CN101322861A - Transplanted organ in vitro preservation and vigor monitoring device as well as method - Google Patents
Transplanted organ in vitro preservation and vigor monitoring device as well as method Download PDFInfo
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- CN101322861A CN101322861A CNA2007100180413A CN200710018041A CN101322861A CN 101322861 A CN101322861 A CN 101322861A CN A2007100180413 A CNA2007100180413 A CN A2007100180413A CN 200710018041 A CN200710018041 A CN 200710018041A CN 101322861 A CN101322861 A CN 101322861A
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Abstract
The invention discloses a device for storing transplanted organs in vitro and monitoring the livingness and a method thereof. The device and the method of the invention provide metabolism maintaining the transplanted organs for the transplanted organs in vitro to realize the multicriteria, atraumatic and real-time monitoring of the livingness of the organs, automatically adjust or prompt to manually adjust and improve the storage process of organ bodies, and improve the storage effect of the organ bodies; by analyzing and calculating monitoring data of the organs, the device provides data relating to the tumefaction change of the organs, unblocks condition of vascellums, survival condition of organ cells, completely and comprehensively reports the overall condition of the livingness of the transplanted organs, thus the safety of organ transplantation can be improved and selection range of the transplanted organs is extended.
Description
Background technology
Along with surgical operation, immunosuppressive drug, organ and cell separation are preserved developing rapidly of technology and transplantation immunology basis, organ transplantation has become effective, irreplaceable, the treatment means routinely of treatment organ disease in whole latter stage, now become a new branch of science of medical domain, obtained great successes and huge progress.Just because of this, an incident problem also more shows outstanding: the organ donor source is not enough.Organ donor is in great shortage on the one hand, and many patients die in the wait of despair; But wasting surprising, effective and huge organ resource on the other hand can not be fully used.The wasting reason of organ resource is a lot, but lacks effective organ In vitro culture preservation technology, can't judge simply effectively that organ vitality also is one of wasting major reason, and many available organ resources are not utilized.
Preserving transplant organ safely and effectively is to transplant successful prerequisite, create low temperature from scholars such as Belzer in 1967 and continue the extensive use of perfusion (United States Patent (USP) 3632473) to UW liquid, Organ Preservation has had very big development from the rationale to the clinical practice.The meaning that organ is preserved is to guarantee to utilize to the full extent organ, prolongs to preserve the time limit and meet clinical needs, as preparing before organ transportation, tissue matching, the art etc.; Guarantee that the transplant organ postoperative function recovers immediately, reduces the incidence rate that graft function postpones (DGF) and no function (PNF); Guarantee the long-term surviving of transplant organ.DGF is the puzzled doctor's of transplanting a problem, organ generation postoperative do not have function (PNF) and postoperative function not complete (IPF) not only need to remigrate immediately and threat patient life security.The DGF incidence rate is relevant with many factors, and as donor age, nutritional status, the cause of death, preservation process etc., DGF incidence rate and store method, to preserve the liquid type relevant, and prolongs and increase with preserving the time limit.
Mainly guarantee to preserve the vigor of organ when preserving organ clinically at present with the setting organ safe storage time limit, because organ vitality may change in the preservation process, and lack the real-time vigor monitoring technology of the external noinvasive of effective organ, therefore has certain risk according to the safe storage time limit, DGF, PNF, IPF etc. take place easily, and this setting simultaneously also is unfavorable for needing because of various reasons to preserve by effective preservation technology the utilization of the organ of longer time.
The vigor of organ is a key factor that influences the organ transplantation success rate, and the surge of not having heart beating donor number in recent years makes the preceding vigor of understanding organ of art more show important, causes various complication to avoid transplanting non-functional organ.Prior art still do not have a kind of can be between the organ storage life noinvasive monitor, can provide accurately the technology of reflection transplant organ overall activity comprehensively in real time.Existing organ vitality detection method has: biopsy, fluorescent technique monitoring NADH (nicotinamide adenine dinucleotide reduced), organ resistance, pO
2, pC O
2, pH, LDH etc., wherein biopsy is the main method of sense organ vigor, but because of it has wound, can not monitor, represent local circumstance in real time, application is restricted, additive method is many because of variable, describes the local circumstance of organ, thereby lacks clear diagnostic value.The organ resistance (also is called the organ Peripheral resistance, equal pressure/flow) with the unobstructed blood vessel situation dependency is arranged, under the normal condition during organ size variation, variation because of its required amount of blood supply, its organ Peripheral resistance also can change, and may there be bigger variation in the organ size, so the organ resistance lacks comparability between the organ.
The organ store method has at present: simple hypothermia perfusion is preserved, profound hypothermia is preserved, continuous hypothermical perfu sion is preserved, the room temperature perfusion is preserved.
Though this method is simple and convenient, there are two aspect distinct disadvantage in the present clinical simple hypothermia perfusion preservation organ that still generally adopts:
1. because be once to pour into, the harmful substance that body produces can not be got rid of, and because IFV＞tissue fluid capacity＞blood volume in the organ, the concentration that preservation liquid once pours into some composition of back will reduce because of spreading and diluting, and can't accomplish the end in view;
Though 2. low temperature can reduce the activity of enzyme greatly, intracellular enzymatic activity does not stop, i.e. metabolism does not reach complete halted state, and cold anoxia is along with time lengthening still can increase the weight of cell injury, especially for hot anoxybiotic organ is more obvious.By the existing described low temperature accretion rate of document, with 4 degrees centigrade of organ accretion rates is that 1/12 of normal body temperature is calculated, the accumulation metabolism amount of 4 degrees centigrade of organs preservations in 12 hours is equivalent to the metabolism amount of 1 hour hot ischemia of normal body temperature, though can not directly be equal to, but also be equivalent to prolong warm ischemia time, so its damage to organ is unavoidable.
