Restoration Of Coronary Blood Flow Research Articles

Abstract 14708: Temporal Relationship Between Erythropoietin Administration and Mitochondrial Dysfunction in Cardiac Ischemia/reperfusion Injury

Introduction: Acute myocardial infarction remains a leading cause of mortality. Rapid restoration of coronary blood flow is the cornerstone of treatment. Paradoxically, it leads to a condition known as ischemia/reperfusion (I/R) injury which precipitates more injuries to the heart. Erythropoietin (EPO), a hormone produced by the kidneys in response to cellular hypoxia, reportedly provides cardioprotection following cardiac I/R injury in many preclinical experiments. Unfortunately, clinical trials failed to demonstrate cardioprotection when EPO was given after reperfusion. Therefore, we aim to determine the temporal influences on administering EPO in cardiac I/R injury. Hypothesis: Administration of EPO at different time points provides varying efficacy in reducing arrhythmias, LV and cardiac mitochondrial dysfunction after cardiac I/R injury. Methods: Male Wistar rats were divided into sham-operated and cardiac I/R group. In I/R group, rats were subdivided into 4 groups (n=10/group): vehicle, EPO pretreatment (P-EPO), EPO given during ischemia (I-EPO), and EPO given at reperfusion onset (R-EPO). EPO was intravenously given to the rats (5000 unit/kg). Rats underwent 30-min LAD ligation followed by 120-min reperfusion. Arrhythmia scores and LV function were recorded throughout the protocol. Then, rats were sacrificed to determine infarct size and mitochondrial function. Results: Cardiac I/R injury induced arrhythmias, LV and mitochondrial dysfunction (Fig . Administration of EPO before or during ischemia, but not at the onset of reperfusion, significantly attenuated LV dysfunction and infarct size. However, EPO did not reduce arrhythmia scores. Although EPO given at all time points reduced mitochondrial reactive oxygen species, EPO given at reperfusion failed to prevent mitochondrial swelling (Fig) . Conclusions: Acute EPO treatment before or during ischemia, but not at the onset of reperfusion, exerted cardioprotection against I/R injury.

The importance of clinically relevant background therapy in cardioprotective studies

Treatment of acute myocardial infarct patients (AMI) includes rapid restoration of coronary blood flow and pharmacological therapy aimed to prevent pain and maintain vessel patency. Many interventions have been investigated to offer additional protection. One such intervention is remote ischaemic conditioning (RIC) involving short-episodes of ischaemia of the arm with a blood pressure cuff, followed by reperfusion to protect the heart organs from subsequent severe ischaemia. However, the recent CONDI2-ERIC-PPCI multicentre study of RIC in STEMI showed no benefit in clinical outcome in low risk patients. It could also be argued that these patients were already in a partially protected state, highlighting the disconnect between animal- and clinical-based outcome studies. To improve potential translatability, we developed an animal model using pharmacological agents similar to those given to patients presenting with an AMI, prior to PPCI. Rats underwent MI on a combined background of an opioid agonist, heparin and a platelet-inhibitor thereby allowing us to assess whether additional cardioprotective strategies had any effect over and above this “cocktail”. We demonstrated that the “background drugs” were protective in their own right, reducing MI from 57.5 ± 3.7% to 37.3 ± 2.9% (n = 11, p < 0.001). On this background of drugs, RIC did not add any further protection (38.0 ± 3.4%). However, using a caspase inhibitor, which acts via a different mechanistic pathway to RIC, we were able to demonstrate additional protection (20.6 ± 3.3%). This concept provides initial evidence to develop models which can be used to evaluate future animal-to-clinical translation in cardioprotective studies.

