CN104207857B - Ischemic limb controlling perfusion system - Google Patents
Ischemic limb controlling perfusion system Download PDFInfo
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- CN104207857B CN104207857B CN201410452326.8A CN201410452326A CN104207857B CN 104207857 B CN104207857 B CN 104207857B CN 201410452326 A CN201410452326 A CN 201410452326A CN 104207857 B CN104207857 B CN 104207857B
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Abstract
The invention discloses a kind of ischemic limb controlling perfusion system and method thereof.Multichannel lavation feed tube is connected with Micropump import respectively through Valve for compressing tubular liner, Micropump outlet is connected with perfusate temperature controlling groove entrance, solid-liquid-gas separator it is provided with in perfusate temperature controlling groove, solid-liquid-gas three-phase separator flows out pipeline through irrigating solution and is connected with output pipe module, being connected with perfusion input pipe, pressure detecting module, output adjustment module and the biochemistry detection module of output pipe module respectively through tee T, main control unit is connected with Micropump, collection container, pressure detecting module, biochemistry detection module, remote communication module, situ interfacial operation module respectively.The present invention can collect perfusate and carry out Activity determination, or directly measure biological activity change or the biochemical reaction of perfusate, and setting up model based on this for pharmaceutical research, the present invention can significantly alleviate ischemic limb reperfusion injury, and the application of this system has stability and repeatability.
Description
Technical field
The present invention relates to a kind of ischemic limb controlling perfusion system.Can be applicable to the research of ischemic limb protection
Technology platform is provided, for developing treatment internal organs ischemical reperfusion injury new way for front clinical translational medicine.
Background technology
Due to the extensive application of the interventional techniques such as sacculus dilating catheter, make safety, fast quick-recovery blood flow becomes can
Can, this has greatly promoted the clinical treatment to acute internal organs ischemia.Although fast quick-recovery ischemia organ blood flow fills
Note is important, but it may result in " ischemical reperfusion injury " (Ischemia Reperfusion Injury,
IR injury)[1], thus aggravate local damage and systemic complications can be caused, make patients clinical prognosis poor.
From nineteen sixty, Jennings proposes the concept of reperfusion injury of cardiac muscle first[2], existing it has proven convenient that brain[3]、
Kidney[4-5], liver[6], gastrointestinal tract[7]In Various Tissues organ, ischemical reperfusion injury all can occur.
How reducing ischemical reperfusion injury is the most basic and the focus of clinical research." controlling is again
Perfusion " by initial flush phase is intervened, it is successfully applied to organ transplantation[8]And cardiovascular surgery hands
Art field[9], it is considered have great potential to reduce " ischemical reperfusion injury ", improves clinical efficacy.
For " controlled reperfusion ", its Mechanism Study is not yet in full swing, and there is not been reported for systematic study.
One of major reason is to there is no stably effective infusion liquid and standardization control Reperfu-sion flow process at present, and lacks
Weary suitable in situ perfusion device, this is that it is carried out the bottleneck of the deep front clinical basic of system.
List of references
1.Yellon,D.M.and D.J.Hausenloy,Myocardial Reperfusion Injury.N
Engl J Med,2007.357(11):p.1121-1135.
2.Jennings,R.B.,et al.,Myocardial necrosis induced by temporary
occlusion of a coronary artery in the dog.Arch Pathol,1960.70:p.
68-78.
3.Traystman,R.J.,J.R.Kirsch,and R.C.Koehler,Oxygen radical
mechanisms of brain injury following ischemia and reperfusion.J Appl
Physiol,1991.71(4):p.1185-95.
4.Ratych,R.E.,G.B.Bulkley,and G.M.Williams,Ischemia/reperfusion
injury in the kidney.Prog Clin Biol Res,1986.224:p.263-89.
5.Soullier,S.,et al.,[Molecular mechanisms involved in kidney
ischemia-reperfusion].Nephrol Ther,2005.1(5):p.315-21.
6.Vardanian,A.J.,R.W.Busuttil,and J.W.Kupiec-Weglinski,Molecular
mediators of liver ischemia and reperfusion injury:a brief review.Mol
Med,2008.14(5-6):p.337-45.
7.Mallick,I.H.,et al.,Ischemia-reperfusion injury of the intestine
and protective strategies against injury.Dig Dis Sci,2004.49(9):p.
1359-77.
