Abstract
Restenosis occurs in approximately one-third of patients with coronary or peripheral vascular disease who undergo balloon angioplasty or a surgical bypass procedure primarily because of the development of pseudointimal hyperplasia (PIH). Corticosteroids were effective in suppressing PIH in several experimental studies, but no clinical studies have been reported. To resolve this discrepancy, we studied the effects of preinjury administration of several doses of methylprednisolone (MP) at targeted times in a rat model of balloon aortic injury. Rats were given either no treatment or an intravenous injection of MP (0.5, 5.0, 50, or 500 mg/kg) 2 hours before aortic injury. Four hours later interleukin-6 (IL-6), IL-10, and macrophage migration inhibitory factor (MIF) concentrations in serum and tissue of injured aortas were assessed. Two weeks after injury, damaged aortas were harvested and studied histopathologically. Compared with results in controls, MP at a dose of 5 mg/kg significantly inhibited increases in plasma and tissue levels of IL-6 and significantly reduced the pseudointimal area, pseudointimal/medial area ratio, and proliferating cell nuclear antigen index in injured vessels. Administration of MP had no significant effect on the IL-10 or MIF level. Thus in a rat model of balloon aortic injury, preinjury administration of MP 5 mg/kg mitigated the development of PIH and cell proliferation and suppressed the postinjury increase in serum and tissue IL-6 concentrations. These results suggest that there is an appropriate dosage as well as appropriate timing for MP administration to suppress PIH.
Similar content being viewed by others
References
LM Taylor SuffixJr RD DeFrang EJ Harris SuffixJr et al. (1991) ArticleTitleThe association of elevated plasma homocyst(e)ine with progression of symptomatic peripheral arterial disease J. Vasc. Surg. 13 128–136 Occurrence Handle1987384
R Berguer RF Higgins DJ Reddy (1980) ArticleTitleIntimal hyperplasia: an experimental study Arch. Surg. 115 332–335 Occurrence Handle1:STN:280:Bi%2BC38bksFY%3D Occurrence Handle7356389
R Ross (1993) ArticleTitleThe pathogenesis of atherosclerosis: a perspective for the 1990s Nature 362 801–809 Occurrence Handle10.1038/362801a0 Occurrence Handle1:CAS:528:DyaK3sXktVGqu7c%3D Occurrence Handle8479518
K Bendtzen (1988) ArticleTitleInterleukin 1, interleukin 6 and tumor necrosis factor in infection, inflammation and immunity Immunol. Lett. 19 182–191 Occurrence Handle10.1016/0165-2478(88)90141-1
A Shenkin WD Fraser J Series et al. (1989) ArticleTitleThe serum interleukin 6 response to elective surgery Lymphokine Res. 8 123–127 Occurrence Handle1:STN:280:BiaB1c%2FnsFQ%3D Occurrence Handle2786596
N Haeffner-Cavaillon N Roussellier O Ponzio et al. (1989) ArticleTitleInduction of interleukin-1 production in patients undergoing cardiopulmonary bypass J. Thorac. Cardiovasc. Surg. 98 1100–1106 Occurrence Handle1:STN:280:By%2BD28rmtFI%3D Occurrence Handle2586127
JB Dahl H Kehlet (1991) ArticleTitleNon-steroidal anti-inflammatory drugs: rationale for use in severe postoperative pain Br. J. Anaesth. 66 703–712 Occurrence Handle1:STN:280:By6B1M7ls1I%3D Occurrence Handle2064886