Profound hypothermia organ preservation method is preserved in the liquid because of low excessively temperature (＜0 ℃) ice crystal will occur, be unfavorable for the organ preservation, so profound hypothermia only limit to preserve isolated cells, cell suspension.
Continue perfused organ's preservation method and constantly supply with essential nutrition of metabolism and oxygen, and remove the refuse that metabolism produces, more simple cold preservation more meets physiological situation, organ resistance, pO when some technology provides perfusion
2, pC O
2, monitorings such as pH, LDH are used for vigor and judge, but the information changing factor that provides is many, diagnostic value is low.
The external preservation technology of ideal organ should be able to realize: 1. holding time long enough, set up the donor organ storehouse to satisfy clinical growing needs; 2. can understand the vigor of organ at any time, in time non-functional organ is treated and abandoned to impaired organ; 3. can carry out antigen between the organ storage life and modify, to alleviate the immunological rejection after the transplanting.
Regrettably prior art still can't reach the external preservation state of ideal organ, the existing external preservation technology holding time of organ is limited, the external vigor monitoring technology of organ deficiency not only threatens patient's safety, and has influenced the improvement and the development of organ In vitro culture preservation technology.Do not have the support of effective organ In vitro culture preservation technology, treat the basis that just lacks research and implement with epidemic prevention rejection etc. between the organ storage life.
Summary of the invention
In order to remedy the deficiency in the existing external preservation technology of transplant organ, improve the external vigor monitoring technology of transplant organ, the invention provides the external preservation of a kind of transplant organ and vigor monitoring device and method.
The invention provides a kind of device by the transplant organ external counterpulsation being kept the metabolism of transplant organ, realize that simultaneously many indexs of organ vitality noinvasive monitors in real time, automatically or the prompting manual adjustment, improve the preservation process; The present invention is according to the characteristics of the external preservation of transplant organ, design the organ vitality monitoring method and the index that adapt with it, swelling situation of change, the unobstructed blood vessel situation of organ, the data of organ cell's survival condition aspect, concentrated expression transplant organ overall activity situation comprehensively are provided.Technical scheme provided by the invention is specific as follows:
1, external preservation of a kind of transplant organ and noinvasive are monitored the device of organ vitality in real time, basic composition is: be placed between the organ storage life on the weight meter, the angioaccess of organ and outlet are connected to sensor cluster by pipeline respectively, sensor cluster is useful on two ports that infusion liquid is come in and gone out, sensor cluster is used to detect the pressure and the oxygen content of infusion liquid at least, the another port that is positioned at the sensor cluster of organ angioaccess links to each other with the infusion liquid outlet of perfusion equipment by pipeline, the another port that is positioned at the sensor cluster of organ blood vessel outlet links to each other with the infusion liquid inlet of perfusion equipment by pipeline, infusion liquid in this loop to organ perfusion.
In infusion liquid perfusion loop, at least one place temperature and pH pick off can be arranged, be included in the sensor cluster, also can match pick offs such as carbon dioxide, glucose, ion, so that more monitoring informations to be provided.Can seal in filter in the perfusion loop and be used for the possible big material of filtering.
Perfusion equipment realize infusion liquid storage, oxygenate, perfusion power and control irrigation flow and pressure are provided, various ways can be arranged, perfusion equipment can be made up or is composed in series by pipeline at least by reservoir, oxygenator, liquor pump, the another port of reservoir is perfusion equipment infusion liquid inlet, and the liquor pump liquid outlet is the outlet of perfusion equipment infusion liquid.According to the organ difference, organ can have 1 to 2 angioaccess, when organ during for liver perfusion equipment have two liquor pumps to provide infusion liquid for organ, shown in figure two.Perfusion equipment also can be made up of at least one liquor pump, the tremulous pulse of accepting the organ grafter by pipeline and preparation links to each other with vein blood vessel, this person's arterial blood is filled into the external organ of preparing transplanting, blood returns this person's vein blood vessel again, carry out the monitoring of organ extracorporeal circulation test and organ vitality, test the reaction after the organ transplantation in advance, avoid the invalid transplanting that causes because of hyperacute rejection etc.
The control of organ storage temperature can be used the oxygenator that has heat exchange or adopt mode such as pipeline heat exchanger, and preferable mode is that organ and perfusion closed circuit part all can be placed in the calorstat, but not only constant temperature but also can increase protective action to organ.
The work process of whole device, irrigation flow and date processing can be controlled by a controller, provide the user to operate and the information demonstration by an operation interface plate.
