Bidirectional Role of Tumor Necrosis Factor-α in Coronary Microembolization

Skyschally, Andreas; Gres, Petra; Hoffmann, Simone; Haude, Michael; Erbel, Raimund; Schulz, Rainer; Heusch, Gerd

doi:10.1161/01.res.0000255031.15793.86

Cited by 143 publications

(51 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The combination of inflammatory cells and thrombi inside the blood vessels in subacute microinfarction may contribute to LV dysfunction (9,10,(48)(49)(50). The pattern of microinfarction crossing the LV wall was similar to that observed at autopsy in patients with coronary microembolization (43,51).…”

mentioning

confidence: 68%

“…Other investigators (47) also found a lack of correlation between regional function, by using electron-beam CT in beating hearts, and microinfarction volume, by using micro-CT in the excised hearts. This mismatch was attributed to the presence of inflammation, mediated by tumor necrosis factor-␣ around the microinfarcted region (periinfarction zone) (9,10,(48)(49)(50).…”

Section: Experimental Studies: Microinfarction After Coronary Microemmentioning

confidence: 99%

See 1 more Smart Citation

Myocardial Microinfarction after Coronary Microembolization in Swine: MR Imaging Characterization

Carlsson¹,

Wilson²,

Martin³

et al. 2009

Radiology

View full text Add to dashboard Cite

Purpose:To use first-pass perfusion and delayed-enhanced (DE) magnetic resonance (MR) imaging for the detection of the early effects of coronary microembolization on myocardial perfusion and viability. Materials and Methods:Approval was obtained from the institutional committee on animal research. A hybrid x-ray and MR imaging system was used to guide the endovascular catheter and quantify the left anterior descending coronary artery (LAD) perfusion territory before microembolization and ischemic myocardium and microinfarction after microembolization. The embolic agent was selectively delivered in the LAD in six pigs. First-pass perfusion MR imaging was performed 1 hour and 1 week after microembolization. Microinfarction was measured on DE MR images in beating and nonbeating hearts (high-spatial-resolution sequence) by using extracellular and blood pool MR contrast media and after death. The Wilcoxon signed rank test and correlation analysis were used. Results:The LAD perfusion territory was 35% of left ventricular (LV) mass Ϯ 2 (standard error of the mean). Microembolization caused perfusion deficit in 15.7% of LV mass Ϯ 2.6 compared with that of LAD territory (P ϭ .03). At 1 week, perfusion parameters improved and the extent of hypoperfused territory declined (4.6% of LV mass Ϯ 1.4, P ϭ .03). Microinfarction size expanded from 1.4% of LV mass Ϯ 0.2 at 1 hour to 7.5% of LV mass Ϯ 1.2 at 1 week. In nonbeating hearts and at triphenyltetrazolium chloride staining at 1 week, microinfarction size was 7.6% of LV mass Ϯ 1.4 and 7.2% of LV mass Ϯ 1.5, respectively. There was no correlation between the ejection fraction and the extents of microinfarction or hypoperfused territory. Histopathologic findings confirmed the presence of patchy microinfarction. Conclusion:Coronary microembolization caused persistent decline in myocardial perfusion at first-pass perfusion imaging. DE MR imaging has the potential to help reliably quantify subacute microinfarction. The magnitude of LV dysfunction is not related to the extents of microinfarction or hypoperfused territory. RSNA, 2009 See also Science to Practice in this issue. Note: This copy is for your personal, non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, use the Radiology Reprints form at the end of this article. Coronary microemboli fragmented from atherosclerotic plaque in acute coronary syndrome and unstable angina (1,2) and after reperfusion at percutaneous coronary intervention (3-7) cause microinfarction and release of myocardial ischemic markers. It is difficult to separate the effects of reperfusion injury (8) from distal microinfarction after coronary intervention because they overlap in an uncontrolled fashion. Furthermore, invasive physiologic studies (9-12) have shown that the magnitude of left ventricular (LV) dysfunction is not closely related to the mass of microinfarction. Methodologic difficulties have hindered the use of noninvasive techniques in simultaneously measuring and linking microinfarct...

show abstract

mentioning

confidence: 68%

Section: Experimental Studies: Microinfarction After Coronary Microemmentioning

confidence: 99%

Myocardial Microinfarction after Coronary Microembolization in Swine: MR Imaging Characterization

