Design, Manufacturing And Applied Basic Study For A Hepatic Vein Occlusion Device

1. ObjectiveIn hepatic surgery and liver transplantation it is extremely difficult to directly control the blood flow of the hepatic vein. The Heaney process indirectly controls the blood flow of hepatic vein through exclusion of the inferior vena cava, which is complicated in operation with much blood loss, high risk and a great disturbance in the hemodynamics of the whole body. Approximately 10-20% of the patients are not able to endure the process. In order to reduce the impact on hemodynamics various vein-shunting techniques have been applied. Even the method of direct hepatic vein exclusion outside the hepatic parenchyma has been attempted. Although these methods are more complicated, they have not resulted in any decrease in risk and blood loss during operation, so the practical application has been limited. In spite of the development and improvement in the past half century there is still not yet a simple, safe and feasible method of total hepatic vein exclusion having less impact on hemodynamics. Therefore the difficult hepatectomy in relation to the second hepatic hilum and third hepatic hilum is full of risk and challenge. The objective of this study is to explore a simple, convenient and reliable method of hepatic vein occlusion under total hepatic vascular occlusion with less impact on hemodynamics. The principle and manufacturing method of inferior vena cava stent have been used for reference, the shape-memory feature as well as the good flexible function of nickel-titanium alloy and the good performance of silicon rubber material utilized and a hepatic vein occlusion device designed for the vena cava. Animal experiments have been conducted to test the effectiveness of the device and to evaluate its impact on hemodynamics during hepatic vein occlusion. As the result practical experience and theoretic basis have been provided for further clinical application. The study has been conducted in three steps: 1. Applied anatomical study of the second hilum and the third hepatic hilum; 2. Design and manufacturing of the hepatic vein occlusion device made of nickel-titanium alloy for the vena cava; 3. Animal experiments of the hepatic vein occlusion device.2. Materials and methods2.1 Applied anatomical study of the second hepatic hilum and the third hepatic hilumFifty six liver specimens of embalmed adult cadavers were used respectively. The cadavers perfused with red plasticand without obvious enhancement, atrophy and deforming were selectcd. On the transection side the circumference of the inferior vena cava was evenly divided into 12 spots by o'clock measurement. The 12th spot was in the front, the 6th in the back, the 9th on the left side and the 3rd on the right side.The inferior vena cava was then incised along their posterior wall at the 6th spot and the inferior vena was spread from the inside of the cava. On the vertical axis of the retrohepatic inferior vena cava four planes were found from the head to the end. Plane a was located on the upper edge of the highest hepatic vein ostia; Plane b was on the lower edge of the lowest hepatic vein ostia; Plane c was on the upper edge of the highest accessory hepatic vein ostia over 5mm in diameter below the hepatic vein ostia; Plane d is on the lower edge of the hepatic vein ostia over 1mm in diameter. The vertical space and width (circumference) among the four planes of the retrohepatic inferior vena cava were measured; the size and position of hepatic vein ostias recorded and the course of the vein was traced. Finally the inner wall shape of the retrohepatic inferior vena cava was observed. The range of the second hepatic hilum and third hepatic hilum as well as each section circumference of the circumference was determined and basic data provided for the design and manufacturing of the hepatic vein occlusion device.2.2 Materials and methods for manufacturing the framework of the hepatic vein occlusion device Nickel-titanium alloy has not only a good anti-fatigue performance, a fine compatibility with MRI, an extraordinary anti-corrosion capability and biocompatibility, but also a unique shape memory and super-elastic capability. The material has been widely used to manufacture medical instruments to be put into human bodies. NiTi alloy (Ni 49.8%/Ti 50.2%) wire material, which is 0.25mm in diameter, was selected as the framework material for manufacturing the hepatic vein occlusion device. The deforming temperature of NiTi alloy (Ni 49.8%/Ti 50.2%) is 0-28℃, and the shape-recovery temperature is 28-40℃. The basic state can be maintained at normal temperature. When the temperature is kept at 0-28℃, the shape can be molded at will. After being put inside the human body at the temperature above 28℃, the shape will restore to its basic state due to its inherent recovering and super-elastic capability, supporting the hepatic vein occlusion device.The manufacturing method is based on the sinusoidal curve process with the manual knitting technique of the multi-wire matrix to form a radial diamond net so as to suit the radial deforming in the inner wall of the blood vessel. The intersection points among metal wires will not be welded so as to facilitate the