От «пустой» липосомы до сложной наноструктуры

В работе подводятся некоторые итоги почти 40-летней работы авторов в области липосомологии, начатые в 80-х годах прошлого века под руководством академика НАМН Украины Александра Викторовича Стефанова.Создание нужной концентрации лекарственных веществ в органе-мишени, не затрагивая при этом не вовлеченные в патологический процесс органы и ткани, – задача непростая. За последние несколько лет предпринято множество попыток решить эту проблему, и оказалось, что лучшимипереносчиками лекарств являются именно липосомы.Преимущества липосом перед другими носителями обусловлены такими их свойствами:– сродство с природными мембранами клеток по химическому составу;– универсальность. Липосомы способны переносить разнообразные фармакологически активныевещества, а также дополнительные источники энергии для клетки и генетический материал; &#x0D; - липосомы сравнительно легко биодеградируют, высвобождая доставленные вещества. В пути следования липосомы надежно укрывают свое содержимое от контакта с иммунной системой и не вызывают защитных и аллергических реакций организма;– способ взаимодействия липосом с клетками, который происходит в разных формах. При этом могут изменяться свойства клеточных мембран, например: вязкость и проницаемость; величина электрического заряда; фосфолипидное окружение ферментов и ионных каналов и, соответственно, их активность (вот почему даже так называемая пустая липосома может быть биологически активным агентом).Благодаря липосомам появляется новый способ направленного воздействия на клетку, который можно назвать «мембранной инженерией», то есть, появляется возможность модифицировать клеточную мембрану в заданном направлении.Оказалось, что липосомы могут быть не только переносчиками лекарств, но и обладают самостоятельной биологической активностью. Продемонстрирована способность так называемых пустых фосфатидилхолиновых липосом (ФХЛ) оказывать влияние на электрическую и сократительную активность сосудистых гладких мышц. При гипоксии ФХЛ восстанавливают измененную для ионов проницаемость плазматических мембран гладких мышц сосудов, а у крыс со спонтанной артериальной гипертензией улучшают эндотелий-зависимые дилататорные реакции сосудов.Кроме того, было показано, что «пустые» ФХЛ эффективно восстанавливают вызванное ацетилхолином эндотелий-зависимое расслабление изолированных колец грудной аорты, нарушенное воздействием гамма-облучения. Липосомы также восстанавливают пониженную после облучения чувствительность сосудистой ткани к ацетилхолину и оксиду азота.С целью усиления антигипоксического и антиоксидантного действия липосом в их структуру был внедрен антиоксидант кверцетин. Использование липосомальной формы кверцетина приводит к полноценному восстановлению коронарного кровотока в послеокклюзионном периоде приострой субтотальной ишемии миокарда, в значительной степени уменьшает проявления характерного для репеперфузионного периода окислительного стресса и предупреждает повышение содержания лейкотриенов С4 и Е4. Синтез простациклина при этом не уменьшается. Применение липосомальной формы кверцетина приводит к уменьшению зоны некроза миокарда в два раза.Липосомальная форма кверцетина практически полностью предотвращает или в значительной степени корригирует нарушения ритма сердечных сокращений и восстанавливает сократительную активность миокарда.Липосомальная форма кверцетина эффективно восстанавливает функцию калиевых каналов большой проводимости у облученных крыс.Перспективным может оказаться включение в состав липосом цитохрома С. Липосомальная форма цитохрома С приводит к коррекции нарушений гемостаза и предотвращает развитие синдрома ДВС при острой массивной кровопотере.Многочисленные патологические процессы, такие как гипертония, атеросклероз, нарушение кровотока в центральной нервной системе, вызваны недостаточностью эндогенного синтеза/высвобождения NO. В таких случаях дополнительное введение NO может быть очень эффективнойстратегией в лечении заболеваний, связанных с указанными патологическими процессами.Разработка современных доноров оксида азота, обладающих способностью контролируемого и дозированного высвобождения действующего вещества, представляет собой чрезвычайно сложную задачу. Создание липидной системы доставки NO, способной обеспечить естественную скорость высвобождения, и разработка ее стабильной лекарственной формы стало следующей целью наших исследований.Проведенные исследования специфического действия сконструированной липосомальной формы оксида азота (ЛФ NO) свидетельствуют о его ее чрезвычайно высокой дилататорной, антиишемической активности. Это подтверждается выраженным дозозависимым расслаблением сегментов интактной аорты крыс и продолжительной гипотензивной реакцией системного кровообращения. ЛФ NO предотвращает развитие критических нарушений насосной функции сердца и способствует сохранению его сократительной активности при субтотальной ишемии. Действие ЛФ NOпроявляется значительным также дозозависимым расслаблением полосок пещеристых тел полового члена и миометрия.Новый NO-содержащий липосомальный конструкт эффективно открывает одиночные кальцийзависимые калиевые каналы большой проводимости в сосудистых гладких мышцах и значительно увеличивает вероятность их нахождения в открытом состоянии.Таким образом, ЛФ NO обещает быть эффективной при лечении ангиопатий различного генеза (включая диабетическую), эректильной дисфункции, гиперактивного мочевого пузыря, артериальной гипертензии, геморрагического и ишемического инсульта. Учитывая возможность применения в ингаляционной форме, она может быть использована для лечения легочной гипертензии.Высказывается мнение, что потенциальные возможности липосом существенно выше пока известных нам. Мы только начали понимать, как липосомы работают с клеткой.

