CN105379707B - Liver normal temperature irrigates repair system - Google Patents
Liver normal temperature irrigates repair system Download PDFInfo
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- CN105379707B CN105379707B CN201510941335.8A CN201510941335A CN105379707B CN 105379707 B CN105379707 B CN 105379707B CN 201510941335 A CN201510941335 A CN 201510941335A CN 105379707 B CN105379707 B CN 105379707B
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- liver
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- oxygenator
- irrigates
- arteria hepatica
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0236—Mechanical aspects
- A01N1/0242—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components
- A01N1/0247—Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts
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Abstract
Liver normal temperature irrigates repair system, including liver container, liver container includes body and upper lid, both, which can seal, covers tightly, the soft net of silica gel is fixed with liver vessel, liver vessel lower end offers blood back passage, blood back passage is connected through storing up blood tank with centrifugal pump, store up blood tank front end and be provided with filter membrane, the port of export of centrifugal pump is connected with oxygenator, and oxygenator connects control oxygen device, and the transducer potector of oxygenator is divided into two-way through heat exchanger, arteria hepatica is irrigated through roller pump all the way, another road directly irrigates portal vein.Arteria hepatica act as pulsatile flow through roller pump in the present invention, and the hepatic arterial perfusion feature of liver under physiology is simulated well, the protection during being more beneficial for irrigating to bile duct cell.The present invention maintains the aerobic metabolism of liver cell at normal temperatures, and the repairing and treating of short time can be carried out to liver, expands for liver source.
Description
Technical field
The present invention relates to irrigate repair system under a kind of liver normal temperature.
Background technology
Liver transfer operation is the unique effective means for saving End-stage liver disease.It is short for liver with the increase year by year of liver transfer operation demand
Lack and also become clear day by day, seriously restrict its development.Marginal donor liver or expansion standard supply liver（ECD）Range of choice is gradually included, wherein
Including fatty liver, advanced age and heart death donor（DCD）.With the standardization of domestic organ donation system, DCD liver transfer operations by
Year increases, but the type donor average age is higher, and the ratio that liver fat becomes also accordingly increases.According to statistics, liver transfer operation donor
The recall rate of fatty liver is close to 30%, and nearly 50% belongs to fatty liver in the confession liver given up.In liver-severe fat become have a strong impact on confession
Liver quality, is postoperative primary liver graft nonfunction（PNF）Most important reason.Bullous fatty liver more than 60% is discomfort
Preferably row liver transfer operation.The PNF most of preoperative liver function of ECD donors is caused to be in normal range (NR), therefore supposition is obtained for liver
It is to cause the immediate cause of the irreversible damages of ECD that cooling jet flow after taking, which is preserved,.
Liver normal temperature perfusion be using blood pass through in vitro perfusion system, abundant oxygen and, keep with body temperature identical temperature,
Supply is maintained after nutrition and the energy matter of organization survival, is protected with certain pressure and flow velocity circumfusion for a whole set of perfusion of liver
Deposit method.Normal temperature perfusion can maintain the aerobic metabolism of liver cell, the potential with pretreatment before transplanting, can in real time monitor and supply liver function
Can, the safety extension holding time.
Earlier than 20th century mid-term, normal temperature perfusion is shown up prominently, yet with filling machine is huge, somewhat expensive, and
Cold to preserve developing rapidly for liquid, normal temperature perfusion is occurred in that and stagnated for a long time.Until nearly 20 years, with the increase for liver demand, fat
The ECD such as fat liver, DCD expansion application, normal temperature perfusion turns into the focus on transplanting circle again with the advantage of its protrusion.Have multinomial grind
Study carefully confirmation, normal temperature perfusion can improve DCD Donor liver qualities, improve post-transplantation survival rate.
Liver normal temperature irrigates the foundation of system, and difficult point is that liver has two enter liver blood stream accesses, be respectively portal vein and
Arteria hepatica.Portal vein provides the 50% of 75% and total oxygen demand of the total CBF of liver, and normal portal venous pressure is 5 ~ 10mmHg, arteria hepatica
The 50% of 25% and total oxygen demand of total CBF is provided.Normal arteria hepatica is pulsed blood flow, and pressure is human body systolic pressure 90-139/
Diastolic pressure 60-89mmHg.The portal vein and arteria hepatica pressure and flow velocity for how maintaining physiological level are the passes that normal temperature irrigates system
Key.
