CN104207857A - Control perfusion system and control perfusion method for ischemia of lower extremity - Google Patents
Control perfusion system and control perfusion method for ischemia of lower extremity Download PDFInfo
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Abstract
The invention discloses a control perfusion system and a control perfusion method for ischemia of lower extremity, wherein multiple channels of lavage liquid inlet pipes are respectively connected with an entrance of a micro-pump by a press pipe valve; an exit of the micro-pump is connected with an entrance of a perfusion liquid temperature control slot; the perfusion liquid temperature control slot is internally provided with a solid-liquid-gas separator; the solid-liquid-gas separator is connected with an output pipeline module by a perfusion liquid outflow pipeline, and is respectively connected with a perfusion input pipe of the output pipeline module, a pressure detection module, an output adjusting module and a biochemical detection module by a tee-joint pipe; a main control unit is respectively connected with the micro-pump, a collecting container, the pressure detection module, the biochemical detection module, a remote communication module and a field interface operation module. After the system and the method are used, the perfusion liquid can be collected for activity detection, or the biological activity or biochemical reaction of the perfusion liquid can be directly measured, and a model is built by taking the measured results as basis for pharmacological study. The system and the method can be used for remarkably relieving the injury caused by reperfusion for the ischemia of lower extremity; the application of the system has stability and repeatability.
Description
Technical field
The present invention relates to a kind of ischemic limb controlling perfusion system and method thereof.The research that can be applicable to ischemic limb protection provides technology platform for front clinical translational medicine, is developing treatment internal organs ischemical reperfusion injury new way.
Background technology
Due to the extensive use of the interventional techniques such as sacculus dilating catheter, make safety, soon quick-recovery blood flow become possibility, this has greatly promoted the clinical treatment to acute internal organs ischemia.Although fast quick-recovery ischemia organ blood flow perfusion is important, it can cause " ischemical reperfusion injury " (Ischemia Reperfusion Injury, IR injury)
[1], thus aggravation local damage also can cause systemic complications, makes patients clinical prognosis poor.
From nineteen sixty, Jennings proposes the concept of reperfusion injury of cardiac muscle first
[2], now confirm, brain
[3], kidney
[4-5], liver
[6], gastrointestinal tract
[7]all ischemical reperfusion injury can be there is in Various Tissues organ.
What how to reduce ischemical reperfusion injury is the focus of at present basis and clinical research." controlled reperfusion ", by intervening initial flush phase, has been successfully applied to organ transplantation [8] and cardiovascular surgical procedure field [9], has been considered to great potential 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 there is no stable effective infusion liquid and standardization control Reperfu-sion flow process at present, and lack suitable in situ perfusion device, this to its carry out system deep before the bottleneck of clinical basic.
List of references
1.Yellon,D.M.and?D.J.Hausenloy,Myocardial?Reperfusion?In?jury.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
The object of the invention is to overcome the deficiencies in the prior art, a kind of ischemic limb controlling perfusion system and method thereof are provided.
Ischemic limb controlling perfusion system comprises Micropump, perfusate temperature controlling groove, lavation feed tube, irrigating solution outflow conduit, collection container, Valve for compressing tubular liner, adjustment module, perfusion input pipe, pressure detecting module, biochemistry detection module, remote communication module situ interfacial operational module, main control unit;
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 is provided with in perfusate temperature controlling groove, solid-liquid-gas three-phase separator is connected with output pipe module through irrigating solution outflow conduit, output pipe module comprises perfusion input pipe, pressure detecting module, Drazin inverse module and biochemistry detection module, through tee T respectively with perfusion input pipe, pressure detecting module, Drazin inverse module is connected with biochemistry detection module, main control unit respectively with Micropump, collection container, pressure detecting module, biochemistry detection module, remote communication module, situ interfacial operational module is connected, Drazin inverse module with treat that perfusion ischemic limb is connected, perfusate is after treating perfusion ischemic limb inner loop, collected by catcher, in perfusate catcher, semipermeable membrane is had to be separated by perfusate, liquid after separation is connected with Micropump.。
Described Micropump is Miniature injection pump and syringe or peristaltic pump.