2, the monitoring scheme of organ swelling situation of change:
Swelling or dehydration easily take place in organ in external preservation process, prevent that organ swelling or dehydration from being one of main purpose of the external preservation of organ.Organ weight's variation mainly is because cell and tissue water content variation cause between the short-term storage life.The present invention is when organ is preserved in perfusion, and the operating weight meter is monitored the organ weight change in real time, measuring and calculating organ swelling rate of change reflection organ swelling situation of change, and according to organ swelling rate of change adjustment infusion liquid composition and osmotic pressure.Organ swelling rate of change computing formula is:
k＝m/m
1×100％
K represents organ swelling rate of change, and m represents the organ weight that monitors between storage life, m
1The original weight of expression organ;
Organ swelling rate of change promptly can be used as the foundation of adjusting infusion liquid concentration between storage life, can be used for analyzing the quality of preserving the back organ again.Organ swelling changes and will exert an influence to calculating organic unit's oxygen metabolism speed, and this index also is used for organ cell's relative survival rate is revised.
3. organ unobstructed blood vessel condition monitoring scheme:
Organ resistance (organ Peripheral resistance) R
vIt is the quantitative target of reflection blood vessel microcirculation degree of mobility.
It is defined as: R
v=P
m/ Q
m
P
mAnd Q
mRepresent average pressure and average discharge respectively.
Under the normal condition during organ size variation, variation because of its required amount of blood supply, its organ resistance also can change, and may there be bigger variation in the organ size, in order to overcome the deficiency that the organ resistance changes with the organ size, the present invention can overcome the influence of organ size by the method for measuring and calculating unit (weight) organ resistance, better reflects organ blood vessel microcirculation degree of mobility, realizes the comparability between the organ.The organ resistance is the resistance of many microcirculatory vascular parallel connections, so unit organ resistance equals the organ resistance and multiply by the organ weight.
For the ease of understanding, the present invention adopts measurement unit's weight organ unobstructed blood vessel degree (hereinafter to be referred as unit unobstructed blood vessel degree, the inverse of the unit's of equaling organ resistance) method reflection blood vessel microcirculation degree of mobility, its method is: with a kind of infusion liquid perfused organ at a certain temperature, keep the survival and the metabolism of organ, the pressure of the angioaccess infusion liquid by monitoring organ respectively, the pressure and the irrigation flow of blood vessel outlet infusion liquid, the organ weight, measuring and calculating unit (weight) unobstructed blood vessel degree, reflection organ blood vessel microcirculation degree of mobility, organic unit's unobstructed blood vessel degree computing formula is:
C＝Q
m/(P
m1-P
m2)/m
C representation unit unobstructed blood vessel degree, Q
mThe expression flow, P
M1Expression angioaccess pressure, P
M2Expression blood vessel outlet pressure, m represents the organ weight.
Use for the ease of the user, the normal phase of user's input test in advance can calculate the unimpeded relatively rate of blood vessel with the unit unobstructed blood vessel degree of organ-tissue under identical component infusion liquid and uniform temp condition, and its computing formula is:
N
b＝C/C
1×100％
N
bThe unimpeded relatively rate of expression blood vessel, C represents tested organic unit's unobstructed blood vessel degree, C
1The normal phase of expression test in advance is with the unit unobstructed blood vessel degree of organ-tissue under identical component infusion liquid and uniform temp condition.
The unimpeded relatively rate of blood vessel has certain normal variation scope because of the difference of blood vessel.Cell generation swelling compressing blood capillary, vascular endothelial cell swelling, blood capillary obstruction or organ lesion all can cause the relative unimpeded rate of blood vessel to descend with vasoconstriction.
Organ for two angioaccesses of liver: the arteries inlet pours into by the fixed proportion near human body with the infusion liquid flow or the pressure of portal vein tube inlet, calculate tremulous pulse unit's unobstructed blood vessel degree and portal vein unit's unobstructed blood vessel degree respectively, calculate the relative unimpeded rate of the unimpeded relatively rate of arteries then respectively with the portal vein blood vessel.
4. the cell survival condition monitoring scheme of organ:
The present invention is by the oxygen metabolism speed reflection of organ under the monitoring certain condition and calculating organ cell's survival condition.Its principle is: the intracellular plastochondria is that mitochondrial function is impaired will to cause cell generation irreversible damage, cause cell death to one of the most responsive organelle of various damages; The essence of cellular metabolism is a kind of biochemical reaction under the enzyme effect, and the metabolism of oxygen is to finish in mitochondrion in the cell, and by the synthetic ATP (adenosine triphosphate) of mitochondrion oxygen consumed, mitochondrial dysfunction will influence oxygen metabolism; The intracellular ATP circulation under the aerobic situation of the living cells of tranquillization will tend towards stability, and cell oxygen metabolism speed also tends towards stability, and the oxygen consumption of dead cell is very little; Other factors that influence oxygen metabolism speed (cellular metabolism speed) also have a lot, the present invention is by analyzing, limit and unified various influence factors, make in the organ the mitochondrial function of the survival of cell and oxygen metabolism speed set up constant corresponding relation under certain condition, promptly the oxygen metabolism speed of organ is relevant with the cell ATP synthesis capability with cell survival quantity in the organ under uniform temperature and infusion liquid situation, reflection organ cell's survival condition.
The closed cycle of organ-tissue provides convenience for measuring the oxygen metabolism amount, by containing oxygen infusion liquid perfused organ at a certain temperature with a kind of, keep the survival and the metabolism of organ, monitor the oxygen content of the angioaccess infusion liquid of organ, the oxygen content and the irrigation flow of blood vessel outlet infusion liquid simultaneously respectively, organ oxygen metabolism speed can be calculated, the cell survival and the change conditions thereof of organ can be reflected by monitoring oxygen metabolism speed.
