Myocardial dysfunction with coronary microembolization -: Signal transduction through a sequence of nitric oxide, tumor necrosis factor-α, and sphingosine

被引:172
作者
Thielmann, M [1 ]
Dörge, H [1 ]
Martin, C [1 ]
Belosjorow, S [1 ]
Schwanke, U [1 ]
van de Sand, A [1 ]
Konietzka, I [1 ]
Büchert, A [1 ]
Krüger, A [1 ]
Schulz, R [1 ]
Heusch, G [1 ]
机构
[1] Univ Essen Gesamthsch Klinikum, Zentrum Innere Med, Abt Pathophysiol, D-45122 Essen, Germany
关键词
coronary microembolization; tumor necrosis factor-alpha; nitric oxide; sphingosine;
D O I
10.1161/01.RES.0000014451.75415.36
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Coronary microembolization results in progressive myocardial dysfunction, with causal involvement of tumor necrosis factor-alpha (TNF-alpha). TNF-a uses a signal transduction involving nitric oxide (NO) and/or sphingosine. Therefore, we induced coronary microembolization in anesthetized dogs and studied the role and sequence of NO, TNF-a, and sphingosine for the evolving contractile dysfunction. Four sham-operated dogs served as controls (group 1). Eleven dogs received placebo (group 2), 6 dogs received the NO synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME, group 3), and 6 dogs received the ceramidase inhibitor N-oleoylethanolamine (NOE, group 4) before microembolization was induced by infusion of 3000 microspheres (42-mum diameter) per milliliter inflow into the left circumflex coronary artery. Posterior systolic wall thickening (PWT) remained unchanged in group I but decreased progressively in group 2 from 20.6+/-4.9% (mean+/-SD) at baseline to 4.1+/-3.7% at 8 hours after microembolization. Leukocyte count, TNF-a, and sphingosine contents were increased in the microembolized posterior myocardium. In group 3, PWT remained unchanged (20.3+/-2.67% at baseline) with intracoronary administration of L-NAME (20.8+/-3.4%) and 17.7+/-2.3% at 8 hours after microembolization; TNF-a and sphingosine contents were not increased. In group 4, PWT also remained unchanged (20.7+/-4.6% at baseline) with intravenous administration of NOE (19.5+/-5.7%) and 16.4+/-6.3% at 8 hours after microembolization; TNF-alpha, but not sphingosine content, was increased. In all groups, systemic hemodynamics, anterior systolic wall thickening, and regional myocardial blood flow remained unchanged throughout the protocols. A signal transduction cascade of NO, TNF-a, and sphingosine is causally involved in the coronary microembolization-induced progressive contractile dysfunction.
引用
收藏
页码:807 / 813
页数:7
相关论文
共 51 条
[11]   Coronary microembolization:: The role of TNF-α in contractile dysfunction [J].
Dörge, H ;
Schulz, R ;
Belosjorow, S ;
Post, H ;
van de Sand, A ;
Konietzka, I ;
Frede, S ;
Hartung, T ;
Vinten-Johansen, J ;
Youker, KA ;
Entman, ML ;
Erbel, R ;
Heusch, G .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2002, 34 (01) :51-62
[12]   Perfusion-contraction mismatch with coronary microvascular obstruction:: role of inflammation [J].
Dörge, H ;
Neumann, T ;
Behrends, M ;
Skyschally, A ;
Schulz, R ;
Kasper, C ;
Heusch, G .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2000, 279 (06) :H2587-H2592
[13]   Effects of tumour necrosis factor-α on left ventricular function in the rat isolated perfused heart:: possible mechanisms for a decline in cardiac function [J].
Edmunds, NJ ;
Lal, H ;
Woodward, B .
BRITISH JOURNAL OF PHARMACOLOGY, 1999, 126 (01) :189-196
[14]   ATTENUATION OF MYOCARDIAL STUNNING BY THE ACE-INHIBITOR RAMIPRILAT THROUGH A SIGNAL CASCADE OF BRADYKININ AND PROSTAGLANDINS BUT NOT NITRIC-OXIDE [J].
EHRING, T ;
BAUMGART, D ;
KRAJCAR, M ;
HUMMELGEN, M ;
KOMPA, S ;
HEUSCH, G .
CIRCULATION, 1994, 90 (03) :1368-1385
[15]   NITRIC OXIDE-RELEASING AGENTS ENHANCE CYTOKINE-INDUCED TUMOR-NECROSIS-FACTOR SYNTHESIS IN HUMAN MONONUCLEAR-CELLS [J].
EIGLER, A ;
SINHA, B ;
ENDRES, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 196 (01) :494-501
[16]   THE RELEVANCE OF PLATELET AND FIBRIN THROMBOEMBOLISM OF THE CORONARY MICRO-CIRCULATION, WITH SPECIAL REFERENCE TO SUDDEN CARDIAC DEATH [J].
ELMARAGHI, N ;
GENTON, E .
CIRCULATION, 1980, 62 (05) :936-944
[17]   Coronary microembolization [J].
Erbel, R ;
Heusch, G .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2000, 36 (01) :22-24
[18]  
FALK E, 1983, BRIT HEART J, V50, P127
[19]   NEGATIVE INOTROPIC EFFECTS OF CYTOKINES ON THE HEART MEDIATED BY NITRIC-OXIDE [J].
FINKEL, MS ;
ODDIS, CV ;
JACOB, TD ;
WATKINS, SC ;
HATTLER, BG ;
SIMMONS, RL .
SCIENCE, 1992, 257 (5068) :387-389
[20]  
Flach R, 1997, J ENDOTOXIN RES, V4, P241, DOI 10.1177/096805199700400401