Ischemic limb controlling perfusion is: Micropump is under Systematical control, realize the perfusion of setting flow and pressure, Micropump exports to perfusate temperature controlling groove, in perfusion temperature controlling groove cavity, solid-liquid-gas separator is installed, utilize this volume to realize three phase separation and enough heating-up times simultaneously, for guaranteeing intensification pressure and stability of flow, connection tube between Micropump and perfusion temperature controlling groove adopts spiral type stringing technique, solid-liquid-gas three-phase separator exports to output pipe module, output pipe module comprises perfusion input pipe, pressure detecting module, Drazin inverse module and biochemistry detection module, through tee T by perfusion input pipe, pressure detecting module, Drazin inverse module and biochemistry detection model calling get up, perfusion Drazin inverse module controls open and-shut mode by Valve for compressing tubular liner, when the low pressure lower than set-up of control system or the high pressure higher than set-up of control system appearred in pressure, then main control unit controls the pressure pipe pipe closedown perfusion output module of Drazin inverse module, play a protective role, perfusion output module adopts BULKHEAD UNION and puncture needle and lower limb or other to test organ or tissue-welding, perfusate is after lower limb or other test object inner loop, collected by catcher, in perfusate catcher, semipermeable membrane is had to be separated by perfusate, liquid after separation is connected to Micropump, reenter perfusion system, system adopts remote communication module or situ interfacial operational module that operator is operated system.
Described Micropump provides perfusion power as system, working method is continuous operation and pulsed operation, Micropump provides the flow-control of 0ml/min-1000ml/min, and can carry out the adjustment of output relative pressure according to the degree of tightness state of Valve for compressing tubular liner, and range of accommodation is 0mmHg-200mmHg.
Confirm through result of study, carry out practical at body controlled reperfusion by the present invention to ischemic hindlimb, this perfusion system establishing techniques is reliable and stable.Simultaneously compared with traditional operation group (non-controlling Reperfu-sion group), 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, is applicable to the protection of class Ischaemia-Reperfusion of Lower Extremities damage, and is applicable to the developmental research of novel perfusate.Perfusate can be collected and carry out Activity determination, or directly measure biological activity change or the biochemical reaction of perfusate, and Modling model is used for pharmaceutical research based on this, 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 doppler flow inaging detector carries out detection (A, B) in real time to ischemic limb, and hind limb blood flow perfusion continues to reduce (C) schematic diagram;
Carry out In situ perfusion method through inferior epigastric arterial cannulation to ischemic hindlimb in figure, irrigating solution flows out through inferior epigastric vein intubate.Fig. 2 (A-B) is test perfusion path feasibility, first carries out Evans Blue perfusion through inferior epigastric arterial cannulation to ischemic hindlimb, ischemic hindlimb color can be become blue; (C-D) carry out standard controlled reperfusion through inferior epigastric arterial cannulation to ischemic hindlimb, ischemic hindlimb color can be bleached, prompting is poured into successfully;
Fig. 4 significantly improves postoperative ischemic limb blood perfusion schematic diagram relative to traditional non-perfusing group (dotted line) at body controlled perfusion (solid line);
Fig. 5 is relative to traditional non-perfusing group (black) hind leg edema degree schematic diagram after body controlled perfusion (white) significantly improves postoperative ischemic limb recovery blood perfusion.