Clinical features of the acute period of myocardial infarction with ST segment elevation in patients after reperfusion therapy

Aim: to determine the clinical features of the course of myocardial infarction with ST segment elevation in the acute period in patients after reperfusion therapy.Materials and methods. The clinical and instrumental examination data of 100 patients with ST-elevation myocardial infarction (STEMI) in the acute period were analyzed. The patients were divided into 3 groups: group 1 – patients (n = 46) who underwent primary percutaneous coronary intervention (PCI) or thrombolytic therapy (TLT) followed by PCI in the acute period of myocardial infarction (MI), group 2 – patients (n = 33) who underwent TLT, group 3 – patients (n = 21) who received standard drug therapy.Results. The left ventricular (LV) end-systolic diameter and LV myocardial mass index were significantly smaller by 5.73 % (P = 0.0471) and 10.06 % (P = 0.0076), respectively, in group 1 patients than in group 3. Among the group 1 patients, pulmonary hypertension, local hypokinesia and LV systolic dysfunction were significantly less often detected by 17.72 % (P = 0.028), 26.15 % (P = 0.0293) and 1.99 % (P = 0.0135), respectively, compared with group 2, and zones of LV dyskinesia were much less identified by 19.46 % (P = 0.027) than in group 3. Among the group 2 patients, there was a tendency towards the prevalence of ventricular fibrillation and extrasystolic arrhythmia occurrence. Acute LV failure (ALVF) was less common in group 2 as compared with group 1 and 3, by 24.34 %, P = 0.0067 and 7.7 %, P = 0.0049, respectively.Conclusions. Reperfusion syndrome (RS) after restoration of coronary blood flow, manifested in ALVF and arrhythmias, was transient and sometimes required short-term symptomatic therapy. A common manifestation of RS after TLT was extrasystolic arrhythmia, in contrast to RS after PCI with more common ALVF (Killip III). In patients who did not undergo reperfusion therapy, systolic and diastolic myocardial function violation as well asLV aneurysm formation occurred more frequently. Restoration of coronary blood flow using PCI had advantages over TLT, such as less pronounced clinical manifestations of systemic inflammation, dilatation, local and global contractility impairment and indicators ofLV afterload.

Inhibition of the long non-coding RNA NEAT1 protects cardiomyocytes from hypoxia in vitro via decreased pri-miRNA processing

While restoration of coronary blood flow to the ischemic heart is the most effective strategy for reducing infarct size, reperfusion injury represents a significant limiting factor on clinical outcomes in myocardial infarction patients. Ischemic preconditioning (IPC) has been shown to inhibit reperfusion injury and represents an attractive model for studying cardioprotective signal transduction pathways. Long non-coding RNAs (lncRNAs) are a structurally and functionally heterogenous class of RNA transcripts with unknown roles in IPC-induced cardioprotection. Through microarray-based expression profiling of 31,423 lncRNAs in cardiac tissue from IPC mice, we identified the nuclear transcript Neat1 to be rapidly and robustly decreased in response to IPC. siRNA-mediated knock down of Neat1 reduced apoptosis and necrosis in murine cardiomyocytes (CM) and human iPS-derived CMs in response to prolonged hypoxia and hypoxia-reoxygenation, assessed with Annexin V/propidium iodide-staining, a Caspase 3/7 activity assay, LDH release, and western blot for cleaved Caspase 3. Mechanistically, Neat1 was shown to regulate processing of pro-apoptotic microRNA-22 (miR-22) in murine and human CM nuclei using a luciferase reporter assay. Hypoxia-induced downregulation of Neat1 was shown to result in accumulation of unprocessed pri-miRNA and decreased availability of biologically active miRNA, including miR-22. Addition of exogenous synthetic miR-22 reversed the protective effect of Neat1 knock down in human iPS-CM. In conclusion, we have identified the nuclear lncRNA Neat1 as part of a conserved oxygen-sensitive feedback mechanism by regulation of miRNA processing and a potential target in cardioprotection.

Iron imaging in myocardial infarction reperfusion injury

Restoration of coronary blood flow after a heart attack can cause reperfusion injury potentially leading to impaired cardiac function, adverse tissue remodeling and heart failure. Iron is an essential biometal that may have a pathologic role in this process. There is a clinical need for a precise noninvasive method to detect iron for risk stratification of patients and therapy evaluation. Here, we report that magnetic susceptibility imaging in a large animal model shows an infarct paramagnetic shift associated with duration of coronary artery occlusion and the presence of iron. Iron validation techniques used include histology, immunohistochemistry, spectrometry and spectroscopy. Further mRNA analysis shows upregulation of ferritin and heme oxygenase. While conventional imaging corroborates the findings of iron deposition, magnetic susceptibility imaging has improved sensitivity to iron and mitigates confounding factors such as edema and fibrosis. Myocardial infarction patients receiving reperfusion therapy show magnetic susceptibility changes associated with hypokinetic myocardial wall motion and microvascular obstruction, demonstrating potential for clinical translation.

