Clinical Laboratory Medicine, Hokkaido University School of Medicine, Sapporo, Japan
Accepted for publication September 14, 2000.
Address reprint requests to Dr Kunihara, Department of Cardiovascular Surgery, Hokkaido University School of Medicine, N14, W5, Kita-ku, Sapporo, Japan 0608648
e-mail: kunihara{at}med.hokudai.ac.jp
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Abstract
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Background. Little is known about alterations of cytokine levels in cerebrospinal fluid (CSF) during thoracoabdominal aortic surgery. We measured perioperative CSF cytokine levels to determine their clinical significances.
Methods. Perioperative serum and CSF levels of cytokine were measured in 15 adult patients undergoing repair of the descending thoracic aorta (n = 4) or thoracoabdominal aorta (n = 11). All patients underwent prosthetic replacement and perioperative CSF drainage. Serum and CSF levels of tumor necrosis factor-
, Interleukin- (IL-) 1ß, IL-6, IL-8, IL-10, and IL-12 were measured before operation and at 0, 6, 12, 18, 24, 48, and 72 hours postoperatively using enzyme-linked immunosorbent assays.
Results. There were no hospital deaths, but 1 patient suffered paraplegia. Cerebrospinal fluid IL-8 levels peaked at immediately after operation (751.7 ± 42.1 pg/mL versus preoperative levels, 54.9 ± 24.6 pg/mL; p < 0.001), and the higher levels persisted for 72 hours. In contrast, serum IL-8 levels did not change and remained lower than CSF levels. The patient with paraplegia had the highest CSF IL-8 levels throughout the study period. Serum and CSF levels of tumor necrosis factor-, IL-1ß, IL-6, and IL-12 did not significantly change. Serum and CSF levels of IL-10 were significantly elevated after operation compared with preoperative levels. In contrast to IL-8, serum IL-10 levels surpassed CSF levels.
Conclusions. Cerebrospinal fluid IL-8 levels are significantly elevated in thoracoabdominal aortic operation, and may be the most sensitive to the inflammatory response in the ischemic spinal cord injury. Persistent elevation of CSF IL-8 levels may be predictive of further development of neurologic deficits, and a reduction of proinflammatory cytokine levels may be a beneficial effect of CSF drainage, but this requires further investigation.
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Introduction
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Spinal cord injury resulting from surgical repair of the descending thoracic or thoracoabdominal aortic disease remains a devastating complication [1, 2]. Mechanisms of spinal cord injury consist of inadequate blood supply and ischemia-reperfusion injury of the spinal cord [2]. The inadequate blood supply may result from either inadequate collateral blood flow during aortic cross-clamping (AXC) or failure to reconstruct segmental arteries that are critical to the spinal cord. Spinal cord ischemia in the perioperative period can result from perioperative hypotension, distal aortic hypotension after AXC, the interruption of critical intercostal and lumbar arteries, and thrombosis and embolism of intercostal arteries [2]. In the pathogenesis of ischemia-reperfusion injury, recent studies have demonstrated that the endothelium plays a key role in the injury suffered after ischemia and reperfusion, and that the proinflammatory cytokines are involved with endothelial cell–neutrophil interactions and the regulation of transendothelial neutrophil migration [3].
We have previously shown that IL-8 levels were significantly elevated in the spinal tissue that suffered ischemic injury, leading to neurologic deficit [4]. In general, the most common sources of elevated IL-8 levels are derived from endothelial cells or activated leukocytes [3]. The leukocytes most likely to have interacted with those within the parenchyma of the spinal cord would be the lymphocytes in the cerebrospinal fluid (CSF) [5]. However, alterations of CSF cytokine levels have not been well determined in thoracic aortic surgical procedures, which may cause ischemic spinal cord injury. The purpose of this study is to determine clinical significances of CSF cytokine levels in the thoracic aortic surgical procedures. Another purpose is to identify predictors of further development of neurologic deficits among proinflammatory and antiinflammatory cytokines.
