No abstract

Фибрилляция предсердий-это распространенное и нежелательное осложнение после оперативных вмешательств на сердце, которое увеличивает смертность пациентов и экономические затраты на лечение. Фибрилляция предсердий осложняет 27,6% случаев после операций аортокоронарного шунтирования, 48,8% случаев после замены митрального клапана, 32,9% случаев после замены аортального клапана и значительно чаще возникает после комбинированных операций. В настоящее время вопрос профилактики фибрилляции предсердий не решен. Применение препаратов системного действия не обладает высокой эффективностью, что было продемонстрировано во многих проведенных исследованиях. Амиодарон-антиаритмический препарат III класса-наиболее эффективен для профилактики и лечения послеоперационной фибрилляции предсердий. Однако амиодарон имеет ряд недостатков, включая необходимость достижения насыщающей дозы, взаимодействие со многими другими препаратами и, самое главное, наличие значимых экстракардиальных побочных эффектов, таких как дисфункция щитовидной железы, пульмонотоксичность и гепатотоксичность. Данные побочные эффекты частично обусловлены необходимостью системного введения препарата. Хорошие результаты в профилактике послеоперационной фибрилляции предсердий показали некоторые противовоспалительные средства, в том числе нестероидные противовоспалительные препараты, колхицин, глюкокортикоиды и статины. Методика применения дисков с антиаритмическими препаратами ограничена временем экспозиции препарата, что уменьшает длительность антиаритмического эффекта. Эпикардиальная аппликация адгезивного гидрогеля с амиодароном-это менее инвазивный, хорошо переносимый, быстро выполняемый и эффективный терапевтический метод для профилактики послеоперационной фибрилляции предсердий. Результаты исследований указывают на то, что данный метод является более многообещающим для профилактики послеоперационной фибрилляции предсердий с более низким риском желудочковых и системных побочных эффектов по сравнению с внутривенным и пероральным применением амиодарона. К л ю ч е в ы е с л о в а: послеоперационная фибрилляция предсердий; фибрилляция предсердий; перикардит; воспаление; кардиохирургия; биомаркеры.

Background: The purpose of the experiment was to study the safety of local epicardial use of the hydrogel with amiodarone, as well as the influence of its different dosages on the heart rate of mongrel rabbits. Methods: The epicardial application of the hydrogel material with amiodarone was performed in 46 rabbits. Rabbits were divided into 5 groups: Group No. 1-dose of amiodarone in the hydrogel 1 mg, Group No. 2-dose 3 mg; Group No. 3-dose 6 mg; Group No. 4-hydrogel without amiodarone; Group No. 5amiodarone intravenously, 60 mg. Results: The application of hydrogel with amiodarone is not accompanied by a systemic inflammatory reaction. In group No. 2, there was a significant reduction in the heart rate (before surgery: 158±16, after: 130±11, (P<0,001), without any disturbances to the conduction system of the heart functioning. With an increase in amiodarone concentration (Group No. 3), significant atrial and atrioventricular (AV) conduction defects (up to 70%) were noted; when the dosage of amiodarone (Group No. 1) was reduced, there was no influence on the heart rate reduction. The hydrogel without amiodarone has no effect on the conductive system. Conclusions: The method of local epicardial delivery of amiodarone in the form of a hydrogel material is safe. The hydrogel with amiodarone is effective for the heart rate reduction (according to the experiment on animals), compared to the control group and the group with intravenous drug administration. The optimal dosage of amiodarone in the hydrogel is 3 mg.

