Boundary Element Modeling of Acoustic Fields Generated During Ultrasonic Angioplasty

We investigated possibilities of application of boundary element method (BEM) to modelling of acoustic fields generated during ultrasonic angioplasty. It was shown that modelling by means of BEM can be more efficient comparing with traditionally used modelling by means of finite element method (FEM). We also considered test problem of calculation of acoustic field created by ultrasonic waveguide in semi-infinite fluid media and the problem was solved by means of BEM and FEM with comparative analysis of obtained results. Modelling by means of BEM additionally involves application of mirror source method for avoidance of treatment of infinite fluid boundary. On the basis of analysis of the test problem we shown that BEM can be used as efficient tool for modelling of acoustic fields generated during ultrasonic surgical procedures, particularly, during ultrasonic angioplasty. BEM has several advantages in comparison with FEM and can be used as alternative to traditionally used modelling by means of FEM or as supplementary method

Combined effect of low-frequency high-intensity ultrasound and streptokinase on the efficiency of thrombi destruction

Results of numerous experimental studies indicate that low-intensity ultrasound (US) intensifies the drug induced fibrinolysis. However, exits opinion, what high-intensity ultrasound could be not recommending for use in combination with thrombolytic agents due to the transience of exposure of thrombus to ultrasound and relatively low speed of the enzymatic process. We also hypothesise that high-intensity low-frequency US can accelerate the drug induced fibrinolysis. During in vitro studies, we showed that the administration of streptokinase (SK) prevents the formation of particle conglomerates resulting due to destruction of fibrin clots by using low-frequency high-intensity US. In addition, it was established that in conditions of the combined effect of streptokinase and high-intensity US, the process of acoustic-mechanical destruction of thrombus is prevailing, and the fibrinolytic effect of streptokinase is generally witnessed after the termination of US and manifests itself in enzymatic lysis of both resultant particles and residual clot mass. In this study we verified the effect of low-frequency high-intensity ultrasound on the dynamics and efficiency of fibrinolysis induced by streptokinase on various structure thrombi model, characteristic features of the fibrin clot network structure occurring during the combined effect of ultrasound and streptokinase

Electronic-microscopic estimation of changes in erythrocytes ultrastructure under influence of low-frequency ultrasound

The paper presents the estimation of changes of erythrocytes ultra-structure under influence of low-frequency ultrasound using various types of waveguides. It was demonstrated that application of ultrasound contributes to change of erythrocyte form and size, which depend on intensity, duration and type of the waveguide

Low frequency and high intensity ultrasound in vascular surgery: theory, instrumentation and possibilities of clinical application

This paper presents a brief review of applications of ultrasound in modern surgery and results of original studies of the authors in the field of application of low frequency (24-36 kHz) high-intensity (up to 20 W/cm2) ultrasonic vibrations for disruption of thrombi and calcified atherosclerotic plaques in blood vessels. Application of non-rigid wire ultrasonic waveguides with length up to 980 mm and diameter of working tip down to 0.3 mm enables minimally invasive surgical intervention, since a waveguide can be introduced along curved segments of blood vessels through a small incision situated at substantial distance from occlusion. Ultrasonic angioplasty can be successfully applied in combination with administration of thrombolytic drugs. The paper also considers physical mechanisms of thrombus disruption under influence of ultrasonic vibrations, particularly, effects of cavitation and acoustic streaming. We described design of ultrasonic waveguides for endovascular surgery and their manufacturing technology based on plasma-electrolytic etching. Application of finite element method and transfer matrix approach for design and model of wire waveguides is considered. Description of clinical system for ultrasonic angioplasty with automated resonance tuning of a waveguide is also provided. In addition, we report results of clinical application of ultrasonic angioplasty in patients with occlusion of iliofemoral segment

Combined effect of low-frequency high-intensity ultrasound and streptokinase on the efficiency of thrombi destruction

