CD11b/CD18 Contributes to Susceptibility of Ventricular Arrhythmias and Infarct Size

Introduction The role of polymorphonuclear neutrophils (PMN) in myocardial ischemia and reperfusion (I/R) is controversially discussed. The PMN surface protein CD11b/CD18 plays a critical role for PMN activation and adhesion. Using CD11b/CD18 deficient (CD11b -/- ) mice we herein sought to further elucidate the effects of infiltrating PMN on ventricular remodeling and arrhythmogenesis in the context of myocardial I/R. Methods and Results Wildtype (WT) and CD11b -deficient ( CD11b -/- ) mice of C57BL/6J background were subjected to 40 minutes of myocardial ischemia by ligation of the left anterior descending artery following 6- or 48 hours of reperfusion (I/R). CD11b -/- resulted in significantly less myocardial myeloperoxidase release (MPO + cells / field of view: WT: 308.4 ± 22.2 vs. CD11b -/- : 178.3 ± 13.1, p CD11b -/- : 0.18 ± 0.04, p CD11b -/- hearts after 48 hours of reperfusion (Ly6g + cells / field of view : WT: 84.07±2.74 vs. CD11b -/- : 64.72 ± 2.53, p CD11b -/- compared to WT mice (infarct area / area at risk: WT: 37.26 ± 7.72% vs. CD11b -/- : 21.8 ± 6.73%; p in vivo indicated a significantly reduced susceptibility of CD11b -/- animals to ventricular tachycardias (VT) (WT: 8.11±2.85 vs. CD11b -/- : 4.75±1.5, p = 0.009) and a reduced VT length (WT: 8.11±2.85 vs. CD11b -/- : 4.75±1.5, p = 0.009) as compared to WT mice after ischemia followed by 2 days of reperfusion (WT: 8.11±2.85 vs. CD11b -/- : 4.75±1.5, p Conclusions Decreased myocardial PMN infiltration and oxidative protein modifactions caused by the absence of CD11b/CD18 suggests a clear role of PMN infiltration for maldadaptive left ventricular remodelling and arrhythmogenesis following myocardial I/R.