HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Katsuhiko Matsuyama Yukio Chiba Akio Ihaya Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matsuyama, K. Articles by Muraoka, R. Search for Related Content PubMed PubMed Citation Articles by Matsuyama, K. Articles by Muraoka, R.

Ann Thorac Surg 1997;63:1315-1320
© 1997 The Society of Thoracic Surgeons

---

Original Article: Cardiovascular

Effect of Spinal Cord Preconditioning on Paraplegia During Cross-Clamping of the Thoracic Aorta

Second Department of Surgery, Fukui Medical School, Yoshida-Gun, Fukui, Japan

Accepted for publication November 23, 1996.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Experiment 1 Experiment 2 Immunohistochemical Studies Statistical Analysis Results Comment References

 
Background. Paraplegia is a devastating complication of operations for thoracic or thoracoabdominal aneurysms. Preconditioning the brain with sublethal ischemia induces resistance to subsequent ordinarily lethal ischemia (ischemic tolerance). We investigated whether ischemic tolerance could be induced by preconditioning canine spinal cord. The role of heat-shock proteins (HSP) in this process was investigated.

Methods. In experiment 1, the preconditioning group (n = 6) had aortic cross-clamping for 20 minutes, whereas controls (n = 6) had no cross-clamping. After 48 hours the aorta was cross-clamped for 60 minutes in both groups. Neurologic examination was performed 24 hours later and the spinal cord was studied for immunohistochemically. In experiment 2, either 48 hours after 20 minutes of clamping or after sham operation (n = 4), HSP were investigated immunohistochemically.

Results. In experiment 1, 3 of 6 controls became paraplegic but none of the 6 preconditioning group dogs became paraplegic. The HSP appeared on sections from all 6 PC dogs and 3 control dogs that did not exhibit paraplegia. In experiment 2, HSP were present in clamped animals but could not be detected after sham operation.

Conclusions. Ischemic tolerance was induced by preconditioning the canine spinal cord, in which HSP are believed to be involved.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Experiment 1 Experiment 2 Immunohistochemical Studies Statistical Analysis Results Comment References

 
Paraplegia is a major complication of operations for thoracic or thoracoabdominal aneurysms [1], which appears related to spinal cord ischemia induced by low perfusion pressure during cross-clamping of the thoracic aorta. The reported incidence of paraplegia ranges from 3.8% to 17.6% [2]. Paraplegia is devastating and usually irreversible once it occurs. During the past decade, several attempts have been made experimentally and clinically to prevent paraplegia by the following methods: maintenance of distal aortic perfusion with shunts and bypasses [3], rapid identification and reimplantation of critical intercostal vessels [4], increasing spinal cord perfusion pressure with cerebrospinal fluid drainage [5], and administration of pharmacologic agents such as steroids [6], superoxide dismutase [7], and calcium blockers [8]. Somatosensory evoked potentials [9], evoked spinal cord potentials [10], and motor evoked potentials [11] have been monitored intraoperatively to detect spinal cord ischemia. Despite such efforts, no method has totally prevented the development of paraplegia.

Kitagawa and colleagues [12] reported that preconditioning the brain with sublethal cerebral ischemia, which permits recovery without morphologically evident neuronal damage, induced resistance to subsequent ordinarily lethal period of ischemia in a gerbil model, a phenomenon called ischemic tolerance. Other experimental evidence indicates that prolonged but mild hypoperfusion and reversible oxidative stress have induced tolerance to subsequent lethal ischemia in gerbil hippocamal neurons [13, 14]. However, even a brief, nonlethal ischemic insult repeatedly administered at short intervals has been found to result in severe neuronal damage. To induce a neuroprotective effect, the interval between nonlethal ischemia and potentially lethal ischemia must be greater than 1 or 2 days, but not more than 14 [15]. Although a possible role of the stress response is suggested, the mechanism of acquisition of ischemic tolerance is currently unknown. One possible mechanism of the protective effects of preliminary exposures relates to the synthesis of heat-shock proteins (HSP) observed in gerbil [12] and rat models [16] of cerebral ischemia.

