Inducible nitric oxide production is an adaptation to cardiopulmonary bypass-induced inflammatory response

被引:41
作者
Hayashi, Y
Sawa, Y
Fukuyama, N
Nakazawa, H
Matsuda, H
机构
[1] Osaka Univ, Grad Sch Med, Course Intervent Med E1, Dept Surg, Suita, Osaka 5650871, Japan
[2] Tokai Univ, Sch Med, Dept Physiol 2, Kanagawa 2591100, Japan
关键词
D O I
10.1016/S0003-4975(01)02637-6
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background. Cardiopulmonary bypass (CPB) increases nitric oxide (NO) production by the activation of NO synthases (NOS). However, the role of NO from inducible NOS (iNOS) in CPB-induced inflammatory response remains unclear. We examined the effect of a selective iNOS inhibitor, aminoguanidine, on CPB-induced inflammatory response in a rat-CPB model. Methods. Adult Sprague-Dawley rats underwent 60 minutes of CPB (100 mL (.) kg(-1 .) min(-1), 34 degreesC). Group A (n = 10) received 100 mg/kg of aminoguanidine intraperitoneally 30 minutes before the initiation of CFB, and group B (n = 10) served as controls. Results. There were significant time-dependent changes in plasma interleukin (IL)-6, IL-8, nitrate + nitrite, the percentage ratio of nitrotyrosine to tyrosine (%NO2- Tyr, an indicator of peroxynitrite formation), and respiratory index (RI). Three hours after CPB termination, IL-6, IL-8, and RI were significantly higher in group A (IL-6, 397.5 +/- 80.6 pg/mL; IL-8, 26.99 +/- 6.57 ng/mL; RI, 1.87 +/- 0.31) than in group B (IL-6, 316.5 +/- 73.9 pg/mL, p <0.05; IL-8, 17.21 +/- 3.12 ng/mL, p < 0.01; RI, 1.57 +/- 0.24, p < 0.05) although nitrate + nitrite (31.8 +/- 4.1 mu mol/L) and %NO2-Tyr (1.15% +/- 0.20%) were significantly lower in group A than in group B (nitrate + nitrite, 50.2 +/- 5.0 mu mol/L, p < 0.01; %NO2-Tyr, 1.46% +/- 0.21%, p < 0.01). Western immunoblot analysis from lung tissue of group A identified marked iNOS inhibition without inhibiting endothelial-constitutive NOS, and neutrophil accumulation in the lung specimens was significantly greater in group A (6.5 +/- 0.7/alveoli) than in group B (4.4 +/- 0.4/alveoli, p < 0.01). Conclusions. These results suggest that NO production from iNOS may be an adaptive response for attenuating the CPB-induced inflammatory response. (C) 2001 by The Society of Thoracic Surgeons.
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页码:149 / 155
页数:7
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共 35 条
  • [1] Successful weaning from cardiopulmonary bypass after cardiac surgery using inhaled nitric oxide
    Bichel, T
    SpahrSchopfer, I
    Berner, M
    Jaeggi, E
    Velkovski, Y
    Friedli, B
    Kalangos, A
    Faidutti, B
    Rouge, JC
    [J]. PAEDIATRIC ANAESTHESIA, 1997, 7 (04): : 335 - 339
  • [2] Differing patterns of P-selectin expression in lung injury
    Bless, NM
    Tojo, SJ
    Kawarai, H
    Natsume, Y
    Lentsch, AB
    Padgaonkar, VA
    Czermak, BJ
    Schmal, H
    Friedl, HP
    Ward, PA
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 1998, 153 (04) : 1113 - 1122
  • [3] Inducible nitric oxide synthase in the lung and exhaled nitric oxide after hyperoxia
    Cucchiaro, G
    Tatum, AH
    Brown, MC
    Camporesi, EM
    Daucher, JW
    Hakim, TS
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1999, 277 (03) : L636 - L644
  • [4] RELEASE OF VASOACTIVE SUBSTANCES DURING CARDIOPULMONARY BYPASS
    DOWNING, SW
    EDMUNDS, LH
    [J]. ANNALS OF THORACIC SURGERY, 1992, 54 (06) : 1236 - 1243
  • [5] 2-amino-4-methylpyridine as a potent inhibitor of inducible NO synthase activity in vitro and in vivo
    Faraci, WS
    Nagel, AA
    Verdries, KA
    Vincent, LA
    Xu, H
    Nichols, LE
    Labasi, JM
    Salter, ED
    Pettipher, ER
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1996, 119 (06) : 1101 - 1108
  • [6] Contribution of macrophages to pulmonary nitric oxide production in septic shock
    Fujii, Y
    Goldberg, P
    Hussain, SNA
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1998, 157 (05) : 1645 - 1651
  • [7] Peroxynitrite formation from activated human leukocytes
    Fukuyama, N
    Ichimori, K
    Su, Z
    Ishida, H
    Nakazawa, H
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 224 (02) : 414 - 419
  • [8] TRACKING RESPIRATORY THERAPY IN TRAUMA PATIENT
    GOLDFARB, MA
    CIUREJ, TF
    MCASLAN, TC
    SACCO, WJ
    WEINSTEIN, MA
    COWLEY, RA
    [J]. AMERICAN JOURNAL OF SURGERY, 1975, 129 (03) : 255 - 258
  • [9] ANALYSIS OF NITRATE, NITRITE, AND [N-15]-LABELED NITRATE IN BIOLOGICAL-FLUIDS
    GREEN, LC
    WAGNER, DA
    GLOGOWSKI, J
    SKIPPER, PL
    WISHNOK, JS
    TANNENBAUM, SR
    [J]. ANALYTICAL BIOCHEMISTRY, 1982, 126 (01) : 131 - 138
  • [10] P-selectin participates in cardiopulmonary bypass-induced inflammatory response in association with nitric oxide and peroxynitrite production
    Hayashi, Y
    Sawa, Y
    Nishimura, M
    Tojo, SJ
    Fukuyama, N
    Nakazawa, H
    Matsuda, H
    [J]. JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 2000, 120 (03) : 558 - 565