Manual thromboaspiration as a method of prevention on no-reflow phenomenon

The primary goal of treatment for myocardial infarction with ST-segment elevation (STEMI) is the early restoration of coronary blood flow. However, the restoration of the pathogenesis of the epicardial coronary artery during primary coronary intervention (PPVC) is not always accompanied by normalization of myocardial perfusion, that may be associated with microvascular obstruction and the lack of fusion phenomenon, developing, in particular, due to its long duration of intracoronary thrombus and open distal embolism during PCP. The article is devoted to a review of literature data on predictors of the development of the no-reflow phenomenon and its prevention.

Novel Findings and Therapeutic Targets on Cardioprotection of Ischemia/ Reperfusion Injury in STEMI.

Acute ST-segment elevation myocardial infarction (STEMI) remains a leading cause of morbidity and mortality around the world. A large number of STEMI patients after the infarction gradually develop heart failure due to the infarcted myocardium. Timely reperfusion is essential to salvage ischemic myocardium from the infarction, but the restoration of coronary blood flow in the infarct-related artery itself induces myocardial injury and cardiomyocyte death, known as ischemia/reperfusion injury (IRI). The factors contributing to IRI in STEMI are complex, and microvascular obstruction, inflammation, release of reactive oxygen species, myocardial stunning, and activation of myocardial cell death are involved. Therefore, additional cardioprotection is required to prevent the heart from IRI. Although many mechanical conditioning procedures and pharmacological agents have been identified as effective cardioprotective approaches in animal studies, their translation into the clinical practice has been relatively disappointing due to a variety of reasons. With new emerging data on cardioprotection in STEMI over the past few years, it is mandatory to reevaluate the effectiveness of "old" cardioprotective interventions and highlight the novel therapeutic targets and new treatment strategies of cardioprotection.

Ways to improve the results of surgical treatment of patients with multiple valve correction in combination with coronary pathology

Aim of the study. To determine the effect of surgical tactics on the duration of ischemic period with simultaneous combined correction of two or three valves of the heart and myocardial revascularization&#x0D; Materials and methods. The work is based on the analysis of the results of single-stage multivalve correction in conjunction with coronary artery bypass grafting in 93 patients, which was performed at the National Amosov Institute of Cardiovascular Surgery for the period from 2014 to 2016. Depending on the tactical approach and the sequence of surgical procedures, patients were divided into groups. 1 – “CABG off pump and subsequent correction of heart valves” (n = 15); 2 – “Correction of heart valves and bypass grafting in conditions of cardioplegia” (n = 78).&#x0D; Results. Using different approaches to achieve high-quality protection of the myocardium at the time of its ischemia, minimizing the impact of artificial circulation on the body by improving the conditions and reducing the ischemic heart time showed significant advantages of the method of pre-shunting CA in the working heart.&#x0D; Conclusions.1. Correction of combined multiple valve pathology with coronary heart disease requires prolonged cardiopulmonary bypass time and ischemic heart time, which requires reliable protection of the myocardium, which is difficult to carry out in the presence of stenoses in the lumen of the CA. 2. The use of the method of preventive restoration of coronary blood flow by bypassing the spacecraft on the working heart before clamping of the aorta, has significant advantages in the duration of the cardiopulmonary bypass time and ischemic time of the heart.

Unresolved issues in left ventricular postischemic remodeling and progression to heart failure.

: In the past decades, myocardial infarction periacute mortality markedly declined since coronary reperfusion therapy has been adopted. Despite immediate benefits of coronary blood flow restoration, the percentage of new onset heart failure has increased over time suggesting that ischemia can run detrimental consequences beyond the immediate anoxic hit. By accepting to aggregate all types of heart failure regardless of underlying cause, the current practice did not help to shed light on the complex postischemic cardiac biology indicating that heart failure is somewhat unavoidable. In the ischemic sequel, the activated mechanisms aim to repair the infarcted zone and to compensate for the lost myocyte functions, thus allowing the heart to maintain the efficient cardiac output for vital organs. The variety of underlying preexisting conditions, as well as the multifaceted components of cardiac molecular structure, cellular state, and electrophysiological postischemic events pave the way for long-term adverse cardiac remodeling. We focused our attention on multiple factors, which include myocyte loss, hypertrophy, hyperplasia, extracellular matrix changes linked to myocardial fibrosis and scar, metabolic imbalance, as well as immunologic response occurring in the acute myocardial aftermath. Moreover, we reported both current pharmacological strategies and future perspectives that might be useful in clinical practice. Furthermore, we discussed the cardiac magnetic resonance as the most promising noninvasive imaging tool, which could be helpful in identifying the amount of myocardial damage. Despite the redundancy of molecular pathogenic mechanisms making it impossible to estimate the proportionate contributions in generating the heart failure phenotype, a deeper understanding will contribute to more customized patient management.

