CN107088107A - The method and its application of animal blood cooling and the preparation method and animal model of CPR low temperature animal model - Google Patents
The method and its application of animal blood cooling and the preparation method and animal model of CPR low temperature animal model Download PDFInfo
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- CN107088107A CN107088107A CN201710383947.9A CN201710383947A CN107088107A CN 107088107 A CN107088107 A CN 107088107A CN 201710383947 A CN201710383947 A CN 201710383947A CN 107088107 A CN107088107 A CN 107088107A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
- A61D7/00—Devices or methods for introducing solid, liquid, or gaseous remedies or other materials into or onto the bodies of animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F7/12—Devices for heating or cooling internal body cavities
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3607—Regulation parameters
- A61M1/3609—Physical characteristics of the blood, e.g. haematocrit, urea
- A61M1/3612—Physical characteristics of the blood, e.g. haematocrit, urea after treatment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/369—Temperature treatment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F2007/0001—Body part
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F2007/0054—Heating or cooling appliances for medical or therapeutic treatment of the human body with a closed fluid circuit, e.g. hot water
- A61F2007/0056—Heating or cooling appliances for medical or therapeutic treatment of the human body with a closed fluid circuit, e.g. hot water for cooling
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F7/12—Devices for heating or cooling internal body cavities
- A61F2007/126—Devices for heating or cooling internal body cavities for invasive application, e.g. for introducing into blood vessels
Abstract
The invention provides a kind of method and its application of animal blood cooling and the preparation method and animal model of CPR low temperature animal model, it is related to the technical field of medical science.The method for the animal blood cooling that the present invention is provided, carries out heat exchange by 4 DEG C of liquid and the blood of animal, can realize fast cooling, simple to operate, cost is low, cooling rate is fast；In addition, the animal model that the preparation method of CPR low temperature animal model provided according to the present invention is prepared from, can the CPR of science simulation and low temperature therapy scheme, for the correlative study of low temperature therapy in CPR, there is provided the basis of research；In addition, the method for the animal blood cooling that the present invention is provided, simple to operate, cost is low, cooling rate is fast, can be applied among preparation CPR low temperature animal model.
Description
Technical field
The present invention relates to medicine technology field, the method and its application cooled more particularly, to a kind of animal blood and the heart
The preparation method and animal model of lung recovery low temperature animal model.
Background technology
At present, the common hypothermia by animal has physical method and chemical method etc., example to the method for expected level
Such as it is cooled using hypothermic blanket, ice cap parcel animal, or inject the medicines such as chlorpromazine, fenazil to reach reduction animal
The effect of temperature.And the general cooling rate of these cool-down methods is slower, it is impossible to be properly arrived at intended effect.
In addition, though presently, there are the method for some fast coolings, but in general, there is cost height, operation mostly again
It is miscellaneous, have the shortcomings that wound.
It is proved in view of therapeutic Mild Hypothermal in heart arrest, hypoxic-ischemic encephalopathy (HIE), cerebral apoplexy, acute myocardial infarction AMI
Etc. having organ protection in a variety of diseases, and early stage, fast low temperature are further lifting Mild Hypothermal Organoprotective effects
Important means, accordingly, it is desirable to provide the animal cool-down method that a kind of cooling rate is fast, cost is low, effect is good.
In view of this, it is special to propose the present invention.
The content of the invention
First purpose of the present invention is the method for providing animal blood cooling, and second object of the present invention is to carry
For the preparation method of CPR low temperature animal model, third object of the present invention is to provide CPR low temperature animal mould
Type, fourth object of the present invention is the application for providing the method for animal blood cooling, to alleviate present in prior art
The technical problem that animal cooling rate is slow, effect is poor, cost is high.
The invention provides a kind of method of animal blood cooling, it is characterised in that this method is by 4 DEG C of liquid and blood
Liquid carries out heat exchange and realized.
Further, methods described includes：Esophagus cooling conduit is inserted into animal esophagus, and is led to esophagus cooling
Pipe interior circulation irrigates 4 DEG C of liquid, and hot friendship is carried out by adjoining the heart of esophagus, big endovascular blood in 4 DEG C of liquid and animal
Change, so as to realize the cooling of animal whole blood.
Further, the esophagus cooling conduit includes core, and attaches what the core spiral was set
Spiral part；The esophagus cooling conduit is made up of medical silica-gel flexible pipe.
Further, methods described includes：Venous blood is led to outside animal using blood purification instrument, dropped in vitro
Wen Houzai is fed back in vivo, so as to realize the cooling of animal whole blood；It is described in vitro carry out cooling be by 4 DEG C of liquid with
Blood in blood purification instrument pipeline carries out heat exchange realization.
