Background: Revascularization after myocardial infarction (MI) induces a strong inflammatory response resulting in an increase of circulating neutrophils. Neutrophil quantities have found to be a good predictor for future adverse events. In this study, we hypothesized that the extent of morphological changes in circulating neutrophils also reflects the myocardial damage after MI and therefore relates to outcome.
Methods: One hundred seven STEMI patients treated between 2009 and 2012 with at least one white blood cell count determined by an automated hematology analyzer within 24 hours after PCI were selected. This analyzer differentiates between leukocyte subsets based on morphological characteristics derived from light scatter patterns. Neutrophil morphology was compared with simultaneously measured creatine kinase (CK). Pigs (n=9) were subjected to left anterior descending artery (LAD) occlusion for 75 minutes followed by 3 days of reperfusion. Blood was collected at baseline, during ischemia and at multiple time-points during reperfusion followed by whole-blood analysis with the same hematology analyzer as above. Cardiac damage was determined by histological infarct size, 3D-echocardiography and Troponin measurements. Coronary blood sampling was performed to determine differences in neutrophil morphology between simultaneously sampled arterial and venous coronary blood.
Results: In STEMI patients, a significant increase in neutrophil axial light loss (ALL) over time was seen (p<0.001) correlating with CK levels (R=0.314, p<0.001). In pigs, neutrophil ALL increased over time (p<0.001). Neutrophil ALL measured at 15 min after reperfusion correlated significantly with infarct size (R=0.745, p=0.021) and Troponin I levels (R=0.792, p=0.019). Neutrophil ALL also negatively correlated with LVEF measured by 3D-echocardiography (R=-0.760, p=0.017). Coronary sinus sampling revealed structural differences in neutrophil morphology between arterial and coronary venous blood (p=0.013), pinpointing the infarcted myocardium as the source of the observed changes.
Conclusion: MI alters the morphology of circulating neutrophils in both patients and pigs in relation to the extent of damage reflected by CK and Troponin I levels. In pigs, neutrophil morphology early after reperfusion predicts infarct size and cardiac function after 3 days. Neutrophil scatter profiles might therefore prove valuable markers for the prediction of cardiac damage after MI.