ANALYSIS OF MEDICAL PURPOSES ANDPRICE AVAILABILITY OF THE ASSORTMENT OF BETA-ADRENOBLOCKERS USED FOR THE TREATMENT OF MYOCARDIAL INFARCTION

Patients who have had myocardial infarction (MI) represent a group of patients with a very high risk of cardiovascular complications: first of all, recurrent myocardial infarction, chronic heart failure and cardiovascular death. Clinical studies have shown an increase in life expectancy after MI when prescribing selective β-blockers for long-term prophylaxis, especially in the presence of chronic heart failure complicating the course of MI. The main clinical goals of prescribing β-blockers are to improve the supply of oxygen to the myocardium and to prevent the development of life-threatening cardiac arrhythmias. In view of the above, drugs in this group should be used indefinitely in patients with MI [7]. In recent years, the analysis of the affordability of the use of treatment technologies, including for cardiovascular diseases (CVD), has stood out as a serious scientific area with its methodology, scientific tools and is currently an important source of information that helps in making management decisions in healthcare [3.6]. The purpose of this article was to conduct such an analysis in relation to the use of β-blockers in MI in Kuzbass.

Successful treatment of severe adrenaline-resistant anaphylactic shock with glucagon in a patient taking a beta-blocker: a case report

Background The efficacy of glucagon for adrenaline-resistant anaphylactic shock in patients taking β-blockers is controversial. However, understanding the efficacy of glucagon is important because adrenaline-resistant anaphylactic shock is fatal. We present a case of severe adrenaline-resistant anaphylactic shock in a patient taking a β-blocker, and glucagon was effective in improving hemodynamics. Case presentation An 88-year-old woman with severe aortic stenosis and taking a selective β-1 blocker underwent transcatheter aortic valve implantation under general anesthesia. Postoperatively, she received 100 mg sugammadex, but 2 min later developed severe hypotension and bronchospasm. Suspecting anaphylactic shock, we intervened by administering adrenaline, fluid loading, and an increased noradrenaline dose. Consequently, the bronchospasm improved, but her blood pressure only increased minimally. Therefore, we administered 1 mg glucagon intravenously, and the hypotension resolved immediately. Conclusions Glucagon may improve hemodynamics in adrenaline-resistant anaphylactic shock patients taking β-blockers; however, its efficacy must be further evaluated in more cases.

Evaluation of molecular target of ademol by chemoinformatic method

Background. Glutamate excitotoxicity and intracranial hypertension are potential targets for possible developments of pathogenetic therapy of brain lesions, in particular those associated with high intracranial pressure. The purpose of the work: using chemoinformatic methods to justify the intravenous use of ademol, to detect the ability of ademol to block β-adrenergic receptors, as well as to assess the possibility of its passage through the blood-brain barrier in terms of drug-likeness and bioavailability criteria. Materials and methods. All calculations of molecular descriptors were made using the software package SIB Swiss Institute of Bioinformatics, computing platform and Molinspiration Cheminformatics v2016.09, available online. Results. The molecular weight of ademol does not exceed 500, the average lipophilicity value calculated using software package is in the acceptable range for the above compounds. For ademol, the value of LogP is 2,736, which is higher than that of rimantadine (2,456), but lower than that of propranolol (2,967). The total polar surface area is calculated based on the methodology developed by Ertl et al. in the form of contributions of the sum of the planes of O- and N-atoms etc., as a part of the functional groups of polar fragments. To predict ademol pe-netration through the blood-brain barrier, descriptors calculated in silico were used — average lipophilicity, which appeared to be close to previously described lipophilicity coefficient in a mixture of octanol and phosphate buffer, and the total polar surface area of mo-lecules. Affinity correlation (LogKi, nM) with polarity for known β-blockers and ademol is described as a second-degree parabolic polynomial function. Conclusions. A model of affinity correlation with lipophilicity for a number of β-blockers was created and the affinity of ademol is predicted, which is close to that of high-affi-nity non-selective β-blockers.