Further, the parameter of the blood purification instrument is set to：CVVH patterns, velocity of blood flow starting 180ml/min, dimension
120ml/min, displacement liquid speed 30ml/kg/h are held, 0ml/kg/h is dehydrated, first dose of static push 1000U of heparin, Micropump maintain 150U/
h。
In addition, present invention also offers a kind of preparation method of CPR low temperature animal model, the preparation method according to
It is secondary to set up process and temperature-fall period including animal set-up procedure, CPR model；
The animal set-up procedure includes：
(a) water is can't help in 12h before testing, animal fasting；
(b) when testing, animal is weighed, intramuscular injection of ketamine induced anesthesia, and the injection volume of the ketamine is 20mg/
kg；Animal is fixed, SPO is connected2, electrocardio and anus thermometre, and maintain animal normal body temperature to exist using temperature control blanket before induction room quivers
(38.0±0.5)℃；
(c) auricular vein passage, the sodium intravenous induction general anesthesia of amobarbital, the injection volume of the yellow Jackets are set up
For 30mg/kg；Hereafter narcosis, and the μ g/ of fentanyl 2 are maintained according to 8mg/ (kgh) amount injection yellow Jackets
(kgh) continuous analgesia is treated；
(d) oral trachea cannula, connects ETCO2/SPO2Monitor and lung ventilator, carry out mechanical ventilation；The lung ventilator
Parameter is set to tidal volume 12mL/kg, peak flow velocity 40L/min and FiO221%；By the respiratory rate for adjusting the lung ventilator
Maintain ETCO2In 35~40mm Hg；
(e) exposure right femoral vein, inserts Swan-Ganz conduits to atrium dextrum, for monitoring DIE Temperature；
(f) the right vena jugularis externa of exposure, inserts and lures the electrode that quivers to right ventricle, for inducing ventricular fibrillation；
(g) oral indwelling esophagus cooling conduit, external ice blanket instrument, for irrigating 4 DEG C of liquid to esophagus cooling circulating within conduit
Body；
The CPR model, which sets up process, to be included：
(h) through luring the electrode that quivers to discharge 1mA alternating currents to right ventricle, ventricular fibrillation is induced；
(i) after ventricular fibrillation success, lung ventilator is disconnected, CPR, institute are carried out after stopping mechanical ventilation, no Observation on Intervention 8min
Stating CPR includes manual chest compression and sacculus assisted ventilation, ratio 30：2；The according to pressing depth 5-6cm of the external chest compression, frequency
100-120 beats/min；
(j) when CPR continues 2.5min, adrenaline is injected intravenously according to 20 μ g/kg amount, it is every thereafter according to recovery situation
3min duplicate injections adrenaline is once；
(k) when CPR continues 5min, the two-way ripple electric defibrillation for the 150J that energizes 1 time, and judge whether that spontaneous circulation is extensive
It is multiple；The standard that the spontaneous circulation recovers is supraventricular autonomous cardiac rhythm with mean arterial pressure>50mm Hg, continue more than 5min；If
Animal spontaneous circulation recovers, then is considered as Successful Resuscitation；
The temperature-fall period includes：After Successful Resuscitation during 5min, using the method described in claim 3 to Successful Resuscitation
Animal is cooled, 33 DEG C of target temperature, continues to Successful Resuscitation 24h.
In addition, present invention also offers a kind of preparation method of CPR low temperature animal model, the preparation method according to
It is secondary to set up process and temperature-fall period including animal set-up procedure, CPR model；
The animal set-up procedure includes：
(A) water is can't help in 12h before testing, animal fasting；
(B) when testing, animal is weighed, intramuscular injection of ketamine induced anesthesia, and the injection volume of the ketamine is 20mg/
kg；Animal is fixed, SPO is connected2, electrocardio and anus thermometre, and maintain animal normal body temperature to exist using temperature control blanket before induction room quivers
(38.0±0.5)℃；
(C) auricular vein passage, the sodium intravenous induction general anesthesia of amobarbital, the injection volume of the yellow Jackets are set up
For 30mg/kg；Hereafter narcosis, and the μ g/ of fentanyl 2 are maintained according to 8mg/ (kgh) amount injection yellow Jackets
(kgh) continuous analgesia is treated；
(D) oral trachea cannula, connects ETCO2/SPO2Monitor and lung ventilator, carry out mechanical ventilation；The lung ventilator
Parameter is set to tidal volume 12mL/kg, peak flow velocity 40L/min and FiO221%；By the respiratory rate for adjusting the lung ventilator
Maintain ETCO2In 35~40mm Hg；
(E) exposure right femoral vein, inserts Swan-Ganz conduits to atrium dextrum, for monitoring DIE Temperature；
(F) the right vena jugularis externa of exposure, inserts and lures the electrode that quivers to right ventricle, for inducing ventricular fibrillation；
(G) exposure left femoral vein, inserts CVC, for connecting blood purification instrument；
The CPR model, which sets up process, to be included：
(H) through luring the electrode that quivers to discharge 1mA alternating currents to right ventricle, ventricular fibrillation is induced；
(I) after ventricular fibrillation success, lung ventilator is disconnected, stops carrying out CPR after mechanical ventilation, 8min, the CPR includes people
Work external chest compression and sacculus assisted ventilation, ratio 30：2；The according to pressing depth 5-6cm of the external chest compression, frequency 100-120 times/
Point；
(J) when CPR continues 2.5min, adrenaline is injected intravenously according to 20 μ g/kg amount, it is every thereafter according to recovery situation
3min duplicate injections adrenaline is once；
(K) when CPR continues 5min, the two-way ripple electric defibrillation for the 150J that energizes 1 time, and judge whether that spontaneous circulation is extensive
It is multiple；The standard that the spontaneous circulation recovers is supraventricular autonomous cardiac rhythm with mean arterial pressure>50mm Hg, continue more than 5min；If
Animal spontaneous circulation recovers, then is considered as Successful Resuscitation；
The temperature-fall period includes：After Successful Resuscitation during 5min, using the method described in claim 5 to Successful Resuscitation
Animal is cooled, 33 DEG C of target temperature, continues to Successful Resuscitation 24h.
In addition, present invention also offers the CPR low temperature animal model being prepared from according to described preparation method.
In addition, preparing CPR low temperature animal model present invention also offers the method that described animal blood cools
In application.
The method for the animal blood cooling that the present invention is provided, heat exchange is carried out by 4 DEG C of liquid and the blood of animal, can
Fast cooling is realized, simple to operate, cost is low, cooling rate is fast；In addition, the CPR low temperature animal provided according to the present invention
The animal model that the preparation method of model is prepared from, can the CPR of science simulation and low temperature therapy scheme, for
There is provided the basis of research for the correlative study of low temperature therapy in CPR；In addition, the animal blood cooling that the present invention is provided
Method, simple to operate, cost is low, cooling rate is fast, can be applied among preparation CPR low temperature animal model.