JF Hansbrough RL Zapata-Sirvent EM Bender (1986) ArticleTitlePrevention of alterations in postoperative lymphocyte subpopulations by cimetidine and ibuprofen Am. J. Surg. 151 249–255 Occurrence Handle10.1016/0002-9610(86)90080-2 Occurrence Handle1:STN:280:BimC38jpvVY%3D Occurrence Handle3484914
A Munck PM Guyre NJ Holbrook (1984) ArticleTitlePhysiological functions of glucocorticoids in stress and their relation to pharmacological actions Endocr. Rev. 5 25–44 Occurrence Handle1:CAS:528:DyaL2cXhvVGrtrk%3D Occurrence Handle6368214
RM Engelman JA Rousou JE Flack SuffixIII et al. (1995) ArticleTitleInfluence of steroids on complement and cytokine generation after cardiopulmonary bypass Ann. Thorac. Surg. 60 801–804 Occurrence Handle10.1016/0003-4975(95)00211-3 Occurrence Handle1:STN:280:ByqH3cfgsVI%3D Occurrence Handle7677537
GE Hill A Alonso JR Spurzem et al. (1995) ArticleTitleAprotinin and methylprednisolone equally blunt cardiopulmonary bypass-induced inflammation in humans J. Thorac. Cardiovasc. Surg. 110 1658–1662 Occurrence Handle1:STN:280:BymC3c7ns1c%3D Occurrence Handle8523876
KH Teoh CA Bradley J Gauldie et al. (1995) ArticleTitleSteroid inhibition of cytokine-mediated vasodilation after warm heart surgery Circulation 92 347–353
T Kawamura K Inada H Okada et al. (1995) ArticleTitleMethylprednisolone inhibits increase of interleukin 8 and 6 during open heart surgery Can. J. Anaesth. 42 399–403 Occurrence Handle1:STN:280:ByqA3sbltVQ%3D Occurrence Handle7614647
Y Tabardel J Duchateau D Schmartz et al. (1996) ArticleTitleCorticosteroids increase blood interleukin-10 levels during cardiopulmonary bypass in men Surgery 119 76–80 Occurrence Handle1:STN:280:BymC2cvmsFI%3D Occurrence Handle8560390
M Seghaye J Duchateau J Bruniaux et al. (1996) ArticleTitleInterleukin-10 release related to cardiopulmonary bypass in infants undergoing cardiac operations J. Thorac. Cardiovasc. Surg. 111 545–553 Occurrence Handle1:STN:280:BymC2snpt1U%3D Occurrence Handle8601968
N Sato K Koeda K Ikeda et al. (2002) ArticleTitleRandomized study of the benefits of preoperative corticosteroid administration on the postoperative morbidity and cytokine response in patients undergoing surgery for esophageal cancer Ann. Surg. 236 184–190 Occurrence Handle10.1097/00000658-200208000-00006 Occurrence Handle12170023
W Huang M Richardson MZ Alavi et al. (1984) ArticleTitleProteoglycan distribution in rat aortic wall following indwelling catheter injury Atherosclerosis 51 59–74 Occurrence Handle1:CAS:528:DyaL2cXitVOgtL0%3D Occurrence Handle6202306
T Ogata M Kurabayashi Y Hoshino et al. (2000) ArticleTitleInducible expression of basic transcription element-binding protein 2 in proliferating smooth muscle cells at the vascular anastomotic stricture J. Thorac. Cardiovasc. Surg. 119 983–989 Occurrence Handle1:CAS:528:DC%2BD3cXktVOgtLo%3D Occurrence Handle10788819
XM Pan N Nelken N Colyvas et al. (1992) ArticleTitleInhibition of injury induced intimal hyperplasia by saralasin in rats J. Vasc. Surg. 15 693–698 Occurrence Handle10.1067/mva.1992.33295 Occurrence Handle1:STN:280:By2B3MbksVY%3D Occurrence Handle1560560
PH Groves AP Banning WJ Penny et al. (1995) ArticleTitleKinetics of smooth muscle cell proliferation and intimal thickening in a pig carotid model of balloon injury Atherosclerosis 117 83–96 Occurrence Handle10.1016/0021-9150(95)05562-B Occurrence Handle1:CAS:528:DyaK2MXnt1Kkt7Y%3D Occurrence Handle8546758
