In patients with coronary heart disease, sudden cardiac death, caused by aberrant electrical conduction, commonly happens. Arrhythmia and significant myocardial leukocyte alterations are brought on by myocardial ischemia at the same time. In this study, we improved a mouse model in which myocardial infarction and hypokalemia caused ambulatory animals to spontaneously develop ventricular tachycardia, and we demonstrated that major leukocyte subsets have opposing effects on cardiac conduction. In mice, neutrophils promoted ventricular tachycardia through lipocalin-2, but in patients, neutrophilia was linked to ventricular tachycardia. Macrophages, on the other hand, provide protection from arrhythmia. When Csf1 receptor blockade was used to reduce recruited macrophages in Ccr2/ mice or all macrophage subsets, it enhanced ventricular tachycardia and fibrillation. When evaluated in conjunction with decreased mitochondrial integrity and accelerated cardiomyocyte death in the absence of macrophages, higher arrhythmia burden and mortality in Cd36/+ and Mertk/+ mice suggested that receptor-mediated phagocytosis protects against deadly electrical storm. Leukocyte function modification thus offers a potential therapeutic route for lowering the risk of sudden cardiac mortality.