Brief description of the drawings
, below will be to specific in order to illustrate more clearly of the specific embodiment of the invention or technical scheme of the prior art
The accompanying drawing used required in embodiment or description of the prior art is briefly described, it should be apparent that, in describing below
Accompanying drawing is some embodiments of the present invention, for those of ordinary skill in the art, before creative work is not paid
Put, other accompanying drawings can also be obtained according to these accompanying drawings.
Fig. 1 is the structural representation for the esophagus cooling conduit that the embodiment of the present invention 1 is provided；
Fig. 2 for the present invention in esophagus cooling conduit Optimal Experimental in using different model esophagus cool conduit corresponding to temperature
Spend variation diagram；
Fig. 3 for the present invention in esophagus cooling conduit Optimal Experimental in using different model esophagus cool conduit corresponding to drop
Warm rate diagram；
Fig. 4 for the present invention in esophagus cooling conduit Optimal Experimental in using different model esophagus cool conduit corresponding to the heart
Rate variation diagram；
Fig. 5 is flat corresponding to conduit to be cooled in esophagus cooling conduit Optimal Experimental in the present invention using different model esophagus
Equal angiosthenia variation diagram；
Fig. 6 is animal temperature variation in the embodiment of the present invention 2 and comparative example 1-3 each groups；
Fig. 7 is the rate of temperature fall of animal in the embodiment of the present invention 2 and comparative example 3；
Fig. 8 is the cooling duration up to standard of animal in the embodiment of the present invention 2 and comparative example 3；
Fig. 9 is animal temperature variation in the embodiment of the present invention 4 and comparative example 5-7 each groups；
Figure 10 is the rate of temperature fall of animal in the embodiment of the present invention 4 and comparative example 6；
Figure 11 is the cooling duration up to standard of animal in the embodiment of the present invention 4 and comparative example 6.
Icon：1- cores；2- spiral parts.
Embodiment
Technical scheme is clearly and completely described below in conjunction with embodiment, it is clear that described reality
It is a part of embodiment of the invention to apply example, rather than whole embodiments.Based on the embodiment in the present invention, the common skill in this area
The every other embodiment that art personnel are obtained under the premise of creative work is not made, belongs to the model that the present invention is protected
Enclose.
In the description of the invention, it is necessary to explanation, such as occur term " " center ", " on ", " under ", "left", "right",
The orientation or position relationship of the instruction such as " vertical ", " level ", " interior ", " outer " be based on orientation shown in the drawings or position relationship,
It is for only for ease of the description present invention and simplifies description, rather than to indicate or imply that signified device or element must have specific
Orientation, with specific azimuth configuration and operation, therefore be not considered as limiting the invention.
In the description of the invention, it is necessary to which explanation, unless otherwise clearly defined and limited, term " peace such as occurs
Dress ", " connected ", " connection " should be interpreted broadly, for example, it may be fixedly connected or be detachably connected, or integratedly
Connection；Can be mechanical connection or electrical connection；Can be joined directly together, can also be indirectly connected to by intermediary,
It can be the connection of two element internals.For the ordinary skill in the art, above-mentioned art can be understood with concrete condition
The concrete meaning of language in the present invention.
If not otherwise specified, CRRT of the present invention refers to the blood purification instrument used in Sequential spot film；This
It is cardiopulmonary resuscitation to invent the CPR (cardiopulmonary resuscitation) being related to；CVVH of the present invention is (even
Continuous Veno-Venous Hemofiltration filtration) it is one kind in Sequential spot film application technology.
If not otherwise specified, instrument of the present invention is conventional instrument, and the reagent being related to is conventional commercial reagent.
If not otherwise specified, the experimental animal that following examples are related to is the domestic white pig of health male, body weight (30-35)
Kg, purchased from Shanghai Jia Gan bio tech ltd, animal quality certification number SCXK (Shanghai) 2015-0005；All minimal standards are raised
Material is fed, free water.
Embodiment 1
The method for present embodiments providing the animal blood cooling induced through esophagus, including：After fixed animal, esophagus cooling
In the external ice blanket instrument of conduit, the esophagus of conduit insertion animal that esophagus is cooled, the circulation low temperature for 4 DEG C of the catheter perfusion that cools through esophagus
Liquid, carries out heat exchange by 4 DEG C of liquid and the blood adjoined in the heart of esophagus, big blood vessel, realizes the purpose of fast cooling.
Wherein, 4 DEG C of liquid for example can be, but be not limited to：4 DEG C of sterilizeds water for injection.
As shown in figure 1, esophagus cools, conduit includes core 1 to the esophagus cooling conduit that the present embodiment 1 is applied, and
The spiral part 2 that the spiral of core 1 is set is attached, such setting ensure that the contact area of esophagus cooling conduit and esophagus
Maximize, and equipment is simple and convenient to operate, and the scope of application is extremely wide；External ice blanket instrument respectively with core 1 and spiral part
2 connections, form 4 DEG C of liquid circulation systems, such as 4 DEG C liquid can enter spiral part 2 from ice blanket instrument, then through center
Part 1 flows out to ice blanket instrument, and 4 DEG C of liquid after cooling through ice blanket instrument enter back into spiral part 2；Wherein, esophagus cooling conduit by
Medical silica-gel flexible pipe is made.
4 DEG C of liquid enter from spiral part 2, are flowed out from core 1, because spiral part 2 is directly contacted with esophagus, because
Blood of this 4 DEG C of liquid directly with animal after the outflow of ice blanket instrument is swapped, and reduces unnecessary loss.
In the present embodiment, the transverse diameter of esophagus cooling conduit is 20mm.The transverse diameter herein being related to, refers to whole esophagus cooling and leads
The maximum outside diameter of pipe.
