WO2000029046A2 - Systeme de perfusion - Google Patents

Systeme de perfusion Download PDF

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Publication number
WO2000029046A2
WO2000029046A2 PCT/JP1999/006320 JP9906320W WO0029046A2 WO 2000029046 A2 WO2000029046 A2 WO 2000029046A2 JP 9906320 W JP9906320 W JP 9906320W WO 0029046 A2 WO0029046 A2 WO 0029046A2
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WO
WIPO (PCT)
Prior art keywords
perfusion
catheter
lumen
organ
seal
Prior art date
Application number
PCT/JP1999/006320
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English (en)
Other versions
WO2000029046A3 (fr
Inventor
Mats Allers
Krasnodar Ivancev
Bengt Jeppson
Satoru Murata
Original Assignee
Jostra Ab
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Jostra Ab filed Critical Jostra Ab
Priority to AU11793/00A priority Critical patent/AU1179300A/en
Publication of WO2000029046A2 publication Critical patent/WO2000029046A2/fr
Publication of WO2000029046A3 publication Critical patent/WO2000029046A3/fr

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Classifications

    • 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
    • A61M1/3621—Extra-corporeal blood circuits
    • 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
    • A61M1/3613—Reperfusion, e.g. of the coronary vessels, e.g. retroperfusion
    • 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
    • A61M1/3615—Cleaning blood contaminated by local chemotherapy of a body part temporarily isolated from the blood circuit
    • 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
    • A61M2210/00—Anatomical parts of the body
    • A61M2210/10—Trunk
    • A61M2210/1042—Alimentary tract
    • A61M2210/1071—Liver; Hepar