Many experiments have been reported the effect of ischemic preconditioning in the brain. We investigated whether the ischemic tolerance phenomenon could be induced in the spinal cord by brief cross-clamping of the canine descending aorta. The HSP were also assessed immunohistochemically to determine whether they were induced by spinal ischemia.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Experiment 1 Experiment 2 Immunohistochemical Studies Statistical Analysis Results Comment References

 
All animals received humane care in compliance with the "Guide for the Care and Use of Laboratory Animals" published by the National Institutes of Health (NIH publication 85-23, revised 1985) and Guidelines for Animal Experiments, Fukui Medical School.

	Experiment 1

Top Footnotes Abstract Introduction Material and Methods Experiment 1 Experiment 2 Immunohistochemical Studies Statistical Analysis Results Comment References

 
Twelve adult beagle dogs weighing from 12 to 13 kg were anesthetized with intramuscular ketamine hydrochloride (10 mg/kg) and intravenous pentobarbital sodium (25 mg/kg) and paralyzed with pancuronium bromide (0.3 mg/kg). The trachea was intubated and ventilated on room air and low-flow oxygen (Harvard Apparatus Co, South Natick, MA). Respiratory settings included a tidal volume of 12 mL/kg, a respiratory rate to maintain the partial pressure of carbon dioxide between 35 and 45 mm Hg and that of oxygen above 100 mm Hg, as measured by arterial blood gas analysis (Ciba Corning Diagnostics Corp, Medfield, MA). A nasopharyngeal temperature probe was inserted. The electrocardiogram was recorded using needle electrodes. Catheters were inserted into the left carotid artery and femoral artery to record the arterial pressure proximal and distal to aortic cross-clamping. All pressures were continuously monitored with a pressure transducer (P23XL, Nihon Koden, Tokyo, Japan). A left thoracotomy in the fourth intercostal space was performed under sterile conditions. The aorta was isolated distal to the left subclavian artery and 100 U/kg of heparin was administered. The dogs were randomly assigned to two experimental groups. The preconditioning operation (PC group: n = 6) included 20 minutes of aortic cross-clamping and the control operation (control group: n = 6) had no aortic cross-clamping. The aorta was cross-clamped distal to the left subclavian artery. No pharmacologic agents were used for control of blood pressure. After unclamping the aorta, 1 mg/kg of protamine was administered. The chest was closed in anatomic fashion and the animals were allowed to recover. All animals were noted to have a completely normal neurologic outcome. Reoperation was performed 48 hours after the initial operation. Under similar anesthesia, left thoracotomy was again performed under sterile conditions. The aorta was cross-clamped distal to the left subclavian artery for 60 minutes. Distal and proximal arterial pressure were continuously monitored. No pharmacologic agents were used for control of blood pressure. The chest was closed in anatomic fashion, and the animals were allowed to recover.

Neurologic examination of all animals was performed by a investigator blinded to treatment group 24 hours after the second operation. The animals were graded according to a modification of the Tarlov classification [17], as follows: grade 0, spastic paraplegia and no movement of the lower limbs; grade 1, spastic paraplegia and slight movement of the lower limbs; grade 2, good movement of the lower limbs but unable to stand; grade 3, able to stand but unable to walk normally; and grade 4, complete recovery.

All animals were killed with an overdose of pentobarbital sodium after neurologic assessment. The lumbar spinal cord was immediately removed by posterior laminectomy after formalin perfusion fixation for immunohistochemical analysis.

	Experiment 2

Top Footnotes Abstract Introduction Material and Methods Experiment 1 Experiment 2 Immunohistochemical Studies Statistical Analysis Results Comment References

 
To investigate whether HSP synthesis was induced by ischemic preconditioning of the spinal cord, eight adult beagle dogs weighing between 12 and 13 kg were anesthetized, and four dogs received 20 minutes of aortic cross-clamping. For the control operation four dogs had no aortic cross-clamping. The animals were allow to recover for 48 hours after the surgical procedure. All animals then were killed with an overdose of pentobarbital sodium. The lumbar spinal cord was immediately removed by posterior laminectomy after formalin perfusion fixation for immunohistochemical analysis and postfixed in 10% formalin for 1 week.