8.Peter Wamser,R.A.,Peter Goetzinger,Gert Mayer,Gabriela
Berlakovich,Thomas Soliman,Ferdinand Muehlbacher,Rudi Steininger,,
Detrimental effects of controlled reperfusion on renal function after
porcine autotransplantation are fully compensated by the use of Carolina
rinse solution.Transplant International,2003.16(3):p.191-196.
Summary of the invention
It is an object of the invention to overcome the deficiencies in the prior art, it is provided that a kind of ischemic limb controlling perfusion system.
Ischemic limb controlling perfusion system includes Micropump, perfusate temperature controlling groove, lavation feed tube, irrigating solution
Flow out pipeline, collect container, Valve for compressing tubular liner, adjustment module, perfusion input pipe, pressure detecting module, biochemistry
Detection module, remote communication module, situ interfacial operation module, main control unit；
Multichannel lavation feed tube is connected with Micropump import respectively through Valve for compressing tubular liner, Micropump outlet and perfusate temperature controlling groove
Entrance is connected, and is provided with solid-liquid-gas separator in perfusate temperature controlling groove, and solid-liquid-gas three-phase separator is through lavation liquid stream
Go out pipeline to be connected with output pipe module, output pipe module comprise perfusion input pipe, pressure detecting module,
Output adjustment module and biochemistry detection module, through tee T respectively with perfusion input pipe, pressure detecting module,
Output adjustment module is connected with biochemistry detection module, and main control unit is examined with Micropump, collection container, pressure respectively
Survey module, biochemistry detection module, remote communication module, situ interfacial operation module are connected, output regulation mould
Block with treat that perfusion ischemic limb is connected, perfusate is after treating perfusion ischemic limb inner loop, by catcher
Collecting, in perfusate catcher, have semipermeable membrane to be separated by perfusate, the liquid after separation is with micro-
Pump is connected.
Described Micropump is Miniature injection pump and syringe or peristaltic pump.
Ischemic limb controlling perfusion is: Micropump is under system control, it is achieved set flow and pressure
Perfusion, Micropump exports to perfusate temperature controlling groove, installs solid-liquid-gas separator, simultaneously in perfusion temperature controlling groove cavity
This volume is utilized to realize three phase separation and enough heating-up times, for guaranteeing intensification pressure and stability of flow,
Connecting tube between Micropump and perfusion temperature controlling groove uses spiral type stringing technique, and solid-liquid-gas three-phase separator is to defeated
Going out ducting module output, output pipe module comprises perfusion input pipe, pressure detecting module, output regulation mould
Block and biochemistry detection module, through tee T by perfusion input pipe, pressure detecting module, output adjustment module
Coupling together with biochemistry detection module, perfusion output adjustment module is controlled open and-shut mode by Valve for compressing tubular liner, works as pressure
The low pressure less than set-up of control system or the high pressure higher than set-up of control system occurred, then main control unit controls
Perfusion output module closed by the pressure pipe pipe of output adjustment module, plays a protective role, and perfusion output module is adopted
Be connected with lower limb or other test organ or tissue with BULKHEAD UNION and puncture needle, perfusate through lower limb or its
After its test object inner loop, collected by catcher, in perfusate catcher, have semipermeable membrane
Being separated by perfusate, the liquid after separation is connected to Micropump, reenters perfusion system；System
Remote communication module or situ interfacial operation module is used to make operator that system to be operated.
Described Micropump provides perfusion power as system, and working method is continuously work and pulsed operation, micro-
Pump provides the flow-control of 0ml/min-1000ml/min, and can carry out defeated according to the degree of tightness state of Valve for compressing tubular liner
Going out relative pressure regulation, range of accommodation is 0mmHg-200mmHg.
Confirm through result of study, by the present invention, ischemic hindlimb implementation conscientiously may be used at body controlled reperfusion
OK, this perfusion system establishing techniques is reliable and stable.Simultaneously with traditional operation group (non-controlling Reperfu-sion group)
Comparing, controlled reperfusion significantly alleviates ischemic skeletal muscle edema and is formed, and saves muscular contraction force and muscle
Activity.
The present invention establishes ischemic limb controlling Perfusion, it is adaptable to preventing of class Ischaemia-Reperfusion of Lower Extremities damage
Protect, and be applicable to the developmental research of novel perfusate.Perfusate can be collected and carry out Activity determination, or directly survey
Determine biological activity change or the biochemical reaction of perfusate, and set up model based on this for pharmaceutical research,
The present invention can significantly alleviate ischemic limb reperfusion injury, and the application of this system has stability and repeatability.