Furthermore it is also possible to which difference according to the actual requirements, sets a stomach tube, likewise, stomach tube parallel with core 1
Surrounded by spiral part 2.
The method that the present embodiment is provided, has the following advantages that：1) the raw material simple cheap of esophagus cooling conduit, made
Journey is convenient, and holistic cost is cheap；2) cryogenic liquid is irrigated by external traditional ice blanket instrument, existing medical treatment money can be made full use of
Source；3) stomach tube of Clinical practice is similar to, using technology maturation, indwelling is convenient, and safety is noninvasive；4) it creatively make use of food
Road surface area is big, centrifuge the features such as dirty and big blood vessel is near, can reach the quick purpose for carrying out heat exchange and cooling.
The optimization of esophagus cooling conduit
In order to obtain optimum esophagus cooling conduit, inventor is entered by herein below to the selection of esophagus cooling conduit
Screening is gone：
(1) the domestic white pig 5 of health male is selected, body weight 30-35kg under gastroscope guiding, measures the total length model of esophagus
Enclose, select its average value as indwelling length in the esophagus of esophagus cooling conduit.
(2) the distensible physiological property of esophagus is combined, with reference to the esophagus length of test, by the cylindrical software of different-diameter
In the whole esophagus for inserting above-mentioned 5 experiment pigs, the maximum cylinder area of section that test esophagus can be accommodated, while seeing closely
Examine the change of the physiological parameters such as animal blood pressure, heart rate, so in the esophagus that can bear of clear and definite animal indwelling software size.
(3) according to heat exchange influent factors such as fluid flow, contact area and heat transfer materials, select that wall is thin, matter first
The transparent silica gel flexible pipe that soft, plasticity is good, heat transfer is good；Secondly using stomach tube as axle center, attached around its outer wall screw type
Silica gel hose, attaches the esophagus total length of length reference test, to maximize heat exchange contact area in esophagus；Furthermore, in animal
In the indwelling software magnitude range that esophagus can bear, the different silica gel hose of selection caliber produces 5 kinds of different size models
Through esophagus cool conduit.
Wherein, the transverse diameter of the esophagus cooling conduit of different model is respectively 11mm, 14mm, 17mm, 20mm, 23mm in 5.
In addition, in this Optimal Experimental, preparing esophagus cooling silica gel hose used in conduit that transverse diameter is 11mm
Internal-and external diameter is respectively 1.5mm and 3mm；Prepare the internal-and external diameter point for esophagus cooling silica gel hose used in conduit that transverse diameter is 14mm
Wei not 2.5mm and 4mm；Preparing esophagus cooling internal-and external diameter of silica gel hose used in conduit that transverse diameter is 17mm is respectively
3.5mm and 5mm；Prepare transverse diameter be 20mm esophagus cooling conduit used in silica gel hose internal-and external diameter be respectively 4.5mm and
6mm；It is respectively 5.5mm and 7mm to prepare esophagus cooling internal-and external diameter of silica gel hose used in conduit that transverse diameter is 23mm.
(4) above-mentioned 5 experiment pigs are utilized, the drop of the catheter samples that cool through esophagus of above-mentioned 5 kinds of different size models is carried out
Warm testing experiment (with the esophagus cooling conduit of 5 kinds of models tested by every experiment pig.For every experiment pig,
After one kind cooling conduit test terminates, after the state of experiment pig recovers normal, then next model esophagus cooling conduit is carried out
Test), the esophagus cooling external ice blanket instrument of conduit is cooled, duration 4h, the physiology such as close observation rate of temperature fall and blood pressure, heart rate
The change of parameter, filters out that a kind of cryogenic liquid flow is big, rate of temperature fall is good and animal is resistant to cools conduit through esophagus,
For Pigs Hearts lung recovering experiment.The selection result is as follows：
(i) temperature change
The temperature change of experiment pig is as shown in Fig. 2 wherein in the esophagus cooling conduit operation of 5 kinds of different models, conduit 23,
Conduit 20, conduit 17, conduit 14 and conduit 11, represent transverse diameter and cool as 23mm, 20mm, 17mm, 14mm, 11mm esophagus respectively
Conduit.
After handling the data in Fig. 2, the rate of temperature fall figure of the esophagus cooling conduit of 5 kinds of different models is obtained, such as
Shown in Fig. 3.The rate of temperature fall of conduit 23, conduit 20, conduit 17, conduit 14 and conduit 11 be respectively (2.8 ± 0.4) DEG C/h,
(2.7 ± 0.4) DEG C/h, (2.3 ± 0.3) DEG C/h, (2.0 ± 0.3) DEG C/h, (1.6 ± 0.2) DEG C/h, can be seen by data above
Go out, with the increase of conduit transverse diameter, rate of temperature fall is accelerated；But for conduit 23 and conduit 20, both basic phases of rate of temperature fall
When.
(ii) heart rate and blood pressure
Further analyze the change of the heart rate and blood pressure of experiment pig in the esophagus cooling conduit operation of 5 kinds of different models
Change, as a result respectively as shown in Figure 4 and Figure 5.It can be seen that with the decline of body temperature, what heart rate presentation was fallen after rising becomes
Gesture, blood pressure keeps stable or declined；But 23 groups of conduit faster for rate of temperature fall, compared with baseline value, continuous observation to the heart
Rate is fast, high blood pressure, points out animal not tolerate.
Experiment shows above, when the transverse diameter of esophagus cooling conduit is 20mm, can either fast and effectively cool, and not
Not tolerating for animal can be caused.Therefore 20mm is selected as the optimal transverse diameter of esophagus cooling conduit.
