Document Detail

Toll-like receptor 2 signaling triggers fatal arrhythmias upon myocardial ischemia-reperfusion.
MedLine Citation:
PMID:  20855990     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Restoration of myocardial blood flow after ischemia triggers an inflammatory response involving toll-like receptors. Toll-like receptor 2 deficiency is associated with a reduced infarct size after myocardial ischemia and reperfusion. Because a marked mortality was observed in C3HeN wild-type mice, which was absent in TLR2 mice, we tested whether cardiac arrhythmias are the underlying pathology and aimed to elucidate how toll-like receptor 2 ligation might prevent lethal arrhythmias. DESIGN: Experimental animal model. SETTING: University hospital research laboratory. SUBJECTS: Male C3HeN mice. INTERVENTIONS: Myocardial ischemia and reperfusion was surgically induced by ligation of the left anterior descending coronary artery for 20 mins followed by 24 hrs of reperfusion. Electrocardiography was continuously recorded during the observation period through an implantable telemetry transmitter to detect cardiac arrhythmias during reperfusion. MEASUREMENTS AND MAIN RESULTS: Toll-like receptor 2 expression was associated with a 51% mortality rate (23 of 45 mice died) after myocardial ischemia and reperfusion. Absence of toll-like receptor 2 improved survival toward 100% (17 of 17 mice survived). Electrocardiography diagnostics in conscious animals and histologic analysis revealed that absence of toll-like receptor 2 signaling prevented the formation of pathologic heart rate turbulence after myocardial ischemia and reperfusion and modulated the density of connexin 43-positive gap junctions in the ischemic area compared with wild-type hearts, indicating arrhythmia as the cause underlying the observed mortality. CONCLUSIONS: The results presented here indicate toll-like receptor 2 as a novel target for the prevention of lethal arrhythmic complications after myocardial ischemia and reperfusion.
Jan Mersmann; Alexander Koch; Nguyen Tran; René Zimmermann; Tiago F Granja; Jan Larmann; Christine Herzog; Gregor Theilmeier; Stefan R Bornstein; Carsten J Kirschning; Kai Zacharowski
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  38     ISSN:  1530-0293     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-21     Completed Date:  2010-10-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1927-32     Citation Subset:  AIM; IM    
Clinic of Anaesthesiology, Intensive Care Medicine, and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany.
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MeSH Terms
Arrhythmias, Cardiac / mortality,  physiopathology*
Connexin 43 / analysis,  physiology
Disease Models, Animal
Gap Junctions / chemistry,  physiology
Heart Rate / physiology
Mice, Inbred C3H
Mice, Knockout
Myocardial Ischemia / physiopathology*
Myocardial Reperfusion* / mortality
Myocardium / chemistry
Signal Transduction
Toll-Like Receptor 2 / analysis,  biosynthesis,  physiology*
Troponin T / blood
Reg. No./Substance:
0/Connexin 43; 0/Toll-Like Receptor 2; 0/Troponin T
Comment In:
Crit Care Med. 2010 Oct;38(10):2062-3   [PMID:  20855992 ]

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