Accompanying drawing explanation
Fig. 1 is ischemic limb controlling perfusion system structural representation；
Fig. 2 is ligation femoral artery induction severe rat hindlimb ischemia schematic diagram；
Fig. 3 is that ischemic limb is carried out detection (A, B) in real time by doppler flow inaging detector, and hind limb blood flow irrigates
Persistently reduce (C) schematic diagram；
Through inferior epigastric arterial cannulation, ischemic hindlimb being carried out In situ perfusion method in figure, irrigating solution is inserted through inferior epigastric vein
Pipe flow goes out.Fig. 3 (A-B) is test perfusion path feasibility, first through inferior epigastric arterial cannulation to ischemic hindlimb
Carry out Evans Blue perfusion, ischemic hindlimb color can be become indigo plant；(C-D) through inferior epigastric arterial cannulation to lacking
Blood hind leg carries out standard controlled reperfusion, can ischemic hindlimb color be bleached, and prompting irrigates successfully；
Fig. 4 is to significantly improve art relative to tradition non-perfusing group (dotted line) at body controlled perfusion (solid line)
Rear ischemic limb blood perfusion schematic diagram；
Fig. 5 significantly improves art relative to tradition non-perfusing group (black) at body controlled perfusion (white)
Rear ischemic limb recovers hind leg edema degree schematic diagram after blood perfusion.
Detailed description of the invention
As it is shown in figure 1, ischemic limb controlling perfusion system includes Micropump 1, perfusate temperature controlling groove 2, lavation
Feed tube 3, irrigating solution flow out pipeline 4, collect container 5, Valve for compressing tubular liner 6, adjustment module 7, perfusion input
Pipe, pressure detecting module 8, biochemistry detection module 9, remote communication module 10, situ interfacial operation module
11, main control unit 12；
Multichannel lavation feed tube 3 is connected with Micropump 1 import respectively through Valve for compressing tubular liner 6, and Micropump 1 exports and perfusion
Liquid temperature control slot 2 entrance is connected, and is provided with solid-liquid-gas separator in perfusate temperature controlling groove 2, and solid-liquid-gas three phase separates
Device through irrigating solution flow out pipeline 4 be connected with output pipe module, output pipe module comprise perfusion input pipe,
Pressure detecting module 8, output adjustment module 7 and biochemistry detection module 9, defeated with perfusion respectively through tee T
Enter pipe, pressure detecting module 8, output adjustment module 7 be connected with biochemistry detection module 9, main control unit 12
Respectively with Micropump 1, collection container 5, pressure detecting module 8, biochemistry detection module 9, remote communication module
10, situ interfacial operation module 11 is connected, and exports adjustment module 7 and treats that perfusion ischemic limb is connected, perfusion
Liquid, after treating perfusion ischemic limb inner loop, is collected by catcher 5, in perfusate catcher 5,
Having semipermeable membrane to be separated by perfusate, the liquid after separation is connected with Micropump.
Described Micropump 1 is Miniature injection pump and syringe or peristaltic pump.
Wherein, Micropump 1 is suitable for range of flow from 0-1000ml/min, and rotary speed precision is not less than on flow range
Limit rotating speed 1%, such as Lange BT100-2J etc., perfusate temperature controlling groove 2 use dimroth's condensing tube or
Serpentine condenser realizes, and lavation feed tube 3 uses medical silicone tube, external diameter 4-6mm, wall thickness 1mm, lavation
Liquid stream goes out pipeline 4 and uses snakelike medical silicone tube to connect Rule BULKHEAD UNION realization, and collecting container 5 is funnel
Formula filter, Valve for compressing tubular liner 6 is suitable for operating distance and is mainly influidic switch knob in 2-6mm, adjustment module 7,
Controlling perfusion flow or pressure size, pressure detecting module 8 is suitable for detection pressure limit absolute pressure
500mmHg-2000mmHg such as Honeywell 24PCEFD6G, biochemistry detection module 9 mainly includes PH electrode such as
Shanghai thunder magnetic E-201-C or PHS-3C etc., ion-selective electrode such as Shanghai thunder magnetic PCa-1-01 etc., molten
Solution oxygen electrode such as Shanghai thunder magnetic DO-957 etc., remote communication module 10 mainly include RS232 etc., on-the-spot behaviour
Make module and mainly include touch screen such as enlightening literal arts skill DMT80480T070 series.
