Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
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.
Coronary microembolization: the role of TNF-alpha in contractile dysfunction.
J Mol Cell Cardiol. 2002; 34(1):51-62
Doi: 10.1006/jmcc.2001.1489
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Post Heiner
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Coronary microembolization is a frequent complication of atherosclerotic plaque rupture in acute coronary syndromes and during coronary interventions. Experimental coronary microembolization results in progressive contractile dysfunction associated with a local inflammation. We studied the causal role of tumor necrosis factor-alpha (TNF-alpha) in the progressive contractile dysfunction resulting from coronary microembolization. Anesthetized dogs were subjected to either coronary microembolization with infusion of 3.000 microspheres (42 microm diameter) per ml coronary inflow into the left circumflex coronary artery (n=9), or to intracoronary infusion of recombinant human TNF-alpha without microembolization (n=4), or to treatment with anti-murine TNF-alpha sheep antibodies prior to microembolization (n=4). Posterior systolic wall thickening (PWT; sonomicrometry) decreased from 21.1+/-5.3% (s.d.) at baseline to 5.5+/-2.2% (P<0.05) at 8 h after microembolization. Infarct size (1.8+/-1.9%; TTC and histology) and the amount of apoptosis (<0.1%; TUNEL and DNA-laddering) were small. TNF-alpha at the protein level (WEHI cytolytic assay) was increased and localized to leukocytes (immunostaining), which were increased in number (quantitative histology). In situ hybridization for TNF-alpha mRNA identified viable cardiomyocytes surrounding the microinfarcts as the major source of TNF-alpha. Supporting the role of TNF-alpha, infusion of TNF-alpha without microembolization decreased PWT from 27.3+/-6.9% at baseline to 10.1+/-4.9% after 8 h (P<0.05); in contrast, in the presence of TNF-alpha antibodies, microembolization no longer reduced PWT (19.3+/-7.0% at baseline v 16.9+/-5.0% at 8 h). In conclusion, TNF-alpha is the mediator responsible for the profound contractile dysfunction following coronary microembolization.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis -
- Arteriosclerosis - physiopathology
- Coronary Circulation - drug effects
- Dogs - drug effects
- Immunohistochemistry - drug effects
- In Situ Hybridization - drug effects
- In Situ Nick-End Labeling - drug effects
- Leukocytes - metabolism
- Microcirculation - physiology
- Microscopy, Fluorescence - physiology
- Myocardial Contraction - physiology
- Myocardial Infarction - physiology
- Necrosis - physiology
- RNA, Messenger - metabolism
- Regional Blood Flow - metabolism
- Time Factors - metabolism
- Tumor Necrosis Factor-alpha - metabolism
- Find related publications in this database (Keywords)
- microspheres
- microcirculation
- inflammation
- ischemia