Restoration Of Coronary Blood Flow Research Articles

A mobile application for STEMI care optimization: Pilot implementation project report

BackgroundClinical outcomes of patients presenting with STEMI are significantly improved by reducing time from vessel occlusion to coronary blood flow restoration. In an effort to improve outcomes, we developed a secure mobile application, STEMIcathAID, and designed a pilot project implementing the app into the workflow for STEMI patients transfer. The aim of the study is to assess the impact of the app on key metrics for STEMI transfer before (historic) and after app launch. MethodsThe pilot project included physicians, nurses and technicians from the Emergency Medicine and Nursing Departments at the referring center, the catheterization laboratory and transfer center. From July 2021 to February 2023, the referring center activated STEMIcathAID alarms in parallel with the previously established STEMI activation with traditional phone call to transfer center. ResultsOne hundred eleven suspected STEMI calls were activated through the app with 66 accepted and 45 rejected cases; thirty-one STEMI cases with available device time were compared with 42 STEMIs activated through the traditional pathway before the app implementation. Median door-to-device time for STEMIcathAID-assisted transfer decreased from 106 to 86 min (p < 0.001). The significant improvement, 20 min (19%), of the key metric for interhospital transfer resulted in all STEMI cases meeting the AHA goal of door-to-device time ≤ 120 min. In addition, median door-in-door-out time at the referral hospital decreased from 56 to 50 min (p = 0.01). ConclusionsImplementation of a mobile app into STEMI workflow of a large urban healthcare system significantly improved the quality of care for transfer of STEMI patients. Trial registrationAHA Get With The Guidelines-Coronary Artery Disease® (GWTG-CAD) registry is a national quality improvement program and is not subject to the institutional review board approval.

Role of M6a Methylation in Myocardial Ischemia-Reperfusion Injury and Doxorubicin-Induced Cardiotoxicity.

Cardiovascular disease remains the leading cause of death worldwide, with acute myocardial infarction and anticancer drug-induced cardiotoxicity being the significant factors. The most effective treatment for acute myocardial infarction is rapid restoration of coronary blood flow by thrombolytic therapy or percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury (MI/RI) after reperfusion therapy is common in acute myocardial infarction, thus affecting the prognosis of patients with acute myocardial infarction. There is no effective treatment for MI/RI. Anthracyclines such as Doxorubicin (DOX) have limited clinical use due to their cardiotoxicity, and the mechanism of DOX-induced cardiac injury is complex and not yet fully understood. N6-methyladenosine (m6A) plays a crucial role in many biological processes. Emerging evidence suggests that m6A methylation plays a critical regulatory role in MI/RI and DOX-induced cardiotoxicity (DIC), suggesting that m6A may serve as a novel biomarker and therapeutic target for MI/RI and DIC. M6A methylation may mediate the pathophysiological processes of MI/RI and DIC by regulating cellular autophagy, apoptosis, oxidative stress, and inflammatory response. In this paper, we first focus on the relationship between m6A methylation and MI/RI, then further elucidate that m6A methylation may mediate the pathophysiological process of MI/RI through the regulation of cellular autophagy, apoptosis, oxidative stress, and inflammatory response. Finally, briefly outline the roles played by m6A in DIC, which will provide a new methodology and direction for the research and treatment of MI/RI and DIC.

Efficacy of a new system of targeted delivery of tenecteplase in acute myocardial infarction in an in vivo experiment

A new system of targeted delivery of tissue plasminogen activator tenecteplase for restoration of coronary blood flow in acute myocardial infarction in animal experiments was developed.The new system of targeted delivery of fibrinolytic consists of native (“free”) and encapsulated (“bound”) tenecteplase in liposomes, in the percentage ratio (60 and 40 %, respectively), which are conjugated through carboxylated dextran with fibrin-specific monoclonal antibodies Fnl-3C.The physicochemical characteristics of the obtained liposomes conjugated with fibrin-specific monoclonal antibodies (immunoliposomes) with tenecteplase were determined: immunoliposomes have a hydrodynamic diameter of ~76‒77 nm, a zeta potential of ~(‒33) mV, a polydispersity index of ~0.55. Modification of liposomes with fibrin-specific monoclonal antibodies does not alter thrombolytic activity.When using immunoliposomes the survival rate of animals with acute myocardial infarction is ~90 %, liposomal and native form of the drug ‒ 80 %.The use of immunoliposomal delivery system in animals with acute myocardial infarction leads to an increase in the free lumen of the infarct-related artery (p &lt; 0.05) by 26 % compared to the liposomal delivery system and by 46 % compared to native tenecteplase. At the same time, the mass of ischemic myocardium on the background of thrombolytic therapy with&gt;&lt; 0.05) by 26 % compared to the liposomal delivery system and by 46 % compared to native tenecteplase. At the same time, the mass of ischemic myocardium on the background of thrombolytic therapy with immunoliposomes decreases (p &lt; 0.05) by 16 % in rats in comparison with the liposomal system and by 26 % in comparison with native tenecteplase. The new system of targeted delivery of tenecteplase provides effective and safe thrombolysis in animal experiment&gt; &lt; 0.05) by 16 % in rats in comparison with the liposomal system and by 26 % in comparison with native tenecteplase.The new system of targeted delivery of tenecteplase provides effective and safe thrombolysis in animal experiment.