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Patients and methods
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The study subjects were 15 patients with descending thoracic (n = 4) or thoracoabdominal aortic aneurysms (n = 11) who have undergone surgical repair at Hokkaido University Hospital between August 1996 and January 1999. All patients underwent prosthetic replacement and cerebrospinal fluid drainage (CSFD) during and after operation. Cerebrospinal fluid drainage was approved by the medical ethical committee of Hokkaido University, and a written informed consent was given by all patients. There were 9 male and 6 female patients, ranging in age from 26 to 75 years, with a mean age of 60.6 ± 3.7 years. Causes of the aneurysms were dissection for 4 and medial degenerative disease for 11 patients. Fourteen patients underwent elective operation, but 1 patient underwent emergency operation because of sealed rupture of the descending thoracic aortic aneurysm. Four patients had aortic aneurysms in the descending thoracic aorta and 11 patients, in the thoracoabdominal aorta (Crawford type I for 2, type II for 3, and type III for 6 patients) [1]. Six patients had undergone previous aortic surgical procedures in other lesions; from aortic root to aortic arch in 2, aortic arch in 2, and descending thoracic aorta in 2 patients. Four patients had previous operation for malignant disease.
Anesthesia technique, operative methods, and adjuncts
All patients received a standard general anesthesia in the same manner using neuromuscular blockade and intermittent intravenous injection of fentanyl, with a total dosage of 40.1 ± 4.5 µg/kg. Separate bronchial ventilation was used, and the left lung was collapsed during the operative procedure if necessary. Operation was performed through a left posterolateral thoracotomy with or without thoracoabdominal incision. All patients underwent prosthetic replacement of the diseased aorta (Gelseal; Vascutek Inc, Inchinnan, Scotland). Among 8.3 ± 1.0 (range, 2 to 15) pairs of the intercostal or lumbar arteries (ICA/LAs) involved with aneurysmal lesions, 2.9 ± 0.4 (range, 0 to 6) pairs of ICA/LAs were reattached using a tube branched graft. Determination of the critical ICA/LAs were performed by evoked spinal cord potential guidance (MS-91, Medelec, England) [6]. Distal aortic perfusion during AXC was maintained by cardiopulmonary bypass (CPB). Initial distal flow was set at 40 mL · kg-1 · min-1 and was controlled until the distal aortic pressure reached more than 40 mm Hg. After the distal aortic pressure reached 40 mm Hg, the flow was controlled to keep distal aortic pressure more than 40 mm Hg, except for patients undergoing open distal anastomosis under a deep hypothermic circulatory arrest (DHCA). Partial femorofemoral (F-F) CPB with moderate hypothermia (minimum rectal temperature, 34.0° ± 1.0°C) was used in 11 patients, and total CPB with DHCA was used in 4 patients (minimum rectal temperature, 19.8°C ± 1.3°C). Sequential clamp (within two pairs of ICA/LAs) technique was applied as far as possible, and rewarming was started after completion of reattachment of all ICA/LAs. When reconstruction of visceral branches was needed, each branch was cannulated by balloon catheter and perfused at the rate of 150 mL/min for each branch until they were reattached to the graft. Open distal anastomosis under total CPB with DHCA was used for 3 patients.
The system for CPB consisted of a heparin-coated circuit (Terumo Co, Tokyo, Japan), a centrifugal pump (Medtronic Bio-Medicus Inc, Eden Prairie, MN), and a membrane oxygenator (Capiox SX-18TM, Terumo Co). This system was primed with lactated Ringer’s solution before the operation, and 5 mg/kg of betamethasone was added to the priming solution of the CPB circuit. The same dose of betamethasone was also given intravenously before starting CPB. Alpha-stat strategy was applied during CPB.