The oxygen metabolism speed calculation formula of organ is as follows,
Organ oxygen metabolism speed (V when organ has an angioaccess
o) computing formula be:
V
o＝(D
o1-D
o2)×Q
D
O1Expression organ angioaccess infusion liquid oxygen content, D
O2Expression organ blood vessel outlet infusion liquid oxygen content, Q represents the flow of organ vascular perfusion liquid.
When organ is liver organ oxygen metabolism speed (V when two angioaccesses are arranged
o) computing formula be:
V
o＝(D
o1-D
o2)×Q
1+(D
o3-D
o2)×Q
2，
Work as D
O3=D
O1The time formula be: V
o=(D
O1-D
O2) * (Q
1+ Q
2)
D
O1Expression arteries inlet infusion liquid oxygen content, D
O2Expression vein blood vessel outlet infusion liquid oxygen content, D
O3Expression portal vein tube inlet infusion liquid oxygen content, Q
1Expression arteries inlet infusion liquid flow, Q
2Expression portal vein tube inlet infusion liquid flow.
Preserving the incipient cell survival condition with organ is reference, by monitoring organ oxygen metabolism speed, can calculate organ self cell relative survival rate between the organ storage life, and the measure formula of organ self cell relative survival rate is:
N＝V
o/V
o1×100％
N represents organ self cell relative survival rate, V
oThe organ oxygen metabolism speed of monitoring between the expression storage life, V
O1The expression organ is preserved the oxygen metabolism speed behind the initial stage metabolic stability, V
oAnd V
O1It is the measuring and calculating value under identical component infusion liquid and uniform temp condition.
In order to have comparability between the homolog tissue that makes different sizes, the present invention adopts the measurement organ weight to calculate organic unit's (weight) oxygen metabolism speed, and organic unit's oxygen metabolism speed measure formula is:
V
u＝V
o/m
V
uExpression organic unit oxygen metabolism speed, V
oExpression organ oxygen metabolism speed, m represents the organ weight.
By measuring and calculating organic unit's oxygen metabolism speed and with the normal phase of test in advance with (equal conditions is meant and uses uniform temp and identical component infusion liquid under the organ-tissue equal conditions, unit oxygen metabolism velocity ratio down together), can calculate cell relative survival rate in the organ-tissue, (principle of measuring enzyme concentration in the serum with employing relative quantification method is identical), its formula is:
N＝V
u/V
u1×100％
N represents organ cell's relative survival rate, V
uRepresent tested organic unit's oxygen metabolism speed, V
U1The normal phase of expression test in advance is with the unit oxygen metabolism speed of organ-tissue under use uniform temp and identical component infusion liquid condition.
The organic death cell still has a spot of oxygen consumption, and the organ change of moisture content all can influence the precision of the organ cell's relative survival rate of surveying, and improves precision for getting rid of its influence, can calculate correction to survey organ cell relative survival rate, and correction formula is:
N
c＝[1-(1-kN)/(1-n)]×100％
N
cRepresent revised organ cell's relative survival rate; N represents organ cell's relative survival rate of measuring and calculating in claim 2 or 4; N represents the ratio of the oxygen metabolism speed of dead organ cell's under the same conditions averaged oxygen depletion rate and normal organ cell, and this value records in advance by other tests; K represents organ change of moisture content rate, organ change of moisture content rate reflects that mainly organ swelling causes the aqueous rate of change of organ, equal to change the back organ weight than original organ weight, human body difference causes that the rate of change accessible region of organ water content divides the sex of donor, age to be added up consideration.
It is as follows to get rid of the various methods that influence the oxygen metabolism factor:
1. get rid of the influence of organ weight change: organ varies in size, total oxygen metabolism speed difference of whole organ then, after measuring whole organ oxygen metabolism speed, divided by the organ weight unit of obtaining (weight) oxygen metabolism speed, this index has been got rid of the influence of organ weight's change, makes the data between the homolog have comparability;
2. get rid of temperature and infusion liquid composition influence: use uniform temp and the monitoring of identical component infusion liquid by normal organ tissue, get rid of the influence of its change with reference; These factors are artificial controlled condition in the external preservation of organ, can in use progressively optimize unification;
3. get rid of intracellular matter and influence oxygen metabolism speed: by the infusion liquid composition with get rid of its influence stabilization time.Infusion liquid should contain keeps cellular metabolism and synthetic ATP desired substance, keeps intracellular matter and metabolic stability; The ATP circulation products has regulating and controlling effect to the ATP aggregate velocity in the cell, influence oxygen metabolism speed, organ carries out after external anoxia in the aerobic perfusion preservation again, oxygen metabolism speed is very high during beginning, (the different temperatures asynchronism(-nization) through after a while, temperature reduces time lengthening) aerobic perfusion preservation, the ATP circulation will tend towards stability in the cell, and cell oxygen metabolism speed also tends towards stability.Living cells ATP generation will equate with the cell consumption amount under the ideal preservation condition.
4. get rid of organ swelling influence: prevent that organ swelling from being one of target of preservation technology, by being fit to the infusion liquid perfusion of composition and osmotic pressure, the organ that swelling has taken place can recover, and can reduce its influence, and can pass through organ swelling rate of change Monitoring Data, analyze and revise its influence.