Oxidative Post-translational Protein Modifications upon Ischemia/Reperfusion Injury.

While reperfusion, or restoration of coronary blood flow in acute myocardial infarction, is a requisite for myocardial salvage, it can paradoxically induce a specific damage known as ischemia/reperfusion (I/R) injury. Our understanding of the precise pathophysiological molecular alterations leading to I/R remains limited. In this study, we conducted a comprehensive and unbiased time-course analysis of post-translational modifications (PTMs) in the post-reperfused myocardium of two different animal models (pig and mouse) and evaluated the effect of two different cardioprotective therapies (ischemic preconditioning and neutrophil depletion). In pigs, a first wave of irreversible oxidative damage was observed at the earliest reperfusion time (20 min), impacting proteins essential for cardiac contraction. A second wave, characterized by irreversible oxidation on different residues and reversible Cys oxidation, occurred at late stages (6-12 h), affecting mitochondrial, sarcomere, and inflammation-related proteins. Ischemic preconditioning mitigated the I/R damage caused by the late oxidative wave. In the mouse model, the two-phase pattern of oxidative damage was replicated, and neutrophil depletion mitigated the late wave of I/R-related damage by preventing both Cys reversible oxidation and irreversible oxidation. Altogether, these data identify protein PTMs occurring late after reperfusion as an actionable therapeutic target to reduce the impact of I/R injury.

Abstract 13573: Association of Increased Eicosapentaenoic Acid to Arachidonic Acid Ratio With Early Restoration of Coronary Blood Flow in ST-Elevation Myocardial Infarction

Background: Early restoration of coronary blood flow is important to reduce myocardial damage in patients with ST-elevation myocardial infarction (STEMI). Cardiovascular protection of increased levels of eicosapentaenoic acid (EPA) to arachidonic acid (AA) has been shown in recent clinical trials. Therefore, this study examined whether increased EPA / AA ratio was related to early restoration of coronary blood flow in STEMI patients underwent primary percutaneous coronary intervention (PCI). Methods: Serum levels of EPA, AA, and EPA/AA ratio were measured in consecutive 216 STEMI patients. The angiographic findings of TIMI-flow grade in the infarct related artery before PCI were compared between patients with and without increased EPA / AA ratio (&amp;gt;0.291). Results: TIMI-flow grade 3 before PCI were obtained in 25 (11.6%) of all study patients. Smaller enzymatic infarct size was obtained in patients with TIMI-flow grade 3 before PCI compared with TIMI-flow grade 0-2 before PCI (Peak CK-MB; 358 &amp;plusmn; 252 mg/dL, vs. 280 &amp;plusmn; 260 mg/dL, p &amp;lt;0.05). There were significant differences between 2 groups in the distribution of TIMI-flow grade (p&amp;lt;0.05). Moreover, multivariate logistic regression analysis showed that patients with increased EPA/AA ratio was significantly associated with the presence of TIMI-flow grade 3 before PCI after adjustment for conventional risk factors (OR 5.0, 95% CI 1.92-12.8, p&amp;lt;0.01). Conclusions: Increased levels of EPA /AA ratio is independently associated with early restoration of coronary blood flow, leading to reduced myocardial damage in patients with STEMI. These results might support the new strategy of administration of EPA before PCI in STEMI care.

Revascularization and Left Ventricular Dysfunction for ICD Eligibility.

