Aims: The aim of the present study was to investigate the inhibition of classically activated macrophages in myocardial infarction (MI) under the influence of the chemokine (C‐C motif) receptor 2 (CCR2) antagonist propagermanium (PPG). Methods and Results: Mice (C57BL/6; n = 121) were subjected to occlusion of the left anterior descending artery and were randomized to the following groups: (a) MI with daily oral administration of 0.9% sodium chloride (“MI”), (b) MI with oral administration of 8 mg/kg PPG (“MI + PPG”), and (c) sham‐operated mice served as control. Mice were euthanized 2, 5, 10, or 21 days after MI for isolation of total RNA, protein, and immunofluorescence measurements. Flow cytometry was performed to investigate peripheral blood leucocytes. Scar size and cardiac function were determined by MRI on Day 7 after surgery and by trichrome staining on Day 21. PPG administration led to a significantly improved ejection fraction (MI + PPG: 38.5 % ± 3.4 % vs. MI: 23.8 % ± 3.0 % ; p < 0.05) after MI. MRI also revealed improved wall thickness (34.7 % ± 3.2 % vs. 21.8 % ± 2.9 % ; p < 0.05) associated with a diminished akinetic area (13.8 % ± 4.0 % vs. 37.3 % ± 5.6 % ; p < 0.01). Trichrome staining confirmed less collagen scar formation in the PPG‐treated group (12.7 % ± 1.4 % vs. 21.9 % ± 3.9 % ; p < 0.05). Flow cytometry showed fewer peripheral blood monocytes in MI + PPG than in MI 2 days after treatment (4.0 % ± 0.7 % vs. 12.7 % ± 1.2 % of total leucocytes; p < 0.05). Immunostaining and western blotting using activation type‐specific markers CCR2 and MRC1 demonstrated that the number of alternatively activated macrophages within the infarct zone increased, whereas the overall number was reduced after PPG treatment. PPG led to increased expression of VEGF‐ α and VEGF‐ β in THP‐1 cells in vitro and increased capillary density in vivo 2 days after MI (MI‐PPG: 1071 ± 81/mm 2 vs. MI: 648 ± 79/mm 2 ( p < 0.05)). Conclusion: Our results suggest that altering the activation type and distribution of invading macrophages in favor of alternative activation improves cardiac remodeling and function following MI.
16 June 2017 in Pacing and Clinical Electrophysiology
Background: Atrial fibrillation (AF) ablation is increasingly effective for managing heart rhythm but poses risks like esophageal fistulas. Minimizing esophageal thermal lesions while simplifying procedures is crucial. Methods: This prospective study involved 100 consecutive AF patients undergoing cryoballoon ablation with simplified sedation, without esophageal temperature monitoring. Patients with paroxysmal AF (Group A) received pulmonary vein isolation only, while those with persistent AF (Group B) also had left atrial roof ablation. Gastroesophageal endoscopy was performed post-procedure to detect lesions, and cardiological follow-ups were conducted at 3, 12, and 24 months. Results: The cohort included 69% men, with a median age of 65.5 years. Post-ablation endoscopy was performed in 92 patients; esophageal lesions were found in 1.1% of Group A and none of Group B. GERD was diagnosed in 14% of patients, evenly distributed between groups and not linked to lesion occurrence. Gastric hypomotility was observed in 16% of patients, with no significant difference between groups. At 24 months, arrhythmia-free survival was 88% in Group A and 74% in Group B. Conclusion: Cryoballoon-assisted pulmonary vein isolation, with or without additional left atrial roof ablation and without esophageal temperature monitoring during a simplified sedation strategy, shows low risk of esophageal thermal injury and effective ablation outcomes.
There is considerable uncertainty regarding the impact of microembolic signals (MESs) on neuropsychological abilities in patients receiving pulmonary vein isolation and beyond using the cryoballoon technique. We conducted the largest prospective observational study on this topic, providing insights into the gradual unmasking of procedure-related MESs and their impacts on neuropsychological outcomes. MESs were continuously detected periprocedurally using transcranial Doppler ultrasonography. Neuropsychological status was evaluated comprehensively using the CERAD Plus test battery, which consists of 11 neuropsychological subtests. Patients with atrial fibrillation were included in the study with an equal distribution (50:50) of paroxysmal or persistent presentations. Of 167 consecutive eligible patients, 100 were included within the study enrollment period from February 2021 to August 2022. The study, including the documentation of all follow-up visits, ended in November 2022. This paper focuses on describing the study protocol and methodology and presenting the baseline data.