The Extracellular Matrix in Heart Failure: The Role of Adamts5 In Proteoglycan Remodelling

Background: Remodelling of the extracellular matrix (ECM) is a hallmark of heart failure (HF). Our previous analysis of the secretome of murine cardiac fibroblasts returned ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) as one of the most abundant proteases. ADAMTS5 cleaves chondroitin sulphate proteoglycans (CSPGs) such as versican. The contribution of ADAMTS5 and its substrate versican to HF is unknown. Methods: Versican remodelling was assessed in mice lacking the catalytic domain of ADAMTS5 (Adamts5 △Cat ). Proteomics was applied to study ECM remodelling in left ventricular samples from HF patients, with a particular focus on the effects of common medications used for the treatment of HF. Results: Versican and versikine, an ADAMTS-specific versican cleavage product, accumulated in ischemic HF patients. Versikine was also elevated in a porcine model of cardiac ischemia/reperfusion injury and in murine hearts after angiotensin II (Ang II) infusion. In Adamts5 △Cat mice, Ang II infusion resulted in an aggravated versican build-up and hyaluronic acid disarrangement, accompanied by reduced levels of integrin beta 1, filamin A and connexin 43. Echocardiographic assessment of Adamts5 △Cat mice revealed a reduced ejection fraction and an impaired global longitudinal strain upon Ang II infusion. Cardiac hypertrophy and collagen deposition, however, were similar to littermate controls. In a proteomics analysis of a larger cohort of cardiac explants from ischemic HF patients (n=65), the use of β-blockers was associated with a reduction in ECM deposition, with versican being among the most pronounced changes. Subsequent experiments in cardiac fibroblasts confirmed that β1-adrenergic receptor stimulation increased versican expression. Despite similar clinical characteristics, HF patients treated with β-blockers had a distinct cardiac ECM profile. Conclusions: Our results in animal models and patients suggest that ADAMTS proteases are critical for versican degradation in the heart, and that versican accumulation is associated with impaired cardiac function. A comprehensive characterisation of the cardiac ECM in ischemic HF patients revealed that β−blockers may have a previously unrecognized beneficial effect on the cardiac CSPG content.

HIPERTENSIUNE PORTALĂ STÂNGĂ PRIN CHIST HIDATIC LIENAL

Left portal hypertension, caused by hydatic cyst of spleen is a rare complication. We present the clinical case of a 41 years old patient, diagnosed and surgically managed in our clinic. Positive diagnosis was confirmed by imaging methods and intraoperatively. Splenectomy, associated in postoperative period with antiparasitic medication and β-blockers, had a positive influence over the disease evolution.

Effects of β-Blockers on the Sympathetic and Cytokines Storms in Covid-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative virus in the development of coronavirus disease 2019 (Covid-19) pandemic. Respiratory manifestations of SARS-CoV-2 infection such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) leads to hypoxia, oxidative stress, and sympatho-activation and in severe cases leads to sympathetic storm (SS). On the other hand, an exaggerated immune response to the SARS-CoV-2 invasion may lead to uncontrolled release of pro-inflammatory cytokine development of cytokine storm (CS). In Covid-19, there are interactive interactions between CS and SS in the development of multi-organ failure (MOF). Interestingly, cutting the bridge between CS and SS by anti-inflammatory and anti-adrenergic agents may mitigate complications that are induced by SARS-CoV-2 infection in severely affected Covid-19 patients. The potential mechanisms of SS in Covid-19 are through different pathways such as hypoxia, which activate the central sympathetic center through carotid bodies chemosensory input and induced pro-inflammatory cytokines, which cross the blood-brain barrier and activation of the sympathetic center. β2-receptors signaling pathway play a crucial role in the production of pro-inflammatory cytokines, macrophage activation, and B-cells for the production of antibodies with inflammation exacerbation. β-blockers have anti-inflammatory effects through reduction release of pro-inflammatory cytokines with inhibition of NF-κB. In conclusion, β-blockers interrupt this interaction through inhibition of several mediators of CS and SS with prevention development of neural-cytokine loop in SARS-CoV-2 infection. Evidence from this study triggers an idea for future prospective studies to confirm the potential role of β-blockers in the management of Covid-19.