Common triggers for sudden cardiac death (SCD) are transient ischemia, hemodynamic fluctuations, neurocardiovascular influences, and environmental factors. SCD occurs rapidly when sinus rhythm degenerates into ventricular tachycardia (VT) and/or ventricular fibrillation (VF), followed by asystole. Such progressive worsening of the cardiac rhythm is in most cases observed in the setting of ischemic heart disease and often associated with advanced left ventricular (LV) impairment. Revascularization prevents negative outcomes including SCD and heart failure (HF) due to LV dysfunction (LVD). The implantable cardioverter-defibrillator (ICD) on top of medical therapy is superior to antiarrhythmic drugs for patients with LVD and VT/VF. The beneficial effects of ICD have been demonstrated in primary prevention of SCD as well. However, yet debated is the temporal management for patients with LVD who are eligible to ICD prior to revascularization, either through percutaneous or surgical approach. Restoration of coronary blood flow has a dramatic impact on adverse LV remodeling, while it requires aggressive long-term antiplatelet therapy, which might increase complication for eventual ICD procedure when percutaneous strategy is pursued; on the other hand, when LV and/or multiorgan dysfunction is present and coronary artery bypass grafting is chosen, the overall risk is augmented, mostly in HF patients. The aims of this review are to describe the pathophysiologic benefits of revascularization, the studies addressing percutaneous, surgical or no revascularization and ICD implantation, as well as emerging defibrillation strategies for patients deemed at transient risk of SCD and/or at higher risk for transvenous ICD implantation.

The Results of Surgical Treatment of Patients with Many Valve Defects in Combination with Coronary Pathology

The objective: to analyze the impact of various surgical management on the duration of the ischemic period and the quality of myocardial protection during simultaneous combined correction of two-three heart valves and myocardial revascularization. Materials and methods. The results of the treatment of single-stage multivalve correction in combination with coronary artery bypass grafting in 93 patients, which was performed at the M.M. Amosov National Institute of Cardiovascular Surgery for the period from 2014 to 2021, were studied. Depending on the methods and the sequence of surgical manipulations, the patients were divided into three groups. I group – 42 patients who had the correction of heart valves firstly and then aortocoronary shunting in conditions of pharmaco-cold cardiac arrest, II group – 36 patients who first had aortocoronary bypass surgery, then valve correction in conditions of pharmaco-cold cardiac arrest, III group – 15 patients, who at the first stage had coronary artery bypass grafting on a working heart, then – correction of valve damage in conditions of pharmaco-cold cardiac arrest. Results. The use of the technique of primary restoration of coronary blood flow by shunting coronary arteries in a working heart before clamping the aorta (before pharmaco-cold cardiac arrest and the start of artificial blood circulation) allows to reduce the duration of artificial blood flow and ischemic time, which positively affects the heart rhythm in the postoperative period. Conclusions. The technique of performing aortocoronary shunting on a working heart is more effective than when performing aortocoronary shunting in conditions of pharmaco-cold cardiac arrest. This technique requires more time to perform and is technically more difficult, but it can statistically significantly reduce the time of myocardial ischemia, which reduces the frequency of severe heart failure and the frequency of postoperative complications.

PECULIARITIES OF CONNECTIVE TISSUE METABOLISM IN PATIENTS WITH POST-INFARCTION REMODELING AND REPERFUSION SYNDROME

Early restoration of coronary blood flow in acute myocardial infarction with elevation helps reduce the area of myocardial necrosis, prevent dilatation of the ventricular cavity, and reduce the development of arrhythmias and mortality. However, despite modern technologies in STEMI treatment, the development of reperfusion syndrome, in particular, arrhythmias, is possible after the restoration of blood flow in the infarct-related artery, which is a consequence of acute cellular, metabolic and local electrophysiological changes in the myocardium.&#x0D; The aim: is to investigate the long-term effects of reperfusion syndrome on the catabolic/anabolic activity of connective tissue and the processes of connective tissue framework formation in the post-infarction period in patients with myocardial infarction.&#x0D; Materials and methods. The study involved 156 patients with acute myocardial infarction with ST segment elevation (STEMI), and 15 apparently healthy individuals (control of laboratory parameters). The average age of the patients was (57.8±1.2) years. The percent of male patients prevailed (76 %).&#x0D; All MI patients were divided into two groups: Group I (98 people) – MI patients without clinical signs of reperfusion syndrome during revascularization, Group II (58 people) – MI patients with the signs of reperfusion syndrome in the form of rhythm and conductivity disturbances during revascularization of coronary arteries by percutaneous coronarography intervention (PCI) with prolonged stenting of the infarct-dependent coronary artery.&#x0D; Peculiarities of connective tissue metabolism were studied by the content of free and bound oxyproline, glycosaminoglycans, and antibodies to atypical collagens (Ig M and Ig G) in blood serum.&#x0D; Results. The recovery period after myocardial infarction showed an increase in collagen catabolism over collagen synthesizing processes in patients with MI who had reperfusion syndrome. The described patterns were also established by changes in glycosaminoglycans. The study showed an increase in the level of antibodies to atypical collagens. Particularly, the level of Ig M, which was within the norm (0.43±0.18) ng/ml, in patients with MI without reperfusion manifestations was three times higher (p&lt;0.001), and in cases of combination of MI and reperfusion syndrome – the highest (p&lt;0.001).&#x0D; Conclusions:&#x0D; &#x0D; Changes in collagen-synthesizing processes are observed in patients with MI, with a tendency to increase the processes of catabolism of the connective tissue matrix.&#x0D; The presence of reperfusion syndrome manifestations in MI patients after revascularization aggravates the processes of catabolism, even in the recovery period after MI.&#x0D; Increase in the activity of catabolic processes stimulates fibrosis and formation of rigid matrix and atypical collagen, to which antibodies are synthesized, thus blocking the pathological circuit of restructuring of the heart connective tissue framework, and accordingly its pathological remodeling.&#x0D; The obtained study results contribute to the identification of more sophisticated approaches to revascularization techniques to avoid negative effects of reperfusion syndrome, as well as new effective medications for collagen synthesis correction, which can increase the effectiveness of rehabilitative management of such&#x0D;

