Abstract
We aimed to investigate the association between local interleukin-6 (IL-6) levels at the infarct-related artery and the risk of slow flow/microvascular dysfunction after PCI in ST-elevation acute myocardial infarction (AMI) patients treated by successful primary PCI. 56 eligible ST-elevation AMI patients (34 male/22 female, mean age: 63.5 ± 10.3 years), undergoing successful primary PCI, were included in the current study. Blood samples were obtained from the extraction catheter placed distal to the lesion before PCI. Plasma IL-6 levels were determined by immunoassay method. Slow flow/microvascular dysfunction was observed in 21 patients (37.5 %). Using multiple logistic regression analysis, local IL-6 levels (OR 1.592, CI 1.135–2.268; P = 0.007) were found to be a significant risk factor of slow flow/microvascular dysfunction together with diabetes mellitus (OR = 8.065, CI 1.244–52.632; P = 0.029) and thrombus score (OR = 12.500, CI 1.100–142.857; P = 0.042). Receiver operating characteristic (ROC) curve analysis revealed that local IL-6 (ROC area 0.824, OR 1.704, CI 1.274–2.281, P < 0.001; optimal threshold ≥11.3 pg/ml) had a predictive value of slow flow/microvascular dysfunction with sensitivity of 73 % and specificity of 71 %. Our study indicated that inflammatory response as presented by local IL-6 levels was associated with slow flow/microvascular dysfunction in patients with ST-elevation AMI after successful primary PCI.
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Rezkalla SH, Kloner RA (2008) Coronary no-reflow phenomenon: from the experimental laboratory to the cardiac catheterization laboratory. Catheter Cardiovasc Interv 72:950–957
Tanriverdi H, Evrengul H, Kilic ID, Taskoylu O, Dogan G et al (2010) Aortic pressures, stiffness and left ventricular function in coronary slow flow phenomenon. Cardiology 116:261–267
Morishima I, Sone T, Okumura K, Tsuboi H, Kondo J et al (2000) Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction. J Am Coll Cardiol 36:1202–1209
Resnic FS, Wainstein M, Lee MK, Behrendt D, Wainstein RV et al (2003) No-reflow is an independent predictor of death and myocardial infarction after percutaneous coronary intervention. Am Heart J 145:42–46
Cheng L, Wang J, Li X, Xing Q, Du P (2011) Interleukin-6 induces Gr-1+CD11b+ myeloid cells to suppress CD8+T cell-mediated liver injury in mice. PLoS One 4;6(3):17631
Pedroza M, Schneider DJ, Karmouty-Quintana H, Coote J, Shaw S et al (2011) Interleukin-6 contributes to inflammation and remodeling in a model of adenosine mediated lung injury. PLoS One 6(7):e22667
Xing Z, Gauldie J, Cox G, Baumann H, Jordana M et al (1998) IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest 101:311–320
Kefer JM, Galanti LM, Hanet CE (2004) Time course of transcardiac interleukin-6 release after coronary stenting for stable angina. Heart 90:943–944
Liuzzo G, Buffon A, Biasucci LM, Gallimore JR, Caligiuri G et al (1998) Enhanced inflammatory response to coronary angioplasty in patients with severe unstable angina. Circulation 98:2370–2376
Biasucci LM, Liuzzo G, Fantuzzi G, Caligiuri G, Rebuzzi AG et al (1999) Increasing levels of interleukin (IL)-1Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events. Circulation 99:2079–2084
Szkodzinski J, Blazelonis A, Wilczek K, Hudzik B, Romanowski W et al (2009) The role of interleukin-6 and transforming growth factor-beta1 in predicting restenosis within stented infarct-related artery. Int J Immunopathol Pharmacol 22:493–500
Funayama H, Ishikawa SE, Kubo N, Yasu T, Saito M et al (2006) Close association of regional interleukin-6 levels in the infarct-related culprit coronary artery with restenosis in acute myocardial infarction. Circ J 70:426–429
Biasucci LM, Vitelli A, Liuzzo G, Altamura S, Caligiuri G et al (1996) Elevated levels of interleukin-6 in unstable angina. Circulation 94:874–877
de Boer MJ, Reiber JHC, Suryapranata H, van den Brand MJBM, Hoorntje JCA et al (1995) Angiographic findings and catheterisation lab-oratory events in patients with primary coronary angioplasty or strep-tokinase therapy for acute myocardial infarction. Eur Heart J 16:1347–1356
Gibson CM, Murphy SA, Rizzo MJ, Ryan KA, Marble SJ et al (1999) Relationship between TIMI frame count and clinical outcomes after thrombolytic administration. Thrombolysis in myocardial infarction (TIMI) study group. Circulation 99:1945–1950