	Immunohistochemical Studies

Top Footnotes Abstract Introduction Material and Methods Experiment 1 Experiment 2 Immunohistochemical Studies Statistical Analysis Results Comment References

 
After formalin fixation and embedding in paraffin, the spinal cord was serially sectioned using a microtome at a thickness of 5 µm. The sections were deparaffinized using xylene and graded alcohols. Endogenous peroxidase was inactivated using 3% hydrogen peroxide in 0.05 mol/L phosphate-buffered saline for 10 minutes. Nonspecific protein binding was blocked with normal bovine serum for 10 minutes. This was followed by an overnight incubation with a mouse monoclonal antibody against HSP70 (SPA-810, Stressgen, Victoria, BC, Canada) diluted 1:200 at 4°C. The sections were then incubated with a biotinylated goat antimouse second antibody (LSAB kit; Dako Japan, Kyoto, Japan) and then visualized with diaminobenzidine hydrochloride. The sections were counterstained with hematoxylin. Control sections were incubated without the primary antibody.

	Statistical Analysis

Top Footnotes Abstract Introduction Material and Methods Experiment 1 Experiment 2 Immunohistochemical Studies Statistical Analysis Results Comment References

 
Each value was expressed as the mean ± the standard deviation. Statistical evaluation was performed by means of Student's unpaired t test for comparison of experimental variables between the groups. The difference among groups in terms of the Tarlov scores was determined by nonparametric statistical analysis using the Mann-Whitney U test. A p value of less than 0.05 was considered significant.

	Results

Top Footnotes Abstract Introduction Material and Methods Experiment 1 Experiment 2 Immunohistochemical Studies Statistical Analysis Results Comment References

 
Experiment 1
HEMODYNAMIC MEASUREMENTS.
There was no significant difference between the PC and the control groups with regard to esophageal temperatures, hemoglobin, hematocrit, pH, base excess, and preconditioning operation time (Table 1). Also, there was no statistically significant difference between the two groups with regard to proximal and distal mean arterial pressures during the baseline interval and reperfusion (Table 2). There was no significant difference between the two groups with regard to esophageal temperatures, hemoglobin, hematocrit, pH, base excess, and operation time for 60 minutes of aortic cross-clamping (Table 3). Proximal mean arterial pressure during cross-clamping was 172 ± 9 mm Hg and 177 ± 13 mm Hg in PC and control groups, respectively. Distal mean arterial pressure was 26 ± 3 mm Hg and 24 ± 4 mm Hg in PC and control groups, respectively. There was no significant difference between the two groups in distal and proximal mean arterial pressure during 60 minutes of aortic cross-clamping (Table 4).

View larger version (92K): [in this window] [in a new window]   Fig 1. . Immunohistochemical staining using anti-HSP70 antibody in the anterior horn of the lumbar spinal cord. (A) Histologic section from neurologically recovered animal in the preconditioning group. Immunoreactivity was seen with granular pattern in the cytoplasm of neurons. Also, the glial cells were densely stained. (B) Histologic section from paraplegic animal in the control group. Severe damage including neuronal degeneration, necrosis, and spongiosis was observed. No immunoreactivity was seen. (C) Histologic section from the animal 48 hours after the control operation. No staining was detected. (Original magnification of all figures, x200.)

	Comment

Top Footnotes Abstract Introduction Material and Methods Experiment 1 Experiment 2 Immunohistochemical Studies Statistical Analysis Results Comment References

 
Paraplegia, a major complication of operations for thoracic or thoracoabdominal aneurysms, is devastating and usually irreversible. Despite various efforts, no method has totally prevented the development of paraplegia. Kitagawa and colleagues [12] have reported that preconditioning the brain with sublethal cerebral ischemia induced resistance to subsequent normally lethal period of ischemia. This phenomenon of ischemic tolerance has been described in both rats and gerbils.