5. pathological changes such as organ cell's fatization can the unit's of making oxygen metabolism speed diminish, and organ cell's relative survival rate of monitoring this moment still has the unusual effect of prompting, can determine whether organ is available by biopsy for the abnormal conditions doctor.
When infusion liquid is used the carrier of oxygen,,, can calculate corresponding oxygen content as content of hemoglobin by input carrier of oxygen data.
5. the scheme of arbitrary temp monitoring organ vitality in infusion liquid allowable temperature scope:
Calculating organ cell's relative survival rate or organ blood vessel relatively during unimpeded rate, need normal organ tissue at the unit oxygen metabolism speed or the unit unobstructed blood vessel degree that use under uniform temp and the identical component infusion liquid condition, by data base or the mathematical model of setting up normal organ tissue in advance, the unit oxygen metabolism speed or the unit unobstructed blood vessel degree of normal organ tissue different temperatures in various infusion liquid storage temperature ranges are provided, can in every kind of infusion liquid allowable temperature scope, monitor organ by arbitrary temp, provide organ cell's relative survival rate relative unimpeded rate with the organ blood vessel, need not strictly control storage temperature, be easy to use, reduction is to the requirement of thermostat.
The data base of normal organ tissue or mathematical model can be set up according to statistical data or The Arrhenius Equation (the Arrhenius equation claims the reaction rate exponential law again).
Beneficial effect of the present invention:
1. the present invention can improve the transplant organ preservation effect:
The present invention can make external transplant organ recover from the reversibility anoxia-induced apoptosis, long duration keeps normal function, fully guarantees the quality of transplant organ, monitors in real time by the not damaged organ vitality, improve the preservation process, and can in time carry out the correspondence treatment impaired organ; The present invention can be the patient and preceding competent time of operation is provided and selects best tissue matching, and temporary transient no organ can effectively be preserved, and promotes to stride hospital, trans-regional organ resource provisioning.
2. the present invention can improve the safety of organ transplantation:
The surge of not having heart beating donor number in recent years makes the preceding vigor of understanding organ of art more show important, the organ vitality aspect data of the present invention's monitoring, concentrated expression transplant organ overall activity situation comprehensively, have noinvasive, in real time, convenient, characteristics that accuracy is high, can understand the vigor of organ at any time, abandon non-functional organ, avoid transplanting non-functional organ and cause various complication; The present invention measures the cell survival situation that organ ATP complex functionality comes dynamic reflection organ integral body by oxygen metabolism, and to the pathological changes and the abnormal response sensitivity of organ, its effect is better than existing organ vitality detection technique; The present invention can be easily before organ transplantation with accept the organ grafter and carry out the test of organ extracorporeal circulation of blood, test the reaction after the organ transplantation in advance, avoid the invalid transplanting that causes because of hyperacute rejection etc.
3. the present invention can enlarge transplant organ and selects scope, helps to reduce the organ wasting of resources, enlarges organ origin, for more people provide the therapy apparatus meeting.
4. the present invention can promote the development of organ transplantation correlation technique:
Organ In vitro culture preservation technology still has the space of developing on a large scale very much, if when the research organ culture preserves technology, use the present invention, can understand in real time by monitoring and cultivate preservation effect, can monitor easily and cultivate continuous change procedure and maximum duration and effect in the preservation, reduce the animal organ and transplant quantity, alleviate the influence that result of the test is produced because of animal individual difference, also can use the present invention links to each other with the experimental animal blood vessel, adopting the test of organ extracorporeal circulation of blood to substitute the part animal organ transplants, the variation of observation in vitro organ, research organ In vitro culture preservation technology is become easily, thereby promote the organ culture to preserve the improvement of technology, the realization of development and desirable preservation technology; The present invention can be before the organ transplantation immunizing antigen modification etc. research platform is provided.
Description of drawings
The present invention is further described below in conjunction with drawings and Examples.
Fig. 1 implements sketch map for the device of preserving and monitor the organ that an angioaccess is arranged according to the present invention
Fig. 2 implements sketch map for the device of preserving and monitor the liver that two angioaccesses are arranged according to the present invention
Fig. 3 is a circuit block diagram of the present invention
In Fig. 1, Fig. 2: 1. organ, 2. poidometer, 3. sensor cluster, 4. sensor cluster, 5. perfusion equipment, 6. filter, 7. liquid storing bag, 8. oxygenator, 9. liquor pump, 10. calorstat, 11. liquor pump, 12. sensor clusters, 13. discharge liquor catchers, 14. pipelines.
The specific embodiment
Fig. 1 implements sketch map for the device of preserving and monitor the organ that an angioaccess is arranged according to the present invention, organ 1 is placed on the poidometer 2 in Fig. 1, the arteries of organ is connected to sensor cluster 3 by pipeline, the vein blood vessel of organ is connected to sensor cluster 4 by pipeline, sensor cluster 3,4 is used for detecting pressure, pH, temperature and the oxygen content of infusion liquid, sensor cluster 3 another port link to each other with the infusion liquid outlet of perfusion equipment 5 by pipeline, and sensor cluster 4 another port link to each other by the inlet of pipeline with perfusion equipment 5; Perfusion equipment 5 is composed in series by pipeline by liquid storing bag 7, oxygenator 8, filter 6, liquor pump 9, and the another port of liquid storing bag 7 is a perfusion equipment infusion liquid inlet, and liquor pump 9 liquid outlets are the outlet of perfusion equipment infusion liquid; Discharge liquor catcher 13 is used for liver and kidney is preserved, and links to each other with organ 1 by pipeline, is used to collect the discharge liquor of organ; The above part all is placed in the calorstat 10; The pressure detecting position of sensor cluster 3,4 should be at sustained height.Work process, irrigation flow and date processing are controlled by controller, having an operation interface plate to provide the user to operate with information shows, circuit block diagram as shown in Figure 3, controller is composed of control sequence, carry out data acquisition and work control, available microcontroller or industrial control board design can use liquid crystal touch screen as man machine operation interface.