Results of numerous experimental studies indicate that low-intensity ultrasound (US) intensifies the drug induced fibrinolysis. However, exits opinion, what high-intensity ultrasound could be not recommending for use in combination with thrombolytic agents due to the transience of exposure of thrombus to ultrasound and relatively low speed of the enzymatic process. We also hypothesise that high-intensity low-frequency US can accelerate the drug induced fibrinolysis. During in vitro studies, we showed that the administration of streptokinase (SK) prevents the formation of particle conglomerates resulting due to destruction of fibrin clots by using low-frequency high-intensity US. In addition, it was established that in conditions of the combined effect of streptokinase and high-intensity US, the process of acoustic-mechanical destruction of thrombus is prevailing, and the fibrinolytic effect of streptokinase is generally witnessed after the termination of US and manifests itself in enzymatic lysis of both resultant particles and residual clot mass. In this study we verified the effect of low-frequency high-intensity ultrasound on the dynamics and efficiency of fibrinolysis induced by streptokinase on various structure thrombi model, characteristic features of the fibrin clot network structure occurring during the combined effect of ultrasound and streptokinase

Low frequency and high intensity ultrasound in vascular surgery: theory, instrumentation and possibilities of clinical application

This paper presents a brief review of applications of ultrasound in modern surgery and results of original studies of the authors in the field of application of low frequency (24-36 kHz) high-intensity (up to 20 W/cm2) ultrasonic vibrations for disruption of thrombi and calcified atherosclerotic plaques in blood vessels. Application of non-rigid wire ultrasonic waveguides with length up to 980 mm and diameter of working tip down to 0.3 mm enables minimally invasive surgical intervention, since a waveguide can be introduced along curved segments of blood vessels through a small incision situated at substantial distance from occlusion. Ultrasonic angioplasty can be successfully applied in combination with administration of thrombolytic drugs. The paper also considers physical mechanisms of thrombus disruption under influence of ultrasonic vibrations, particularly, effects of cavitation and acoustic streaming. We described design of ultrasonic waveguides for endovascular surgery and their manufacturing technology based on plasma-electrolytic etching. Application of finite element method and transfer matrix approach for design and model of wire waveguides is considered. Description of clinical system for ultrasonic angioplasty with automated resonance tuning of a waveguide is also provided. In addition, we report results of clinical application of ultrasonic angioplasty in patients with occlusion of iliofemoral segment

Кинетика разрушения фибриновых сгустков под действием ультразвуковой кавитации

We studied the kinetic features of fibrin clot destruction in vitro under the action of ultrasonic cavitation generated by low-frequency (36 kHz) ultrasound (US) with the intensity I0  of 4.4–51.2 W/cm2, using a flexible waveguide concentrator. It was established that the rate of US destruction of clots immersed in saline at the initial stage of the process is proportional to I0 in the range of 12–51 W/cm2, corresponds to first-order kinetics, and is determined by the erosive processes without the formation of D-dimers and other fibrinolysis products at a minimum contribution of sonochemical reactions. The clot destruction rate is maximum at the initial time moment and decreases with increasing the US exposure duration (by 35 % in 1 min and by 72 % by the end of the second minute at I0 = 51.2 W/cm2). It was shown that in order to increase the completeness of clot destruction at a minimum administered US dose, it is advisable to minimize the US exposure time when using the highest values of the US intensity limited by the level of safe cavitation exposure to the vascular wall, hemostasis, and blood cells.Изучены кинетические особенности разрушения фибриновых сгустков in vitro под действием ультразвуковой кавитации, генерированной низкочастотным (36 КГц) с интенсивностью I0 4,4–51,2 Вт/см2  ультразвуком (УЗ), с использованием гибкого волновода-концентратора. Установлено, что скорость УЗ разрушения сгустков, погруженных в физиологический раствор, на начальных стадиях процесса пропорциональна I0 в интервале 12–51 Вт/см2, соответствует  кинетике  первого  порядка  и  определяется  протеканием  эрозионных  процессов  без  образования D-димеров и других продуктов фибринолизиса при минимальном вкладе сонохимических реакций. Скорость разрушения сгустка максимальна в начальный момент времени и снижается при увеличении продолжительности УЗ воздействия (на 35 % за 1 мин и на 72 % к концу второй минуты при I0  = 51,2 Вт/см2). Показано, что для увеличения полноты разрушения сгустка при минимально вводимой УЗ дозе целесообразно минимизировать время УЗ воздействия при использовании наиболее высоких значений УЗ интенсивности, ограниченных уровнем безопасного воздействия кавитации на сосудистую стенку, гемостаз и форменные элементы крови