Carlsson¹,

Wilson²,

Martin³

et al. 2009

Radiology

View full text Add to dashboard Cite

show abstract

“…24 Whereas the present study revealed major differences in signal transduction by RISK between rodents and pigs, both sphingosine 25 and STAT3 26 are parts of the signal transduction of tumor necrosis factor (TNF)␣-induced cardioprotection, TNF␣-induced cardioprotection does not rely on AKT and ERK1/2, 26 and TNF␣ is also cardioprotective in pigs. 27 Thus, the role of STAT3 and sphingosine kinase in ischemic postconditioning in pigs or other large mammals should be studied further.…”

Section: Discussionmentioning

confidence: 99%

Ischemic Postconditioning in Pigs

Skyschally

Caster

Boengler

et al. 2009

Circulation Research

Self Cite

238

View full text Add to dashboard Cite

I schemic postconditioning (IPoC) reduces infarct size by attenuation of reperfusion injury 1 and is operative in all species studied so far, including humans. 2,3 The phosphorylation of RISK (reperfusion injury salvage kinases), ie, phosphatidylinositol 3-kinase/protein kinase B (PI3K-AKT), 4,5 mitogen-activated protein kinase kinase/extracellular signal regulated kinase (ERK) (MEK1/2-ERK1/2), 6 p70 ribosomal S6 protein kinase (P70S6K), and glycogen synthase kinase (GSK)3␤ was proposed to be causal for protection by IPoC. 4 -7 Activation of sarcolemmal receptors projects through parallel pathways of either PI3K-AKT or MEK1/2-ERK1/2 onto P70S6K and ultimately on GSK3␤, which, when phosphorylated, inhibits mitochondrial permeability transition pore opening. 8 Whether specific RISK kinases or a concert of different RISK kinases confer the protection by postconditioning is less clear. 4,6,7,9,10 In 2 studies, there was RISK phosphorylation but no protection by postconditioning. 11,12 Most studies on the role of RISK in postconditioning were performed in rodent hearts, 4,6,7 which, apart from species differences to larger mammals including humans, may pose methodological limitations: the small amount of tissue available for Western blots permits neither determination of baseline values nor that of infarct size in an individual heart. The association of RISK phosphorylation with less infarction could therefore be cause or consequence of the observed protection.The present study evaluates the role of RISK for postconditioning in pigs. With regard to size, coronary anatomy, and heart rate, the pig heart resembles more closely the human heart than smaller species, and it permits taking multiple biopsies at different time points and determining infarct size in an individual heart. Materials and MethodsThe experiments were performed in an established pig model of regional ischemia/reperfusion with infarct size determination and Western blot analysis (see the expanded Materials and Methods section in the online data supplement, available at http://circres. ahajournals.org). Protocol 1IPoC (nϭ13) was induced by 6 cycles of 20 seconds of reperfusion and 20 seconds of reocclusion at the onset of reperfusion. Immediate full reperfusion (IFR) (nϭ15) was established for comparison. Protocol 2In 8 animals, 4 with IPoC (B-IPoC) and 4 with IFR (B-IFR), the 2 major upstream RISK pathways PI3K-AKT and MEK1/2-ERK1/2 were blocked before the onset of reperfusion (see the online data supplement). StatisticsData are meansϮSEM. Data were analyzed by 2-way ANOVA for repeated measures with least significant difference tests or doublesided t tests; PϽ0.05 was considered significant.

show abstract

“…1 In addition, accumulation of endogenous TNF-␣ after coronary microembolization reduces infarct size. 9 Finally, the protection of delayed ischemic preconditioning is absent after pretreatment with TNF-␣ antibodies and in TNF-␣-, TNFR1-, and TNFR2-knockout mice 13 ; the latter result reflects the involvement of both TNFRs in cardioprotection. 13,14 …”

Section: Tnf-␣ and Cardioprotectionmentioning

confidence: 98%

“…TNF-␣ contributes to both reversible (contractile dysfunction 4,9 ) and irreversible (MI) injury. 1 Preischemic treatment with TNF-␣ antibodies 10 or soluble TNFR1, 11 permanent TNF-␣ knockout, 12 or knockout of TNFR1 but not TNFR2 13 all reduce infarct size.…”

Section: Tnf-␣ and Myocardial Ischemia/ Reperfusion Injurymentioning

confidence: 99%