Cerebrospinal fluid drainage and measurements of cytokine levels
An epidural minipack (Portex Inc, Hythe, Kent, UK) was used for CSFD. A 16-gauge Tuohy needle was inserted into the intervertebral space between L4 and L5. Cerebrospinal fluid drainage started just after the induction of anesthesia and lasted until 72 hours after the operation unless no drainage of CSF was obtained. Cerebrospinal fluid drainage was performed by overflow method at the level of 13 cm H2O above the porus acusticus externus. The samples of CSF and serum were collected from patients just before and at 0, 6, 12, 18, 24, 48, and 72 hours after the operation. Tumor necrosis factor- (TNF-), interleukin- (IL-) 1ß, IL-6, IL-8, IL-10, and IL-12 in the CSF and serum were measured by enzyme-linked-immunosorbent assay method (BioSource International, Inc, Camarillo, CA). We measured TNF, IL-1ß, IL-6, and IL-8 levels as proinflammatory cytokines that would mediate reactions in various pathophysiologic aspects including ischemia-reperfusion injury [3]. Interleukin-10 and IL-12 were measured as a representative antiinflammatory cytokines, which can counterbalance or control the proinflammatory response [3, 4]. The minimum detectable levels for TNF, IL-1ß, IL-6, IL-8, IL-10, and IL-12 were 1, 1, 2, 10, 5, and 1 pg/mL, respectively. Alterations of these cytokine levels were compared between those in the serum and CSF.
Statistical analysis
All values are presented as mean ± standard error of the mean. Statistical analysis for comparisons of the cytokine levels between those in the serum and CSF were performed using repeated measured analysis of variance. Wilcoxon signed-rank test was used for nonparametric comparisons of the cytokine levels between preoperative and postoperative values. Mann-Whitney U test was used for comparisons of the mean distal aortic perfusion pressure and mean duration of operation, CPB, and AXC between subgroups based on adjunct or postoperative spinal cord injury. A p value less than 0.05 was considered statistically significant.
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Results
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There were no hospital deaths, but 1 patient (a 73-year-old woman), who underwent emergency operation because of sealed rupture of descending thoracic aortic aneurysm, suffered paraplegia. Left hemiparesis developed in 1 patient (a 66-year-old man) with thoracoabdominal aortic aneurysm of Crawford’s type I, who had a history of distal aortic arch replacement. This patient was treated by combination of CSFD, postoperative continuous infusion of naloxone hydrochloride, and maintaining high arterial pressure to establish spinal blood flow, and the symptoms were completely reversed within 2 months after operation. Other neurologic complications included temporary convulsion caused by hemangioma in 1, asymptomatic small cerebellar infarction in 1, and delirium in 1 patient. These 3 patients underwent DHCA. Mean duration of postoperative CSFD was 3.0 ± 0.3 days, and total amount of CSFD was 268 ± 67 mL (78 ± 18 mL/d). When the amount of CSFD was compared between subgroups based on perfusion technique (F-F CPB versus DHCA) and extent (more or less than 10 ICA/LAs managed within AXC), the amount was significantly larger in patients undergoing DHCA than in those undergoing F-F CPB (p = 0.0080), and also larger in patients with 10 or more ICA/LAs managed within AXC than in those with less than 10 (p = 0.0023). There was no complication related to CSFD except 1 patient who suffered from postdural puncture headache.
Mean durations of operation, CPB, and AXC in all 15 patients were 618 ± 69 minutes, 168 ± 23 minutes, and 114 ± 16 minutes, respectively. When these intervals are compared between subgroups based on perfusion technique (F-F CPB versus DHCA), mean duration of CPB was longer in patients undergoing DHCA than in those undergoing F-F CPB (264 ± 21 minutes versus 133 ± 23 minutes; p = 0.0131). Mean duration of operation and AXC were not significantly different. Regarding the distal aortic perfusion, the mean distal aortic perfusion pressure in 11 patients undergoing F-F CPB was maintained at 61.3 ± 0.7 mm Hg. The mean distal aortic perfusion pressure in 2 patients who suffered paraplegia or left hemiparesis was 86.0 ± 2.9 mm Hg, which was significantly higher than that in patients without neurologic sequelae (57.4 ± 0.5 mm Hg; p < 0.001). Thus neurologic sequelae in these 2 patients did not result from low perfusion pressure during CPB.
