title: Elevated mean neutrophil volume represents altered neutrophil composition and reflects damage after myocardial infarction.
abstract: Myocardial infarction (MI) induces an inflammatory response in which neutrophils fulfill a prominent role. Mean neutrophil volume (MNV) represents the average size of the circulating neutrophil population. Our goal was to determine the effect of MI on MNV and investigate the mechanisms behind MNV elevation. MNV of 84 MI patients was compared with the MNV of 209 stable angina patients and correlated to simultaneously measured CK levels. Fourteen pigs were subjected to temporary coronary balloon occlusion and blood was sampled at multiple time points to measure MNV. Echocardiography was performed followed by ex vivo infarct size assessment after 72 h. MNV was higher in MI patients compared to stable angina patients (602 SD26 AU vs. 580 SD20 AU, p < 0.0001) and correlated with simultaneously measured CK levels (R = 0.357, p < 0.0001). In pigs, MNV was elevated post-MI (451 SD11 AU vs. 469 SD12 AU), p < 0.0001). MNV correlated with infarct size (R = 0.705, p = 0.007) and inversely correlated with left ventricular ejection fraction (R = -0.718, p = 0.009). Cell sorting revealed an increased presence of banded neutrophils after MI, which have a higher MNV compared to mature neutrophils post-MI (495 SD14 AU vs. 478 SD11 AU, p = 0.012). MNV from coronary sinus blood was higher than MNV of neutrophils from simultaneously sampled arterial blood (463 SD7.6 AU vs. 461 SD8.6 AU, p = 0.013) post-MI. The current study shows MNV is elevated and reflects cardiac damage post-MI. MNV increases due to altered neutrophil composition and systemic neutrophil activation. MNV may be an interesting parameter for prognostic assessment in MI and provide new insights into pathological innate immune responses evoked by ischemia-reperfusion.
authors.affiliation: Laboratory of Experimental Cardiology (room G02.523), University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA, Utrecht, The Netherlands. g.p.j.vanhout@umcutrecht.nl.
authors.forename: G P J
authors.initials: GP
authors.lastname: van Hout
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: W W
authors.initials: WW
authors.lastname: van Solinge
authors.affiliation: Laboratory of Experimental Cardiology (room G02.523), University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA, Utrecht, The Netherlands.|ICIN, Netherlands Heart Institute, Utrecht, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: Gijsberts
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M P J
authors.initials: MP
authors.lastname: Teuben
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: P H C
authors.initials: PH
authors.lastname: Leliefeld
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Heeres
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Nijhoff
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: de Jong
authors.affiliation: Laboratory of Experimental Cardiology (room G02.523), University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Bosch
authors.affiliation: Laboratory of Experimental Cardiology (room G02.523), University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
authors.forename: S C A
authors.initials: SC
authors.lastname: de Jager
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Huisman
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: P R
authors.initials: PR
authors.lastname: Stella
authors.affiliation: Laboratory of Experimental Cardiology (room G02.523), University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA, Utrecht, The Netherlands.|Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Pasterkamp
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: L J
authors.initials: LJ
authors.lastname: Koenderman
authors.affiliation: Laboratory of Experimental Cardiology (room G02.523), University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA, Utrecht, The Netherlands.|Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: I E
authors.initials: IE
authors.lastname: Hoefer
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D009203:Myocardial Infarction / Q000276:immunology* / Q000473:pathology; D009504:Neutrophils / Q000473:pathology*; D013552:Swine
keywords: Ischemia–reperfusion injury; Myocardial infarction; Neutrophil biology; Neutrophil subsets