Test Procedure for a New Type of a Ventricular Assist Device Based on a Viscous Friction Pump

Maksim O Zhulkov; Жульков Максим Олегович; Alexander M Golovin; Головин Александр Михайлович; Alexander S Grenaderov; Гренадеров Александр Сергеевич; Vitaliy R Tsirikhov; Цирихов Виталий Русланович; Azat K Sabetov; Сабетов Азат Керинбекович; Hava A Agaeva; Агаева Хава Абдуллаевна; Sergey A Alsov; Альсов Сергей Анатольевич; Alexander M Chernyavskiy; Чернявский Александр Михайлович

doi:10.18499/2070-478X-2020-13-3-256-261

Test Procedure for a New Type of a Ventricular Assist Device Based on a Viscous Friction Pump

Authors: Zhulkov M.O¹, Golovin A.M², Grenaderov A.S³, Tsirikhov V.R¹, Sabetov A.K¹, Agaeva H.A¹, Alsov S.A¹, Chernyavskiy A.M¹
Affiliations:
1. national medical research center named after academician E. N. Meshalkin
2. joint-stock company "IMPULSE-project" Research and production company
3. Institute of high-current electronics of the Siberian branch of the Russian Academy of Sciences
Issue: Vol 13, No 3 (2020)
Pages: 256-261
Section: New in surgery
URL: https://vestnik-surgery.com/journal/article/view/1406
DOI: https://doi.org/10.18499/2070-478X-2020-13-3-256-261
ID: 1406

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Abstract
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Abstract

Introduction. Currently, the possibility of effective correction of multiple organ failure and increasing the life expectancy of patients with critical heart failure using the ventricular assist devices (VAD) is absolutely evidenced. The development of alternative analogues of such devices produced within the country has been an urgent problem for many decades. The design of this machine requires the development of a protocol for carrying out complex biomedical studies on the biocompatibility and safety of the new device.
The aim of the study was to develop a protocol for testing and conducting comprehensive biomedical biocompatibility studies of a new ventricular assist device in an acute animal experiment.
Materials and methods. The study to develop a technique for implanting a left-ventricular assist device (LVAD) in an acute experiment included female mini-pigs, weighed 40-60 kg. In a series of acute experiments, 5 implantations of a disk pump as a LVAD were performed with a maximum observation period equal 6 hours.
Results. In the series of acute experiments, an implantation technique was developed and the fundamental possibility of a viscous friction pump application as a ventricular assist device was evidenced. In all experiments (n = 5), the average level of free hemoglobin did not exceed 2.6 mg%, which supports safety of performance of the viscous friction pump regarding blood erythrocytes. None of the experiments recorded episodes of pump shut-off or breakdown.
Conclusions. The series of acute experiments on mini-pigs helped reveal a number of anatomical and physiological features of this animal species that significantly complicated implementation of persistent observation. However, the developed experimental LVAD test methodology can be recommended for use in further chronic experiments on large laboratory animals (calves).

Keywords

heart failure, mechanical support of the heart, Tesla disk pump, left ventricular bypass system

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JUSTIFICATION
Over the past decade, the use of assisted circulatory devices in clinical practice has increased significantly [1-3]. According to the literature, by 2014, about half of heart transplantations in the world were performed against the background of an early implanted circulatory support apparatus (LVAD) [4]. Moreover, in recent years, the need for LVAD has increased sharply, as the number of patients for whom a mechanical circulatory support device has been implanted as the final treatment for the terminal stage of chronic heart failure has increased [5]. The high cost of foreign assisted circulatory devices sharply limits their use, therefore, domestic research in the field of development and implementation of circulatory support systems is the most relevant and relevant [6]. The introduction of such products into clinical practice requires a full range of studies of all the characteristics and qualities of the device. To this end, on the basis of the NICC named after Meshalkin conducted a series of experiments on large laboratory animals and developed a test protocol for the apparatus for auxiliary circulation based on a viscous friction pump.
TARGET
The aim of this study was to develop a protocol for implantation and conduct comprehensive biomedical biocompatibility studies of a new circulatory support device in an acute animal experiment.
METHODS
In order to develop a technique for implanting an auxiliary circulatory system (LVAD) in an acute experiment, mini-pig pigs of a female sex of 40-60 kg were selected as models. Caring for animals, providing an experiment, observing and removing animals from it was carried out in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experiments or for Other Scientific Purposes (Strasbourg, 03/18/1986). A paracorporeal pump implantation scheme was chosen for LVAD implantation, since this scheme made it possible to significantly simplify the process of postoperative monitoring of the device, although it posed a greater threat to the animal's life compared to the implantation implantation scheme. The data of preliminary mathematical modeling of the flow along the paracorporal loop, taking into account the shapes and lengths of the supply and return lines, proved the physiological (laminar) flow of blood, without affecting the hemodynamics in the tested apparatus for mechanical support of blood circulation (Fig. 1).