The normal temperature perfusion system of more maturation is researched and developed by Oxford University directly under company OrganOx at present.It utilizes centrifugal pump
Effect maintains perfusion circulation, and the blood of inferior caval vein backflow is pushed to oxygenator through centrifugal pump, then divides arteria hepatica and portal vein
Two-way irrigates liver；Wherein portal venous flow is introduced into after blood storage bag is irrigated by gravity, by adjusting centrifugation revolution speed,
Folder closes the valve of blood storage bag entrance and adjusts portal vein flow and pressure by the height of blood plane in blood storage bag in good time.
The shortcoming of this mode is：Nourish liver main blood supply --- pylic pressure and flow are by storing up blood
Liquid level is come what is adjusted in bag, and pylic resistance is larger by Microcirculation Effect in liver in filling process, its flow and pressure
Power can change in real time, be difficult to keep irrigating the stabilization circulated by adjusting the valve of centrifugation revolution speed and blood storage bag entrance.
Applicant repeatedly carries out the experiment that normal temperature irrigates system using OrganOx schemes, from being connected to for each blood vessel of liver
Stable circulation averagely needs 30 minutes or so, and after liver blood flow opening, due to microcirculation dredging, enters hepatic blood flow and pressure
Power can be continually changing, and be monitored when operator takes, frequently regulation centrifugal pump and valve, to maintain the liquid in vertical perfusion blood storage bag
Plane.Once liquid level is relatively low, then portal venous pressure can decline, and flow increase, liquid level further declines, and air can enter cyclic system
Unite and centrifugal pump is decommissioned, ultimately result in test failure.
The content of the invention
Repair system is irrigated there is provided a kind of stable easy liver normal temperature to solve the deficiencies in the prior art, to greatest extent
Simulated liver physiology is circulated, and monitoring in real time supplies liver function, and the Liver Allograft Preservation time before safety extension transplanting, the present invention is using following
Technical scheme：
Liver normal temperature irrigates repair system, including liver container, and liver container includes body and upper lid, and both can seal
Cover tightly, the soft net of silica gel is fixed with liver vessel, liver vessel lower end offers blood back passage, blood back passage warp
Storage blood tank is connected with centrifugal pump, and storage blood tank front end is provided with filter membrane, and the port of export of centrifugal pump is connected with oxygenator, and oxygenator connects control
Oxygen device, the transducer potector of oxygenator is divided into two-way through heat exchanger, irrigates arteria hepatica through roller pump all the way, another road is directly filled
Portal vein is noted, arteria hepatica, portal vein pipeline are provided with ultrasonic flowmeter to be connected to pressure sensing before recording flow, two-way enter liver
Device is used to measure arteria hepatica and portal venous pressure, enters hepatic arterial logical provided with blood sample collection before roller pump is entered all the way
Road.
The fixed soft net of silica gel, plays a part of flexibly support liver, it is to avoid liver on liver vessel of the present invention
Compressive deformation；Liver vessel lower end offers blood back passage, is easy to collect a small amount of oozing of blood around Hilar；Container transparent
Upper lid and body are closely connected, it is to avoid the forfeiture of temperature in filling process.
The present invention provides total output using centrifugal pump, and roller pump provides arteria hepatica pulsed blood flow, quickly and accurately adjusted
Arteria hepatica and portal venous flow and pressure.The present invention by the portal vein of enter liver, arteria hepatica and go out liver infrahepatic vena cava take over
To perfusion, adjustment centrifugal pump and roller bearing revolution speed is started after success, until stable circulation, whole operation was completed in 1 minute,
Previous experiments and OrganOx scheme comparisons, set up the easy to operate of the circulatory system, stable, and the time is greatly shortened.
The present invention easily can adjust irrigation flow according to injection pressure, can be by arteria hepatica and portal vein Flow-rate adjustment essence
± 1ml is really arrived, the portal vein and arteria hepatica flow-rate ratio under liver physiology state is reached（3:1）.And in following Continuous Perfusion
During, operator only needs to be changed according to injection pressure per hour, appropriate regulation roller pump and centrifugation revolution speed, i.e., adjust pressure
Save physiological level.
Arteria hepatica act as pulsatile flow through roller pump in the present invention, and the hepatic arterial filling of liver under physiology is simulated well
Note feature, the protection during being more beneficial for irrigating to bile duct cell.
