期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 34, 期 1, 页码 51-62出版社
ELSEVIER SCI LTD
DOI: 10.1006/jmcc.2001.1489
关键词
microspheres; microcirculation; inflammation; ischemia
资金
- NHLBI NIH HHS [HL 42550] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL042550] Funding Source: NIH RePORTER
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 mum 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. (C) 2002 Elsevier Science Ltd.
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