Detailed description of the invention
As shown in Figure 1, ischemic limb controlling perfusion system comprises Micropump 1, perfusate temperature controlling groove 2, lavation feed tube 3, irrigating solution outflow conduit 4, collection 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 operational 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, Micropump 1 exports and is connected with perfusate temperature controlling groove 2 entrance, solid-liquid-gas separator is provided with in perfusate temperature controlling groove 2, solid-liquid-gas three-phase separator is connected with output pipe module through irrigating solution outflow conduit 4, output pipe module comprises perfusion input pipe, pressure detecting module 8, Drazin inverse module 7 and biochemistry detection module 9, through tee T respectively with perfusion input pipe, pressure detecting module 8, Drazin inverse module 7 is 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 operational module 11 is connected, Drazin inverse module (7) with treat that perfusion ischemic limb is connected, perfusate is after treating perfusion ischemic limb inner loop, collected by catcher 5, in perfusate catcher 5, semipermeable membrane is had to be separated by perfusate, 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, rotary speed precision is not less than 1% of flow range upper limit rotating speed, such as Lange BT100-2J etc., perfusate temperature controlling groove 2 adopts dimroth's condensing tube or serpentine condenser to realize, lavation feed tube 3 adopts medical silicone tube, external diameter 4-6mm, wall thickness 1mm, irrigating solution outflow conduit 4 adopts snakelike medical silicone tube to connect Rule BULKHEAD UNION and realizes, collection container 5 is filter funnel, Valve for compressing tubular liner 6 is suitable for operating distance at 2-6mm, adjustment module 7 is mainly influidic switch knob, control perfusion flow or pressure size, pressure detecting module 8 is suitable for detected pressures scope absolute pressure 500mmHg-2000mmHg as Honeywell 24PCEFD6G, , biochemistry detection module 9 mainly comprises PH electrode as Shanghai thunder magnetic E-201-C or PHS-3C etc., ion-selective electrode is as Shanghai thunder magnetic PCa-1-01 etc., dissolved oxygen electrode is as Shanghai thunder magnetic DO-957 etc., remote communication module 10 mainly comprises RS232 etc., execute-in-place module mainly comprises touch screen as Di Wenke skill DMT80480T070 series.
Ischemic limb controlling perfusion is: Micropump 1 is under Systematical control, realize the perfusion of setting flow and pressure, Micropump exports to perfusate temperature controlling groove 2, in perfusion temperature controlling groove cavity, solid-liquid-gas separator is installed, utilize this volume to realize three phase separation and enough heating-up times simultaneously, for guaranteeing intensification pressure and stability of flow, connection tube between Micropump 1 and perfusion temperature controlling groove adopts spiral type stringing technique, solid-liquid-gas three-phase separator exports to output pipe module, output pipe module comprises perfusion input pipe, pressure detecting module 8, Drazin inverse module 7 and biochemistry detection module 9, through tee T by perfusion input pipe, pressure detecting module 8, Drazin inverse module 7 and biochemistry detection module 9 couple together, perfusion Drazin inverse module 9 controls open and-shut mode by Valve for compressing tubular liner, when the low pressure lower than set-up of control system or the high pressure higher than set-up of control system appearred in pressure, then main control unit 12 controls the pressure pipe pipe closedown perfusion output module 9 of Drazin inverse module, play a protective role, perfusion output module 9 adopts BULKHEAD UNION and puncture needle and lower limb or other to test organ or tissue-welding, perfusate is after lower limb or other test object inner loop, collected by catcher 5, in perfusate catcher 5, semipermeable membrane is had to be separated by perfusate, liquid after separation is connected to Micropump, reenter perfusion system, system adopts remote communication module 10 or situ interfacial operational module 11 that operator is operated system.
Described Micropump 1 provides perfusion power as system, working method is continuous operation and pulsed operation, Micropump provides the flow-control of 0ml/min-1000ml/min, and can carry out the adjustment of output relative pressure according to the degree of tightness state of Valve for compressing tubular liner 6, and 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 tracheal intubation straight.Rear connection respirator, controls tidal volume (10ml/kg), respiratory frequency (60 beats/min).Do oblique otch in left groin, shallow for stomach wall arteriovenous is slightly done free, opens femoral sheath, stock arteriovenous and femoral nerve are separated, the preset ligature of difference (whole operation process should note neuroprotective and tunica adventitia) under two blood vessels.Temporary transient ligation femoral artery, after will make tourniquet (No. 0 line) by oneself and pass by under femoral sheath, one end connects gravity Chui, arranging tension gradient is 0g, 100g, 150g, 200g, 250g, 300g, 350g, 400g, 450g, and two hind limb blood flow perfusion monitoring is carried out by Laser Doppler under corresponding tension force, computer data acquisition, related software carries out perfusion index analysis
After successful induced rat severe lower limb ischemia, careful free superficial epigastric artery, the ligation of No. 0 line far-end, draws; Under 20-40 times of mirror, microscissors does otch in the left superficial epigastric artery apart from femoral artery point source 1-1.5cm, after by polyethylene tube (by PE-10; Internal diameter, 0.28mm; External diameter, 0.64mm; 20cm is long) thus otch insert left superficial epigastric artery, tubes connection will be inserted to accurate miniature syringe pump (Harvard Pump 11 Plus Advanced Single Syringe with Dual RS-232, Harvard Apparatus, cat.no.702211), femoral vein is by micro-vessel clamps temporary interruption, and inferior epigastric vein intubate flows out for irrigating solution and collects.Adopt cooling anaerobic heparin liquid (15 DEG C, ad 1000 IU heparin and Ringer ' s lactate 1000mL), control flow (0.3ml/min), perfusion limbs 20 minutes.For confirming that the feasibility through left stomach wall arterial perfusion ischemic limb adopts methylene blue to replace cold heparin liquid to pour into group 2 rats, direct-view is carried out perfusion and is observed.Control at 250C with postoperative room temperature in art, in experimentation, maintain anus temperature at 37 scholar 0.50C by electric blanket.
