The estimation of intensity of inflammatory alterations of blood in early postinfarction remodeling

Funding Acknowledgements Type of funding sources: None. Introduction Structural postinfarction abnormalities is connected with inflammation. For better understanding of pathogenesis of postinfarction remodeling, it was studied the intensity of inflammatory disorders in early postinfarction period. Purpose Research of the intensity of inflammatory response in early postinfarction remodeling. Materials and methods 772 of patients with myocardial infarction (MI) were examined. Clinical blood analysis was performed at admission and on the 5th day of MI, as well as immunological examination, Echocardiography. Results In patients with end-diastolic diameter (EDD) of left ventricle (LV) ≥ 55 mm, 5 day MI white blood cells (WBC) level (8,0 ±2,1*109/l vs 7,3 ± 1,9*109/l, p = 0,0001), absolute number of neutrophils (5,0 ± 1,7* 109/l vs 4,5 ± 1,4*109/l, p = 0,0006) and monocytes (0,64 ± 0,30*109/l vs 0,57 ± 0,30*109/l, p = 0,005) were higher compared patients with EDD ≤ 55 mm. The inflammatory alterations in patients with increased end-diastolic volume (EDV) and end-systolic volume (ESV) of left ventricle was similar. The LV EDD was correlated with WBC level (r = 0,3; p = 0,00002), also with absolute number of neutrophils (r = 0,3; p = 0,0002) and monocytes (r = 0,3; p = 0,007). The positive connection of EDV LF with level of WBC (r = 0,3; P = 0,007) and absolute number of neutrophils (r = 0,3; p = 0,0002) was revealed. The positive connection of ESV LV with absolute number of neutrophils (r = 0,3, р=0,04; accordingly). It should be noted that increase of ESD LV more 37mm was not accompanied by authentic increase of inflammatory factors, but the connection of ESV LV with Il-6 was noted (ρ=0,3; р=0,03). As far as contractive function of myocardium declined, it was registered the increase of neutrophils (neutrophils on the 5 day in EF 55% and more - 4,5 ± 1,4*109/l, EF 55-40% - 4,8 ± 1,5*109/l, EF less 40% - 5,1 ± 2,1*109/l, p = 0,002), also in formation of areas of akinesia (neutrophils on the 1 days - 9,2 ± 3,3*109/l vs 8,3 ± 3,1*109/l, р=0,05) and aneurysm of LV (5,08 ± 1,71*109/l vs 4,52 ± 1,48*109/l, р=0,0006). It should be noticed that functional activity of monocytes in patients with aneurism of LV was lower than in patients without aneurism (CD14 0,035 ± 0,02*109/l vs 0,049 ± 0,02*109/l, р=0,05). It appears important obtained data that with hypertrophy LV and diastolic disfunction was noticed authentic increase of lymphocytes, expressing the marker of apoptosis CD95 (0,458 ± 0,276*109/l vs 0,335 ± 0,155*109/l, р=0,05; 0,441 ± 0,26*109/l vs 0,342 ± 0,21*109/л, р=0,01, accordingly). Conclusion The increased activity of inflammatory markers, decline of functional activity of monocytes, the elevation of apoptosis marker, associated with bigger intensity of postinfarction remodeling processes. The acute phase of inflammation is necessary stage of healing, but with long-term clinical case, excessive activation or alteration of functional activity of leukocytes can lead to growth of structural and electrical remodeling.

The role of aldosterone inhibitors in cardiac ischemia–reperfusion injury

Myocardial ischaemia–reperfusion (I/R) injury is a well-known term for exacerbation of cellular destruction and dysfunction after the restoration of blood flow to a previously ischaemic heart. A vast number of studies that have demonstrated that the role of mineralocorticoids in cardiovascular diseases is based on the use of pharmacological mineralocorticoid receptor (MR) antagonists. This review paper aimed to summarize current knowledge on the effects of MR antagonists on myocardial I/R injury as well as postinfarction remodeling. Animal models, predominantly the Langendorff technique and left anterior descending coronary artery occlusion, have confirmed the potency of MR antagonists as preconditioning and postconditioning agents in limiting infarct size and postinfarction remodeling. Several preclinical studies in rodents have established and proved possible mechanisms of cardioprotection by MR antagonists, such as reduction of oxidative stress, reduction of inflammation, and apoptosis, therefore limiting the infarct zone. However, the results of some clinical trials are inconsistent, since they reported no benefit of MR antagonists in acute myocardial infarction. Due to this, further studies and the results of ongoing clinical trials regarding MR antagonist administration in patients with acute myocardial infarction are being awaited with great interest.

The comparison of revalcularization outcomes in acute coronary syndrom following primary coronary angioplasty

Purpose. To compare clinical and morphofunctional outcomes of revascularization in patients after primary coronary angioplasty with different degree of coronary arteries damage and type of myocardial infarction. Material and methods. The research involved 258 patients after myocardial infarction who underwent coronary balloon angioplasty with stenting infarct-related artery. By electrocardiographic and angiographic picture all patients were divided into 4 groups: Q-wave myocardial infarction and without Q-wave myocardial infarction with single-vessel and multivessel disease. Results. The study found that the patients with non Q-wave myocardial infarction and single-vessel disease had no adverse clinical outcomes during a year. The wall motion index and the ejection fraction almost recovered completely (wall motion index varied from 1.18 0.02 to 1.05 0.02 and ejection fraction from 57.4 0.5% to 63.3 0.6%; р 0.001). All the patients with Q-wave myocardial infarction revealed similar clinical outcomes and morphofunctional characteristics. The group of patients with non Q-wave and multivessel disease had the highest rate of adverse clinical outcomes with progressing left-ventricular disfunction according to echocardiography (wall motion index varied from 1.15 0.01 to 1.19 0.04 and ejection fraction from 53.9 0.5% to 55.1 0.6%; р 0.001). Conclusion. The degree of coronary arteries damage in the patients with Q myocardial infarction did not influence postinfarction remodeling and long-term cardiac outcomes. The patients with non-Q myocardial infarction and single-vessel disease had fewer signs of postinfarction remodeling and complications in postinfarction period. The worst prognosis was revealed by patients with similar forms of myocardial infarction and multivessel disease.

miRNAs in Extracellular Vesicles from iPS-Derived Cardiac Progenitor Cells Effectively Reduce Fibrosis and Promote Angiogenesis in Infarcted Heart

Cardiac stem cell therapy offers the potential to ameliorate postinfarction remodeling and development of heart failure but requires optimization of cell-based approaches. Cardiac progenitor cells (CPCs) induction by ISX-9, a small molecule possessing antioxidant, prosurvival, and regenerative properties, represents an attractive potential approach for cell-based cardiac regenerative therapy. Here, we report that extracellular vesicles (EV) secreted by ISX-9-induced CPCs (EV-CPCISX-9) faithfully recapitulate the beneficial effects of their parent CPCs with regard to postinfarction remodeling. These EV contain a distinct repertoire of biologically active miRNAs that promoted angiogenesis and proliferation of cardiomyocytes while ameliorating fibrosis in the infarcted heart. Amongst the highly enriched miRNAs, miR-373 was strongly antifibrotic, targeting 2 key fibrogenic genes, GDF-11 and ROCK-2. miR-373 mimic itself was highly efficacious in preventing scar formation in the infarcted myocardium. Together, these novel findings have important implications with regard to prevention of postinfarction remodeling.