Background: Knowledge of the immune response following acute myocardial infarction is mainly derived from a permanent coronary artery occlusion mouse model using ex-vivo read-outs. Therefore, we profiled and compared cardiac function and the systemic immune response in transient and permanent coronary artery occlusion mouse models using in-vivo multiparametric immunoimaging.

Methods: The MI models encompassed either transient (40 min, refered to as ischemia reperfusion, IR) or permanent occlusion (PO) of the left coronary artery, and non-infarcted mice were used as controls. Both models were applied to male C57BL/6 mice. One, two or three days after MI, the animals subjected to systemic immunoimaging of the bone marrow, spleen and myocardium. We performed late gadolinium-enhanced (LGE) and 19F-cardiac magnetic resonance imaging (cMRI), 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and 18F-fluorothymidine (FLT) PET. We also performed PET imaging using a 64Cu-labeled tracer targeting chemokine receptor 2 (CCR2) and an 89Zr-labeled nanobody targeting CD11b. Finally, the same MI models were applied to atherosclerosis-prone Apoe-/- mice and systemic inflammation and plaque progression were assessed by flow cytometry and immunohistochemistry four weeks after infarction.

Results: We found that immune cell influx in the infarct was more pronounced in the permanent occlusion model, as assessed by nanotracer-based fluorine MRI and PET imaging using a CD11b-specific nanobody and a C-C motif chemokine receptor 2-binding probe. Further, using ¹⁸F-FLT and ¹⁸F-FDG PET, we detected increased hematopoietic activity after myocardial infarction, with no difference between the models. Finally, we observed persistent systemic inflammation and exacerbated atherosclerosis in Apoe^-/- mice, regardless of which infarction model was used.

Conclusion: We employed multimodal, multiparametric immunoimaging protocols to characterize the response in the heart, bone marrow and spleen in two models of myocardial infarction. While cardiac function and survival was superior in the IR model, both types of MI accelerated atherosclerosis.