Claims (4)
1. an ischemic limb controlling perfusion system, it is characterized in that, comprise Micropump (1), perfusate temperature controlling groove (2), lavation feed tube (3), irrigating solution outflow conduit (4), collection 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 operational 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), 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 is connected with output pipe module through irrigating solution outflow conduit (4), output pipe module comprises perfusion input pipe, pressure detecting module (8), Drazin inverse module (7) and biochemistry detection module (9), through tee T respectively with perfusion input pipe, pressure detecting module (8), Drazin inverse module (7) is 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 operational module (11) is connected, Drazin inverse module (7) with treat that perfusion ischemic limb is connected, perfusate is after treating perfusion ischemic limb inner loop, collected by catcher (5), in perfusate catcher (5), semipermeable membrane is had to be separated by perfusate, liquid after separation is connected with Micropump.
2. a kind of ischemic limb controlling perfusion system as claimed in claim 1, is characterized in that described Micropump (1) is for Miniature injection pump and syringe or peristaltic pump.
3. one kind uses the ischemic limb controlling perfusion of system as claimed in claim 1, it is characterized in that: Micropump (1) is under Systematical control, realize the perfusion of setting flow and pressure, Micropump exports to perfusate temperature controlling groove (2), in perfusion temperature controlling groove cavity, solid-liquid-gas separator is installed, utilize this volume to realize three phase separation and enough heating-up times simultaneously, for guaranteeing intensification pressure and stability of flow, connection tube between Micropump (1) and perfusion temperature controlling groove adopts spiral type stringing technique, solid-liquid-gas three-phase separator exports to output pipe module, output pipe module comprises perfusion input pipe, pressure detecting module (8), Drazin inverse module (7) and biochemistry detection module (9), through tee T by perfusion input pipe, pressure detecting module (8), Drazin inverse module (7) and biochemistry detection module (9) couple together, perfusion Drazin inverse module (9) controls open and-shut mode by Valve for compressing tubular liner, when the low pressure lower than set-up of control system or the high pressure higher than set-up of control system appearred in pressure, then main control unit (12) controls pressure pipe pipe closedown perfusion output module (9) of Drazin inverse module, play a protective role, perfusion output module (9) adopts BULKHEAD UNION and puncture needle and lower limb or other to test organ or tissue-welding, perfusate is after lower limb or other test object inner loop, collected by catcher (5), in perfusate catcher (5), semipermeable membrane is had to be separated by perfusate, liquid after separation is connected to Micropump, reenter perfusion system, system adopts remote communication module (10) or situ interfacial operational module (11) that operator is operated system.
4. ischemic limb controlling perfusion as claimed in claim 3, it is characterized in that described Micropump (1) provides perfusion power as system, working method is continuous operation and pulsed operation, Micropump provides the flow-control of 0ml/min-1000ml/min, and the adjustment of output relative pressure can be carried out according to the degree of tightness state of Valve for compressing tubular liner (6), range of accommodation is 0mmHg-200mmHg.
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