RG Macdonald RP Panush CJ Pepine (1987) ArticleTitleRationale for use of glucocorticoids in modification of restenosis after percutaneous transluminal coronary angioplasty Am. J. Cardiol. 60 56B–60B Occurrence Handle10.1016/0002-9149(87)90486-3 Occurrence Handle1:STN:280:BiiB1MrnsVE%3D Occurrence Handle2956845
JB Gordon BC Berk MA Bettmann et al. (1987) ArticleTitleVascular smooth muscle proliferation following balloon injury is synergistically inhibited by low molecular weight heparin and hydrocortisone Circulation 76 213
MD Colburn WS Moore HA Gelabert et al. (1992) ArticleTitleDose responsive suppression of myointimal hyperplasia by dexamethasone J. Vasc. Surg. 15 510–518 Occurrence Handle10.1067/mva.1992.32078 Occurrence Handle1:STN:280:By2C28jks1M%3D Occurrence Handle1538508
GW Stone BD Rutherford DR McConahay et al. (1989) ArticleTitleA randomized trial of corticosteroids for the prevention of restenosis in 102 patients undergoing repeat coronary angioplasty Cathet. Cardiovasc. Diagn. 18 227–231 Occurrence Handle1:STN:280:By%2BC3cnmtFE%3D Occurrence Handle2691100
CJ Pepine JW Hirshfeld RG Macdonald et al. (1990) ArticleTitleA controlled trial of corticosteroids to prevent restenosis after coronary angioplasty: M-HEART group Circulation 81 1753–1761 Occurrence Handle1:STN:280:By%2BB28zisl0%3D Occurrence Handle2188753
D Pearce KR Yamamoto (1993) ArticleTitleMineralcorticoid and glucocorticoid receptor activities distintinguished by nonreceptor factors at a composite response element Science 259 1161–1165
RI Scheinman A Gualberto CM Jewell et al. (1995) ArticleTitleCharacterization of mechanisms involved in transrepression of NF-κB by activated glucocorticoid receptors Mol. Cell. Biol. 15 943–953 Occurrence Handle1:CAS:528:DyaK2MXjtlant70%3D Occurrence Handle7823959
SS Staubbs (1975) ArticleTitleCorticosteroids and bioavailability Transplant. Proct. 7 11–19
LE Fisher EA Ludwig JA Wald et al. (1992) ArticleTitlePharmacokinetics and pharmacodynamics of methylprednisolone when administered at 8 AM versus 4 PM Clin. Pharmacol. Ther. 51 677–688 Occurrence Handle1:CAS:528:DyaK38Xks1ehtLw%3D Occurrence Handle1535301
ML Alegre P Vandenabeele M Depierreux et al. (1991) ArticleTitleCytokine release syndrome induced by the 145-2C11 anti-CD3 monoclonal antibody in mice: prevention by high doses of methylprednisolone J. Immunol. 146 1184–1191 Occurrence Handle1:CAS:528:DyaK3MXlt1Ont70%3D Occurrence Handle1825107
U Ikeda M Ikeda T Oohara et al. (1991) ArticleTitleInterleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner Am. J. Physiol. 260 H1713–H1717 Occurrence Handle1:CAS:528:DyaK3MXkt1Onsbs%3D Occurrence Handle1709793
Y Hojo U Ikeda T Katsuki et al. (2000) ArticleTitleInterleukin 6 expression in coronary circulation after coronary angioplasty as a risk factor for restenosis Heart 84 83–87 Occurrence Handle10.1136/heart.84.1.83 Occurrence Handle1:STN:280:DC%2BD3czitFajug%3D%3D Occurrence Handle10862597
Z Mallat C Heymes J Ohan et al. (1999) ArticleTitleExpression of interleukin-10 in advanced human atherosclerotic plaques: relation to inducible nitric oxide synthase expression and cell death Arterioscler. Thromb. Vasc. Biol. 19 611–616 Occurrence Handle1:CAS:528:DyaK1MXitFGnsLg%3D Occurrence Handle10073964
DF Fiorentino A Zlotnik TR Mosmann et al. (1991) ArticleTitleIL-10 inhibits cytokine production by activated macrophages J. Immunol. 147 3815–3822 Occurrence Handle1:CAS:528:DyaK38XlslSgug%3D%3D Occurrence Handle1940369