Systemic GDF11 replenishment ignites myocardial injury through diminishing anti-apoptotic activity of cardiac progenitor cells

Abstract Background Tissue damage due to acute myocardial infarction is caused by both the ischemic insult and subsequent reperfusion injury (I/R). Restoration of coronary blood flow accelerates cardiomyocyte death, a phenomenon referred to as reperfusion injury, the extent of which is partly modulated by cardiac progenitor cells (CPC). Development of novel therapies to reduce infarct size, the main determinant of outcome, represent a huge unmet medical need (1). Systemic levels of growth differentiation factor 11 (GDF11), a TGF-β superfamily member that shares 90% homology with myostatin, decline with age, and GDF11 replenishment by heterochronic parabiosis or systemic recombinant GDF11 (rGDF11) delivery was postulated to have rejuvenating effects (2). Purpose We aimed to probe the effects of systemic GDF11 replenishment on I/R injury and deepen insights into the molecular mechanisms involved. Methods We designed a vehicle-controlled study in which young (3–4 months) and old (22–24 months) C57Bl/6 mice were randomly assigned to either daily systemic rGDF11 or control treatment over 30 days before myocardial I/R injury was induced. Dissected hearts were subjected to in-depth profiling followed by IPA-guided -omics to identify key regulatory mechanisms. Finally, in vitro experiments on human CPCs and HL-1 cardiomyocytes were performed. Results Myocardial Gdf11 expression declined with age, whereas myostatin (Mstn) showed an opposing expression pattern (Fig. 1A), a trend similarly observed upon I/R (Fig. 1B). Surprisingly, after the 30-day study period (Fig. 1C), young and aged rGDF11-treated mice showed higher I/R-induced infarct size and serum cardiac troponin I levels than controls, despite comparable areas at risk (Fig. 1D). Importantly, while proxies of necroptosis/pyroptosis remained unchanged, rGDF11-treated animals showed reduced cardiomyocyte viability irrespective of their age (Fig. 2A). Targeted transcriptomics applied on cardiac tissues of both groups identified the CPC-marker Nkx2–5 to be differentially regulated (Fig. 2B-C), an expression pattern validated in an independent cohort at both mRNA and protein levels (Fig. 2D). In the adult myocardium, the expression of both Nkx2–5 and its cofactor Gata4 is mainly confined to CPCs; indeed, similar reductions in Nkx2–5 and Gata4 expression were observed in CPCs exposed to rGDF11 (Fig. 2E) which coincided with accelerated cardiomyocyte death if cultured in conditioned media obtained from CPCs treated with rGDF11 (Fig. 2F), pointing toward a paracrine signalling pathway. Conclusions Myocardial expression of GDF11 declines with age, and is blunted upon I/R injury, thereby opposing the expression pattern of myostatin. Surprisingly, however, systemic GDF11 replenishment by rGDF11 supplementation enhances rather than reduces myocardial infarct size through augmented apoptosis, a phenomenon mediated by diminished cardioprotective function of CPCs. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Foundation for Cardiovascular Research – Zurich Heart House

Myocardial Infarction: Risk Factors, Pathophysiology, Classification, Assessment and Management