Cerebrospinal fluid IL-8 levels peaked immediately after operation (751.7 ± 42.1 pg/mL versus preoperative levels, 54.9 ± 24.6 pg/mL; p < 0.001) and gradually decreased afterward. However, higher levels persisted for 72 hours (327.9 ± 93.9 pg/mL versus preoperative levels; p < 0.02). In contrast, serum IL-8 levels did not change and remained at significantly lower levels (13.5 ± 9.0 pg/mL to 43.7 ± 9.1 pg/mL) than CSF levels (Fig 1). Among 15 patients, a patient with paraplegia had the highest CSF IL-8 levels throughout the study period (Fig 2). In this patient, the CSF IL-8 levels did not decrease after operation, and the highest level (788.6 pg/mL) persisted at 72 hours after operation. In a patient with left hemiparesis, CSF IL-8 levels peaked just after operation (917.8 pg/mL), but gradually decreased until 72 hours postoperatively as well as those in patients without spinal cord injury (390.0 pg/mL).
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Fig 2. Changes in cerebrospinal fluid interleukin-8 (IL-8) levels during the study period. Data were contrasted between those in a patient who developed paraplegia and those in the rest of 14 patients. (pre = preoperative levels; w/o = without.)
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Serum and CSF levels of TNF- and IL-6 did not significantly change and showed no specific trend (Figs 3, 4). Cerebrospinal fluid IL-6 levels tended to have a peak at 24 hours after operation, but the difference between preoperative values and those at 24 hours after operation was not significant. Interleukin-1ß and IL-12 levels in the serum and CSF were less than the minimum detectable level in all patients. Serum and CSF levels of IL-10, an antiinflammatory cytokine, were significantly elevated after operation compared with preoperative levels. In contrast to IL-8, serum IL-10 levels surpassed CSF levels (Fig 5).
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Fig 4. Changes in serum and cerebrospinal fluid (CSF) interleukin-6 (IL-6) levels during the study period. No significant difference was noted. (pre = preoperative levels.)
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Fig 5. Changes in serum and cerebrospinal fluid (CSF) interleukin-10 (IL-10) levels during the study period. *p < 0.05, **p < 0.01 versus preoperative values. (pre = preoperative levels.)
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Because we had a striking finding regarding IL-8 and IL-10, CSF levels of IL-8 and serum levels of IL-10 were compared between subgroups based on extent (descending thoracic versus thoracoabdominal aorta, extent Crawford type I and type II thoracoabdominal versus extent Crawford type III thoracoabdominal aorta, more or less than 10 ICA/LAs managed within AXC), perfusion technique (F-F CPB versus DHCA), and cause (dissection versus nondissection) in 13 patients without postoperative spinal cord injury. The p values determined by repeated measures analysis of variance between the subgroups are as follows (CSF IL-8, serum IL-10, respectively): descending thoracic versus thoracoabdominal aorta, p = 0.5576, 0.9936; extent Crawford type I and type II thoracoabdominal versus extent Crawford type III thoracoabdominal aorta, p = 0.2112, 0.4437; more or less than 10 ICA/LAs managed within AXC, p = 0.9025, 0.4712; perfusion technique (F-F CPB versus DHCA), p = 0.4024, 0.0704; cause (dissection versus nondissection), p = 0.0869, 0.7549. Although the sample number was small, CSF IL-8 levels tended to be higher in the subgroup of dissection than in nondissection, and serum IL-10 levels tended to be higher in the subgroup of DHCA than in the subgroup of F-F CPB. Differences of CSF IL-8 or serum IL-10 levels between other subgroups were not statistically significant.
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Comment
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The inflammatory response and the production of cytokines in the CSF of patients with bacterial meningitis or multiple sclerosis are well documented [7–11]. However, little is known about the production of proinflammatory cytokines in the CSF during the process of spinal ischemia and reperfusion because of the thoracic aortic operation. We have previously shown that IL-8 levels were significantly elevated in the spinal tissue that suffered ischemic injury leading to neurologic deficit [4]. The present study demonstrated that postsurgical IL-8 levels in the CSF were significantly elevated after operation compared with preoperative IL-8 levels. In contrast, serum IL-8 levels did not change and remained at lower levels than CSF levels. In patients without paraplegia, the CSF IL-8 levels peaked immediately after operation and subsequently decreased according to the time course. But in a patient with paraplegia, the elevation of CSF IL-8 levels persisted for at least 72 hours after operation. Of course, we cannot obtain any definitive conclusion from only 1 patient’s data. But it would be beneficial to determine whether CSF IL-8 levels serve as a marker for spinal cord injury in further study.