Additionally need, it is emphasized that inventor chooses different experiment pig (the domestic white pigs of health male, body weight 30-
35kg), multiple above-mentioned esophagus cooling conduit Optimal Experimental has been carried out, its final result is shown as when the horizontal stroke of esophagus cooling conduit
When footpath is 20mm, it can either quickly and efficiently cool, not tolerating for animal will not be caused again.It is therefore intended that above-mentioned esophagus cooling
The result of conduit Optimal Experimental has applicability.
Embodiment 2
The preparation method of CPR low temperature animal model is present embodiments provided, including：
First, experimental animal prepares
1) before testing, animal fasting 12h can't help water.
2) when testing, ketamine 20mg/kg intramuscular injection induced anesthesias are weighed, are placed on operating table set square, fixing limbs,
Connect SPO2, electrocardio and anus thermometre, dynamic monitoring vital sign, and animal normal body temperature is maintained using temperature control blanket before induction room quivers
In (38.0 ± 0.5) DEG C.
3) auricular vein passage is set up, yellow Jackets 30mg/kg intravenous anesthesias, hereafter yellow Jackets 8mg/ (kg
H) narcosis, and the treatment of fentanyl 2 μ g/ (kgh) continuous analgesia are maintained.
4) oral trachea cannula, connects ETCO2/SPO2Monitor and lung ventilator, carry out mechanical ventilation.Ventilator parameter is set
It is set to tidal volume 12mL/kg, peak flow velocity 40L/min and FiO221%.ETCO is maintained by adjusting lung ventilator respiratory rate235
~40mm Hg.
5) exposure right femoral artery, inserts Swan-Ganz conduits to aorta pectoralis, for monitoring aorta pectoralis blood pressure and collection
Arterial blood samples.
6) exposure right femoral vein, inserts Swan-Ganz conduits to atrium dextrum, for monitoring DIE Temperature.
7) the right vena jugularis externa of exposure, inserts and lures the electrode that quivers to right ventricle, quivered for induction room.
8) oral indwelling esophagus cooling conduit, external ice blanket instrument, for irrigating 4 DEG C of liquid to esophagus cooling circulating within conduit
Body.
2nd, CPR modelling
1) 10min before room is quivered, gathers animal basic data such as hemodynamic parameter, arterial blood gas and vein blood specimen
Deng.
2) through luring the electrode that quivers to discharge 1mA alternating currents to right ventricle, ventricular fibrillation is induced.The Success criteria that quivers is lured to be in for electrocardiogram
Quivered waveform for room, and arterial pressure is remarkably decreased, pulse waveform disappears.
3) after room is quivered successfully, lung ventilator is disconnected, stops mechanical ventilation, then no Observation on Intervention 8min starts CPR, it is wrapped
Include manual chest compression and sacculus assisted ventilation, ratio 30：2 (external chest compression 30 times, assisted ventilations 2 times, so circulation).
4) defibrillation monitor monitors external chest compression quality in real time, it is ensured that according to pressing depth 100-120 beats/min of 5-6cm, frequency.
5) during CPR 2.5min, the μ g/kg of adrenaline 20 are injected intravenously, are reused thereafter according to recovery situation per 3min
Once.
6) during CPR 5min, the two-way ripple electric defibrillation for the 150J that energizes 1 time, and judge whether that spontaneous circulation recovers.From
The standard that major cycle recovers is supraventricular autonomous cardiac rhythm with mean arterial pressure>50mm Hg, continue more than 5min.
If 7) spontaneous circulation does not recover, 2min CPR, then electric defibrillation 1 time are carried out immediately.So repeat this flow 5 times
Afterwards, animal is still not up to spontaneous circulation and recovered, and is considered as recovery failure.
8) animal of Successful Resuscitation, mechanical ventilation observation 30h, is injected intravenously yellow Jackets 150mg/kg and is pacified again
It is happy dead, spoil dissection is carried out, the anatomical results of important organ are recorded.
3rd, temperature-fall period
After Successful Resuscitation during 5min, according to the method in embodiment 1, using the esophagus cooling external ice blanket instrument of conduit, warp
Esophagus is cooled, 33 DEG C of target temperature, continues to recovery 24h.Again with 1 DEG C/h rewarmings 5h.
Comparative example 1
Sham-operation group：Only it is operated, does not suffer from cardiopulmonary resuscitation process, whole-process application ice blanket instrument remains normal
38.0 ± 0.5 DEG C of temperature.
Comparative example 2
Normal temperature group：Cardiopulmonary resuscitation process is undergone, whole-process application ice blanket instrument maintains normal temperature 38.0 ± 0.5
℃。
Comparative example 3
Body surface low temperature group：Cardiopulmonary resuscitation process is undergone, and after Successful Resuscitation during 5min, it is external using body surface ice blanket
Ice blanket instrument, is cooled through body surface, 33 DEG C of target temperature, continues to recovery 24h.Again with 1 DEG C/h rewarmings 5h.
With reference to comparative example 1 to 3, the effect for the method that inventor is provided embodiment 2 is evaluated, and evaluation result is such as
Under.