Myocardial infarction is a serious health problem affecting populations worldwide. Proper and prompt diagnosis and management is critical to achieving good prognosis and avoiding or reducing morbidity and mortality. It is essential for clinicians to be aware of the risks, diagnosis and treatment. In this review we aim to update and discuss knowledge of myocardial infarction with respect to risk factors, pathophysiology, types or classification, clinical manifestations, diagnosis and treatment in a concise and simplified manner in order to define a simple comprehensive guide for clinicians. The available literature has been searched, reviewed, studied, analyzed, written in a simple understanding method, discussed and concluded. For prophylaxis, it has been found that moderate muscular exercise, regular consumption of fresh vegetables and fruits, avoidance of smoking and stress, and low consumption of fat are associated with reduced risk of coronary heart disease in populations of all age groups worldwide. The diagnosis of myocardial infarction is based primarily on evaluations of clinical features, typical abnormalities in ST-segment and T wave of ECG findings and rise in cardiac enzymes or biomarkers such as plasma troponin. At the same time, the key to treatment is reperfusion of the myocardium and restoration of coronary blood flow.

PANDORA`S BOX OR «NO-REFLOW» PHENOMENON (CLINICAL CASE)

It has been established that successful repefusion of ocluded infarct-dependent coronary artery (IDCA) during percutaneous coronary intervention does not mean restoration of myocardial perfusion. This «no-reflow» phenomenon is known from the studies of R. Kloner, C. Ganote, R. Jennings (1974). They were among the first to note only a partial restoration of coronary blood flow after the reperfusion of mechanically occluded for 90-180 minutes coronary artery in dogs. The authors considered damage to the capillary endothelium, edema of the damaged wall and extravasal tissues, and protrusion into the capillary cavity to be the cause of this phenomenon.&#x0D; The frequency of the phenomenon of «no-reflow» after the successful restoration of coronary blood flow in the IDCA varies between 5 - 40% of all cases. The development of this phenomenon was an unfavorable prognostic factor, primarily in terms of mortality and deterioration of the functional state of the left ventricle.&#x0D; The pathophysiology of the «no-reflow» phenomenon remains poorly understood. Obviously, it has a multifactorial nature and cannot be described by any one mechanism.&#x0D; Analyzing the phenomenon of «no-reflow», it is noted that in spite of the reperfusion of IDCA, there are pronounced pathophysiological changes in the microcirculatory tract, the essence of which is to block myocardial perfusion in the area of myocardial infarction.&#x0D; During the COVID-19 pandemic, the number of patients with myocardial infarction increased, including an increase in the number of diagnosed «no-reflow» and «slow-flow» phenomena, which is associated with the impact of SARS СOVID-19 virus on the myocardium, namely the development of microvascular damage.&#x0D; There is currently no specific therapy for the prevention and treatment of «no-reflow» phenomen that would be recommended for patients with STEMI.&#x0D; This article presents a clinical case of the phenomenon of «no-reflow» in patient B., 56 years old, who complained of severe chest pain, irradiation in the left shoulder and lower jaw, shortness of breath, general weakness. History of hypertension, coronavirus PCR +. Troponin I - 5.4 ng/ml. According to the electrocardiogram: elevation of the ST segment in II. III, aVF leads. At the time of contrast infusion during stenting of infarct-dependent right coronary artery, its slow filling was recorded - the phenomenon of «no-reflow» TIMI 0, MBG-0. The patient was discharged from the hospital in satisfactory condition under the supervision of a family doctor.&#x0D; Conclusions:&#x0D; &#x0D; The phenomenon of «no-reflow» is a topical and unresolved issue of myocardial revascularization in real clinical practice.&#x0D; The most common prerequisite for the development of the phenomenon of «no-reflow» after myocardial revascularization is late hospitalization, and aggravating circumstances - comorbid pathology (COVID-19, hypertension, diabetes).&#x0D; This clinical case is interesting because the patient with lesions of the lower left ventricular wall PCI was complicated by the phenomenon of «no-reflow», as evidenced by the slowing of ST segment resolution, lack of myocardial perfusion, parietal thrombosis throughout the RCA.&#x0D; Further search for ways to prevent and treat irreversible blood flow syndrome after successful reperfusion of infarct-dependent coronary artery is needed.&#x0D;