In this study we investigated whether the ischemic tolerance phenomenon could be induced by brief cross-clamping of the canine descending aorta. Whether an ischemic insult is sublethal or lethal depends on distal or proximal mean arterial pressure and body temperature during aortic cross-clamping, as well as the duration of clamping.

Major reports have demonstrated that paraplegia in the dog model occurs if the duration of aortic cross-clamping exceeds 30 minutes [18, 19]. Therefore, the aorta was cross-clamped 20 minutes for ischemic preconditioning of spinal cord. In this study, distal and proximal mean arterial pressure were 165 ± 12 mm Hg and 24 ± 5 mm Hg, respectively. Twenty minutes of aortic cross-clamping was confirmed to be a sublethal insult to the spinal cord because all the animals had a completely normal neurologic outcome after the preconditioning operation.

Kato and colleagues [15] reported that in the gerbil model of cerebral ischemia, 2 minutes of ischemia followed by 3 minutes of ischemia at intervals of 1, 2, 4, and 7 days caused a marked protective effect. Five-minute, 1-hour, and 6-hour intervals of the same ischemia resulted in almost complete neuronal damage, no protective effect was observed after 14 days. In our experiment, 60 minutes of spinal cord ischemia was given 48 hours after a 20-minute ischemia episode. Three of 6 animals in the control group became paraplegic, but none of 6 animals in the PC group became paraplegic. There was a significant difference in Tarlov score between the PC and the control groups. This result demonstrated that tolerance to lethal ischemia was induced by preconditioning with a preceding period of brief ischemia that did not itself produce neuronal injury.

Blaisdell and Cooley [20] reported that ligation of the first two pairs of intercostal arteries and occlusion of the descending aorta for 1 hour resulted in a 50% incidence of paraplegia. In our study, three of the six animals in the control group did not become paraplegic. This is presumably attributable to individual differences in the anterior spinal circulatory pattern of the canine spinal cord even when the aorta is cross-clamped for 60 minutes. No pharmacologic agents were used for the control of pressure to exclude their effects on the circulation.

The mechanism of acquisition of ischemic tolerance is currently unknown, although a role of the stress response is suggested. Recent studies have shown protein synthesis in the gerbil brain when partially recovered 24 hours after and fully recovered 48 hours after preconditioning with 2 minutes of sublethal ischemia [21]. Various studies have demonstrated increased synthesis of stress proteins such as HSP70 after transient brain ischemia. A protective role against ischemic insult has been hypothesized for stress proteins [12]. Transient hyperthermia protects against subsequent forebrain ischemic cell damage in the rat [22] and the gerbil [23]. The HSP are among of the most frequently studied stress proteins because of their relatively low level in nonstressed cells and dramatic elevation following stress [24]. The HSP synthesis increases when cells are exposed to a variety of stresses including heat shock, viral infection, ischemia, trauma, and heavy metals, and are known to function as molecular chaperones in normal cellular processes [25] and are involved in facilitating protein folding, the assembly of macromolecular protein complexes, and protein traffic between intracellular compartments [26]. The HSP act to ensure cell membrane stability and facilitate denaturation of irreversibly damaged proteins [27].

In these experiments, HSP appeared in 3 nonparaplegic dogs in the control group from experiment 1. This suggests that the spinal cord ischemic insult due to 60 minutes of aortic cross-clamping was a sublethal stress of such a degree that HSP were induced. In experiment 1, HSP appeared in all nine nonparaplegic animals, but were not present in all 3 paralyzed animals. In experiment 2, HSP were not present in the sham-operated animals but appeared in the preconditioning-operated animals. These results suggest that HSP are involved in the acquisition of ischemic tolerance in the spinal cord.