Ischemic limb controlling perfusion is: Micropump 1 is under system control, it is achieved set flow and pressure
Perfusion, Micropump exports to perfusate temperature controlling groove 2, in perfusion temperature controlling groove cavity install solid-liquid-gas separator,
Utilize this volume to realize three phase separation and enough heating-up times simultaneously, steady for guaranteeing intensification pressure and flow
Fixed, the connecting tube between Micropump 1 and perfusion temperature controlling groove uses spiral type stringing technique, and solid-liquid-gas three phase separates
Device exports to output pipe module, and output pipe module comprises perfusion input pipe, pressure detecting module 8, defeated
Go out adjustment module 7 and biochemistry detection module 9, through tee T by perfusion input pipe, pressure detecting module 8,
Output adjustment module 7 and biochemistry detection module 9 couple together, and perfusion output adjustment module is by Valve for compressing tubular liner control
Open and-shut mode, when the low pressure less than set-up of control system or the high pressure higher than set-up of control system occurred in pressure,
Then main control unit 12 controls the pressure pipe pipe closedown perfusion output module of output adjustment module, plays a protective role,
Perfusion output module uses BULKHEAD UNION to be connected with lower limb or other test organ or tissue with puncture needle, perfusion
Liquid, after lower limb or other test object inner loop, is collected by catcher 5, receives at perfusate
In storage 5, having semipermeable membrane to be separated by perfusate, the liquid after separation is connected to Micropump, again enters
Enter perfusion system；System uses remote communication module 10 or situ interfacial operation module 11 to make operator to being
System operates.
Described Micropump 1 provides perfusion power as system, and working method is continuously work and pulsed operation,
Micropump provides the flow-control of 0ml/min-1000ml/min, and can enter according to the degree of tightness state of Valve for compressing tubular liner 6
Row output relative pressure regulation, range of accommodation is 0mmHg-200mmHg.
Embodiment
Induced rat severe posterior-limb ischemia
After rat anesthesia is reached, cervical region and bilateral inguinal district preserved skin, lie on the back fixing, look at descending trachea straight and insert
Pipe.Rear connection respirator, controls tidal volume (10ml/kg), respiratory frequency (60 beats/min).In left abdomen stock
Ditch does oblique otch, slightly does free by shallow for stomach wall arteriovenous, opens femoral sheath, stock arteriovenous and femoral nerve is divided
From, the preset ligature of difference (whole operation process is it should be noted that protect neural and tunica adventitia) under two blood vessels.
Temporarily ligature femoral artery, after will self-control tourniquet (No. 0 line) passed by under femoral sheath, one end connect gravity Chui,
Arranging tension gradient is 0g, 100g, 150g, 200g, 250g, 300g, 350g, 400g, 450g, and
Double hind limb blood flow perfusion monitoring, computer data acquisition, phase is carried out by Laser Doppler under corresponding tension force
Close software and be irrigated index analysis.
After success induced rat severe lower limb ischemia, careful free superficial epigastric artery, No. 0 line far-end ligation, do
Traction；Under 20-40 times of mirror, microscissors does in the left superficial epigastric artery away from the femoral artery place of separating 1-1.5cm
Otch, after by polyethylene tube (by PE-10；Internal diameter, 0.28mm；External diameter, 0.64mm；20cm length) by
This otch inserts left superficial epigastric artery, and insertion conduit is connected to accurate miniature syringe pump (Harvard Pump 11
Plus Advanced Single Syringe with Dual RS-232, Harvard
Apparatus, cat.no.702211), femoral vein is intubated confession by micro-vessel clamps temporary interruption, inferior epigastric vein
Irrigating solution flows out and collects.Employing cooling anaerobic heparin liquid (15 DEG C, ad 1000IU heparin and
Ringer ' s lactate 1000mL), control flow (0.3ml/min), perfusion limbs 20 minutes.For
Confirm that the feasibility through left stomach wall arterial perfusion ischemic limb uses methylene blue to replace cold liver with 2 rats of group
Element liquid is irrigated, and direct-view is irrigated observing.Art control at 250 DEG C with postoperative room temperature, experimentation
In by electric blanket maintain anus temperature at 37 ± 0.50 DEG C.
