PMID- 17316703
OWN - NLM
STAT- MEDLINE
DCOM- 20070522
LR  - 20070813
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 80
IP  - 18
DP  - 2007 Apr 10
TI  - TNFalpha is required to confer protection in an in vivo model of classical 
      ischaemic preconditioning.
PG  - 1686-91
AB  - Although Tumor Necrosis Factor alpha (TNFalpha) is used as a preconditioning 
      mimetic in vitro, its role in ischaemic preconditioning (IPC) has not been 
      clearly defined. Here, we propose to use an in vivo model (that takes into 
      account the activation of leukocytes which may affect levels of TNFalpha) to 
      demonstrate that i) TNFalpha acts as a trigger in IPC and ii) the dose-dependent 
      nature of this cardioprotective effect of TNFalpha. Male Wistar rats were 
      subjected to 30 min of left coronary artery occlusion (index ischaemia), followed 
      by 24 h reperfusion. In the presence or absence of a soluble TNFalpha receptor 
      (sTNFalpha-R), preconditioning was induced by 3 cycles of ischaemia (3 
      min)/reperfusion (5 min) (IPC) or various doses (0.05-4 microg/kg) of exogenous 
      TNFalpha. Following 24 h reperfusion, infarct size (IS, expressed as % of the 
      area at risk (AAR)) was assessed. Tissue levels of TNFalpha from the AAR, 
      following IPC and TNFalpha stimulus were determined using Western Blot. IPC 
      caused decrease in IS (4.5+/-1.3% vs 30.8+/-4.3% in ischaemic rats; P<0.001) and 
      increase of TNFalpha levels following the IPC stimulus. The protective effect of 
      IPC was abrogated in the presence of the sTNFalpha-R. In addition, exogenous 
      TNFalpha dose-dependently reduced IS with maximal protection at a dose of 0.1 
      microg/kg (IS=12.6%, P<0.01 vs ischaemic). In conclusion our data provide strong 
      evidence for a role of TNFalpha during the trigger phase of IPC. In addition, 
      exogenous TNFalpha mimics IPC by providing a dose-dependent cardioprotective 
      effect against ischaemia-reperfusion injury in vivo.
FAU - Deuchar, Graeme A
AU  - Deuchar GA
AD  - Hatter Institute for Cardiology Research, Department of Medicine, Cape Heart 
      Centre, Faculty of Health Sciences, University of Cape Town, Observatory 7925, 
      South Africa. gdeuchar@staffmail.ed.ac.uk
FAU - Opie, Lionel H
AU  - Opie LH
FAU - Lecour, Sandrine
AU  - Lecour S
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070130
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Cardiotonic Agents/*metabolism/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - *Ischemic Preconditioning, Myocardial
MH  - Male
MH  - Myocardial Infarction/drug therapy/metabolism/pathology
MH  - Myocardial Reperfusion Injury/*drug therapy/metabolism/pathology
MH  - Rats
MH  - Rats, Wistar
MH  - *Receptors, Tumor Necrosis Factor
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/*metabolism/*pharmacology
EDAT- 2007/02/24 09:00
MHDA- 2007/05/23 09:00
CRDT- 2007/02/24 09:00
PHST- 2006/10/10 00:00 [received]
PHST- 2007/01/16 00:00 [revised]
PHST- 2007/01/24 00:00 [accepted]
PHST- 2007/02/24 09:00 [pubmed]
PHST- 2007/05/23 09:00 [medline]
PHST- 2007/02/24 09:00 [entrez]
AID - S0024-3205(07)00105-1 [pii]
AID - 10.1016/j.lfs.2007.01.040 [doi]
PST - ppublish
SO  - Life Sci. 2007 Apr 10;80(18):1686-91. doi: 10.1016/j.lfs.2007.01.040. Epub 2007 
      Jan 30.