Platelet Contributions to Myocardial Ischemia/Reperfusion Injury.

Obstruction of a coronary artery causes ischemia of heart tissue leading to myocardial infarction. Prolonged oxygen deficiency provokes tissue necrosis, which can result in heart failure and death of the patient. Therefore, restoration of coronary blood flow (reperfusion of the ischemic area) by re-canalizing the affected vessel is essential for a better patient outcome. Paradoxically, sudden reperfusion also causes tissue injury, thereby increasing the initial ischemic damage despite restoration of blood flow (=ischemia/reperfusion injury, IRI). Myocardial IRI is a complex event that involves various harmful mechanisms (e.g., production of reactive oxygen species and local increase in calcium ions) as well as inflammatory cells and signals like chemokines and cytokines. An involvement of platelets in the inflammatory reaction associated with IRI was discovered several years ago, but the underlying mechanisms are not yet fully understood. This mini review focusses on platelet contributions to the intricate picture of myocardial IRI. We summarize how upregulation of platelet surface receptors and release of immunomodulatory mediators lead to aggravation of myocardial IRI and subsequent cardiac damage by different mechanisms such as recruitment and activation of immune cells or modification of the cardiac vascular endothelium. In addition, evidence for cardioprotective roles of distinct platelet factors during IRI will be discussed.

Ferroptotic cell death and TLR4/Trif signaling initiate neutrophil recruitment after heart transplantation.

Non-apoptotic forms of cell death can trigger sterile inflammation through the release of danger-associated molecular patterns, which are recognized by innate immune receptors. However, despite years of investigation the mechanisms which initiate inflammatory responses after heart transplantation remain elusive. Here, we demonstrate that ferrostatin-1 (Fer-1), a specific inhibitor of ferroptosis, decreases the level of pro-ferroptotic hydroperoxy-arachidonoyl-phosphatidylethanolamine, reduces cardiomyocyte cell death and blocks neutrophil recruitment following heart transplantation. Inhibition of necroptosis had no effect on neutrophil trafficking in cardiac grafts. We extend these observations to a model of coronary artery ligation-induced myocardial ischemia reperfusion injury where inhibition of ferroptosis resulted in reduced infarct size, improved left ventricular systolic function, and reduced left ventricular remodeling. Using intravital imaging of cardiac transplants, we uncover that ferroptosis orchestrates neutrophil recruitment to injured myocardium by promoting adhesion of neutrophils to coronary vascular endothelial cells through a TLR4/TRIF/type I IFN signaling pathway. Thus, we have discovered that inflammatory responses after cardiac transplantation are initiated through ferroptotic cell death and TLR4/Trif-dependent signaling in graft endothelial cells. These findings provide a platform for the development of therapeutic strategies for heart transplant recipients and patients, who are vulnerable to ischemia reperfusion injury following restoration of coronary blood flow.

Flavonols and Flavones - Protecting Against Myocardial Ischemia/Reperfusion Injury by Targeting Protein Kinases.

In acute myocardial infarction (AMI), the first line of treatment is to rapidly restore blood flow to the ischemic myocardium to limit infarct size. It is now well established that though clearly beneficial, the positive outcomes of this intervention are limited by injury in response to the reperfusion itself in addition to the prior ischemia. This process is described as reperfusion injury and is considered to contribute to the arrhythmias, microvascular dysfunction and impaired cardiac contractility that is observed even after the restoration of coronary blood flow. Thus an important, currently unmet, therapeutic challenge is to address the outcomes of this reperfusion injury. In this article, we review the evidence that flavonols and flavones may prove useful in preserving cardiac function after ischemia and reperfusion and consider the possible mechanisms, in particular, the inhibition of kinases, by which they may exert protection.

