Myocardial remodeling is an inevitable risk factor for cardiac arrhythmias and can potentially be corrected with cell therapy. Although the generation of cardiac cells ex vivo is possible, specific approaches to cell replacement therapy remain unclear. On the one hand, adhesive myocyte cells must be viable and conjugated with the electromechanical syncytium of the recipient tissue, which is unattainable without an external scaffold substrate. On the other hand, the outer scaffold may hinder cell delivery, for example, making intramyocardial injection difficult. To resolve this contradiction, we developed molecular vehicles that combine a wrapped (rather than outer) polymer scaffold that is enveloped by the cell and provides excitability restoration (lost when cells were harvested) before engraftment. It also provides a coating with human fibronectin, which initiates the process of graft adhesion into the recipient tissue and can carry fluorescent markers for the external control of the non-invasive cell position. In this work, we used a type of scaffold that allowed us to use the advantages of a scaffold-free cell suspension for cell delivery. Fragmented nanofibers (0.85 µm ± 0.18 µm in diameter) with fluorescent labels were used, with solitary cells seeded on them. Cell implantation experiments were performed in vivo. The proposed molecular vehicles made it possible to establish rapid (30 min) electromechanical contact between excitable grafts and the recipient heart. Excitable grafts were visualized with optical mapping on a rat heart with Langendorff perfusion at a 0.72 ± 0.32 Hz heart rate. Thus, the pre-restored grafts’ excitability (with the help of a wrapped polymer scaffold) allowed rapid electromechanical coupling with the recipient tissue. This information could provide a basis for the reduction of engraftment arrhythmias in the first days after cell therapy.

Background: The systemic inflammatory response to coronary artery bypass grafting (CABG) is highly variable and a key driver of complications. We hypothesised that a pre-existing pro-inflammatory immune state, characterised by a skewed monocyte profile, ‘primes’ patients for an exaggerated response. This pilot prospective study aimed to test this hypothesis and to evaluate the Neutrophil-to-Albumin Ratio (NAR) as an integrated biomarker of this response, comparing it against the established Neutrophil-to-Lymphocyte Ratio (NLR). Methods: In this pilot prospective, single-centre pilot study, we enrolled 34 patients with multivessel coronary artery disease (CAD) scheduled for off-pump CABG and 20 control subjects. Preoperatively, peripheral blood monocyte subsets were quantified by flow cytometry. Neutrophil, lymphocyte, and albumin levels were measured before and after surgery to calculate NAR and NLR. Multivariable linear regression was used to test for independent predictors of the inflammatory response. Results: Preoperatively, CAD patients exhibited a reduced percentage of the classical monocyte subpopulation (p < 0.001), with a skew toward intermediate and non-classical subpopulations. Postoperatively, both NAR and NLR increased significantly (p < 0.001) and performed comparably in discriminating the postoperative state (AUC: 0.89 vs. 0.86, p > 0.05). Critically, in multivariable linear regression analysis, the preoperative percentage of classical monocytes remained a significant and independent predictor of the magnitude of the postoperative NAR surge (β = −0.028, p = 0.007), after adjusting for clinical confounders including atherosclerotic burden. Conclusion: A patient’s preoperative immune profile, specifically the degree of monocyte skew, is an independent predictor of the acute inflammatory response to CABG. This finding supports a ‘priming’ mechanism in high-risk patients. While NAR and NLR perform similarly as monitoring tools, the independent link between the underlying immunology and the postoperative outcome suggests that combining preoperative immunophenotyping with simple biomarker monitoring could offer a powerful new strategy for personalised risk stratification in cardiac surgery.

Гипертрофия миокарда левого желудочка донорского сердца: результаты и перспективы

The end-stage stage of chronic diseases of solid organs is rather significant in the structure of morbidity and mortality among patients worldwide. To date, there are more than six million patients in this status worldwide. Heart, liver and kidney transplantation is the gold standard of treatment for these patients. The number of transplants is growing every year.At the end of 2019, the world faced a new type of viral infection – SARS-CoV-2 – a highly contagious systemic respiratory disease transmitted by airborne droplets, which in three months led to a pandemic and killed hundreds of thousands of people. The pandemic has made adjustments to the structure of planned medical care. The number of planned operations has decreased significantly, and the number of the infection-associated complications has increased.Patients with end-stage chronic diseases initially have weakened immunity and represent the category most susceptible to the infection. At the moment, the question of patient management tactics remains open. There is no consensus on the patient management tactics before surgery and in the posttransplantation period for patients at the end-stage chronic disease of different organs. This topic requires further study and the development of treatment algorithms for such patients.

Heart failure (HF) is a common condition, and its overall prevalence is constantly growing. HF ultimately progresses to end-stage disease that is refractory to optimal medical therapy and requires implantable devices or heart transplant. In recent years, cardiac resynchronization therapy (CRT) has been generally accepted in patients with NYHA class III or IV, reduced left ventricular ejection fraction (less than 35%), and the wide QRS complex (>120 msec). CRT improves the efficacy of heart ventricle function and, as a result, physical performance and quality of life. Reverse cardiac remodeling occurs at a pathophysiological level that improves systolic function. Patients with end-stage HF who are on the heart transplant list are a specific group in whom CRT is considered a “bridge” to surgery. This review paper discusses state-of-the-art, advances, and unresolved issues in this area. KEYWORDS: cardiac resynchronization therapy, heart failure, left ventricular remodeling, ejection fraction, heart transplant. FOR CITATION: Shumakov D.V., Zybin D.I., Popov M.A. et al. Resynchronization therapy in end-stage heart failure. Russian Medical Inquiry. 2021;5(4):206–211 (in Russ.). DOI: 10.32364/2587-6821-2021-5-4-206-211.

Background/Objectives: Patient-derived mesenchymal stem cells (MSCs) represent a promising avenue for myocardial regeneration, yet therapeutic application remains limited by inconsistent differentiation capacity and the absence of standardized cardiogenic induction protocols. This study demonstrates a proof-of-concept for guiding patient-specific bone marrow MSCs toward a functional cardiomyocyte phenotype using paracrine signals from differentiating iPSC-derived cardiomyocytes (iPSC-CMs). Materials and Methods: MSCs were maintained in conditioned medium from a concurrent, validated iPSC-CM differentiation protocol, with evaluation via immunocytochemistry, optical mapping, and whole-cell patch-clamp recordings. Results: Differentiated MSCs acquired organized sarcomeric architecture with cross-striations and displayed spontaneous calcium oscillations with decay kinetics matching source iPSC-CMs (CaT50 ≈ 283 ms vs. 301 ms). In co-culture, MSC-derived cells exhibited synchronized calcium dynamics with iPSC-CMs, confirming functional coupling, while patch-clamp detected hallmark cardiac ion currents (INa, ICa,L, and IKv). Morphologically, MSC-CMs displayed more mature, elongated rod-like shapes. Conclusions: Although current densities indicate partial immaturity, their reproducible detection validates successful cardiomyogenic commitment. This “parallel differentiation” platform eliminates donor-specific protocol tuning, providing a streamlined, paracrine-mediated approach to generate autologous cardiomyocyte-like cells for disease modeling, pharmacological testing, and future regenerative applications.