Traditionally, the thermodynamic values of affinity are considered as the main criterion for the development of new drugs. Usually, these values for drugs are measured in vitro at steady concentrations of the receptor and ligand, which are differed from in vivo environment. Recent studies have shown that the kinetics of the process of drug binding to its receptor make significant contribution in the drug effectiveness. This has increased attention in characterizing and predicting the rate constants of association and dissociation of the receptor ligand at the stage of preclinical studies of drug candidates. A drug with a long residence time can determine ligand-receptor selectivity (kinetic selectivity), maintain pharmacological activity of the drug at its low concentration in vivo. The paper discusses the theoretical basis of protein-ligand binding, molecular determinants that control the kinetics of the drug-receptor binding. Understanding the molecular features underlying the kinetics of receptor-ligand binding will contribute to the rational design of drugs with desired properties.
Objective: To evaluate the efficacy and safety of a modified technique for totally thoracoscopic left atrial posterior wall and pulmonary vein isolation in patients with long-standing persistent atrial fibrillation. Methods: From April 2017 to December 2018, we included in this study 28 consecutive patients who underwent thoracoscopic left atrial posterior wall and pulmonary vein radiofrequency isolation combined with left atrial appendage resection. We used a device with irrigated electrodes (Medtronic Cardioblate Gemini-s). The original surgical technique "GALAXY" proposed by Doty in 2012 was modified. The number of ablations was significantly increased, and frequent position changing of the ablation device and change of device angulation were added. Results: Sinus rhythm was restored in all patients. There was no operative mortality, no myocardial infarction, and no stroke or transient ischemic attack. One patient required sternotomy and another survived left anterolateral thoracotomy due to bleeding. A 180-day follow-up (24-hour Holter monitoring) revealed no sign of recurrence of atrial fibrillation or other supraventricular arrhythmia in any patient. Mean follow-up was nine months (range: 6-16 months). At the last follow-up, 26 patients (92,9%) were in sinus rhythm (24-hour Holter monitoring). Conclusion: A frequent ablation device position changing during the surgery makes it possible to achieve complete left atrial posterior wall and pulmonary veins isolation. An increased number of applications allows to avoid a false positive transmural damage assessment showed by impedance drop. Also, frequent position changing of the ablation device and increased number of applications do not affect the number of postoperative complications.
Coronary artery bypass grafting techniques have been unchangeable for many years, whereas development and enhancement of myocardial protection methods in coronary bypass grafting for patients with ischemic heart disease are still actual issues of current coronary surgery. Coronary artery bypass grafting techniques include the traditional/conventional technique with cardiopulmonary bypass, aortic cross-clamping and cardioplegia, off-pump and on-pump beating heart coronary artery bypass grafting. Coronary artery bypass grafting with cardiopulmonary bypass and cardioplegia remains the most common method of coronary revascularization. However the cardiac arrest inevitably leads to global cardiac ischemia, and current cardioplegias do not prevent ischemic damage to the myocardium in all cases, especially in high-risk surgical patients. Off-pump coronary artery bypass grafting allows preventing global myocardial ischemia (due to the constant native coronary blood-flow) and avoiding possible negative consequences of cardiopulmonary bypass use. The main limitations of this technique are associated with high risk of hemodynamic instability due to low cardiac output and systolic output caused by target arteries exposition. On-pump beating heart technique is a reasonable compromise between conventional on-pump coronary artery bypass grafting, cardioplegia and off-pump procedure. It is a safe and effective technique with outcomes that are equivalent or superior to the outcomes reported for conventional coronary artery bypass grafting in patients with unstable hemodynamics, low left ventricular ejection fraction and in high-risk patients. The literature review presents the results of on-pump beating heart coronary artery bypass grafting.
РефератДефекты межпредсердной перегородки -вторые по частоте после дефектов межжелудочковой перегородки среди врождённых пороков сердца. Эндоваскулярное закрытие дефекта межпредсердной перегородки выпол-няют по строгим показаниям у пациентов со значимым сбросом крови слева направо. Развитие инфекционного эндокардита после транскатетерной имплантации окклюдера бывает чрезвычайно редким осложнением. В дан-ном клиническом наблюдении рассмотрен случай развития инфекционного эндокардита митрального клапана (с развитием выраженной недостаточности) через 13 лет после эндоваскулярного закрытия дефекта межпред-сердной перегородки у пациентки 39 лет. Перед выполнением хирургического вмешательства проведена ком-плексная антибиотикотерапия. В ходе операции выполнены удаление окклюдера дефекта межпредсердной пе-регородки, протезирование митрального клапана, пластика дефекта межпредсердной перегородки и резекция ушка левого предсердия. Послеоперационный период протекал без особенностей. Ключевые слова: окклюдер дефекта межпредсердной перегородки, инфекционный эндокардит, протезирова-ние митрального клапана, недостаточность митрального клапана.
Surgical removal of atrial septal defect occlusion device and mitral valve replacement in a 39-year-old female patient with infective endocarditis
A.S. Zotov, D.V. Borisov, T.V. Klypa, S.A. Vachev Federal Research Clinical Center for Specialized Types of Health Care and Medical Technologies of Federal Medical and Biology Agency, Moscow, RussiaAtrial septal defects represent the second most frequent congenital heart disease after ventricular septal defects. Transcatheter closure of an atrial septal defect is usually performed following strict indications on patients with significant left-to-right shunt. Infective endocarditis after transcatheter implantation of atrial septal defect occluder is an extremely rare complication. We report a case of infective endocarditis of the mitral valve (with severe mitral valve insufficiency) in a 39-year-old female patient 13 years after transcatheter closure of an atrial septal defect. Complex prophylactic antibiotic coverage was performed prior to surgical intervention. Surgical removal of atrial septal defect occluder, mitral valve replacement, atrial septal defect closure and left atrial appendage resection were performed. Postoperative course was uneventful. Keywords: atrial septal defect occluder, infective endocarditis, mitral valve replacement, mitral valve insufficiency.Адрес для переписки: dan-cer@inbox.ru Поступила 11.09.2017; принята в печать 03.10.2017.
Cardiac rhythm disorders are common in many patients with cancer. The management of synchronous long-standing persistent atrial fibrillation and pulmonary lesions remains a serious surgical dilemma due to the lack of clinical data and surgical guidelines. To the best of our knowledge, this is the first described case of simultaneous thoracoscopic pulmonary segmentectomy and left atrial posterior wall and pulmonary vein isolation combined with left atrial appendage resection in a patient with early-stage primary lung cancer and long-standing persistent atrial fibrillation.
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