Claims (2)
1. an ischemic limb controlling perfusion system, it is characterized in that, flow out pipeline (4) including Micropump (1), perfusate temperature controlling groove (2), lavation feed tube (3), irrigating solution, collect container (5), Valve for compressing tubular liner (6), output adjustment module (7), perfusion input pipe, pressure detecting module (8), biochemistry detection module (9), remote communication module (10) situ interfacial operation module (11), main control unit (12)；
nullMultichannel lavation feed tube (3) is connected with Micropump (1) import respectively through Valve for compressing tubular liner (6)，Micropump (1) outlet is connected with perfusate temperature controlling groove (2) entrance，Perfusate temperature controlling groove is provided with solid-liquid-gas separator in (2)，Solid-liquid-gas three-phase separator flows out pipeline (4) through irrigating solution and is connected with output pipe module，Output pipe module comprises perfusion input pipe、Pressure detecting module (8)、Output adjustment module (7) and biochemistry detection module (9)，Through tee T by pressure detecting module (8)、Output adjustment module (7) and biochemistry detection module (9) couple together，Output adjustment module (7) is connected with perfusion input pipe，Main control unit (12) respectively with Micropump (1)、Collect container (5)、Pressure detecting module (8)、Biochemistry detection module (9)、Remote communication module (10)、Situ interfacial operation module (11) is connected，Export adjustment module (7) and treat that perfusion ischemic limb is connected，Perfusate is after treating perfusion ischemic limb inner loop，It is collected container (5) to collect，In perfusate collects container (5)，Semipermeable membrane is had to be separated by perfusate，Liquid after separation is connected with Micropump；System uses remote communication module (10) or situ interfacial operation module (11) to operate.
2. ischemic limb controlling perfusion system as claimed in claim 1 a kind of, it is characterised in that described Micropump (1) is Miniature injection pump and syringe or peristaltic pump.
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| WO2000071072A1 (en) * | 1999-05-25 | 2000-11-30 | Viacirq, Inc. | Hyperthermia method and apparatus |
| CN2783992Y (en) * | 2004-09-24 | 2006-05-31 | 陈炳华 | Blood perfusion device |
| CN201445523U (en) * | 2009-06-09 | 2010-05-05 | 杨惠林 | Minimally invasive vertebral perfusion pressure measuring system with micro pressure sensor |
| DE102009027195A1 (en) * | 2009-06-25 | 2010-12-30 | Sorin Group Deutschland Gmbh | Device for pumping blood in an extracorporeal circuit |
| KR101489111B1 (en) * | 2010-12-27 | 2015-02-02 | 아사히 가세이 메디컬 가부시키가이샤 | Blood processing filter, blood circuit system, and centrifugation method |
| CN103719075B (en) * | 2014-01-14 | 2015-01-28 | 吕凌 | Isolated organ preserving device and preserving method thereof |
| CN204133636U (en) * | 2014-09-05 | 2015-02-04 | 浙江大学 | A kind of ischemic limb controlling perfusion system |
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Inventor after: Li Jianhui Inventor after: Zhang Jing Inventor after: Zhou Lin Inventor after: Xie Haiyang Inventor after: Zheng Shusen Inventor after: Chen Xudong Inventor after: Hu Guiquan Inventor after: Zheng Jun Inventor after: Chu Dianjun Inventor after: Hu Qiang Inventor after: Jia Junjun Inventor after: Jiang Chi Inventor after: Zhou Yanfei Inventor before: Chen Xudong Inventor before: Zhang Jing Inventor before: Zhou Lin Inventor before: Xie Haiyang Inventor before: Zheng Shusen Inventor before: Li Jianhui Inventor before: Hu Guiquan Inventor before: Zheng Jun Inventor before: Chu Dianjun Inventor before: Hu Qiang Inventor before: Jia Junjun Inventor before: Jiang Chi Inventor before: Zhou Yanfei |
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Effective date of registration: 20181218 Address after: 310018 Room 2001-2010, No. 452, No. 6 Street, Baiyang Street, Hangzhou Economic and Technological Development Zone, Zhejiang Province Patentee after: Hangzhou Laipu Sheng Medical Technology Co Ltd Address before: 310027 No. 38, Zhejiang Road, Hangzhou, Zhejiang, Xihu District Patentee before: Zhejiang University |