The blood back of vena hepatica is connected in storage blood tank in the present invention, has filter, adsorbable filling process in storage blood tank
Cell fragment, microthrombus and the impurity of middle generation, are effectively ensured the pure of blood circulation.What the setting of storage blood tank was also avoided completely
Circulate air inlet, after tested, the experiment of 20 people's liver perfusions of early stage and 16 pork livers perfusion experiments, do not find circulation air inlet cause from
Heart pump stops situation.Medicine, cell and gene therapy can be directly added into storage blood tank, fully mixed with circulation fluid in storage blood tank
Close, it is to avoid drug dose is excessive caused by circulation fluid is directly entered hepatic circulatory system.
Infusion pump is connected with storage blood tank, and nutrient energy is provided for liver by infusion pump, such as injects Fat Emulsion, amino
Acid, trace element, B B-complex, electrolyte；Colloid osmotic pressure injection albumin is improved for liver；To control the blood glucose of liver
And infusing insulin；Alprostadil is injected in microcirculation for improvement liver；Bear is injected to promote liver to carry out choleresis
Deoxycholic aicd；Heparin etc. is injected for anti-freezing.Meanwhile, corresponding medicine is injected by infusion pump, moreover it is possible to provide and repair for liver
Multiple mescenchymal stem cell and gene therapy is carried out to liver.
The liver normal temperature perfusion repair system of the present invention, is to maintain the aerobic metabolism under liver cell normal temperature pre- there is provided medicine
The preferable carrier of processing, by the repairing and treating of short time, is expected to reverse Marginal donor liver, expands for liver source.
Brief description of the drawings
Fig. 1 irrigates the structural representation of system for the liver normal temperature of OrganOx companies.
Fig. 2 irrigates the structural representation of system for the liver normal temperature of the present invention.
Fig. 3 is arteria hepatica during testing（HA）, portal vein（PV）Pressure measxurement figure.
Fig. 4 is arteria hepatica during testing（HA）, portal vein（PV）Flow measurement figure.
Fig. 5 is the osmotic pressure of circulation fluid during testing and partial pressure of oxygen measurement figure.
The measurement figure of pH value during Fig. 6 is experiment.
The measurement figure of urea nitrogen, bile and blood glucose during Fig. 7 is experiment.
Fig. 8 is glutamic-pyruvic transaminase during testing（ALT）, glutamic-oxalacetic transaminease（AST）Measurement figure.
Marked in figure：1 liver, 2 bile, 3 centrifugal pumps, 4 liver sound flow pressure detectors, 5 heat exchangers, 6 control oxygen
Device, 7 oxygenators, 8 transfusion bags, 9 infusion pumps, 10 portal vein flow pressure detectors, 11 storage blood tanks, 12 roller pumps, 31 livers move
Pulse pressure broken line, 32 portal venous pressure broken lines, 41 arteria hepatica flow broken lines, 42 portal vein flow broken lines, 51 osmotic pressure broken lines, 52
Partial pressure of oxygen broken line, 61 be PH broken lines, 71 urea nitrogen measurement broken lines, 72 bile measurement broken line, 73 blood glucose measurement broken lines, 81 third turn of paddy
Ammonia enzyme（ALT）Survey broken line, 82 glutamic-oxalacetic transamineases（AST）Survey broken line.