CAROTID ARTERY STENTING IN A PATIENT WITH SINUS BRADYCARDIA: CLINICAL CASE

Syndrome of hemodynamic depression is a frequent complication of the carotid artery endovascular intervention and, as a rule, is transient in nature. This article presents a clinical case of carotid artery stenting in a 63-year-old patient. The specific feature of this patient was the initial sinoatrial node dysfunction as a permanent sinus bradycardia. The examination verified multisite atherosclerosis, including coronary artery stenosis, manifested by the presence of stable angina, without history of myocardial infarction. Therefore, coronary endovascular treatment was firstly performed. Reexamination after coronary blood flow restoration revealed stable sinus bradycardia persistence without any positive or negative changes. According to anamnesis, examination and instrumental diagnostic results, indications for permanent cardiac pacing were not identified. Carotid artery stenting after the necessary preventive measures was successful. The article also considers possible risk factors of significant perioperative bradycardia during carotid angioplasty with stenting and measures preventing cardiac conduction perioperative worsening.

The Lectin Pathway of Complement in Myocardial Ischemia/Reperfusion Injury-Review of Its Significance and the Potential Impact of Therapeutic Interference by C1 Esterase Inhibitor.

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality in modern medicine. Early reperfusion accomplished by primary percutaneous coronary intervention is pivotal for reducing myocardial damage in ST elevation AMI. However, restoration of coronary blood flow may paradoxically trigger cardiomyocyte death secondary to a reperfusion-induced inflammatory process, which may account for a significant proportion of the final infarct size. Unfortunately, recent human trials targeting myocardial ischemia/reperfusion (I/R) injury have yielded disappointing results. In experimental models of myocardial I/R injury, the complement system, and in particular the lectin pathway, have been identified as major contributors. In line with this, C1 esterase inhibitor (C1INH), the natural inhibitor of the lectin pathway, was shown to significantly ameliorate myocardial I/R injury. However, the hypothesis of a considerable augmentation of myocardial I/R injury by activation of the lectin pathway has not yet been confirmed in humans, which questions the efficacy of a therapeutic strategy solely aimed at the inhibition of the lectin pathway after human AMI. Thus, as C1INH is a multiple-action inhibitor targeting several pathways and mediators simultaneously in addition to the lectin pathway, such as the contact and coagulation system and tissue leukocyte infiltration, this may be considered as being advantageous over exclusive inhibition of the lectin pathway. In this review, we summarize current concepts and evidence addressing the role of the lectin pathway as a potent mediator/modulator of myocardial I/R injury in animal models and in patients. In addition, we focus on the evidence and the potential advantages of using the natural inhibitor of the lectin pathway, C1INH, as a future therapeutic approach in AMI given its ability to interfere with several plasmatic cascades. Ameliorating myocardial I/R injury by targeting the complement system and other plasmatic cascades remains a valid option for future therapeutic interventions.

CONTRAST-EHANCED MRI IN TIME-STRUCTURE ANALYSIS OF MYOCARDIAL DAMAGE IN ACUTE INFARCTION AND EARLY PREHOSPITAL THROMBOLYTIC THERAPY

Purpose:to evaluate the dependence of absolute and relative thickness of damaged myocardium in the acute myocardial infarction (AMI) area from the time interval between oncet of pain and start of intravenous thrombolysis (so-called “pain–needle time”), in AMI patients treated with prehospital intravenous thrombolysis and also later on with subsequent percutaneous coronary angiplasty (PCA) and stenting, using contrast-enhanced MRI of the heart Materials and methods. The study comprised data of CE-MRI studies in 25 patients with theyr first acute myocardial infarction, in whom the pre-hospital thrombolytic therapy (TLT) was carried out in the course of 35–300 min after onset of chest pain, with coronarography and percutaneous coronary angioplasty and stenting after admission to the institute of cardiology. In six patients the TLT was not success ful and in these the restoration of coronary blood flow was obtained only at PCA. In all patients in terms 18–34 hours after TLT the CE-MRI of the heart was carried out using gadobutrol or gadoversetamid, as 0.1 mM per kg of BW, in T1-weighted mode with fat suppression and as inversion-recovery with inversion time adjusted to get the normal myocardium “nulled”. We calculated the segmental extension of damage, the thickness of infarcted irreversibly damaged myocardium and of non-damaged myocardium in the same locations, the index of transmurality, as ratio of thickness of damaged myocardium to the overall wall thickness. We analyzed the dependence of these indices of damage from the time interval between pain oncet and beginning of intravenous thrombolytic therapy (or PCA – when TLT was unsuccessful).Results.The dependence of thickness of non-damaged myocardium from the “pain-needle” time was as exponential as Y = 2.08 + 17.11 · exp(−t/42.4), r = 0.843, p &lt; 0.002. Index of transmurality did depend on the time interval “pain – needle” as Boltzmann function, pretty closely to reverse exponential one: No-reflow zone with absent blood flow in the infarcted area was present only in cases with the “pain–needle” time interval over 70 min. Later on the full or partial restoration of contractility in infarcted segments was observed only if the IT was below 0.55–0.6.Conclusion.CE-MRI delivers adequate quantitative estimates of anatomic transmural extent of myocardial infarction from early acute period of the AMI. The depth of myocardial damage is a function of “pain–needle” time and approaches the half of wall thickness for as short as 55–65 min, determining by this the future prognosis of the mechanical restitution of contractility in the infarcted region. It is suggested the CE-MRI of the heart must be carried out in every patient in whom due to AMI the thrombolytic therapy and/or percutaneous coronary angioplasty has been done, for unbiased myocardium-focused control of efficiency of restoration of coronary arterial patency.