We investigated six cytokines in this study to demonstrate inflammatory response in the spinal cord that suffered ischemia-reperfusion. Tumor necrosis factor-, IL-1ß, IL-6, and IL-8 levels were measured as proinflammatory cytokines that would mediate reactions in various pathophysiologic aspects including ischemia-reperfusion injury [3]. Interleukin-10 and IL-12 were measured as representative antiinflammatory cytokines, which can counterbalance or control the proinflammatory response [3, 4]. Interleukin-8, a member of the proinflammatory cytokines, is produced by a wide variety of cells in response to various types of stimulation [12]. Under ischemic conditions, IL-8 is released by endothelial cells and plays an important role for endothelial cell–neutrophil interactions [3]. Interleukin-8 can increase the adhesiveness of endothelial cells for neutrophils [13] and is also important in the regulation of transendothelial neutrophil migration [3, 14]. Matsukawa and associates [12] reported that IL-8 was not only a potent and selective neutrophil attractant but is also a neutrophil activator in vivo. In general, lymphocyte migration into a tissue depends on properties of both the lymphocyte and the tissue’s vascular endothelium. The central nervous system possesses a specialized microvasculature, and CSF appears to be enriched, compared with peripheral blood, in its content of surveillance lymphocytes [5]. Activated monocytes or macrophages, lymphocytes, and neutrophils can permeate the blood–brain barrier and produce a variety of cytokines, including IL-1, IL-6, IL-8, and TNF- [15]. In addition to these immunocompetent cells, astrocytes and microglial cells in the CNS can also produce these cytokines [15, 16]. Because the endothelial cells and activated leukocytes can produce IL-8 after reperfusion [3], the increase in CSF IL-8 levels in our study may result from either endothelial cells or microglial cells in the spinal cord that suffered ischemia and reperfusion or activated leukocytes in the CSF after reperfusion, or both. Because CSF IL-8 levels tended to be higher in the subgroup of dissection than in the subgroup of nondissection, these changes in endothelial cells and activated leukocytes may be enhanced in operations for aortic dissection.
In addition to the elevation of IL-8 levels as a result of spinal ischemic injury, the elevated IL-8 itself may precipitate the degree of spinal injury [17]. It is well documented that elevated proinflammatory cytokines can lead to inflammatory cell extravasation and edema of the central nervous system. In the experimental study, the intracisternal injections of proinflammatory cytokines such as TNF- and IL-1 can induce these reactions, but the administration of their antibodies can attenuate tissue damage [15, 16]. In addition to the proinflammatory cytokines with deleterious effects, other negative neurotrophic proteins that inhibit spinal cord healing may be released into the CSF [18]. Therefore, prolonged CSFD may enhance spinal cord recovery after ischemia, because of preventing excessive pressures and because of removal of negative neurotrophic proteins and proinflammatory cytokines. This concept has also been advocated by Svensson and colleagues [19].
Surprisingly, CSF TNF- levels were not significantly elevated, for this cytokine is generally considered a nonspecific mediator of the inflammatory process. Tumor necrosis factor- is a proinflammatory cytokine that is mainly released by macrophages under the condition of ischemia and reperfusion. The increase in TNF- levels might promote the increase in IL-8 levels, but the present study demonstrated no significant changes in the CSF TNF- levels. Thus, a significant difference of IL-8 production in the CSF cannot be attributed to the difference of TNF- production in our study. In the transient and reversible ischemic spinal injury, the CSF TNF- may not be the primary mediator of cellular infiltration, or activity of antiinflammatory cytokines may override the chemotactic effects of TNF-. However, in the severe spinal cord injury that may cause neurologic deficits, the CSF TNF- levels may be elevated because of the continuing inflammatory responses in the spinal tissue or other mechanisms.