T Krakauer (1995) ArticleTitleIL-10 inhibits the adhesion of leukocytic cells to IL-1-activated human endothelial cells Immunol. Lett. 45 61–65 Occurrence Handle10.1016/0165-2478(94)00226-H Occurrence Handle1:CAS:528:DyaK2MXkvFGqu7c%3D Occurrence Handle7542627
CH Selzman DR Meldrum BS Cain et al. (1998) ArticleTitleInterleukin-10 inhibits postinjury tumor necrosis factor-mediated human vascular smooth muscle proliferation J. Surg. Res. 80 352–356 Occurrence Handle10.1006/jsre.1998.5486 Occurrence Handle1:CAS:528:DyaK1MXlt1Snug%3D%3D Occurrence Handle9878337
LJ Feldman L Aguirre M Ziol et al. (2000) ArticleTitleInterleukin-10 inhibits intimal hyperplasia after angioplasty or stent implantation in hypercholesterolemic rabbits Circulation 101 908–916 Occurrence Handle1:CAS:528:DC%2BD3cXhvVOgurg%3D Occurrence Handle10694531
Y Yamashita M Shimada T Hamatsu et al. (2001) ArticleTitleEffects of preoperative steroid administration on surgical stress in hepatic resection: prospective randomized trial Arch. Surg. 136 328–333 Occurrence Handle10.1001/archsurg.136.3.328 Occurrence Handle1:CAS:528:DC%2BD3MXitF2is7c%3D Occurrence Handle11231856
BR Bloom B Bennett (1966) ArticleTitleMechanism of a reaction in vitro associated with delayed-type hypersensitivity Science 153 80–82
T Calandra J Bernhagen CN Metz et al. (1995) ArticleTitleMIF as a glucocorticoid-induced modulator of cytokine production Nature 377 68–71 Occurrence Handle1:CAS:528:DyaK2MXnvFektb8%3D Occurrence Handle7659164
SG Lin XY Yu YX Chen et al. (2000) ArticleTitleDe novo expression of macrophage migration inhibitory factor in atherogenesis in rabbits Circ. Res. 87 1202–1208 Occurrence Handle1:CAS:528:DC%2BD3cXoslynurw%3D Occurrence Handle11110779
JA Elias V Lentz (1990) ArticleTitleIL-1 and tumor necrosis factor synergistically stimulate fibroblast IL-6 production and stabilize IL-6 messenger RNA J. Immunol. 145 161–166 Occurrence Handle1:CAS:528:DyaK3cXltFemsbw%3D Occurrence Handle2358670
K Imamura F Hayashi A Suzumura (1992) ArticleTitleCytokine production by peripheral blood monocytes/macrophages in patients with multiple sclerosis and its suppression by methylprednisolone Rinsho Shinkeigaku 32 276–280 Occurrence Handle1:STN:280:By2A3s7jtlQ%3D Occurrence Handle1628450
EE Gabeler R Hillegersberg ParticleVan RG Statius-Van-Eps et al. (2002) ArticleTitleA comparison of balloon injury model of endovascular lesions in rat arteries B.M.C. Cardiovasc. Disord. 2 16 Occurrence Handle10.1186/1471-2261-2-16
AW Clowes MA Reidy MM Clowers (1983) ArticleTitleKinetics of cellular proliferation after arterial injury Lab. Invest. 49 327–333 Occurrence Handle1:STN:280:BiyB1MrlvFY%3D Occurrence Handle6887785
AW Clowes MA Reidy MM Clowers (1983) ArticleTitleMechanisms of stenosis after arterial injury Lab. Invest. 49 208–215 Occurrence Handle1:STN:280:BiyB28bnvFY%3D Occurrence Handle6876748
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nagasaki, K., Matsumoto, K., Kaneda, M. et al. Effects of Preinjury Administration of Corticosteroids on Pseudointimal Hyperplasia and Cytokine Response in a Rat Model of Balloon Aortic Injury. World J. Surg. 28, 910–916 (2004). https://doi.org/10.1007/s00268-004-7457-6
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00268-004-7457-6