There are several limitations to the present study. First, this is a canine model, and thus it may not necessarily be applicable to humans. The anatomy of the blood supply to the canine spinal cord is also not the same as in humans. Second, this study had a very small sample size. Nevertheless, with this model, we have demonstrated that spinal cord preconditioning significantly protects against paraplegia during cross-clamping of the thoracic aorta. Third, the methods used are impractical for clinical applications. The use of intraaortic balloon occlusion percutaneously for spinal cord preconditioning has many practical difficulties.

The molecular mechanism of the protective effect of HSP is not known, although it is reported that abnormal proteins serve as stress signals that trigger activation of HSP [28]. Whether HSP induced after ischemic preconditioning directly play a protective role in neurons remains unknown. Further study is important because elucidation of the mechanism may provide a clue for the prevention and treatment of paraplegia in humans.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Experiment 1 Experiment 2 Immunohistochemical Studies Statistical Analysis Results Comment References

 
Address reprint requests to Dr Matsuyama, Second Department of Surgery, Fukui Medical School, Matsuoka-Cho, Yoshida-Gun, Fukui-ken 910-11 Japan.

	References

Top Footnotes Abstract Introduction Material and Methods Experiment 1 Experiment 2 Immunohistochemical Studies Statistical Analysis Results Comment References

 