Interleukin-10 is an antiinflammatory cytokine, and has been reported to inhibit proinflammatory cytokines by up-regulating IL-1 receptor antagonist [20]. In general, IL-10 correlated positively with IL-8, and the rise in IL-10 is regarded as a part of compensation for increased proinflammatory cytokines [21]. In the present study, serum and CSF levels of IL-10 were significantly elevated after operation compared with preoperative levels, and in addition, serum IL-10 levels surpassed CSF levels. Significant elevation of CSF IL-10 levels may occur in response to the elevation of CSF IL-8 levels. However, why were serum IL-10 levels elevated without the increase in serum IL-8 levels? And why did serum IL-10 levels surpass CSF IL-10 levels whereas CSF IL-8 levels surpassed serum IL-8 levels ? Probably, administration of steroid and its permeability to the blood–brain barrier may be a key to answer these questions. Recent studies have demonstrated that methylprednisolone reduced the production of IL-8 but not that of IL-10 and IL-1 receptor antagonist during cardiac operation with the use of CPB [21]. In the present study, the administrated steroid may have also influenced the serum proinflammatory and antiinflammatory cytokine balance, and contributed to the reduction of serum IL-8 levels and the elevation of serum IL-10 levels. However, passage of steroid into the CSF is delayed because it first binds to the brain capillaries and then crosses the BBB at a very low rate [22, 23]. This is one of the possible mechanisms likely to account for the significant elevation of CSF IL-8 levels, which was not suppressed by steroid infusion, whereas serum IL-8 levels did not increase.
There are some limitations in the present study. First, CSFD itself may affect the value of cytokine in the CSF through the reduction of the CSF pressure. Under the increased CSF pressure caused by the postischemic spinal cord edema, production of proinflammatory cytokines in the CSF may be augmented. However, it would not appear reasonable to repeat the spinal tap in the early postoperative period, and may be contrary to therapeutic purposes. Second, because this study does not have a control group, measurements of the baseline CSF cytokine levels in patients undergoing thoracic operations without spinal cord ischemia are absent. Therefore, the effects of simple thoracotomy on the alterations of the CSF cytokine levels cannot be completely ruled out in this study. According to the report by Atwell and associates [24], serum levels of an antiinflammatory cytokine IL-1 receptor antagonist may be elevated in response to surgical stress, but those of IL-8 or TNF- do not increase. The elevation of serum IL-8, IL-1ß, and TNF- was also absent in our study. The likelihood that simple thoracotomy without spinal cord ischemia might induce alterations of proinflammatory cytokine levels in the CSF appears to be remote, but further studies will be necessary to obtain definite results.
In conclusion, postsurgical IL-8 levels in the CSF are significantly elevated in thoracoabdominal aortic operation, and may be the most sensitive cytokine to the inflammatory response in ischemic spinal cord injury. These alterations were transient in patients without paraplegia, but persisted for 72 hours in a patient who suffered paraplegia. Persistent elevation of CSF IL-8 levels may be predictive of further development of neurologic deficits, and a reduction of proinflammatory cytokine levels may be a beneficial effect of CSFD, but these require further investigation.
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References
|
|---|
-
Crawford E., Crawford J., Safi H., et al. Thoracoabdominal aortic aneurysms: preoperative and intraoperative factors determining immediate and long-term results of operations in 605 patients. J Vasc Surg 1986;3:389-404.[Medline]
-
Mauney M.C., Blackbourne L.H., Langenburg S.E., Buchanan S.A., Kron I.L., Tribble C.G. Prevention of spinal cord injury after repair of the thoracic or thoracoabdominal aorta. Ann Thorac Surg 1995;59:245-252.[Abstract/Free Full Text]
-
Boyle E.J., Pohlman T.H., Cornejo C.J., Verrier E.D. Endothelial cell injury in cardiovascular surgery: ischemia-reperfusion. Ann Thorac Surg 1996;62:1868-1875.[Abstract/Free Full Text]
-
Kunihara T., Sasaki S., Shiiya N., et al. Lazaroid reduces production of IL-8 and IL-1 receptor antagonist in ischemic spinal cord injury. Ann Thorac Surg 2000;60:792-798.