All animals on the eve of the experiment were deprived of food intake, while access to water was not limited. Premedication was performed in vivarium by intramuscular injection of a solution of atropine and zoletil in a dose according to weight and height parameters. When the animal fell asleep, the surgical field was prepared. The experiment was carried out under conditions of endotracheal anesthesia with sevoflurane and muscle relaxation (pipecuronium bromide).

During the experiments, monitoring was carried out; invasive blood pressure (IAD) by catheterization of the left carotid artery, central venous pressure (CVP) by catheterization of the left jugular vein, cardiac arrhythmias (electrocardiography), body temperature, blood gas composition, activated coagulation time (AST), hemodynamic parameters of the heart ( ChPEHOKG, Svan-Ganz catheter). In order to correct hypovolemic disorders, infusion therapy with crystalloid and colloidal solutions was performed. Vital parameters were recorded using an IntelliVueMP70 monitor (Philips). Before each experiment, all components of the circulatory support apparatus were sterilized with ethylene oxide. Then, on a sterile table to the inlet and outlet nozzles of the pump fixed ½ inch line. After that, the pump was refilled with physiological saline at low speeds (500-1000 rpm), carefully removing the air emboli. In a series of acute experiments, 5 implantations of a disk pump as LVAD were performed with a maximum observation period of 6 hours.

RESULTS
In the first three experiments, the disk pump was connected according to the scheme “the apex of the left ventricle - the descending part of the thoracic aorta”. Animals were placed on their right side. An anterolateral thoracotomy was performed in the VI intercostal space on the left with partial resection of the VI rib. The LVAD lines were passed paravertebrally through the formed subcutaneous canals. After systemic heparinization (2 mg / kg) and lateral squeezing of the thoracic aorta, an end-to-side anastomosis was formed between the Intergard 14 mm Dacron vascular prosthesis and the 5/0 descending thoracic aorta. The outflow line was connected to the pump outlet. Supply cannula implantation was performed on a working heart through the avascular zone of the apex of the left ventricle. The supply line was connected to the corresponding pump nozzle.

After thorough removal of air from all the nozzles, the pump was gradually turned on and the rated output reached (5-5.5 l / min). The stage of turning on the disk pump in the circulatory system was carried out under the control of the CPECCG, controlling the presence of a slight ejection through the aortic valve and smoothing the peaks of the blood pressure curve on the monitor.

In the first experiment, severe anemia (Hb - 50-60 g / l) was observed in connection with the pronounced loss of blood at the stage of implantation of the supply cannula into the cavity of the left ventricle, given the small body weight of the experimental animal (40 kg) in the early postoperative period. In addition, the main reason that did not allow the pump to reach its rated capacity (5.5-6 l / min) was the “collapse” of the cavity of the left ventricle and the disruption of blood flow to the pump, despite the optimal positioning of the cannula in the cavity of the left ventricle (according to the data from CHPECCG ) and a sufficient volemic load of the animal (DZLK 12-15 mm Hg). However, within 4 hours, LVAD provided adequate systemic perfusion (4–4.5 l / min) under conditions of persistent right ventricular ejection (Fig. 2). The data of the gas composition of the blood and other hemodynamic parameters are shown in table 1.

In experiment No. 2, the implantation scheme was the same, but an animal of greater body weight (67 kg) was used. At the same time, it was possible to develop the performance of the disk pump to 5.0-5.5 l / min and to provide adequate perfusion of the animal's body for 3 hours. The parameters of the gas composition of the blood were also within the reference values. However, after 3 hours of perfusion, on the background of the animal’s awakening, stable ventricular fibrillation developed in the machine, loss of ejection of the right ventricle and, as a result, deficiency of inflow into the pump. A team of researchers decided to terminate the experiment.