Fig. 2 is that the device of preserving and monitor the liver that two angioaccesses are arranged is implemented sketch map, with Fig. 1 difference is to have increased portal vein perfusion inlet branch road, the liver portal vein links to each other with sensor cluster 12 by pipeline, sensor cluster 12 another port link to each other with liquor pump 11 liquid outlets by pipeline, and liquor pump 11 liquid inlets link to each other by the liquid outlet of pipeline with oxygenator 8.The pressure detecting position of sensor cluster 3,4,12 should be at sustained height.
Composition and the osmotic pressure of infusion liquid by being fit to plays armour, prevents swelling, keeps pH, supplies with the effect of organ oxygen and nutrition.The existing preservation liquid that is used for simple cryopreservation generally lacks organ desired nutritional thing, when using UW to preserve liquid as low temperature in device of the present invention, can suitably add nutrient substance, as near the glucose of people's bulk concentration, aminoacid, vitamin etc.The present invention preserves organ by the aerobic perfusion, infusion liquid should contain keeps cellular metabolism and synthetic ATP desired substance, must contain the material of removing free radical, as reductive glutathione etc., room temperature also needs to contain the carrier of oxygen when preserving organ, as adding erythrocyte etc.
In time adjust or change infusion liquid according to infusion liquid pH and organ swelling situation between storage life.
The present invention is the main vigor feature of monitoring organ when organ is preserved, comprehensive concentrated expression transplant organ overall activity situation, and specific implementation method is as follows:
The monitoring method of organ swelling situation of change:
When organ was preserved in perfusion, the operating weight meter was monitored the organ weight change in real time, and measuring and calculating organ swelling rate of change is adjusted infusion liquid composition and osmotic pressure according to organ swelling rate of change; Organ swelling rate of change computing formula is:
k＝m/m
1×100％
K represents organ swelling rate of change, and m represents the organ weight that monitors between storage life, m
1The original weight of expression organ;
The monitoring method of organ unobstructed blood vessel situation:
With a kind of infusion liquid perfused organ at a certain temperature, keep the survival and the metabolism of organ, the pressure of the pressure of the angioaccess infusion liquid by monitoring organ respectively, blood vessel outlet infusion liquid and irrigation flow, organ weight, measuring and calculating unit (weight) unobstructed blood vessel degree, reflection organ blood vessel microcirculation degree of mobility, unit unobstructed blood vessel degree computing formula is:
C＝Q
m/(P
m1-P
m2)/m
C representation unit unobstructed blood vessel degree, Q
mThe expression flow, P
M1Expression angioaccess pressure, P
M2Expression blood vessel outlet pressure, m represents the organ weight.
Unit unobstructed blood vessel degree can be calculated the unimpeded relatively rate of blood vessel of organ by comparing with the unit unobstructed blood vessel degree of the normal phase of testing in advance with organ-tissue, and its computing formula is:
N
b＝C/C
1×100％
N
bThe unimpeded relatively rate of expression blood vessel, C represents tested organic unit's unobstructed blood vessel degree, C
1The normal phase of expression test in advance is with the unit unobstructed blood vessel degree of organ-tissue under identical component infusion liquid and uniform temp condition.
The monitoring method of organ cell's survival condition:
Contain oxygen infusion liquid perfused organ at a certain temperature with a kind of, keep the survival and the metabolism of organ; The oxygen content and the irrigation flow of the oxygen content of the angioaccess infusion liquid by monitoring organ respectively, blood vessel outlet infusion liquid calculate organ oxygen metabolism speed, and computing formula is as follows,
Organ oxygen metabolism speed (V when organ has an angioaccess
o) computing formula be:
V
o＝(D
o1-D
o2)×Q
D
O1Expression organ angioaccess infusion liquid oxygen content, D
O2Expression organ blood vessel outlet infusion liquid oxygen content, Q represents the flow of organ vascular perfusion liquid.
When organ is liver organ oxygen metabolism speed (V when two angioaccesses are arranged
o) computing formula be:
V
o＝(D
o1-D
o2)×Q
1+(D
o3-D
o2)×Q
2，
Work as D
O3=D
O1The time formula be: V
o=(D
O1-D
O2) * (Q
1+ Q
2)
D
O1Expression arteries inlet infusion liquid oxygen content, D
O2Expression vein blood vessel outlet infusion liquid oxygen content, D
O3Expression portal vein tube inlet infusion liquid oxygen content, Q
1Expression arteries inlet infusion liquid flow, Q
2Expression portal vein tube inlet infusion liquid flow.
