Neutrophil numbers correlate with circadian oscillations in infarct severity in human patients. (a) Experimental scheme for I/R protocol (AMI model) during a 24-h cycle and antibody cocktails used as control and to deplete neutrophils. ZT indicates the time at which the infarct was induced. Analyses were performed 1 h and 45 min later. (b) AAR of the myocardium (top) in control and neutropenic mice at different circadian times and infarct sizes (down) after correction for AAR in the same animals subjected to MI followed by 1 h of reperfusion; n = 1–2 mice per time point. The indicated P values were calculated after COSINOR adjustment as indicated in the Materials and methods section (amplitude vs. zero test). The diurnal curves are repeated to better appreciate the pattern. (c) Representative images of infarcted hearts from control and neutropenic mice infarcted at the indicated ZT. Dotted black lines highlight areas of dead myocardium. (d) Summary of the human cohort of STEMI patients. (e) Distribution of blood neutrophils in the 2,041 STEMI patients. (f) Correlation of maximum troponin levels with neutrophils in circulation at admission time. (g) Severity of cardiac injury in the three groups of STEMI patients. (h) Cardiac damage shown as the maximum troponin levels of the cohort of STEMI patients entering the intensive care unit at different times of the day; n = 2,026 patients. (i) Circadian amplitude of cardiac damage in the three virtual experimental groups of STEMI patients. (j) Cardiac damage shown as the maximum troponin levels for each patient group, depending on the time of admission at the intensive care unit; n = 401 (left), 1,228 (middle), and 395 (right). The diurnal curves are repeated to better appreciate the pattern. Data in a–c are from a single experiment. Data are shown as the mean ± SEM. ***P < 0.001, as determined by correlation analysis (f), one-way ANOVA (g and i), and amplitude vs. zero test (b, h, and j).