No-reflow phenomenon and reperfusion injury. Mechanisms and treatment

Currently, one of the key methods of treating a patient with ST-elevation myocardial infarction is to restore blood flow to the infarct-related artery as quickly, completely and steadily as possible. However, in some cases, it is not possible to achieve adequate myocardial reperfusion, despite the restoration of coronary blood flow. This phenomenon was named no-reflow. Due to the lack of a unified approach to the diagnosis of no-reflow, its occurrence varies widely – from 2 to 44 %. Failure to achieve adequate myocardial perfusion leads to a higher mortality rate – from 7.4 to 30.3 %, as well as to more aggressive remodeling of the myocardium. For a long time, distal embolization in percutaneous coronary intervention was considered one of the leading mechanisms. However, the routine use of protective devices did not show a pronounced effect on the outcome and prognosis, although it is justified in certain clinical situations. Ischemic injury directly plays a significant role due to overload of cardiomyocytes with calcium, cellular edema, necrosis and apoptosis, which is significantly aggravated by myocardial reperfusion and forms obstruction at the level of the microcirculatory bed. More data is being accumulated about immune-mediated injury through activation of cellular immunity, intense inflammation and thrombosis in situ. Despite the success in the animal experiment, the clinical use of certain groups of drugs showed an ambiguous results. According to the latest recommendations European Society of Cardiology / European Association for Cardio-Thoracic Surgery (ESC / EACTS) 2018, GPIIb / IIIa platelet receptor inhibitors are recommended in the case of no-reflow. Besides this, according to the literature nicorandil and sodium nitroprusside, as well as IL-1β antagonists, seem to be promising. As a non-drug therapy, selective intracoronary hypothermia also has shown its effectiveness and safety in a pilot study. To date, it is clear that the no-reflow phenomenon is a manifestation of a complex cascade of reactions, including ischemic, reperfusion and immune-related injury, as well as distal embolization. Considering its significant contribution to the frequency of adverse outcomes and late complications, it seems necessary to introduce unified approaches to the diagnosis, prevention and treatment of no-reflow, which requires high-quality clinical studies.

The role of protein kinase C and PI3-kinase in the mechanism of the cardioprotective effect of remote ischemic postconditioning

Background. Acute myocardial infarction (AMI) with ST segment elevation is associated with high incidence of complications. Mortality from AMI is about 5%, which has not decreased in recent years. Revascularization provides recovery of coronary blood flow, but also contributes to the occurrence of reperfusion injury to the heart. Remote ischemic postconditioning (RIPostC) is a promising, non-invasive method that can effectively and safely reduce the infarct size.The aim of the study was to investigate the role of protein kinase C and PI3-kinase in the development of the infarct-limiting effect of remote ischemic postconditioning.Materials and methods. The study was performed on Wistar rats. Coronary artery occlusion (45 min) and reperfusion (2 h) were performed. The infarct size (IS) and the size of area at risk (AAR) were assessed. RIPostC was modeled by applying tourniquets to the hind limbs in the hip joint immediately after the restoration of coronary blood flow. All inhibitors were administered intravenously 10 min before reperfusion.Results. In the control group, the IS / AAR ratio was 44%. RIPostC reduced the IS / AAR ratio by about 50%. Preliminary administration of the protein kinase C inhibitor chelerythrine and the PI3-kinase inhibitor wortmannin eliminated the cardioprotective effect of RIPostC.Conclusion. The mechanism of the infarct-limiting effect of RIPostC is implemented through activation of protein kinase C and PI3-kinase.

MMP 9-instructed assembly of bFGF nanofibers in ischemic myocardium to promote heart repair.

Background: The only effective treatment for myocardial infarction (MI) is the timely restoration of coronary blood flow in the infarcted area, but further reperfusion exacerbates myocardial injury and leads to distal coronary no-reflow, which affects patient prognosis. Angiogenesis could be an important therapeutic strategy for re-establishing the blood supply to save the ischemic myocardium after MI. Basic fibroblast growth factor (bFGF) has been shown to promote angiogenesis. However, direct intravenous administration of bFGF is not a viable option given its poor half-life in vivo. Methods: Herein, we developed a peptide Lys-Lys-Pro-Leu-Gly-Leu-Ala-Gly-Phe-Phe (K2) to encapsulate bFGF to form bFGF@K2 micelle and proposed an enzyme-instructed self-assembly (EISA) strategy to deliver and slowly release bFGF in the ischemic myocardium. Results: The bFGF@K2 micelle exerted a stronger cardioprotective effect than free bFGF in a rat model of myocardial ischemia-reperfusion (MI/R). In vitro results revealed that the bFGF@K2 micelle could be cleaved by matrix metallopeptidase 9 (MMP-9) to yield bFGF@Nanofiber through amphipathic changes. In vivo experiments indicated that intravenous administration of bFGF@K2 micelle could lead to their restructuring into bFGF@Nanofiber and long term retention of bFGF in the ischemic myocardium of rat due to high expression of MMP-9 and assembly-induced retention (AIR) effect, respectively. Twenty-eight days after MI/R model establishment, bFGF@K2 micelle treatment significantly reduced fibrosis and improved cardiac function of the rats. Conclusion: We predict that our strategy could be applied in clinic for MI treatment in the future.