As shown in fig. 6, after recovery, sham-operation group and the body temperature of normal temperature group animal are maintained at metastable normal model
In enclosing, and the change that the body temperature of body surface low temperature group and esophagus low temperature group animal shows the three phases such as cooling, maintenance, rewarming becomes
Gesture.Temperature-fall period, body surface low temperature group and the body temperature of esophagus low temperature group animal decline rapidly, and esophagus low temperature group is compared with body surface low temperature group
Animal heat decline more rapid, statistically significant (the equal P of comparing difference between group<0.05)；Low temperature is maintained and the rewarming stage,
Compare no difference of science of statistics (equal P between the variation tendency that the body temperature of esophagus low temperature group and body surface low temperature group animal is consistent, group>
0.05).Wherein, in Fig. 6, BL represents baseline value；VF quivers the room of expression；PC represents external chest compression；DF represents defibrillation；With sham-operation group
Compare,aP<0.05；Compared with normal temperature group,bP<0.05；Compared with body surface low temperature group,cP<0.05。
As shown in Figure 7 and Figure 8, in temperature-fall period, further data analysis is shown, the average rate of temperature fall of esophagus low temperature group is
2.8 DEG C/h, a length of 102min of average out to timestamp, and the average rate of temperature fall of body surface low temperature group is 1.5 DEG C/h, average out to timestamp is a length of
185min, points out the cooling efficiency of esophagus low temperature group animal apparently higher than body surface low temperature group, comparing difference has statistics meaning between group
Justice (equal P<0.05).Wherein, in Fig. 7 and Fig. 8, compared with body surface low temperature group,*P<0.05。
Embodiment 3
The method through the CRRT animal blood coolings induced is present embodiments provided, including：Using CRRT by venous blood
Lead in vitro, CRRT veins then are returned into heart end pipe road is placed in 4 DEG C of liquid, realizes that blood and 4 DEG C of liquid pass through CRRT pipelines
Quick heat exchange is carried out, then low temperature blood recovery reaches the purpose of fast cooling to internal.
Wherein, CRRT parameter settings：
CVVH patterns, velocity of blood flow starting 180ml/min, maintenance 120ml/min, displacement liquid speed 30ml/kg/h, dehydration
0ml/kg/h, first dose of static push 1000U of heparin, Micropump maintain 150U/h.
CRRT liquid is configured：
Pre- fliud flushing：Heparin 1,0.9%NaCl liquid 1500ml.
Displacement liquid：1) A liquid：0.9%NaCl liquid 2000ml, 5%Glu liquid 100ml, 10%KCl liquid 10ml, 10% glucose
Sour calcium liquid 13ml, 25%MgSO4Liquid 3ml, sterilized water for injection 500ml；2) B liquid：NaHCO3Liquid 125ml.A liquid is not mixed with B liquid
Close, B liquid is individually entered.
The cool-down method that the present embodiment is provided, in the low temperature induction stage, blood recovery end pipe road is placed in 4 DEG C of liquid, profit
In rapid induction low temperature；In the maintenance stage in later stage, pipeline heating device sets preference temperature, parcel blood recovery end pipe road, dimension
Hold target temperature.
Embodiment 4
The preparation method of CPR low temperature animal model is present embodiments provided, including：
First, experimental animal prepares
1) before testing, animal fasting 12h can't help water.
2) when testing, ketamine 20mg/kg intramuscular injection induced anesthesias are weighed, are placed on operating table set square, fixing limbs,
Connect SPO2, electrocardio and anus thermometre, dynamic monitoring vital sign, and animal normal body temperature is maintained using temperature control blanket before induction room quivers
In (38.0 ± 0.5) DEG C.
3) auricular vein passage is set up, yellow Jackets 30mg/kg intravenous anesthesias, hereafter yellow Jackets 8mg/ (kg
H) narcosis, and the treatment of fentanyl 2 μ g/ (kgh) continuous analgesia are maintained.
4) oral trachea cannula, connects ETCO2/SPO2Monitor and lung ventilator, carry out mechanical ventilation.Ventilator parameter is set
It is set to tidal volume 12mL/kg, peak flow velocity 40L/min and FiO221%.ETCO is maintained by adjusting lung ventilator respiratory rate235
~40mm Hg.
5) exposure right femoral vein, inserts Swan-Ganz conduits to atrium dextrum, for monitor right atrial pressure, DIE Temperature and
Gather vein blood specimen.
6) the right vena jugularis externa of exposure, inserts and lures the electrode that quivers to right ventricle, quivered for induction room.
7) exposure left femoral vein, inserts dialysis CVC, for CRRT low temperature therapies.
2nd, CPR modelling
1) 10min before room is quivered, gathers animal basic data such as hemodynamic parameter, arterial blood gas and vein blood specimen
Deng.
2) through luring the electrode that quivers to discharge 1mA alternating currents to right ventricle, ventricular fibrillation is induced.
3) after room is quivered successfully, lung ventilator is disconnected, stops mechanical ventilation, then no Observation on Intervention 8min starts CPR, it is wrapped
Include manual chest compression and sacculus assisted ventilation, ratio 30：2 (external chest compression 30 times, assisted ventilations 2 times, so circulation).
4) defibrillation monitor monitors external chest compression quality in real time, it is ensured that according to pressing depth 100-120 beats/min of 5-6cm, frequency.
5) during CPR 2.5min, the μ g/kg of adrenaline 20 are injected intravenously, are reused thereafter according to recovery situation per 3min
Once.
6) during CPR 5min, the two-way ripple electric defibrillation for the 150J that energizes 1 time, and judge whether that spontaneous circulation recovers.From
The standard that major cycle recovers is supraventricular autonomous cardiac rhythm with mean arterial pressure>50mm Hg, continue more than 5min.
If 7) spontaneous circulation does not recover, 2min CPR, then electric defibrillation 1 time are carried out immediately.So repeat this flow 5 times
Afterwards, animal is still not up to spontaneous circulation and recovered, and is considered as recovery failure.
8) animal of Successful Resuscitation, mechanical ventilation observation 30h, is injected intravenously yellow Jackets 150mg/kg and is pacified again
It is happy dead, spoil dissection is carried out, the anatomical results of important organ are recorded.
3rd, temperature-fall period
5min after Successful Resuscitation, according to the method in embodiment 3, is cooled in vitro through CRRT pipelines, target temperature 33
DEG C, the 8h to after recovering is maintained, then 24h is maintained to recovery with body surface ice blanket.Again with 1 DEG C/h rewarmings 5h.