The measure formula of monitoring transplant organ self cell relative survival rate is between storage life:
N＝V
o/V
o1×100％
N represents organ self cell relative survival rate, V
oThe organ oxygen metabolism speed of monitoring between the expression storage life, V
O1The expression organ is preserved the oxygen metabolism speed behind the initial stage metabolic stability, V
oAnd V
O1It is the measuring and calculating value under identical component infusion liquid and uniform temp condition.
Measure the organ weight and calculate organic unit's oxygen metabolism speed, its measure formula is:
V
u＝V
o/m
V
uExpression organic unit oxygen metabolism speed, V
oExpression organ oxygen metabolism speed, m represents the organ weight.
By measuring and calculating organic unit's oxygen metabolism speed and with the normal phase of test in advance with organ-tissue in the unit oxygen metabolism velocity ratio of using the test of uniform temp and identical component infusion liquid, can calculate cell relative survival rate in the organ-tissue, its formula is:
N＝V
u/V
u1×100％
N represents organ cell's relative survival rate, V
uRepresent tested organic unit's oxygen metabolism speed, V
U1The normal phase of expression test in advance is with the unit oxygen metabolism speed of organ-tissue under use uniform temp and identical component infusion liquid condition.
By the oxygen consumption of getting rid of the organ dead cell and organ change of moisture content to the influence of survey organ cell relative survival rate, can calculate correction to survey organ cell relative survival rate, correction formula is:
N
c＝[1-(1-kN)/(1-n)]×100％
N
cRepresent revised organ cell's relative survival rate; N represents organ cell's relative survival rate of calculating; N represents the ratio of the oxygen metabolism speed of dead organ cell's under the same conditions averaged oxygen depletion rate and normal organ cell, this value records in advance by other tests, wherein a kind of test method is: monitor himself cell relative survival rate with animal organ healthy and relatively approaching human physiological characteristics, write down self cell relative survival rate and organ swelling rate of change when making himself cell relative survival rate drop to about about 70% (considering that mainly vascular system is not subjected to heavy damage) by suitable anoxia or long-time the preservation, and organ carried out biopsy, the Nc of the determined cell survival rate substitution of biopsy following formula, with survey the N of self cell relative survival rate substitution following formula, k with survey organ swelling rate of change substitution following formula can calculate and ask for unknown number n; K represents organ change of moisture content rate, organ change of moisture content rate mainly is that reflection swelling causes the aqueous rate of change of organ, equal to change the back organ weight than original organ weight, human body difference causes that the rate of change accessible region of organ water content divides the sex of donor, age to be added up consideration, can put aside human body difference as no statistical data.
Calculating organ cell's relative survival rate or organ blood vessel relatively during unimpeded rate, need normal organ tissue at the unit oxygen metabolism speed or the unit unobstructed blood vessel degree that use under uniform temp and the identical component infusion liquid condition, by data base or the mathematical model of setting up normal organ tissue in advance, the unit oxygen metabolism speed or the unit unobstructed blood vessel degree of normal organ tissue different temperatures in various infusion liquid storage temperature ranges are provided, can in every kind of infusion liquid allowable temperature scope, monitor organ by arbitrary temp, provide organ cell's relative survival rate relative unimpeded rate with the organ blood vessel, need not strictly control temperature, be easy to use, reduction is to the requirement of thermostat.The data base of normal organ tissue or mathematical model can carry out curve fitting or The Arrhenius Equation (Arrhenius equation according to statistical data, claim the reaction rate exponential law again) set up, can set up mathematical model by animal organ's test statistics earlier, revise with actual measurement people transplant organ data then near the human physiology characteristics.
Claims (10)
1, the device of external preservation of a kind of transplant organ and monitoring organ vitality, it is characterized in that: be placed between the organ storage life on the weight meter, the angioaccess of organ and outlet are connected to sensor cluster by pipeline respectively, sensor cluster is useful on two ports that infusion liquid is come in and gone out, sensor cluster is used to detect the pressure and the oxygen content of infusion liquid at least, the another port that is positioned at the sensor cluster of organ angioaccess links to each other with the infusion liquid outlet of perfusion equipment by pipeline, the another port that is positioned at the sensor cluster of organ blood vessel outlet links to each other with the infusion liquid inlet of perfusion equipment by pipeline, infusion liquid in this loop to organ perfusion.
2, a kind of method of monitoring external transplant organ swelling situation, this method comprises: when organ is preserved in perfusion, the operating weight meter is monitored the organ weight change in real time, and measuring and calculating organ swelling rate of change is adjusted infusion liquid composition and osmotic pressure according to organ swelling rate of change; Organ swelling rate of change computing formula is:
k＝m/m
1×100％
K represents organ swelling rate of change, and m represents the organ weight that monitors between storage life, m
1The original weight of expression organ;
3, a kind of method of monitoring external transplant organ unobstructed blood vessel situation, this method comprises: with a kind of infusion liquid perfused organ at a certain temperature, keep the survival and the metabolism of organ, the pressure of the pressure of the angioaccess infusion liquid by monitoring organ respectively, blood vessel outlet infusion liquid and irrigation flow, organ weight, measuring and calculating unit (weight) unobstructed blood vessel degree, reflection organ blood vessel microcirculation degree of mobility, unit unobstructed blood vessel degree computing formula is:
C＝Q
m/(P
m1-P
m2)/m
C representation unit unobstructed blood vessel degree, Q
mThe expression flow, P
M1Expression angioaccess pressure, P
M2Expression blood vessel outlet pressure, m represents the organ weight.