Management of pacemaker patients after myocardial infarction

Myocardial infarction (MI) is the leading cause of death and disability in the population. Effective restoration of coronary blood flow in the infarction-dependent artery during percutaneous coronary intervention contributes to the regression of structural and functional remodeling of the left ventricle. Meanwhile, in 18% of cases, patients with myocardial infarction require implantation of a pacemaker because of the cardiac conduction disorders, among which atrioventricular blockade is the leading one. The need for pacemaker implantation is determined by the clinical features and the type of bradycardia complicating myocardial infarction. The scope of preventive measures at the stage of outpatient specialized cardiac care for patients with myocardial infarction and pacemaker includes medical, physical, and psychological rehabilitation. In addition, the presence of an implantable pacemaker necessitates specialized dynamic monitoring by an arrhythmologist, including programming the pacemaker. Performing a magnetic test allows to assess the efficiency of the pacemaker, the level of its charge and promptly determine the need to its replacement. Determination of the pacing threshold ensures efficient operation of the implantable device. After discharge from the hospital, a schedule for checking the pacemaker is determined, namely, 3 months after the date of implantation of the pacemaker, then 1-2 times a year. In the event of complaints of dizziness, fainting or damage of the pacemaker implantation site, the pacemaker check is carried out unscheduled. Patients with a history of myocardial infarction and an implantable pacemaker should be informed about the limitations that may be associated with the presence of a pacemaker. It is recommended to exclude contact with possible sources of electrical interference as much as possible, to avoid medical physiotherapy using galvanic currents. When using industrial or household equipment, safety precautions must be followed.

Миокардиальный станнинг в медицине неотложных и критических состояний, ассоциированных с системной гипоксией

Актуальность. Миокардиальный станнинг — феномен, заключающийся в продолжительном снижении сократительной способности миокарда после краткого периода ишемии/реперфузии, при котором не происходит омертвения ткани сердечной мышцы. Если изначально феномен станнинга ассоциировали исключительно с проявлениями ишемической болезни сердца, то в настоящее время имеется все больше свидетельств о том, что миокардиальный станнинг может осложнять совсем другую патологию. Цель: изучение результатов работ оте-чественных и зарубежных ученых, посвященных наблюдению феномена станнинга в медицине неотложных состояний, и систематизация накопленного клинического материала. Материалы и методы. Детальное изучение результатов современных клинических исследований, посвященных диагностике снижения сократительной способности миокарда у пациентов, находящихся в критических состояниях, которые развились не вследствие манифестации острого коронарного синдрома, обсуждению механизмов патогенеза миокардиальной дисфункции при этих состояниях и принципам оказания таким больным экстренной и специализированной медицинской помощи. Результаты. Для феномена миокардиального станнинга характерны следующие отличительные признаки: 1. Коронарный кровоток после перенесенного эпизода ишемии практически полностью восстанавливается. После ишемии очень часто регистрируется кратковременный период гиперперфузии. 2. Несмотря на восстановление коронарного кровотока, имеет место продолжительное снижение сократимости миокарда. 3. Необратимого повреждения кардиомиоцитов в период ишемии не происходит. 4. Снижение сократительной способности сердца, наблюдающееся после ишемии и последующей реперфузии, является полностью обратимым. Основными механизмами развития миокардиального станнинга являются: усиленная генерация активных форм кислорода в период реперфузии; перегрузка кардиомиоцитов кальцием; снижение сопряженности между процессами электрического возбуждения миокарда и его сократимостью. Продукция простациклина, активность ангиотензина I, II и ангиотензинпревращающего фермента, продукция брадикинина моделируют тяжесть мио-кардиальной дисфункции при станнинге. Причиной станнинга может быть индуцированная катехоламинами кардиотоксичность. Миокардиальный станнинг можно наблюдать у пациентов с геморрагическим, септическим шоком, субарахноидальными кровоизлияниями, на фоне проведения гемодиализа, после криза при феохромоцитоме, после реанимационной акции. Выводы. Миокардиальный станнинг требует своевременной диагностики, поскольку проведение гемодинамической коррекции не с помощью инотропной поддержки, а по другим направлениям, а именно за счет увеличения скорости объемной нагрузки (агрессивная инфузионная терапия) или применения вазопрессоров, может резко ухудшить состояние пациента вследствие увеличения нагрузки на ослабленное сердце.

Surgical intervention and outcome for treatment of myocardial bridging refractory to medication.