Embodiment
Referring to the drawings, donor liver 1 is padded on the soft net of silica gel, the soft net of silica gel is fixed on the side of liver vessel
Edge, liver superior and inferior vena cava ligation, liver inferior vena cava cannula, vena hepatica blood can be flowed directly into unobstructed inflow cannulation of venae cava
Blood tank 11 is stored up, a small amount of Hilar oozing of blood flows into storage blood tank by the blood back passage of liver container lower end.Store up in blood tank provided with filtering
Film is with impurity such as the cell fragment in filtering blood, microthrombus.Infusion pump 9 with storage blood tank be connected, for liver circulation provide nutrition with
Drug cell is treated.Storage blood tank is connected with centrifugal pump 3, and centrifugal pump is responsible for total hemodynamic output.The blood of centrifugal pump output
Blood is delivered to oxygenator 7 through centrifugation pumping action, oxygenator connects control oxygen device 6, control oxygen device connection air pump and pure oxygen steel
Bottle, gives circulation and is best suitable for physiological air oxygen ratio.Hemoglobin is oxygen carrying, blood temperature of the heat exchanger 5 by oxygen with after
Degree is adjusted to 37 degree of Human Physiology temperature.Then blood flow is divided into two, and irrigates arteria hepatica through roller pump 12 all the way, and another road is direct
Portal vein is irrigated, wherein roller pump gives liver pulsed pulsation blood flow, can adjust the rotating speed of roller pump to change arteria hepatica
Flow.The flow that outlet of centrifugal pump is shown is total flow, and arteria hepatica and portal vein pipeline are equipped with the use of ultrasonic flowmeter 4,10
In recording the bloody path flow, while provided with determination of pressure sensor arteria hepatica and pylic pressure, temperature measuring probe connection
The temperature interface of oxygenator, for adjusting the temperature of heat exchanger to adjust blood heat.Arteria hepatica, which enters, is provided with blood before roller pump
Liquid sample collection channel.
On September 17th, 2015, deceased donor of coring contributes one, liver.Donor male, height 178cm, body weight 82Kg,
During institute history or CPR history are used without pressor agent.During acquisition liver, Liver warm ischemia time 17 minutes, during cooling jet flow
Between 24 minutes 8 hours.Donor liver quality 2200g, preoperative confession liver pathological examination prompting：Liver severe fatty liver, the denaturation of 50% bulla.
Standard, non-row transfer operation are used because liver mass is less than.This liver is satisfied after donor family members agreement is obtained, row human liver's normal temperature
Perfusion experiment.
Experimental system is that liver normal temperature of the present invention irrigates repair system, and perfusion liquid is the O-shaped red blood cell 600ml+500ml of allosome
Ten thousand river in Shangdong Province+1000ml Ringer's solutions.Medicine is supported to be shown in Table 1.After system debug is stable, 35 separate when being poured into September in 2015 18 days 0
Begin.Every 1 hour extraction perfusion liquid after beginning, detection temperature, vim and vigour, electrolyte, blood glucose, metabolic waste, liver function, osmotic pressure,
And record arteria hepatica and pylic flow and pressure value.Tested in the 6th hour（35 points during September in 2015 18 days 6）Terminate, it is real
System operating is stable during testing.
Liver temperature, vim and vigour, vascular flow pressure are in physiological range during experiment；Persistently there is choleresis, blood glucose, pH
Remain stable, transaminase values open level after blood flow for liver with liver transfer operation fat and are consistent.
As shown in figure 3, arteria hepatica during experiment（HA）, portal vein（PV）Observed pressure figure, show enter liver vascular pressure
Basicly stable physiological level is in during testing.
As shown in figure 4, arteria hepatica during experiment（HA）, portal vein（PV）Measured discharge figure, show enter liver vascular flow
Measure during experiment in the fluctuation of normal physiologic levels scope.
As shown in figure 5, the osmotic pressure of circulation fluid and the measured drawing of partial pressure of oxygen are shown during experiment, and during testing, perfusion
Hydraulic control system is in physiological level upper range；Empty oxygen mixer controls partial pressure of oxygen in 200mmHg or so, it is to avoid because pure oxygen was produced
Biology side effect caused by high partial pressure of oxygen.
As shown in fig. 6, experiment during pH value actual measurement figure.After experiment starts, perfusion liquid acid poisoning substantially, gives carbon
Sour hydrogen sodium corrects acid poisoning, and gives the improvement liver organization aerobic metabolism such as oxygen, and pH value is moved closer to and is stably maintained at just
Normal physiological level.
As shown in fig. 7, experiment during urea nitrogen, bile and blood glucose measured drawing.During experiment, blood sugar level gradually under
Drop, points out liver glycogen transformation function to exist；Amount of Bile gradually increases, and reflection liver synthesis secretion function is present；Urea nitrogen by
Gradually accumulate, point out liver metabolism function to exist.During figure reflection experiment, liver remains the important life played in human body
Change acts on and maintains ideal level.
As shown in figure 8, glutamic-pyruvic transaminase during experiment（ALT）, glutamic-oxalacetic transaminease（AST）Measured drawing.During testing,
ALT and AST remained stables, reflection liver cell is after ischemical reperfusion injury, without bright in the case of artificial
Aobvious secondary necrosis, hepatocyte function and form keep normal.