Post-reperfusion syndrome in patients with ischemic heart disease after coronary stenting.

Post-reperfusion syndrome is a chronic multi-factorial syndrome, caused by restoration of coronary blood flow of de novo in patients after coronary stenting. Pathophysiological processes occurring in stenting segment (incomplete endothelization of vessel, excessive regeneration of neointima, formation of neoatherosclerosis) the risk of partial or total stent thrombosis due to the low level of compliance of the patient, as well as local changes in blood flow to the myocardium and modification of hemodynamics in stented arteries have a significant impact on the clinical course and prognosis of the disease. In contrast to the syndrome of reperfusion occurring after restoration of blood flow in the infarct-dependent coronary artery syndrome and postischemic reperfusion syndrome in patients with acute myocardial infarction after spontaneous or therapeutic thrombolysis, post-reperfusion syndrome is characterized by prolonged course (months and years). Clinical symptoms depend of the localization of pathological process (in stented arteries or in other non-stented arteries of the heart), as well as the presence of comorbidity and the factors of risk of the coronary heart disease.

Рідкісний випадок спонтанного тромболізису у пацієнтки з гострим інфарктом міокарда з елевацією сеґмента ST

In the pathogenesis of acute myocardial infarction an important role belongs to coronary sclerosis and coronary artery thrombosis. Endothelium plays an important role in a regulation of vascular tone, local inflammation, hemostasis, neovascularisation. An impairment of endothelial barrier function occurs after direct damage of endothelial cells as a result of an atherosclerotic plaque destabilization, injury, chronic inflammation or exposure to hazardous substances. Breakage of the endothelial surface causes an exposure of subendothelial collagen and triggers expression of adhesive proteins (e.g. tissue factor and von Willebrand factor) and decreases synthesis of prostacyclin and nitric oxide. In case of its damage and activation, thrombocytes adhere and aggregate to each other which leads to thrombosis and can cause an acute myocardial infarction.&nbsp; Aim.&nbsp;Our aim was to evaluate a cellular mechanisms of thrombosis as well as conditions that leads to spontaneous thrombolysis in acute myocardial infarction for treatment optimisation of acute coronary syndrome. &nbsp; Material and Methods.&nbsp;The case of acute myocardial infarction with ST segment elevation in 79 years old patient is presented that showed spontaneous coronary blood flow recovery.&nbsp; Results and Discussion.&nbsp;In described case in a patient with acute myocardial infarction a rapid regression of ECG changes were documented after medical treatment at home was provided. Those changes were most likely a results of spontaneous thrombolysis with subsequent recovery of coronary blood flow in infarct-related artery due to rarely occurring activation of fibrinolytic system. The fibrinolysis system was triggered by the release of plasminogen activator and affected newly formed thrombus. However unstable atherosclerotic plaque was thrombogenic enough and leaded to recurrence of myocardial infarction. Thus the patient received coronary artery stenting. Clinical and morphological data has shown that in those patients a major role in development of acute coronary syndrome plays not a coronary artery spasm but a coronary thrombosis with subsequent spontaneous thrombolysis and restoration of coronary blood flow which happened upon timely application of antiaggregants, anticoagulants and antianginals drugs. Coronary artery spasm typically occurs more distal from the obstruction place as a result of exposure to vasoconstrictors released after thrombocyte degranulation. Spontaneous thrombolysis by acute myocardial infarction is untypical, hence myocardial infarction with pathological Q wave develops.&nbsp; Conclusions.&nbsp;Patients with acute coronary syndrome, which exhibit spontaneous thrombolysis require angiography and stenting of coronary arteries as soon as possible to prevent recurrence of coronary thrombosis and development of acute myocardial infarction.