LVAD implantation in experiment No. 3 was performed under extracorporeal circulation; for this, the right common carotid artery and the right external jugular vein were cannulated. The conditions of cardiopulmonary bypass made it possible to qualitatively visualize and form a ventriculotomy opening and to position the inflow cannula in the cavity of the left ventricle as correctly as possible (Fig. 3). However, at the time of stopping cardiopulmonary bypass and LVD function transfer, LVAD developed stable ventricular fibrillation, which could not be restored.

With each subsequent experiment, the need for developing the most simple and minimally invasive LVAD connection scheme became apparent. In experiments No. 4 and No. 5, we used a two-stage flat venous cannula (for better modeling in the chest) as a supply cannula Medtronic 29/37 Fr. The supply cannula was preliminarily passed through the chest wall and after the purse string suture was applied to the left atrial ear, it was implanted into the left atrium cavity towards the mouths of the right pulmonary veins (Fig. 4). This technique of implanting a supply cannula made it possible to almost bloodlessly ensure a sufficient inflow into the pump and avoid anemia in the postoperative period. In the last two experiments, animals were successfully extubated in the early postoperative period, LVAD provided an adequate systemic flow (5.0-5.5 l / min) for 6 hours. In all experiments, heparin was administered intravenously at a dose of 2 mg / kg before implantation and then infusion to maintain AST at a level of 250-300 sec.

DISCUSSION
In the course of a series of sharp experiments, a detailed technique was developed for implanting a new type of ancillary blood circulation apparatus and the fundamental possibility of using a viscous friction pump as the main mechanism was proved. In all experiments (n = 5), the average level of free hemoglobin did not exceed the value of 2.6 mg /%, which proves the safety of the mechanism of operation of the viscous friction pump in relation to red blood cells.

However, a number of anatomical and physiological deficiencies of pigs (mini-pigs) led to the rejection of the use of this species of animals in chronic experiments. None of the experiments recorded episodes of stopping or breaking the pump. All the difficulties encountered during testing of the developed circulatory support apparatus based on a viscous friction pump were associated with the topo-morphological features of the experimental model. In all animals, pronounced wall hypertrophy (> 2.5 mm) and a small cavity of the left ventricle (end-diastolic volume less than 40 ml) were determined, which contributed to blockage of the supply cannula even with adequate positioning in the cavity of the left ventricle (if connected according to the “apex” scheme left ventricle - descending aorta).

Experimentally developed and confirmed by methods of mathematical modeling of the flow, the connection scheme “the left atrial ear - the descending thoracic aorta) using the two-stage reinforced venous cannula made it possible to speed up and simplify the experimental LVAD connection procedure, eliminating the need for an artificial blood circulation apparatus.

A significant observation was the fact that the application of a-C: H: SiOx coating obtained using pulsed bipolar bias voltage during plasma-chemical deposition on the internal surfaces and moving parts of the rotor significantly increased the biocompatibility of the device, with the previously proven effect on the decrease in hemolysis level [7]. So, in the first pump models, in the absence of this coating, each time after explantation, multiple thrombotic masses were found, especially at the base of the pump (around the axis of the disk pack). After applying a-C: H: SiOx film, in no case were blood clots detected on the surfaces of moving parts of the pump. The significance of such a refinement has been repeatedly covered in the works of other researchers on the creation of biocompatible coatings [8, 9].
CONCLUSION
Thus, during a series of sharp experiments on animals, the most important knowledge was obtained about the advantages and disadvantages of various methods of experimental implantation of assisted circulatory devices, and an optimal LVAD test protocol was developed. It was also justified the need for a transition to a new model (calves) in a series of chronic experiments. The developed protocol for implantation and postoperative observation can be recommended for use in further chronic experiments on large laboratory animals (calves).

About the authors

Maksim O Zhulkov

national medical research center named after academician E. N. Meshalkin

Author for correspondence.
Email: maks.zhulkov.92@mail.ru
ORCID iD: 0000-0001-7976-596X

trainee researcher at the center for surgery of the aorta, coronary and peripheral arteries Of the national medical research center named after academician E. N. Meshalkin