-
Elfont R.M., Griffin D.E., Goldstein G.W. Enhanced endothelial cell adhesion of human cerebrospinal fluid lymphocytes. Ann Neurol 1995;38:405-413.[Medline]
-
Shiiya N., Yasuda K., Matsui Y., Sakuma M., Sasaki S. Spinal cord protection during thoracoabdominal aortic aneurysm repair: results of selective reconstruction of the critical segmental arteries guided by evoked spinal cord potential monitoring. J Vasc Surg 1995;21:970-975.[Medline]
-
Tunkel A.R., Scheld W.M. Pathogenesis and pathophysiology of bacterial meningitis. Clin Microbiol Rev 1993;6:118-136.[Abstract/Free Full Text]
-
Olsson T. Multiple sclerosis: cerebrospinal fluid. Ann Neurol 1994;36(Suppl):S100-S102.
-
Matusevicius D., Navikas V., Soderstrom M., et al. Multiple sclerosis: the proinflammatory cytokines lymphotoxin-alpha and tumour necrosis factor-alpha are upregulated in cerebrospinal fluid mononuclear cells. J Neuroimmunol 1996;66:115-123.[Medline]
-
Ossege L.M., Sindern E., Voss B., Malin J.P. Expression of tumor necrosis factor-alpha and transforming growth factor-beta 1 in cerebrospinal fluid cells in meningitis. J Neurol Sci 1996;144:1-13.[Medline]
-
Navikas V., Matusevicius D., Soderstrom M., et al. Increased interleukin-6 mRNA expression in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis. J Neuroimmunol 1996;64:63-69.[Medline]
-
Matsukawa A., Yoshimura T., Maeda T., Ohkawara S., Takagi K., Yoshinaga M. Neutrophil accumulation and activation by homologous IL-8 in rabbits. IL-8 induces destruction of cartilage and production of IL-1 and IL-1 receptor antagonist in vivo. J Immunol 1995;154:5418-5425.[Abstract]
-
Karkurum M., Shreeniwas R., Chen J. Hypoxic induction of interleukin-8 gene expression in human endothelial cells. J Clin Invest 1994;93:1564-1570.
-
Huber A.R., Kunkel S.L., Todd R.F., Weiss S.J. Regulation of transendothelial neutrophil migration by endogenous interleukin-8. Science 1991;254:99-102.[Abstract/Free Full Text]
-
Reichlin S. Neuroendocrine-immune interactions. N Engl J Med 1993;329:1246-1253.[Free Full Text]
-
Plata-Salaman C.R. Immunoregulators in the nervous system. Neurosci Biobehav Rev 1991;15:185-215.[Medline]
-
Tang T., Frenette P.S., Hynes R.O., Wagner D.D., Mayadas T.N. Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins. J Clin Invest 1996;97:2485-2490.[Medline]
-
Schnell L., Schneider R., Kolbeck R., Barde Y.A., Schwab M.E. Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion. Nature 1994;367:170-173.[Medline]
-
Svensson L.G., Hess K.R., D’Agostino R.S., et al. Reduction of neurologic injury after high-risk thoracoabdominal aortic operation. Ann Thorac Surg 1998;66:132-138.[Abstract/Free Full Text]
-
Cassatella M.A., Meda L., Gasperini S., Calzetti F., Bonora S. Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation. J Exp Med 1994;179:1695-1699.[Abstract/Free Full Text]
-
Kawamura T., Inada K., Nara N., Wakusawa R., Endo S. Influence of methylprednisolone on cytokine balance during cardiac surgery. Crit Care Med 1999;27:545-548.[Medline]
-
Defer G.L., Barre J., Ledudal P., Tillement J.P., Degos J.D. Methylprednisolone infusion during acute exacerbation of MS: plasma and CSF concentrations. Eur Neurol 1995;35:143-148.[Medline]
-
Chen T.C., Mackic J.B., McComb J.G., Giannotta S.L., Weiss M.H., Zlokovic B.V. Cellular uptake and transport of methylprednisolone at the blood-brain barrier. Neurosurgery 1996;38:348-354.[Medline]
-
Atwell D.M., Grichnik K.P., Newman M.F., Reves J.G., McBride W.T. Balance of proinflammatory and antiinflammatory cytokines at thoracic cancer operation. Ann Thorac Surg 1998;66:1145-1150.[Abstract/Free Full Text]
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Abstract
Introduction