β-arrestin 2 mediates cardiac ischemia-reperfusion injury via inhibiting GPCR-independent cell survival signalling

Ischemic heart disease is a leading cause of morbidity and mortality worldwide. Although timely restoration of coronary blood flow (reperfusion) is the most effective therapeutics of myocardial infarction, reperfusion causes further cardiac damage, i.e. ischemia-reperfusion (I/R) injury. β-arrestins (Arrbs) have been traditionally defined as negative regulators of G protein-coupled receptor (GPCR) signalling, but recent studies have shown that they are essential for G protein-independent, GPCR-mediated biased signalling. Several ligands have been reported to be cardioprotective via Arrbs dependent pathway. However, it is unclear whether Arrbs exert receptor-independent physiological or pathological functions in the heart. Here, we sought to determine whether and how Arrbs play a role in regulating cardiomyocyte viability and myocardial remodelling following I/R injury. The expression of β-arrestin 2 (Arrb2), but not β-arrestin 1 (Arrb1), is upregulated in rat hearts subjected to I/R injury, or in cultured neonatal rat cardiomyocytes treated with hypoxia-reoxygenation (H/R) injury. Deficiency of Arrb2 in cultured neonatal rat cardiomyocytes alleviates H/R-induced cardiomyocyte death and Arrb2-/- mice are resistant to myocardial damage caused by I/R injury. In contrast, upregulation of Arrb2 triggers cardiomyocyte death and exaggerates I/R (or H/R)-induced detrimental effects. Mechanically, Arrb2 induces cardiomyocyte death by interacting with the p85 subunit of PI3K, and negatively regulating the formation of p85-PI3K/CaV3 survival complex, thus blocking activation of PI3K-Akt-GSK3β cell survival signalling pathway. We define an upregulation of Arrb2 as a pathogenic factor in cardiac I/R injury, and also reveal a novel GPCR-independent mechanism of Arrb2-mediated cell death signalling in the heart.

РЕАБІЛІТАЦІЯ ХВОРИХ ІЗ СЕРЦЕВО-СУДИННОЮ ПАТОЛОГІЄЮ.

Серцево-судинні захворювання зумовлюють основні проблеми громадського здоров’я. В Україні проводиться комплекс заходів, спрямованих на створення системи реабілітації серцево-судинних хворих як доповнення до системи лікувально-профілактичної допомоги. Подальшого опрацювання потребують відпрацювання наступності в організації лікувально-профілактичних і реабілітаційних заходів у хворих із серцево-судинною патологією.Мета дослідження вивчення впливу високого рівня артеріального тиску (АТ) на формування реакцій відповідей при проведенні фізичної реабілітації хворих із серцево-судинною патологією на санаторному етапі лікування.Матеріали і методи. Обстежено 175 хворих, з них 100 пацієнтів із артеріальною гіпертензією (АГ) та 75 – з ішемічною хворобою серця (ІХС). У всіх хворих виконували комплекс обстежень, які включали добовий моніторинг АТ, визначення толерантності до фізичних навантажень за даними 6-хвилинного тесту ходьби, тредміл-тесту.Результати досліджень та їх обговорення. Установлено, що серед факторів, що супроводжують неадекватну відповідь на фізичне навантаження, важливе місце посідають як рівень АТ, так і нестабільність артеріальної гіпертензії у процесі відновного лікування, а також ступінь реакції АТ на дозовані фізичні навантаження. У пацієнтів із несприятливим перебігом відновного періоду, незважаючи на своєчасне відновлення коронарного кровотоку, мали місце стійкі середньодобові рівні систолічного та діастолічного АТ у поєднанні з високими значеннями цих показників на висоті фізичного навантаження як у ранньому, так і пізньому реабілітаційному періодах. У хворих з ІХС при неадекватній відповіді на дозовані фізичні навантаження відмічалися тахікардія, короткочасний біль за груднинною, іноді ядуха.Висновки. Основними реабілітаційними заходами при серцево-судинних захворюваннях є дотримання індивідуальної реабілітаційної програми, рухового режиму, раціонального харчування та усунення факторів ризику. Для фізичної реабілітації хворих із серцево-судинною патологією важливим є комплексний підхід, медикаментозний контроль АТ, поліпшення коронарного резерву, раціональне поєднання різних методів лікування, максимальне використання природних факторів, широке застосування санаторно-курортного лікування, кліматотерапії.