The objective of this study was to study the use of the hydrogel biopolymer based on sodium alginate (“Colegel”) with a drug substance—amiodarone—for the prevention of postoperative atrial fibrillation (POAF) in cardiac surgery. The experimental part of the study was performed on 46 rabbits. Five groups were formed: in the first group, the dose of amiodarone in hydrogel was 1 mg; in the second group—3 mg; in the third group—6 mg; in the fourth group, hydrogel was used without amiodarone; in the fifth group, 60 mg amiodarone was administered intravenously. The animals from each group were removed from the experiment for the pathomorphological study of the heart after 3, 7 and 14 days. The studied endpoints were: the heart rate control; the development of the blockades of the conduction system of the heart; and the development of inflammation according to laboratory pathomorphological studies. The translational clinical part involved a randomized clinical trial which included 60 patients, with an average age of 62 ± 8.5 years. All patients were randomized into two groups: the study group (n = 30, with the application of amiodarone hydrogel) and the control group (n = 30, without the application of amiodarone hydrogel). The dose of amiodarone in the hydrogel material was 60 mg for all patients. The heart rhythm was monitored during 5 days. The primary endpoint was the development of POAF. Secondary endpoints were: the dynamics of heart rate; the duration of the QT and PQ intervals; the development of blockades of the cardiac conduction system; as well as the dynamics of AST and ALT. According to the results of the experimental part, it was found that the method of the local epicardial delivery of amiodarone by the hydrogel material was safe. Hydrogel with amiodarone is effective for reducing the heart rate in the animal experiment in comparison to the control group and the group with the intravenous administration of the drug. The optimal dose of amiodarone in hydrogel was 1 mg per 1 kg. According to the results of the clinical part, it was found that the method of the local epicardial delivery of amiodarone as a hydrogel material proved its safety. Hydrogel with amiodarone at a dose of 60 mg was effective in preventing POAF in patients after coronary artery bypass grafting (CABG) operations in comparison to the control group (p < 0.001). The age and procedure of application of the amiodarone gel were significantly associated with POAF (p = 0.009 and p = 0.011, respectively). The use of hydrogel with amiodarone reduced the probability of developing POAF 18.9-fold. The method of the local epicardial delivery of amiodarone in the form of a hydrogel material is safe. The use of hydrogel with amiodarone after CABG reduced the probability of developing POAF.

The purpose of our study was to evaluate safety and efficacy of local epicardial application of amiodarone - releasing hydrogel in the prevention of postoperative atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG). Material and methods We present an open prospective randomised study, in which 60 patients (47 male), mean age of 62±8,5 were included. Baseline clinical, laboratory and instrumental characteristics were similar in all patients. Patients didn't have any arrhythmic complains or previously registered AF. All patients underwent elective CABG and were randomised into two groups: Group #1 (n=30) - had the amiodarone-releasing hydrogel application before chest closure, and Group #2 (n=30) regular CABG surgery, no local application. We used 60 mg of amiodarone in hydrogel. This dose was experimentally determined during previously performed animal study. Heart rhythm control was monitored continuously during first 5 postoperative days and occasionally (mornings and evenings) the remaining days before the discharge. The local ethics committee approved this study design. Results The incidence of postoperative AF occurrence was significantly lower in Group #1: AF was registered in 3.3% cases versus 37% of patients from Group #2 (p<0.001). There was slight increase of PQ interval duration in Group #1 - 0.14 sec (0.12; 0.16), which however was significantly higher then in Group #2 - 0.12 (0.12; 0.14), (p<0.01). QRS and QT intervals were similar in both groups without significant difference. There were no complications associated with the application procedure neither during postoperative period, such as AV block, infection or life-threatening situations. According to 5 days ECG monitoring, the average heart rate in the Group #1 was 59 (52; 60) beats per min versus 69 beats per min (65; 75) in Group #2 (p<0.001). Temporary atrial or atrio-ventricular pacing used for correction of the heart rate if required in both groups. By the time of discharge none of the patients required permanent cardiac pacing. The length of stay in Group #1 was significantly shorter: 6 (6; 7) days versus 8 (8; 9) days (p<0,001). Among all studied parameters, amiodarone-releasing hydrogel application and older age were statistically significant in postoperative AF occurrence (p<0.01). According to the Cox regression model amiodarone-releasing hydrogel application decreases the incidence of postoperative AF by 18,9 folds. The older age instead increases the incidence of postoperative AF by 1,2 folds. Conclusions The local epicardial amiodarone (60 mg) application in hydrogel before chest closure is a safe procedure. This approach showed it's effectiveness in AF prevention in patient undergoing elective CABG.