1. Adams HD, Van Geertruyden HH. Neurological complication of aortic surgery. Ann Surg 1956;144:574–610.[Medline]
2. Crawford ES, Rubio PA. Reappraisal of adjuncts to avoid ischemia in the treatment of aneurysms of descending thoracic aorta. J Thorac Cardiovasc Surg 1973;66:693–704.[Medline]
3. Von Oppell UO, Dunne TT, De Groot KM, Zilla P. Spinal cord protection in the absence of collateral circulation: meta-analysis of mortality and paraplegia. J Cardiol Surg 1994;9:685–91.
4. Svensson LG, Hess KR, Coselli JS, Safi HJ. Influence of segmental arteries, extent, and aortofemoral bypass on postoperative paraplegia after thoracoabdominal aortic operations. J Vasc Surg 1994;20:255–62.[Medline]
5. Bower GT, Murray MJ, Gloviczki P, et al. Effects of thoracic occlusion and cerebrospinal fluid drainage on regional spinal cord blood flow in dogs: correlation with neurologic outcome. J Vasc Surg 1989;9:135–44.[Medline]
6. Laschinger JC, Cunningham JN Jr, Cooper MM, Krieger K, Nathan IM, Spencer FC. Prevention of ischemic spinal cord injury following aortic cross-clamping. Use of corticosteroids. Ann Thorac Surg 1984;38:500–7.[Abstract]
7. Granke K, Hollier LH, Zdrahal P, Moore W. Longitudinal study of cerebral spinal fluid drainage in polyethylene glycol-conjugated superoxide dismutase in paraplegia associated with thoracic aortic cross-clamping. J Vasc Surg 1991;13:615–21.[Medline]
8. De Mol B, Hamerlijnck R, Janssen T, Jageneau A. Infrarenal aortic occlusion in the rabbit to assess the effect of flunarizine in the prevention of ischemic spinal cord injury. Thorac Cardiovasc Surg 1991;39:36–9.[Medline]
9. Grabitz K, Sandmann W, Stuhmeier K, et al. The risk of ischemic spinal cord injury in patients undergoing graft replacement for thoracoabdominal aortic aneurysms. J Vasc Surg 1996;23:230–40.[Medline]
10. Yamamoto N, Takano H, Kitagawa H, Kawaguchi Y, Tsuji H, Uozaki Y. Monitoring for spinal cord ischemia by use of the evoked spinal cord potentials during aortic aneurysm surgery. J Vasc Surg 1994;20:826–33.[Medline]
11. Reuter DG, Tacker WA Jr, Badylak SF, Voorhees WD III, Konrad PE. Correlation of motor-evoked potential response to ischemic spinal cord damage. J Thorac Cardiovasc Surg 1992;104:262–72.[Abstract]
12. Kitagawa K, Matsumoto M, Tagaya M, et al. 'Ischemic tolerance' phenomenon found in the brain. Brain Res 1990;528:21–4.[Medline]
13. Ohtuki T, Matsumoto M, Kitagawa K, et al. Induced resistance and susceptibility to cerebral ischemia in gerbil hippocamal neurons by prolonged but mild hypoperfusion. Brain Res 1993;614:279–84.[Medline]
14. Ohtuki T, Matsumoto M, Kuwabara K, et al. Influence of oxidative stress on induced tolerance to ischemia in gerbil hippocamal neurons. Brain Res 1992;599:246–52.[Medline]
15. Kato H, Liu Y, Araki T, Kogure K. Temporal profile of the effects of pretreatment with brief cerebral ischemia on the neuronal damage following secondary ischemic insult in the gerbil: cumulative damage and protective effects. Brain Res 1991;553:238–42.[Medline]
16. Nishi S, Taki W, Uemura Y, et al. Ischemic tolerance due to the induction of HSP70 in a rat ischemic recirculation model. Brain Res 1993;615:281–8.[Medline]
17. Tarlov IM. Spinal cord compression: mechanisms of paralysis and treatment. Springfield, IL: Charles C. Thomas, 1957;147.
18. Mutch WA, Graham MR, Halliday WC, Thiessen DB, Girling LG. Use of neuroanesthesia adjuncts (hyperventilation and mannitol administration) improves neurological outcome after thoracic aortic cross-clamping in dogs. Stroke 1993;24:1204–11.[Abstract/Free Full Text]
19. Woloszyn TT, Marini CP, Coons MS, et al. Cerebrospinal fluid drainage and steroids provide better spinal cord protection during aortic cross-clamping than does either treatment alone. Ann Thorac Surg 1990;49:78–83.[Abstract]
20. Blaisdell FW, Cooley DA. The mechanism of paraplegia after temporary thoracic aortic occlusion and its relationship to spinal fluid pressure. Ann Thorac Surg 1962;51:351–5.[Medline]
21. Kato H, Kogure K, Nakata N, Araki T, Itoyama Y. Facilitated recovery from postischemic suppression of protein synthesis in the gerbil with ischemic tolerance. Brain Research Bull 1995;36:205–8.[Medline]
22. Chopp M, Chen H, Ho KL, et al. Transient hyperthermia protects against subsequent forebrain ischemic cell damage in the rat. Neurology 1989;39:1396–8.[Abstract/Free Full Text]
23. Kitagawa K, Matsumoto M, Tagaya M, et al. Hyperthermia-induced neuronal protection against ischemic injury in gerbils. J Cereb Blood Flow Metab 1991;11:449–52.[Medline]
24. Voellmy R, Ahmed A, Schiller P, Bromley P, Rungger D. Isolation and functional analysis of a human 70,000-dalton heat shock protein gene segment. Proc Natl Acad USA 1985;82:4949–53.[Abstract/Free Full Text]
25. Lindquist S. The heat shock response. Annu Rev Biochem 1986;55:1151–91.[Medline]
26. Gething MJ, Sambrook J. Protein folding in the cell. Nature 1992;355:33–45.[Medline]
27. Chiang HL, Terlecky SR, Plant CP, Dice JF. A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science 1989;246:382–5.[Abstract/Free Full Text]
28. Ananthan J , Goldberg AL, Voellmy R. Abnormal proteins serve as eukaryotic stress signals and trigger the activation of heat shock genes. Science 1986;232:522–4.[Abstract/Free Full Text]

This article has been cited by other articles:

				D. A. Zvara, A. J. Bryant, D. D. Deal, M. P. DeMarco, K. M. Campos, C. M. Mansfield, and M. Tytell Anesthetic preconditioning with sevoflurane does not protect the spinal cord after an ischemic-reperfusion injury in the rat. Anesth. Analg., May 1, 2006; 102(5): 1341 - 1347. [Abstract] [Full Text] [PDF]