Tested by the present embodiment, in vitro liver is during normal temperature perfusion in 6 hours, and liver cell is bad without a large amount of Secondary cases
Extremely, liver synthesis, metabolic function keep good, and overall in vitro survival condition is good, and function starts to recover.
Claims (1)
1. liver normal temperature irrigates repair system, it is characterised in that：
Including liver container, liver container includes body and upper lid, and both can seal and cover tightly, fixed on liver vessel
There is the soft net of silica gel, liver vessel lower end offers blood back passage, and blood back passage is connected through storing up blood tank with centrifugal pump, stores up blood tank
Front end is provided with filter membrane, and infusion pump is connected with storage blood tank, and the port of export of centrifugal pump is connected with oxygenator, and oxygenator connects control oxygen dress
Put, the transducer potector of oxygenator is divided into two-way through heat exchanger, irrigate arteria hepatica through roller pump all the way, another road directly irrigates door
Vein, arteria hepatica, portal vein pipeline are connected to pressure sensor use provided with ultrasonic flowmeter to record before flow, two-way enter liver
In measurement arteria hepatica and portal venous pressure, enter hepatic arterial all the way before roller pump is entered provided with blood sample collection passage.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201510941335.8A CN105379707B (en) | 2015-12-16 | 2015-12-16 | Liver normal temperature irrigates repair system |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510941335.8A CN105379707B (en) | 2015-12-16 | 2015-12-16 | Liver normal temperature irrigates repair system |
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| CN105379707A CN105379707A (en) | 2016-03-09 |
| CN105379707B true CN105379707B (en) | 2017-10-17 |
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| ES2842435T3 (en) | 2016-07-22 | 2021-07-14 | Eth Zuerich | Perfusion circuit set for ex vivo perfusion of the liver |
| CN107114358B (en) * | 2017-06-14 | 2018-05-15 | 广州军区广州总医院 | liver machine perfusion control system, method and device |
| CN109260571A (en) * | 2018-08-03 | 2019-01-25 | 苏州悬丝诊脉医疗科技有限公司 | Renal blood vessels connector based on air cushion |
| CN109221087A (en) * | 2018-09-30 | 2019-01-18 | 南京国科医工科技发展有限公司 | In vitro liver room temperature oxygen carrying machine perfusion system and method for filling |
| CN112006016A (en) * | 2019-05-31 | 2020-12-01 | 西安赛德欧医疗研究院有限公司 | Normal temperature oxygenation perfusion apparatus |
| CN110199986A (en) * | 2019-06-14 | 2019-09-06 | 吉林大学第一医院 | Lung transplantation lungs save set |
| WO2021036738A1 (en) * | 2019-08-26 | 2021-03-04 | 广东顺德工业设计研究院(广东顺德创新设计研究院) | Ex vivo organ perfusion container |
| CN111248869B (en) * | 2020-03-09 | 2022-11-25 | 中国人民解放军南部战区总医院 | In-vitro liver function detection method and system |
| CN111165471A (en) * | 2020-03-23 | 2020-05-19 | 郑州大学第一附属医院 | Normal temperature low pressure normal oxygen liver perfusion system |
| CN112604048B (en) * | 2020-12-04 | 2021-09-17 | 广东乾晖生物科技有限公司 | Special pipeline for total-liver type bioartificial liver support system |
| CN112772632A (en) * | 2020-12-31 | 2021-05-11 | 重庆北部宽仁医院 | Isolated liver perfusion device |
| CN112772636A (en) * | 2021-01-18 | 2021-05-11 | 吉林大学第一医院 | Mechanical perfusion liver container |
| CN113142192B (en) * | 2021-05-19 | 2024-05-17 | 北京盖兰德生物科技有限公司 | Isolated liver perfusion activity maintaining device and use method thereof |
| CN113498775A (en) * | 2021-06-11 | 2021-10-15 | 首都医科大学宣武医院 | Variable temperature isolated organ mechanical perfusion system |
| CN115120799B (en) * | 2022-06-08 | 2023-05-02 | 中山大学附属第一医院 | Liver rescuing system |
| CN116235846B (en) * | 2023-02-27 | 2024-01-30 | 中国科学院苏州生物医学工程技术研究所 | Organ perfusion control method, system and device |
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