elastic deforming in the radial direction and the sheathing. Since there are no man-made intersection points among the metal wires the bended metal will produce tensile force to keep the transection an approximately round shape. In this way the expansion elasticity is maintained to the maximum with a close integration in the wall of blood vessel. The framework is furled via eight wires so as to decrease blood obstruction.The knitted framework of the occlusion device is treated thermally at 400-500℃, shaped and deformed 3-5 times by cold and thermal treatment so as to train its memory capability with the recovering temperature controlled at 28-40℃. After such procedures as painting, baking, acid pickling, cleaning and drying, the bare framework is made.2.3 Overlay film of the hepatic vein occlusion device and its manufacturing methodSilicon rubber is an organic material containing Si-O, a linear macromolecule elastomer with stable performance. It not only has such excellent performances as the resistance to aging of ozone, oxygen, light and weather, but also the good elasticity, anti-tear properties as well as the adaptability to temperature. It can be stretched into 0.1mm thin film, which can meet the requirement for manufacturing overlay film of the hepatic vein occlusion device. The catalysts of silicon, hydrogen-rich silicon oil and platinum complex compounds are refined in the blender. Organic solvent is added and silicon rubber solution is formed. The bare semi-product is treated with the coupling-agent, soaked in the silicon solution to overlay the film, followed by thermal sulfurization and surface treatment. Then it is inspected, sanitized, sailed and the final product is produced.2.4 Animal experiment for occlusion of hepatic blood flow by the hepatic vein occlusion deviceFifteen local healthy adult dogs weighing 16.8±1.79 were selected regardless of the gender. They were mated by the table of random number and divided into the following three groups with left liver resection performed under hepatic vascular control: Group A was the reference and Pringle hepatic exclusion process was adopted with the blood flow under control only; Group B was also the reference and improved Heaney method applied with total hepatic vascular exclusion; Group C was the experiment group with the hepatic vein occlusion device adopted for the vena cava to directly control the blood flow of the hepatic vein. The three groups of the tested animal were compared and observed in the respect of hepatic vascular control effects and the change in haemodynamics.3. Results3.1 According to the distribution rules of the hepatic vein portal hepatic veins meet at the upper section of retrohepatic inferior vena cava in the range of 21±4.2 (16～28)mm while accessory vena cavas meet at the lower section of retrohepatic inferior vena cava in the range of 36±10.4(21～58)mm. There exists a sparse interval 17+9.5(5～32)mm between the two sections. The spread-out figure of retrohepatic inferior vena cava is mainly displayed as a trapezia with the upper part wider and the lower part narrower. The width of Plane a is 85.3±12.5 (49.6～104.5) mm, Plane b 80.5±10.7 (54.3～95.6) mm wide, Plane c 78.5±10.56. (47.5～96.7) mm, and Plane d 74.6±10.34 (50.6～95.4) mm. In addition both sides of the fifteen specimens are hollow in the middle ( 3-5 mm). It is calculated that the diameter of Plane a is 27.15±3.97 mm, Plane b is 25.62±3.41 mm, Plane c is 25.31±4.97 mm, and Plane d is 23.75±4.27 mm. The retrohepatic inferior vena cava is wider in its upper section and thinner in the lower with a hollow in the middle, forming a tubular structure like a Korean drum.3.2.The wire material made of NiTi alloy (Ni 49.8%/Ti 50.2% ) was selected to knit the framework of the occlusion device. It had a good temperature-deforming memory capability and super elastic function. Within the deforming range it is extremely sensible to the change in temperature. At 0-25℃the material became very pliancy and only with a little external force could it be easily fixed in the pusher. When the temperature is 28-40℃, the deforming memory can be recovered and the shape-recovering rate is up to 90%. Based on the sinusoidal curve method the horizontal diamond net knitted with manual technique of the multi-wire matrix has a good adaptability as the radial diameter is adaptable to the elastic flexibility 1: 10mm. The wire diameter of the NiTi alloy is 0.25 mm, the thickness of silicon rubber overlay film is 0.2 mm, the thickness of product occlusion device is less than 0.5 mm, and the horizontal section area of the whole occlusion device is less than 1/12 area of the inferior vena cava. The surface is quite smooth without static electricity. In-vitro simulation experiments show that the occlusion effect of hepatic veins is satisfactory, the device matches flexibly with the pusher and is easy to operate.3.3. The animal experiment for which the hepatic vein occlusion device is used to control the hepatic blood flow has shown the following results: When the hepatic vein occlusion device was used together with the Pringle process to perform total hepatic vascular exclusion, the amount of blood loss during operation was 61.6±8.792 ml. In comparison with the hepatic surgery for which