No abstract

Inflammatory cell infiltration is central to healing after acute myocardial infarction (AMI). The relation of regional inflammation to edema, infarct size (IS), microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and regional and global LV function is not clear. Here we noninvasively characterized regional inflammation and contractile function in reperfused AMI in pigs using fluorine (19F) cardiovascular magnetic resonance (CMR). Adult anesthetized pigs underwent left anterior descending coronary artery instrumentation with either 90 min occlusion (n = 17) or without occlusion (sham, n = 5). After 3 days, in surviving animals a perfluorooctyl bromide nanoemulsion was infused intravenously to label monocytes/macrophages. At day 6, in vivo 1H-CMR was performed with cine, T2 and T2* weighted imaging, T2 and T1 mapping, perfusion and late gadolinium enhancement followed by 19F-CMR. Pigs were sacrificed for subsequent ex vivo scans and histology. Edema extent was 35 ± 8% and IS was 22 ± 6% of LV mass. Six of ten surviving AMI animals displayed both MVO and IMH (3.3 ± 1.6% and 1.9 ± 0.8% of LV mass). The 19F signal, reflecting the presence and density of monocytes/macrophages, was consistently smaller than edema volume or IS and not apparent in remote areas. The 19F signal-to-noise ratio (SNR) > 8 in the infarct border zone was associated with impaired remote systolic wall thickening. A whole heart value of 19F integral (19F SNR × milliliter) > 200 was related to initial LV remodeling independently of edema, IS, MVO, and IMH. Thus, 19F-CMR quantitatively characterizes regional inflammation after AMI and its relation to edema, IS, MVO, IMH and regional and global LV function and remodeling.

Fluorine-19 magnetic resonance imaging (19F MRI) with intravenously applied perfluorooctyl bromide-nanoemulsions (PFOB-NE) has proven its feasibility to visualize inflammatory processes in experimental disease models. This approach is based on the properties of monocytes/macrophages to ingest PFOB-NE particles enabling specific cell tracking in vivo. However, information on safety (cellular function and viability), mechanism of ingestion and impact of specific disease environment on PFOB-NE uptake is lacking. This information is, however, crucial for the interpretation of 19F MRI signals and a possible translation to clinical application. To address these issues, whole blood samples were collected from patients with acute ST-elevation myocardial infarction (STEMI), stable coronary artery disease (SCAD) and healthy volunteers. Samples were exposed to fluorescently-labeled PFOB-NE and particle uptake, cell viability and migration activity was evaluated by flow cytometry and MRI. We were able to show that PFOB-NE is ingested by human monocytes in a time- and subset-dependent manner via active phagocytosis. Monocyte function (migration, phagocytosis) and viability was maintained after PFOB-NE uptake. Monocytes of STEMI and SCAD patients did not differ in their maximal PFOB-NE uptake compared to healthy controls. In sum, our study provides further evidence for a safe translation of PFOB-NE for imaging purposes in humans.

Collectively, SOD3 has a significant cardioprotective role in cases of IRI and directly affects the myocardium as hypothesized. Exploration of intervention strategies targeting SOD3 may provide therapeutic options against IRI and associated systemic inflammation.

Everolimus (EVL) is widely used in solid organ transplantation. It is known to have antiproliferative and immunosuppressive abilities via inhibition of the mTOR pathway. Preventive EVL administration may lower inflammation induced by cardiopulmonary bypass (CPB) and reduce systemic inflammatory response syndrome (SIRS). After oral loading with EVL 2.5 mg/kg/day (n = 11) or placebo (n = 11) for seven consecutive days, male Wistar rats (400-500 g) were connected to a miniaturised heart-lung-machine performing a deep hypothermic circulatory arrest protocol. White blood cells (WBC) were significantly reduced in EVL-pretreated animals before start of CPB with a preserved reduction by trend at all other time points. Ischemia/reperfusion led to decreased glucose levels. Application of EVL significantly increased glucose levels after reperfusion. In addition, potassium levels were significantly lower in EVL-treated animals at the end of reperfusion. Immunoblotting revealed increased S6 levels after CPB. EVL decreased phosphorylation of S6 in the heart and kidney, which indicates an inhibition of mTOR pathway. Moreover, EVL significantly modified phosphorylation of AKT, while decreasing IL2, IL6, RANTES, and TNFα (n = 6). Preventive application of EVL may modulate inflammation by inhibition of mammalian target of rapamycin (mTOR) pathway and reduction of proinflammatory cytokines. This may be beneficial to evade SIRS-related morbidities after CPB.