van’t Hof AW, Liem A, Suryapranata H et al (1998) Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Zwolle myocardial infarction study group. Circulation 97:2302–2306
Gibson CM, Murphy SA, Morrow DA, Aroesty JM, Gibbons RJ et al (2004) Angiographic perfusion score: an angiographic variable that integrates both epicardial and tissue level perfusion before and after facilitated percutaneous coronary intervention in acute myocardial infarction. Am Heart J 148:336–340
Turhan H, Saydam GS, Erbay AR, Ayaz S, Yasar AS et al (2006) Increased plasma soluble adhesion molecules: iCAM-1, VCAM-1, and E-selectin concentrations in patients with slow coronary flow. Int J Cardiol 108:224–230
Li JJ, Qin XW, Li ZC, Zeng HS, Gao Z et al (2007) Increased plasma C-reactive protein and interleukin-6 concentrations in patients with slow coronary flow. Clin Chim Acta 385:43–47
Ikeda U, Ikeda M, Seino Y, Takahashi M, Kano S et al (1992) Interleukin-6 gene transcripts are expressed in atherosclerotic lesions of genetically hyperlipidemic rabbits. Atherosclerosis 92:213–218
Clinton SK, Fleet JC, Loppnow H, Salomon RN, Clark BD et al (1991) Interleukin-1 gene expression in rabbit vascular tissue in vivo. Am J Pathol 138:1005–1014
Kotani J, Nanto S, Kitakaze M, Ohara T, Morozumi T et al (2002) No-reflow following dilatation of a coronary lesion with a large lipid core. Circ J 66:702–704
Engler RL, Schmid-schonbein GW, Pavelec RS (1983) Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am J Pathol 111:98–111
Meisel SR, Shapiro H, Radnay J, Neuman Y, Khaskia AR et al (1998) Increased expression of neutrophil and monocyte adhesion molecules LFA-1 and Mac-1 and their ligand ICAM-1 and VLA-4 throughout the acute phase of myocardial infarction: possible implications for leukocyte aggregation and microvascular plugging. J Am Coll Cardiol 31:120–125
Piana RN, Paik GY, Moscucci M, Cohen DJ, Gibson CM et al (1994) Incidence and treatment of ‘no-reflow’ after percutaneous coronary intervention. Circulation 89:2514–2518
Taniyama Y, Ito H, Iwakura K, Masuyama T, Hori M et al (1997) Beneficial effect of intracoronary verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction. J Am Coll Cardiol 30:1193–1199
Kloner RA, Przylenk K, Wittaker P (1989) Deleterious effect of oxygen radicals in ischemic/reperfusion: resolved and unsolved issues. Circulation 80:1115–1127
Grech ED, Dodd NJ, Jackson MJ, Morrison WL, Faragher EB et al (1996) Evidence for free radical generation after primary percutaneous transluminal coronary angioplasty recanalization in acute myocardial infarction. Am J Cardiol 77:122–127
Reffelmann T, Kloner RA (2002) The “no-reflow” phenomenon: basic science and clinical correlates. Heart 87:162–168
Dreyer WJ, Michael LH, West MS, Smith CW, Rothlein R et al (1991) Neutrophil accumulation in ischemic canine myocardium: insights into time course, distribution, and mechanism of localization during early reperfusion. Circulation 84:400–411
Ørn S, Manhenke C, Ueland T, Damås JK, Mollnes TE et al (2009) C-reactive protein, infarct size, microvascular obstruction, and left-ventricular remodelling following acute myocardial infarction. Eur Heart J 30:1180–1186
Geisler T, Mueller K, Aichele S, Bigalke B, Stellos K et al (2010) Impact of inflammatory state and metabolic control on responsiveness to dual antiplatelet therapy in type 2 diabetics after PCI: prognostic relevance of residual platelet aggregability in diabetics undergoing coronary interventions. Clin Res Cardiol 99:743–752
Larsen SB, Grove EL, Kristensen SD, Hvas AM (2013) Reduced antiplatelet effect of aspirin is associated with low-grade inflammation in patients with coronary arterydisease. Thromb Haemost 109:920–929
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Fangming Guo and Mei Dong contributed equally to this study.
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Guo, F., Dong, M., Ren, F. et al. Association between local interleukin-6 levels and slow flow/microvascular dysfunction. J Thromb Thrombolysis 37, 475–482 (2014). https://doi.org/10.1007/s11239-013-0974-0
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DOI: https://doi.org/10.1007/s11239-013-0974-0