				I. K. Toumpoulis Immediate ischemic preconditioning for spinal cord protection following descending thoracic aortic cross-clamping Eur. J. Cardiothorac. Surg., January 1, 2006; 29(1): 126 - 126. [Full Text] [PDF]

				M. Basaran, E. Kafali, O. Sayin, M. Ugurlucan, M. H. Us, C. Bayindir, A. T. Yilmaz, and E. Dayioglu Heat stress increases the effectiveness of early ischemic preconditioning in spinal cord protection Eur. J. Cardiothorac. Surg., September 1, 2005; 28(3): 467 - 472. [Abstract] [Full Text] [PDF]

				I. S. B. Contreras, L. F. P. Moreira, G. Ballester, B. A. de Monaco, C. L. P. Lancellotti, A. R. Dias, and S. A. Oliveira Immediate ischemic preconditioning based on somatosensory evoked potentials seems to prevent spinal cord injury following descending thoracic aorta cross-clamping Eur. J. Cardiothorac. Surg., August 1, 2005; 28(2): 274 - 279. [Abstract] [Full Text] [PDF]

				C. S. Isbir, K. Ak, O. Kurtkaya, U. Zeybek, S. Akgun, B. W. Scheitauer, A. Sav, and A. Cobanoglu Ischemic preconditioning and nicotinamide in spinal cord protection in an experimental model of transient aortic occlusion Eur. J. Cardiothorac. Surg., June 1, 2003; 23(6): 1028 - 1033. [Abstract] [Full Text] [PDF]

				D. J. Caparrelli, S. M. Cattaneo II, B. T. Bethea, J. G. Shake, C. Eberhart, M. E. Blue, E. Marban, M. V. Johnston, W. A. Baumgartner, and V. L. Gott Pharmacological preconditioning ameliorates neurological injury in a model of spinal cord ischemia Ann. Thorac. Surg., September 1, 2002; 74(3): 838 - 845. [Abstract] [Full Text] [PDF]

				S. Kazama, Y. Miyoshi, M. Nie, H. Imai, Z. B. Lin, A. Kurata, and M. Machii Protection of the spinal cord with pentobarbital and hypothermia Ann. Thorac. Surg., May 1, 2001; 71(5): 1591 - 1595. [Abstract] [Full Text] [PDF]

				M. Matsumoto, K. Ohtake, H. Wakamatsu, S. Oka, T. Kiyoshima, K. Nakakimura, and T. Sakabe The Time Course of Acquisition of Ischemic Tolerance and Induction of Heat Shock Protein 70 after a Brief Period of Ischemia in the Spinal Cord in Rabbits Anesth. Analg., February 1, 2001; 92(2): 418 - 423. [Abstract] [Full Text] [PDF]

				V. S. Abraham, J. A. Swain, A. J. Forgash, B. L. Williams, and M. M. Musulin Ischemic preconditioning protects against paraplegia after transient aortic occlusion in the rat Ann. Thorac. Surg., February 1, 2000; 69(2): 475 - 479. [Abstract] [Full Text] [PDF]

				D. A. Zvara, D. M. Colonna, D. D. Deal, J. C. Vernon, M. Gowda, and J. C. Lundell Ischemic preconditioning reduces neurologic injury in a rat model of spinal cord ischemia Ann. Thorac. Surg., September 1, 1999; 68(3): 874 - 880. [Abstract] [Full Text] [PDF]

				H. T. Lee, R. Bolli, and M. A. Leesar Adenosine Pretreatment of Human Myocardium and Ischemic Preconditioning • Response Circulation, June 9, 1998; 97(22): 2279 - 2279. [Full Text]

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Katsuhiko Matsuyama Yukio Chiba Akio Ihaya Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matsuyama, K. Articles by Muraoka, R. Search for Related Content PubMed PubMed Citation Articles by Matsuyama, K. Articles by Muraoka, R.