PMID- 9852905
OWN - NLM
STAT- MEDLINE
DCOM- 19990108
LR  - 20141120
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 98
IP  - 19 Suppl
DP  - 1998 Nov 10
TI  - Ischemic preconditioning decreases postischemic myocardial tumor necrosis 
      factor-alpha production. Potential ultimate effector mechanism of 
      preconditioning.
PG  - II214-8; discussion II218-9
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is an autocrine contributor 
      to myocardial dysfunction and cardiomyocyte death in ischemia-reperfusion (I/R) 
      injury, sepsis, chronic heart failure, and cardiac allograft rejection. Cardiac 
      resident macrophages, infiltrating leukocytes, and cardiomyocytes themselves 
      produce TNF-alpha. Although adenosine reduces macrophage TNF-alpha production and 
      protects myocardium against I/R, it remains unknown whether ischemic 
      preconditioning, which is mediated by adenosine, decreases postischemic 
      myocardial TNF-alpha production. METHODS AND RESULTS: Isolated rat hearts were 
      crystalloid perfused with the Langendorff method and subjected to global, 
      normothermic I/R (20/40 minutes), with or without prior transient ischemic 
      preconditioning (5 minutes) or adenosine pretreatment. Postischemic cardiac 
      TNF-alpha (ELISA) and function were determined (Langendorff). I/R increased 
      cardiac TNF-alpha and impaired myocardial function. Ischemic preconditioning or 
      adenosine decreased myocardial TNF-alpha and improved postischemic functional 
      recovery. Sequestration of myocardial TNF-alpha (TNF binding protein) during the 
      I/R experiments similarly improved postischemic myocardial function. CONCLUSIONS: 
      This study constitutes the initial demonstration that in addition to its other 
      beneficial effects, preconditioning decreases postischemic myocardial TNF-alpha, 
      an autocrine contributor to postischemic myocardial dysfunction. Reduced 
      myocardial TNF-alpha production may represent the distal effector mechanism of 
      preconditioning.
FAU - Meldrum, D R
AU  - Meldrum DR
AD  - Department of Surgery, University of Colorado Health Sciences Center, Denver 
      80262, USA.
FAU - Dinarello, C A
AU  - Dinarello CA
FAU - Shames, B D
AU  - Shames BD
FAU - Cleveland, J C Jr
AU  - Cleveland JC Jr
FAU - Cain, B S
AU  - Cain BS
FAU - Banerjee, A
AU  - Banerjee A
FAU - Meng, X
AU  - Meng X
FAU - Harken, A H
AU  - Harken AH
LA  - eng
GR  - GM-08315/GM/NIGMS NIH HHS/United States
GR  - HL-43696/HL/NHLBI NIH HHS/United States
GR  - HL-44186/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Heart/physiopathology
MH  - In Vitro Techniques
MH  - *Ischemic Preconditioning, Myocardial
MH  - Male
MH  - Myocardial Ischemia/*metabolism/physiopathology
MH  - Myocardium/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
EDAT- 1998/12/16 17:00
MHDA- 2001/03/28 10:01
CRDT- 1998/12/16 17:00
PHST- 1998/12/16 17:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1998/12/16 17:00 [entrez]
PST - ppublish
SO  - Circulation. 1998 Nov 10;98(19 Suppl):II214-8; discussion II218-9.