ВЛИЯНИЕ ЛИПОСОМАЛЬНОЙ ФОРМЫ СТРЕПТОКИНАЗЫ НА ОБРАЗОВАНИЕ Д-ДИМЕРОВ

Liposomal streptokinase (a mixture of free (66.3  %) and entrapped (23.7  %) drug) with a diameter of ~60 nm was prepared. The analysis of the D-dimers formation kinetics in the dog’s blood plasma showed that the liposomal streptokinase hada prolonged effect up to 180 minutes.Получены липосомы со стрептокиназой с размерами ~60 нм, представляющие собой смесь, состоящую из свободного (66,3  %) и связанного (23,7  %) препарата. На основании анализа кинетики образования Д-димеров в плазме крови собак установлено, что липосомальная форма стрептокиназы обладает пролонгированным эффектом в течение 180 мин

ПОЛУЧЕНИЕ КОМПЛЕКСНЫХ ПРЕПАРАТОВ НА ОСНОВЕ ЛИПОСОМАЛЬНОЙ ФОРМЫ СТРЕПТОКИНАЗЫ И ИХ ФАРМАКОКИНЕТИЧЕСКИЕ ХАРАКТЕРИСТИКИ

It was obtained that liposomal streptokinase (SK) with a hydrodynamic diameter of ~70 nm and a zeta-potential of –6.2 mV contains 14.1 % wt of drug. The complex formulations based on liposomal SK include “associated” and “free” SK in the ratios of 20/80, 40/60 and 50/50. The in vivo experiments on rats showed an increase in the elimination half-time from 1.8 to 31.9 min and in the time to reach the maximum concentration of streptokinase from 15 to 45 min. The decrease in the elimination rate constant by a factor of 18 compared with SK was also found. The optimal ratio of “associated” and “free” SK in the complex formulation was 40 and 60 % respectively. It was used to obtain liposomal fibrin-specific form of thrombolytic with similar physico-chemical and pharmacokinetic parameters. Получена липосомальная форма стрептокиназы (СК) с гидродинамическим диаметром ~70 нм, дзета-потенциалом –6,2 мВ и степенью включения вещества 14,1 %, на основе которой приготовлены комплексные препараты, содержащие «связанную» и «свободную» СК в соотношениях 20/80, 40/60 и 50/50. Для них в эксперименте in vivo на крысах показано увеличение периода полувыведения от 1,8 до 31,9 мин и времени достижения максимальной концентрации стрептокиназы от 15 до 45 мин, а также уменьшение константы элиминации в ~18 раз по сравнению с нативной СК. Оптимальное соотношение «связанной» и «свободной» СК в комплексном препарате составило 40 и 60 % соответственно, что было использовано для получения липосомальной фибрин-специфичной формы тромболитика, который обладает практически такими же физико-химическими и фармакокинетическими параметрами.

Эластификация артериальной стенки под действием высокоинтенсивного низкочастотного ультразвука

A significant increase in the elasticity of the femoropopliteal artery segments in vitro was found as a result of the action of cavitation generated by powerful low-frequency (24–26 kHz) ultrasound introduced into the vessel by a flexible waveguide. The vessel elasticity was evaluated both by the deflection under the action of an external force and by the degree of its expansion vasodilatation by the internal pressure created by the expanding balloon. The possibility of achieving a more than two-fold decrease in the vascular wall elasticity modulus after 30-s exposure to an ultrasound intensity of 31 W/cm2 was shown. It has been established that at the 10 μm amplitude of ultrasonic vibrations, vascular wall damage occurs in the form of small foci of detachment and rupture of the intima accompanied by delamination in the media layer, when polymorphic slit-like cavities are formed with an increase in the amplitude of oscillations above 23 μm.Установлено существенное повышение эластичности бедренно-подколенных сегментов артерий in vitro в результате действия кавитации, генерированной мощным низкочастотным (24–26 кГц) ультразвуком, вводимым внутрь кровеносного сосуда гибким волноводом. Эластичность сосуда оценивалась как по прогибу под действием внешней силы, так и по степени его вазодилатации внутренним давлением, создаваемым расширяющимся баллоном. Показана возможность достижения более чем двукратного снижения модуля упругости сосудистой стенки после 30 с ультразвукового воздействия интенсивностью 31 Вт/см2. Установлено, что при амплитуде ультразвуковых колебаний 10 мкм имеет место повреждение сосудистой стенки в виде мелких фокусов отслоения и разрыва интимы, сопровождающееся расслоениями в медии с формированием полиморфных щелевидных полостей при увеличении амплитуды колебаний свыше 23 мкм