omega-3 Lipid infusion in a heart allotransplant model - Shift in fatty acid and lipid mediator profiles and prolongation of transplant survival

被引:33
作者
Grimminger, F [1 ]
Grimm, H [1 ]
Fuhrer, D [1 ]
Papavassilis, C [1 ]
Lindemann, G [1 ]
Blecher, C [1 ]
Mayer, K [1 ]
Tabesch, F [1 ]
Kramer, HJ [1 ]
Stevens, J [1 ]
Seeger, W [1 ]
机构
[1] UNIV GIESSEN, DEPT SURG, D-35392 GIESSEN, GERMANY
关键词
transplantation; leukotrienes; lipids; fatty acids; platelets;
D O I
10.1161/01.CIR.93.2.365
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background omega-3 Fatty acids may have a major impact on immune responses involved in heart transplant rejection. We compared the effects of posttransplant intravenous supplementation with omega-3-rich versus omega-6-rich lipid emulsions on graft survival, plasma fatty acid profiles, and levels of arachidonic acid versus eicosapentaenoic acid-derived lipid mediators. Methods and Results Inbred PVG and Wistar-Kyoto rats were used as donors and recipients, respectively, in a model of heterotopic heart transplantation. Animals received 9 g/kg body wt per day of either fish oil-derived (n=8) or soybean oil-derived fat (n=7) in the form of a continuously infused lipid emulsion; controls were sham-infused with saline (n=8). Graft rejection was assessed by loss of activity of the transplant. The fish oil-derived preparation but not that originating from soybean oil caused an increase in total and free plasma fatty acids. Substantial quantities of eicosapentaenoic acid and docosahexaenoic acid appeared in the free fatty acid fraction, surpassing those of arachidonic acid. Ex vivo stimulation of neutrophils with the Ca2+ ionophore A23187 demonstrated an increase in 5-series leukotriene (LT) generation in animals undergoing omega-3 lipid infusion (LTB(5), omega-oxidation products of LTB(5), LTA(5) secretion), with 5-series/4-series LT ratios ranging between 0.08 and 0.36. Ratios of TX B-3/B-2 liberated from ex vivo stimulated platelets even approached 1:1 in omega-3 supple mented rats. Graft survival was 7.6+/-0.3 (mean+/-SEM) days in saline-infused, 10.4+/-0.7 in omega-6 lipid-infused, acid 12.9+/-0.4 in omega-3 lipid-infused animals. Conclusions Posttransplant intravenous alimentation with fish oil-derived lipid emulsions prolongs heart transplant survival in excess to omega-6 lipids. Profound changes in fatty acid profiles and lipid mediator generation may underlie this finding.
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页码:365 / 371
页数:7
相关论文
共 35 条
[1]  
BILLINGHAM ME, 1990, J HEART TRANSPLANT, V9, P587
[2]   UPTAKE AND INCORPORATION OF SATURATED AND UNSATURATED FATTY-ACIDS INTO MACROPHAGE LIPIDS AND THEIR EFFECT UPON MACROPHAGE ADHESION AND PHAGOCYTOSIS [J].
CALDER, PC ;
BOND, JA ;
HARVEY, DJ ;
GORDON, S ;
NEWSHOLME, EA .
BIOCHEMICAL JOURNAL, 1990, 269 (03) :807-814
[3]  
CALDER PC, 1992, IMMUNOLOGY, V75, P108
[4]   CHRONIC THROMBOXANE INHIBITION PRESERVES FUNCTION OF REJECTING RAT RENAL-ALLOGRAFTS [J].
COFFMAN, TM ;
RUIZ, P ;
SANFILIPPO, F ;
KLOTMAN, PE .
KIDNEY INTERNATIONAL, 1989, 35 (01) :24-30
[5]   THE EFFECT OF DIETARY SUPPLEMENTATION WITH N-3 POLY-UNSATURATED FATTY-ACIDS ON THE SYNTHESIS OF INTERLEUKIN-1 AND TUMOR NECROSIS FACTOR BY MONONUCLEAR-CELLS [J].
ENDRES, S ;
GHORBANI, R ;
KELLEY, VE ;
GEORGILIS, K ;
LONNEMANN, G ;
VANDERMEER, JWM ;
CANNON, JG ;
ROGERS, TS ;
KLEMPNER, MS ;
WEBER, PC ;
SCHAEFER, EJ ;
WOLFF, SM ;
DINARELLO, CA .
NEW ENGLAND JOURNAL OF MEDICINE, 1989, 320 (05) :265-271
[6]  
FISHER S, 1983, BIOCHEM BIOPH RES CO, V116, P1091
[7]  
GRIMMINGER F, 1992, MOL PHARMACOL, V41, P757
[8]  
GRIMMINGER F, 1991, J BIOL CHEM, V266, P14262
[9]  
GRIMMINGER F, 1993, J PHARMACOL EXP THER, V267, P259
[10]   AMPLIFICATION OF LTB4 GENERATION IN AM-PMN COCULTURES - TRANSCELLULAR 5-LIPOXYGENASE METABOLISM [J].
GRIMMINGER, F ;
SIBELIUS, U ;
SEEGER, W .
AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 261 (02) :L195-L203