Влияние диборнола-ГЭК на электрофизиологические параметры в период восстановления кровотока в миокарде кролика

Objective. Dibornol-HES, a water-soluble drug based on the derivative of 2,6-diisobornyl-4-methylphenol Dibornol conjugated with hydroxyethyl starch, can reduce the occurrence and severity of arrhythmias by preventive intravenous administration, but it is unknown whether the drug could reduce the myocardial arrhythmogenicity once ischemia has developed at the developed ischemia.Materials and methods. In the model of acute ischemia / reperfusion of the rabbit heart, the effect of Dibornol-HEC (80 mg/kg body weight of the animal) on the electrophysiological indices characterizing myocardial arrhythmogenicity (global and border dispersion of repolarization) was studied during the restoration of blood flow. In the model of acute ischemia / reperfusion with 64 unipolar epicardial leads, the activation-recovery intervals were measured and global and border dispersion of repolarization in the native rabbits (control group, n = 9) and in the rabbits treated by Dibornol-HES (on the 25th minute of occlusion, the experimental group, n = 6).Results. The introduction of Dibornol-HES did not lead to a change in the electrocardiographic parameters of rabbits. By the 30th minute of the coronary occlusion on the ECG in the animals of the control and the experimental groups, the intervals RR, QT, QTc were shortened (p < 0.05). In the animals of both groups by the 30th minute of coronary occlusion, the global dispersion of repolarization increased (p < 0.05), the boundary dispersion of repolarization also increased (p < 0.05), due to the decrease in the duration of the activation-recovery intervals in the ischemic zone (p < 0.05). During the 30-minute reperfusion the magnitude of the global dispersion of repolarization did not change in animals of the both groups, and the magnitude of the border dispersion of repolarization in the control rabbits decreased (p < 0.05), while in the rabbits treated by Dibornol-HES the border dispersion of repolarization did not changed.Conclusion. In rabbits of the experimental group, the values of the global and border dispersions of repolarization did not differ from those of the animals in the control group. Therefore, the administration to Dibornol-HES just prior to reperfusion does not lead to the decrease in the dispersion of repolarization increased as a result of acute ischemic myocardial damage.Введение. Диборнол-ГЭК, водорастворимый лекарственный препарат на основе производного 2,6-диизоборнил-4-метилфенола диборнола, конъюгированного гидроксиэтилкрахмалом, способен снижать возникновение и тяжесть аритмий при превентивном внутривенном введении. Однако о данных, способен ли препарат снижать аритмогенность миокарда при его введении в момент уже развившейся ишемии, не известно.Цель работы – исследование влияния препарата диборнола-ГЭК на электрофизиологические показатели сердца кролика в период восстановления кровотока в миокарде.Материалы и методы. В модели острой ишемии (реперфузии) сердца кролика изучено действие диборнола-ГЭК (80 мг/кг массы тела животного) на электрофизиологические показатели, характеризующие аритмогенность миокарда (глобальная и пограничная дисперсии реполяризации, длительность интервала «активация–восстановление») в период восстановления кровотока. У нативных кроликов (контрольная группа, n = 9) и кроликов, получавших внутривенно диборнол-ГЭК (на 25-й мин окклюзии, опытная группа, n = 6), в модели острой ишемии (реперфузии) в 64 униполярных эпикардиальных отведениях измерены интервалы «активация – восстановление», величина глобальной и пограничной дисперсии.Результаты. Введение диборнола-ГЭК не приводило к изменению электрокардиографических параметров кроликов. К 30-й мин коронарной окклюзии на электрокардиограмме у животных контрольной и опытной групп выявлено укорочение интервалов RR, QT, QTc (p < 0,05). У животных обеих групп к 30-й мин ишемии глобальная дисперсия реполяризации увеличилась (p < 0,05), пограничная дисперсия реполяризации также увеличилась (p < 0,05) за счет уменьшения длительности интервалов «активация – восстановление» в ишемизированной зоне (p < 0,05). В период 30-минутной реперфузии величина глобальной дисперсии реполяризации не изменялась у животных обеих групп, а величина пограничной дисперсии реполяризации у контрольных кроликов уменьшилась (p < 0,05), в то время как у кроликов, которым вводили диборнол-ГЭК, нет.Заключение. Значения глобальных и пограничных дисперсий реполяризации у кроликов экспериментальной группы не отличались от значений животных в контрольной группе. Поэтому введение диборнола-ГЭК непосредственно перед реперфузией не приводит к уменьшению дисперсии реполяризации, увеличенной в результате острого ишемического повреждения миокарда

Influence of dibornol-HES on electrophysiological parameters in the period of restoration of blood flow in rabbit myocardium