only the Pringle exclusion process was adopted with the blood loss 86.4±15.04 ml, there was an obvious difference (p＜0.05); But there was no obvious difference (p＞0.05) when compared with the blood loss (55.0±7.906)ml during the operation for which the improved Heaney process of total hepatic vascular exclusion had been adopted. During the occlusion the hemodynamics was stable. CVC dropped by 0.8 cmH₂O while ICVP decreased by 1.28 cmH₂O, which was a relatively obvious difference (p＜0.01) in comparison with the improved Heaney process, but was not significantly different (p＞0.05) from the Pringle process of hepatic vascular exclusion. It took 14.17±4.420 minutes to establish the whole hepatic vascular occlusion procedure by the hepatic vein occlusion device with the amount of blood loss 26.6±6.427ml, which was obviously different (p＜0.05) in comparison with the improved Heaney process. During the whole hepatic vascular occlusion ICVP was below 9.96 cmH₂O with no obvious difference of blood sludging in the kidney and lower body. However there was an obvious difference (p＜0.05) in the urine amount and anus temperature compared with the improved Heaney process. As for the impact on the blood dotting system there was no obvious difference (p＜0.05) when compared with the two reference groups.4. Conclusion4.1 According to the distribution rules of the hepatic vein portal for the retrohepatic inferior vena cava and in combination with the practical situation of the clinic application it is considered that the second hepatic hilum is located at the 1/4 section of the retrohepatic inferior vena cava within the range 21±4.2mm from the top to the end. The diameter of the upper part is 27.15±3.97 mm with the cava wall circumference 85.3±12.5 mm while that of the lower is 25.62±3.41 mm with the circumference 80.5±10.7mm, The third hepatic hilum is located at the 2/4 section of the retrohepatic inferior vena cava within the range 36±10.4mm from the top to the end. The diameter of the upper part is 25.31±4.97 mm with the cava wall circumference 78.5±15.6.85 mm while that of the lower is 23.75±4.27 mm with the circumference 74.6±10.34 mm. Two hepatic portals are interfaced with the average range 17±9 mm between the upper and lower.4.2 According to the preliminary test of physical performances and based on the applied anatomy of the second and third hilum a hepatic vein occlusion device made of Ni-Ti alloy (Ni 49.8 %/Ti 50.2%) wire material and silicon rubber overlay film has been adopted. The device has a good capability of temperature-deforming memory and super elastic performance, is sensible to temperature change, becomes extremely pliancy, and can be fixed easily into the pusher, which is 3.3 mm in diameter. Memory deforming will take place when the temperature returns to 28℃and the shape-recovering rate is 90% with the maximum recoverable diameter 32 mm, the horizontal contraction ratio 1:10 and vertical contraction ratio 3.5: 1. The device can match the shape change of the hepatic vein with a close integration to the simulated blood vessel wall. It can be flexibly connected into the pusher and is convenient to put in and out.4.3 The animal experiment shows that the hepatic vein device can directly occlude the hepatic vein in the inferior vena cava and the occlusion effect is reliable. It is also featured by uninterruption in the blood flow of the hepatic vein, and the blood sludging in the lower-body vein caused by inferior vena cava exclusion using the Heaney process is relieved without any impact on the normal metabolization of the tissues or organs below the occlusion plane. Further more during the hepatic vein occlusion and re-flow there is not much change in heart rate, average blood pressure, central vena, the pressure of inferior hepatic vein and average pulmonary artery pressure with a stable hemodynamics of the whole body. In addition the device has the advantages of easy, convenient operation and time saving. In the first aid of inferior vena cava the method of femoral venipuncture can be selected and the occlusion device used for rapidly blocking out the crack in the inferior vena cava so as to save time for operation. By using the occlusion device to control the hepatic vein the damage can be decreased with less blood loss, which is the development trend for micro invasive surgery. When the venovenous bypass to portal vein-cava vein and portal vein-right heart is necessary, a bypass interface is especially designed at the end of the occlusion device and the pusher. It can be used either as the transfusion channel or the bypass to the portal vein. The complication problems such as blood clotting and air embolism, which might occur with the use of the occlusion device, can be solved through strict operation procedures and prevention measures in advance. If the overlay film of the occlusion device is covered with the drug coat, the Anti-coagulation effect might be better. In short from the animal experiment it is preliminarily concluded that the hepatic vein occlusion device has made the previous complicated operation simpler and easier, the risky technique of the whole hepatic vascular exclusion safer, and the technique of the whole hepatic vascular occlusion acceptable to all patients.