Comparative example 4
Sham-operation group：Only it is operated, does not suffer from cardiopulmonary resuscitation process, whole-process application ice blanket instrument remains normal
38.0 ± 0.5 DEG C of temperature.
Comparative example 5
Normal temperature group：Cardiopulmonary resuscitation process is undergone, whole-process application ice blanket instrument maintains normal temperature 38.0 ± 0.5
℃。
Comparative example 6
Body surface low temperature group：Cardiopulmonary resuscitation process, and the 5min after Successful Resuscitation are undergone, using the external ice of body surface ice blanket
Blanket instrument, is cooled through body surface, 33 DEG C of target temperature, continues to recovery 24h.Again with 1 DEG C/h rewarmings 5h.
With reference to comparative example 4 to 6, the effect for the method that inventor is provided embodiment 4 is evaluated, and evaluation result is such as
Under.
As shown in Fig. 9, Figure 10 and Figure 11, after recovery, implementing body surface low temperature group and CRRT low temperature groups that low temperature is intervened, can
See that the body temperature of two groups of animals declines rapidly, and CRRT low temperature groups are significantly faster than that between body surface low temperature group, group that comparing difference has statistics
Meaning (P<0.05).Further analysis display, the average rate of temperature fall of CRRT low temperature group is 9.8 DEG C/h, average out to timestamp is a length of
28min, and the average rate of temperature fall of body surface low temperature group is 1.5 DEG C/h, a length of 185min of average out to timestamp, as a result points out CRRT low temperature
The cooling efficiency of group animal is apparently higher than body surface low temperature group, the statistically significant (P of comparing difference between group<0.05).Wherein, Fig. 9
In, BL represents baseline value；VF quivers the room of expression；PC represents external chest compression；DF represents defibrillation；Compared with sham-operation group,aP<0.05；
Compared with normal temperature group,bP<0.05；Compared with body surface low temperature group,cP<0.05.In Figure 10 and Figure 11, with body surface low temperature group phase
Than,*P<0.05。
As shown in figure 9, in the low temperature maintenance stage, CRRT low temperature group is held in target temperature with body surface low temperature group animal heat
33 DEG C or so of degree；Rewarming stage, two groups of animals with 1 DEG C/h or so speed rewarming, finally return to baseline values.
Finally it should be noted that：Various embodiments above is merely illustrative of the technical solution of the present invention, rather than its limitations；To the greatest extent
The present invention is described in detail with reference to foregoing embodiments for pipe, it will be understood by those within the art that：Its according to
The technical scheme described in foregoing embodiments can so be modified, or which part or all technical characteristic are entered
Row equivalent substitution；And these modifications or replacement, the essence of appropriate technical solution is departed from various embodiments of the present invention technology
The scope of scheme.
Claims (10)
1. a kind of method of animal blood cooling, it is characterised in that this method is by 4 DEG C of liquid and blood progress heat exchange
Realize.
2. according to the method described in claim 1, it is characterised in that methods described includes：Esophagus drop is inserted into animal esophagus
Warm conduit, and 4 DEG C of liquid are irrigated to esophagus cooling circulating within conduit, by the heart for adjoining esophagus in 4 DEG C of liquid and animal
Dirty, big endovascular blood carries out heat exchange, so as to realize the cooling of animal whole blood.
3. method according to claim 2, it is characterised in that the esophagus cooling conduit includes core (1), and
Attach the spiral part (2) of the core (1) spiral setting；The esophagus cooling conduit is made up of medical silica-gel flexible pipe.
4. according to the method described in claim 1, it is characterised in that methods described includes：Using blood purification instrument by venous blood
Liquid is led to outside animal, is fed back to again after being cooled in vitro in vivo, so as to realize the cooling of animal whole blood；It is described in body
Outer progress cooling is to carry out heat exchange realization by the blood in 4 DEG C of liquid and the blood purification instrument pipeline.
5. method according to claim 4, it is characterised in that the blood purification instrument is set to：CVVH patterns, blood
Flow velocity starting 180ml/min, maintenance 120ml/min, displacement liquid speed 30ml/kg/h, are dehydrated 0ml/kg/h, first dose of static push of heparin
1000U, Micropump maintain 150U/h.
6. a kind of preparation method of CPR low temperature animal model, it is characterised in that the preparation method includes animal successively
Set-up procedure, CPR model set up process and temperature-fall period；
The animal set-up procedure includes：
(a) water is can't help in 12h before testing, animal fasting；
(b) when testing, animal is weighed, intramuscular injection of ketamine induced anesthesia, and the injection volume of the ketamine is 20mg/kg；Will
Animal is fixed, and connects SPO2, electrocardio and anus thermometre, and maintain animal normal body temperature (38.0 using temperature control blanket before induction room quivers
±0.5)℃；
(c) auricular vein passage, the sodium intravenous induction general anesthesia of amobarbital are set up, the injection volume of the yellow Jackets is
30mg/kg；Hereafter narcosis, and the μ g/ (kg of fentanyl 2 are maintained according to 8mg/ (kgh) amount injection yellow Jackets
H) continuous analgesia is treated；
(d) oral trachea cannula, connects ETCO2/SPO2Monitor and lung ventilator, carry out mechanical ventilation；The parameter of the lung ventilator
It is set to tidal volume 12mL/kg, peak flow velocity 40L/min and FiO221%；Maintained by the respiratory rate for adjusting the lung ventilator
ETCO2In 35~40mm Hg；
(e) exposure right femoral vein, inserts Swan-Ganz conduits to atrium dextrum, for monitoring DIE Temperature；
(f) the right vena jugularis externa of exposure, inserts and lures the electrode that quivers to right ventricle, for inducing ventricular fibrillation；
(g) oral indwelling esophagus cooling conduit, external ice blanket instrument, for irrigating 4 DEG C of liquid to esophagus cooling circulating within conduit；
The CPR model, which sets up process, to be included：
(h) through luring the electrode that quivers to discharge 1mA alternating currents to right ventricle, ventricular fibrillation is induced；
(i) after ventricular fibrillation success, lung ventilator is disconnected, CPR, the CPR are carried out after stopping mechanical ventilation, no Observation on Intervention 8min
Including manual chest compression and sacculus assisted ventilation, ratio 30：2；According to pressing depth 5-6cm, the frequency 100- of the external chest compression
120 beats/min；
(j) when CPR continues 2.5min, adrenaline is injected intravenously according to 20 μ g/kg amount, thereafter according to recovery situation per 3min
Duplicate injection adrenaline is once；
(k) when CPR continues 5min, the two-way ripple electric defibrillation for the 150J that energizes 1 time, and judge whether that spontaneous circulation recovers；Institute
It is supraventricular autonomous cardiac rhythm companion's mean arterial pressure to state the standard of spontaneous circulation recovery>50mm Hg, continue more than 5min；If animal
Spontaneous circulation recovers, then is considered as Successful Resuscitation；
The temperature-fall period includes：After Successful Resuscitation during 5min, using animal of the method described in claim 3 to Successful Resuscitation
Cooled, 33 DEG C of target temperature continues to Successful Resuscitation 24h.