Objective. Dibornol-HES, a water-soluble drug based on the derivative of 2,6-diisobornyl-4-methylphenol Dibornol conjugated with hydroxyethyl starch, can reduce the occurrence and severity of arrhythmias by preventive intravenous administration, but it is unknown whether the drug could reduce the myocardial arrhythmogenicity once ischemia has developed at the developed ischemia.Materials and methods. In the model of acute ischemia / reperfusion of the rabbit heart, the effect of Dibornol-HEC (80 mg/kg body weight of the animal) on the electrophysiological indices characterizing myocardial arrhythmogenicity (global and border dispersion of repolarization) was studied during the restoration of blood flow. In the model of acute ischemia / reperfusion with 64 unipolar epicardial leads, the activation-recovery intervals were measured and global and border dispersion of repolarization in the native rabbits (control group, n = 9) and in the rabbits treated by Dibornol-HES (on the 25th minute of occlusion, the experimental group, n = 6).Results. The introduction of Dibornol-HES did not lead to a change in the electrocardiographic parameters of rabbits. By the 30th minute of the coronary occlusion on the ECG in the animals of the control and the experimental groups, the intervals RR, QT, QTc were shortened (p < 0.05). In the animals of both groups by the 30th minute of coronary occlusion, the global dispersion of repolarization increased (p < 0.05), the boundary dispersion of repolarization also increased (p < 0.05), due to the decrease in the duration of the activation-recovery intervals in the ischemic zone (p < 0.05). During the 30-minute reperfusion the magnitude of the global dispersion of repolarization did not change in animals of the both groups, and the magnitude of the border dispersion of repolarization in the control rabbits decreased (p < 0.05), while in the rabbits treated by Dibornol-HES the border dispersion of repolarization did not changed.Conclusion. In rabbits of the experimental group, the values of the global and border dispersions of repolarization did not differ from those of the animals in the control group. Therefore, the administration to Dibornol-HES just prior to reperfusion does not lead to the decrease in the dispersion of repolarization increased as a result of acute ischemic myocardial damage

РЕПОЛЯРИЗАЦИЯ ЭПИКАРДИАЛЬНОЙ ПОВЕРХНОСТИ ЖЕЛУДОЧКОВ СЕРДЦА КРОЛИКА ПРИ ЭКСПЕРИМЕНТАЛЬНОМ САХАРНОМ ДИАБЕТЕ

The purpose of the study was to find out the spatial pattern of ventricular repolarization in diabetes mellitus in heart of rabbits in vivo.Цель работы: исследование реполяризации эпикарда желудочков сердца кролика с индуцированным аллоксаном сахарным диабетом in vivo

Prolongation of The Activation Time in Ischemic Myocardium is Associated with J-wave Generation in ECG and Ventricular Fibrillation

J-wave pattern has been recognized as an arrhythmic risk marker, particularly in myocardial infarction patients. Mechanisms underlying J-wave development in ischemia remain unknown. In myocardial infarction model, we evaluated activation time delay as a prerequisite of J-wave appearance and predictor of ventricular fibrillation. Body surface ECGs and myocardial unipolar electrograms were recorded in 14 anesthetized pigs. 48 intramural leads were positioned across ventricular free walls and interventricular septum. Myocardial ischemia was induced by ligation of the left anterior descending coronary artery and the recordings were done during 40-minute coronary occlusion. The local activation times were determined as instants of dV/dt minimum during QRS complex in unipolar electrograms. During occlusion, ventricular local activation time prolonged in the middle portion of the left ventricular free wall, and basal and middle portions of septum, while J-waves appeared in precordial leads in 11 animals. In logistic regression and ROC curve analyses, activation time delay at a given time-point was associated with J-wave development, and a longer activation time was associated with ventricular fibrillation appearance. In experimental coronary occlusion, activation delay in ischemic myocardium was associated with generation of the J waves in the body surface ECG and predicted ventricular fibrillation

Contribution of Depolarization and Repolarization Changes to J-Wave Generation and Ventricular Fibrillation in Ischemia

Background: Activation delay in ischemic myocardium has been found to contribute to J-wave appearance and to predict ventricular fibrillation (VF) in experimental myocardial infarction. However, the role of ischemia-related repolarization abnormalities in J-wave generation remains unclear. Objectives: The objective of our study was to assess a contribution of myocardial repolarization changes to J-wave generation in the body surface ECG and VF in a porcine acute myocardial infarction model. Methods: In 22 anesthetized pigs, myocardial ischemia was induced by occlusion of the left anterior descending coronary artery (LAD, n = 14) and right coronary artery (RCA, n = 8). Body surface ECGs were recorded simultaneously with intramyocardial unipolar electrograms led from flexible electrodes positioned across the left ventricular (LV) wall, interventricular septum (IVS), and right ventricular (RV) wall at apical, middle and basal levels of the ventricles (a total of 48 leads). Local activation times (ATs) and activation-repolarization intervals (ARIs, differences between dV/dt maximum during T-wave and dV/dt minimum during QRS) were measured. Results: J-waves appeared in left precordial leads (in 11 out of 14 animals with LAD occlusion) and right precordial leads (in six out of eight animals with RCA occlusion). During ischemic exposure, ATs prolonged, and the activation delay was associated with J-wave development (OR = 1.108 95% CI 1.072–1.144; p < 0.001) and VF incidence (OR = 1.039 95% CI 1.008–1.072; p = 0.015). ARIs shortened in the ischemic regions (in the IVS under LAD-occlusion and the lateral RV base under RCA-occlusion). The difference between maximal ARI in normal zones and ARI in the ischemic zones (ΔARI) was associated with J-wave appearance (OR = 1.025 95% CI 1.016–1.033, p < 0.001) independently of AT delay in multivariate logistic regression analysis. Conclusions: Both AT delay and increase of ΔARIs contributed to the development of J-wave in body surface ECG. However, only AT delay was associated with VF occurrence