Myocardial bridging (MB) is a common and usually benign inborn coronary abnormality that may lead to anginal symptoms, acute coronary syndrome, arrhythmias, and rarely sudden cardiac death. MB are most commonly localized in the middle segment of the left anterior descending coronary artery (LAD). The treatment of LAD-MB is still challenging. Our objective was to assess the short- and long-term results of surgical procedures in patients with LAD-MB who had chest pain refractory to medical therapy. Between March 2005 and January 2020, 26 patients (19 males and 7 females; mean 55.8 ± 12.4 years) with MB underwent surgery. All MB was located in the mid-segment of the LAD with a mean length of 4.2 ± 1.7 cm. Coronary angiography before surgery demonstrated LAD-MB with systolic compression more than or equal to 70% in all patients. Twenty-five patients underwent myotomy and one patient underwent coronary artery bypass grafting (CABG). All patients survived and recovered uneventfully. Neither hospital or late death nor major complications occurred. Follow-up time was 3-173 months (mean 55.7 months). Follow-up of coronary angiography or computed tomography scan performed in 16 patients demonstrated restoration of coronary blood flow and myocardial perfusion without significant residual compression of the artery. All patients were symptom-free and are currently in NYHA Class I. The symptomatic LAD-MB patients who are refractory to medication should actively undergo the surgical intervention such as myotomy and CABG to eliminate the clinical symptoms and achieve satisfactory results by follow-up findings. Myotomy is a preferred procedure because of its safety and satisfactory results.

Predictors of myocardial reperfusion syndrome: a modern view of the issue and current problems. Part 1: Reperfusion arrhythmias, injury and stunning myocardium (review of literature)

Myocardial reperfusion syndrome is a complex set of pathological processes that occur in the heart muscle due to restoration of coronary blood flow in patients with ST-segment elevation myocardial infarction. Despite the fact that it has been known for a long time, there is still no unequivocal opinion about the predictors, and, accordingly, the risk groups for its occurrence. This prevents predicting the further course of the disease and studying the effectiveness of surgical and therapeutic methods for preventing the consequences of reperfusion in patients with ST-segment elevation myocardial infarction, which in turn significantly worsens the postoperative and long-term prognosis in this group of patients. We used the search engines such as E-lilbrary, Google Scholar and Pubmed to search for studies on this issue. The article presents research data highlighting predictors of myocardial reperfusion syndrome. In addition, the problems of verification of irreversible reperfusion injury and myocardial stunning are described.

Influences of tirofiban combined with atorvastatin on coronary blood flow restoration and changes in inflammatory factors, Cys-C, Hcy and MMP-9 in AMI patients after PCI.

article: Influences of tirofiban combined with atorvastatin on coronary blood flow restoration and changes in inflammatory factors, Cys-C, Hcy and MMP-9 in AMI patients after PCI - Minerva Medica 2021 Jun 18 - Minerva Medica - Journals

Expert assessment of the suitability of treatment and diagnostic measures in providing emergency care to patients with acute coronary syndrome

It is known that it is possible to affect the extent of myocardial damage and, as a result, mortality only in the first hours of its development. Therapeutic tactics in ACS with elevation of the ST segment involves the restoration of coronary blood flow, the main method is the reperfusion of the coronary artery by systemic thrombolysis or PCI in a specialized hospital. The effectiveness of treatment is inversely related to the time spent.&#x0D; The aim of the study was to examine the opinion of specialists on the feasibility of implementing the items of the protocol of emergency medical care for patients with ACS at the place of call.&#x0D; Materials and methods. During the study the method of expert evaluations, which consisted of gathering information by interviewing experts and summarizing the individual opinions of experts into a general concept was used. The experts were 48 emergency physicians. The method of expert evaluation included the following stages: development of the questionnaire; survey of experts; summary of examination materials; calculation of statistical indicators; interpretation of the obtained results and formulation of conclusions.&#x0D; Results. In order to assess the actions of the emergency team, depending on the need to conduct them for diagnosis and emergency care for patients with ACS at the scene, we calculated the feasibility indexes for each item of the protocol. In the future, we divided the treatment and diagnostic measures for ACS with ST segment elevation according to the level of expediency at the scene into four groups (n): n1 – high level, n2 – sufficient level and n3 – low level and n4 – very low level. According to the results of the ranking, the scope of measures to be implemented by the head of the emergency team at the ACS with elevation of the ST segment on arrival on call, as well as measures that, according to interviewed experts, are not required at this stage and can be carried out during transportation of the patient to a specialized hospital.&#x0D; Conclusions. Based on the results of the calculation of feasibility indices and subsequent ranking of treatment and diagnostic measures for the relevant groups (n1, n2, n3, n4) from 37 items of the study, to assist patients with ACS with ST segment elevation at the scene, it is recommended to perform 16