7. the CPR low temperature animal model being prepared from according to the preparation method described in claim 6.
8. a kind of preparation method of CPR low temperature animal model, it is characterised in that the preparation method includes animal successively
Set-up procedure, CPR model set up process and temperature-fall period；
The animal set-up procedure includes：
(A) water is can't help in 12h before testing, animal fasting；
(B) when testing, animal is weighed, intramuscular injection of ketamine induced anesthesia, and the injection volume of the ketamine is 20mg/kg；Will
Animal is fixed, and connects SPO2, electrocardio and anus thermometre, and maintain animal normal body temperature (38.0 using temperature control blanket before induction room quivers
±0.5)℃；
(C) auricular vein passage, the sodium intravenous induction general anesthesia of amobarbital are set up, the injection volume of the yellow Jackets is
30mg/kg；Hereafter narcosis, and the μ g/ (kg of fentanyl 2 are maintained according to 8mg/ (kgh) amount injection yellow Jackets
H) continuous analgesia is treated；
(D) oral trachea cannula, connects ETCO2/SPO2Monitor and lung ventilator, carry out mechanical ventilation；The parameter of the lung ventilator
It is set to tidal volume 12mL/kg, peak flow velocity 40L/min and FiO221%；Maintained by the respiratory rate for adjusting the lung ventilator
ETCO2In 35~40mm Hg；
(E) exposure right femoral vein, inserts Swan-Ganz conduits to atrium dextrum, for monitoring DIE Temperature；
(F) the right vena jugularis externa of exposure, inserts and lures the electrode that quivers to right ventricle, for inducing ventricular fibrillation；
(G) exposure left femoral vein, inserts CVC, for connecting blood purification instrument；
The CPR model, which sets up process, to be included：
(H) through luring the electrode that quivers to discharge 1mA alternating currents to right ventricle, ventricular fibrillation is induced；
(I) after ventricular fibrillation success, lung ventilator is disconnected, CPR, the CPR are carried out after stopping mechanical ventilation, no Observation on Intervention 8min
Including manual chest compression and sacculus assisted ventilation, ratio 30：2；According to pressing depth 5-6cm, the frequency 100- of the external chest compression
120 beats/min；
(J) when CPR continues 2.5min, adrenaline is injected intravenously according to 20 μ g/kg amount, thereafter according to recovery situation per 3min
Duplicate injection adrenaline is once；
(K) when CPR continues 5min, the two-way ripple electric defibrillation for the 150J that energizes 1 time, and judge whether that spontaneous circulation recovers；Institute
It is supraventricular autonomous cardiac rhythm companion's mean arterial pressure to state the standard of spontaneous circulation recovery>50mm Hg, continue more than 5min；If animal
Spontaneous circulation recovers, then is considered as Successful Resuscitation；
The temperature-fall period includes：5min after Successful Resuscitation, enters using the method described in claim 5 to the animal of Successful Resuscitation
Row cooling, 33 DEG C of target temperature continues to Successful Resuscitation 24h.
9. the CPR low temperature animal model being prepared from according to the preparation method described in claim 8.
10. application of the method in CPR low temperature animal model is prepared described in claim any one of 1-5.
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| CN110506702A (en) * | 2019-08-09 | 2019-11-29 | 浙江大学 | A kind of method for building up of novel model of cardiac arrest |
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| CN104546279A (en) * | 2015-01-05 | 2015-04-29 | 张茂 | Body cooling device |
| US20170007445A1 (en) * | 2003-02-24 | 2017-01-12 | Zoll Circulation, Inc. | System and method for inducing hypothermia with control and determination of catheter pressure |
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- 2017-05-25 CN CN201710383947.9A patent/CN107088107A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20170007445A1 (en) * | 2003-02-24 | 2017-01-12 | Zoll Circulation, Inc. | System and method for inducing hypothermia with control and determination of catheter pressure |
| CN104546279A (en) * | 2015-01-05 | 2015-04-29 | 张茂 | Body cooling device |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108175538A (en) * | 2018-01-25 | 2018-06-19 | 朱耀斌 | A kind of Deep Hypothermia Circulatory Arrest rat animal model |
| CN110506702A (en) * | 2019-08-09 | 2019-11-29 | 浙江大学 | A kind of method for building up of novel model of cardiac arrest |
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