4, method according to claim 3, this method also comprises: by with the normal phase of test in advance with the unit unobstructed blood vessel degree of organ-tissue relatively, the unimpeded relatively rate of blood vessel of monitoring organ, its computing formula is:
N
b＝C/C
1×100％
N
bThe unimpeded relatively rate of expression blood vessel, C represents tested organic unit's unobstructed blood vessel degree, C
1The normal phase of expression test in advance is with the unit unobstructed blood vessel degree of organ-tissue under identical component infusion liquid and uniform temp condition.
5, a kind of method of monitoring the cell survival situation of external transplant organ, this method is by organ oxygen metabolism speed under the monitoring certain condition, the cell survival situation of reflection organ comprises: contain oxygen infusion liquid perfused organ at a certain temperature with a kind of, keep the survival and the metabolism of organ; The oxygen content and the irrigation flow of the oxygen content of the angioaccess infusion liquid by monitoring organ respectively, blood vessel outlet infusion liquid calculate organ oxygen metabolism speed; The oxygen metabolism speed of organ is relevant with the cell ATP synthesis capability with cell survival quantity in the organ under uniform temperature and infusion liquid situation, the cell survival and the change conditions thereof of reflection organ; The oxygen metabolism speed calculation formula of organ is as follows,
Organ oxygen metabolism speed (V when organ has an angioaccess
o) computing formula be:
V
o＝(D
o1-D
o2)×Q
D
O1Expression organ angioaccess infusion liquid oxygen content, D
O2Expression organ blood vessel outlet infusion liquid oxygen content, Q represents the flow of organ vascular perfusion liquid.
When organ is liver organ oxygen metabolism speed (V when two angioaccesses are arranged
o) computing formula be:
V
o＝(D
o1-D
o2)×Q
1+(D
o3-D
o2)×Q
2，
Work as D
O3=D
O1The time formula be: V
o=(D
O1-D
O2) * (Q
1+ Q
2)
D
O1Expression arteries inlet infusion liquid oxygen content, D
O2Expression vein blood vessel outlet infusion liquid oxygen content, D
O3Expression portal vein tube inlet infusion liquid oxygen content, Q
1Expression arteries inlet infusion liquid flow, Q
2Expression portal vein tube inlet infusion liquid flow.
6, method according to claim 5, this method also comprise the method for monitoring transplant organ self cell relative survival rate between storage life, and the measure formula of organ self cell relative survival rate is:
N＝V
o/V
o1×100％
N represents organ self cell relative survival rate, V
oThe organ oxygen metabolism speed of monitoring between the expression storage life, V
O1The expression organ is preserved the oxygen metabolism speed behind the initial stage metabolic stability, V
oAnd V
O1It is the measuring and calculating value under identical component infusion liquid and uniform temp condition.
7, method according to claim 5, this method also comprise the method for measuring and calculating organic unit oxygen metabolism speed, adopt the measurement organ weight to calculate organic unit's oxygen metabolism speed, and its measure formula is:
V
u＝V
o/m
V
uExpression organic unit oxygen metabolism speed, V
oExpression organ oxygen metabolism speed, m represents the organ weight.
8, method according to claim 7, this method also comprises the method for monitoring transplant organ cell relative survival rate: by measuring and calculating organic unit's oxygen metabolism speed and with the normal phase of test in advance with organ-tissue in the unit oxygen metabolism velocity ratio of using the test of uniform temp and identical component infusion liquid, calculate cell relative survival rate in the organ-tissue, its formula is:
N＝V
u/V
u1×100％
N represents organ cell's relative survival rate, V
uRepresent tested organic unit's oxygen metabolism speed, V
U1The normal phase of expression test in advance is with the unit oxygen metabolism speed of organ-tissue under use uniform temp and identical component infusion liquid condition.
9, according to claim 4 or 8 described methods, this method also is included in the method for arbitrary temp monitoring organ vitality in the infusion liquid allowable temperature scope:
Calculating organ cell's relative survival rate or organ blood vessel relatively during unimpeded rate, need normal organ tissue at the unit oxygen metabolism speed or the unit unobstructed blood vessel degree that use under uniform temp and the identical component infusion liquid condition, by data base or the mathematical model of setting up normal organ tissue in advance, the unit oxygen metabolism speed or the unit unobstructed blood vessel degree of normal organ tissue different temperatures in various infusion liquid storage temperature ranges are provided, can in every kind of infusion liquid allowable temperature scope, monitor organ by arbitrary temp, provide organ cell's relative survival rate relative unimpeded rate with the organ blood vessel.
10, according to claim 6 or 8 described methods, also be included as and improve precision and survey organ cell relative survival rate is calculated the method for correction, correction formula is:
N
c＝[1-(1-kN)/(1-n)]×100％
N
cRepresent revised organ cell's relative survival rate; N represents organ cell's relative survival rate of measuring and calculating in claim 2 or 4; N represents the ratio of the oxygen metabolism speed of the averaged oxygen depletion rate of organic death cell under the same conditions and normal organ cell, and this value records in advance by other tests; K represents organ change of moisture content rate, organ change of moisture content rate reflects that mainly organ swelling causes the aqueous rate of change of organ, equal to change the back organ weight than original organ weight, human body difference causes that the rate of change accessible region of organ water content divides the sex of donor, age to be added up consideration.
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