Definitions

  • the present invention relates to a system and a method for non-surgical perfusion of an organ in a living being, in particular non-surgical perfusion of a liver.
  • Treatment with systemic chemotherapy is one of the presently used possibilities in cancer treatment.
  • substances that are effective in this kind of treatment are often harmful to the system of the body as a whole.
  • the treatment of cancer of the liver presents a serious clinical problem, and the success rate when treating liver cancer is today very low.
  • liver cancer Although primary liver cancer (hepatoma) is rather uncommon in northern Europe and United States, hepatoma is prevalent in other parts of the world, e.g. in Southeast Asia, Japan, the Pacific Islands, Greece, Italy and parts of Africa. Also, many patients with cancer in the gastrointestinal tract develop isolated hepatic metastases, since the liver is the primary target for dissemination. Due to the distribution of the metastases within the liver, only few patients with liver cancer can be cured by resection.
  • Liver cancer is today mainly treated with systemic chemotherapy. However, no substantial increase in the time of survival of the patients is following this treatment (L. M. De Brauw "Isolated liver perfusion. An experimental modality in the treatment of hepatic metastases. " Thesis, University of Leiden, Leiden, The Netherlands.). A reason for these discouraging results seems to be the fact that the toxicity of the chemodrugs limits the possible dosage due to the systemic effects. Local administration by infusion in the hepatic artery does not solve this problem, since the chemodrugs are distributed in the system also during this procedure.
  • a similar catheter is used in the US Patent No. 5,817,046 to Glickman et al., which is hereby incorporated by reference, showing a system for perfusion of the pelvic cavity.
  • the pelvic cavity is isolated between a double catheter, placed in the iliac vein, and bilateral thigh tourniquets.
  • the thigh tourniquets which are used to restrict the flow of blood between the legs and the pelvic cavity of the patient, limit the time during which perfusion can be performed.
  • a balloon catheter with closed tip and device for perfusion with such catheters are described in US Patent No. 5,746,717 to Aigner, which is hereby incorporated by reference.
  • the catheter has at least one contrast marking which enables the position of the catheter inside the body to be determined.
  • the perfusion processes and apparatuses described above all include the return of the blood, which has been contaminated with drugs, to the systemic circulation. This requires treatment to remove the contaminants before this blood can be returned to the body.
  • a particular disadvantage with the prior art occurs when there is a considerable fraction of the blood flow that does not enter or leave the organ through the main input and output blood vessels, which for example is the case in the liver, and there is a risk for leakage of perfusion fluid through these minor vessels to the systemic circulation.
  • the venous side of the liver is close the heart, thus leakage of drugs to the system would potentially very fast cause harm.
  • the object of the present invention is to provide a system for a minimally invasive perfusion of an organ and a method for minimally invasive perfusion, in other words a system and a method for non-surgically isolating and perfusing an organ.
  • a particular object is to provide such a method and system that allow for a prolonged and increased therapeutic effect.
  • Another object and an aspect of the problem to be solved is to decrease the risk of leakage of therapeutic agents, being locally delivered to an essentially isolated organ in a dosage which is harmful for the body as a whole.
  • a further object and aspect of the problem is to provide a method and a system for easily maintaining and controlling flows and pressures of the blood and perfusion fluid in the organ to be perfused and in the body as a whole.
  • a specific aspect of the problem is to provide a system for minimally invasive liver perfusion and thereby to solve the problem of providing a balloon catheter capable of a complete occlusion of blood flow in inferior vena cava between the portion of vena cava inferior that joins the hepatic veins and the portion of vena cava inferior at which the blood flows into the right atrium of the heart.
  • This portion between said vessel junctions is extremely short in human beings, i.e. about 15 mm.
  • the object of the invention is achieved by a system and a method for isolating and perfusing an organ, wherein the main inflow as well as the outflow vessels of the organs are blocked by means of percutaneously introducible occlusive seals.
  • percutaneously introducible passages or conduits preferably in the form of catheters are placed in the main inflow and outflow vessels in order to establish a shunted blood flow for bypassing the normal blood flow of the organ as well as in order to establish an open or a closed circuit for circulating a perfusion fluid.
  • the invention is based on the inventor's realization that, for this kind of operation to be efficient in terms of repeatability and of sparing the patient unnecessary stress that diminishes the positive effect of the treatment, the operation has to be carried out non-surgically.
  • This has been made possible by means of percutaneous catheter technology and specifically designed catheters and perfusion equipment in accordance with the invention.
  • the important advantages of the invention is that the perfusion treatment is invasive to a minimum and therefore repeatable in an unlimited number of treatment occasions.
  • the treatment is also very lenient and would normally take about 2-4 hours in total compared to about 10-12 hours with an invasive, surgical method. Very little stress is therefore imposed on the organism. This entails a substantial saving for the individual patient receiving the treatment as well as for the society bearing the costs of health care and loss of work during treatment.
  • the method comprises the steps of isolating and perfusing the organ by: (a) sealing off the main input and output blood vessels of the organ by means of percutaneously introducible occlusive seals, such that said organ becomes essentially isolated from the systemic blood circulation;
  • the method further comprises the step of: establishing a negative pressure at the outlet of the organ into the perfusion circuit, such that the outflow of said organ is slightly higher than the inflow from the perfusion circuit, whereby the perfusion fluid is supplied with a net volume contribution of blood from the systemic circulation entering the essentially isolated organ.
  • the system according to the invention comprises a catheter set specifically devised to be percutaneously introducible into the blood vessels close to the organ, a pump apparatus for circulating a perfusion fluid and bypassed blood, and a perfusion control apparatus for controlling the operation of the pump apparatus and other components of the system.
  • the catheter set comprises:
  • bypass catheter means being percutaneously introducible into the main inflow and outflow blood vessels of the organ and being devised to lead the systemic blood flow past the organ in a partially extracorporeal bypass circuit;
  • perfusion catheter means being percutaneously introducible into the main inflow and outflow blood vessels of the organ and being devised to lead the flow of perfusion fluid through the organ in a partially extra-corporeal perfusion circuit;
  • occlusive seals being percutaneously introducible in the main inflow and outflow blood vessels and being devised to seal off the main blood inflow and outflow of said organ such that the occlusive seals separate the bypass circuit from the perfusion circuit.
  • a general embodiment of the inventive catheter for use in liver perfusion and adapted to occlude a limited portion of the inferior vena cava is characterised by a first balloon portion positioned at the periphery adjacent to the front end of a catheter tube and being expandable and shrinkable in the radial direction to and from an approximatively disk like shape, thus having a substantially wider extension in the radial than in the axial direction in the expanded state.
  • a liquid path is extending in the axial direction within the catheter tube and is provided for the expansion and shrinkage of said first balloon.
  • Said first balloon is adapted to occlude only the inferior vena at the upper portion of the liver without any occlusion of the hepatic veins and without disturbing the blood flow into the right atrium of the heart.
  • the balloon catheter is adapted to expand radially such that it is capable of occluding the inferior vena cava while having an extension in the axial direction within the range of about 15 mm.
  • the balloon catheter further comprises a second balloon for occluding inferior vena cava mounted at the downstream side in the axial direction with respect to said catheter tube from said first balloon. Said catheter being further provided with side openings for injecting and sucking a liquid, e.g. an anti-cancer agent and the like into and from inferior vena cava between said first and second balloons.
  • said balloon catheter is adapted such that the inferior vena cava is completely occludable by said first and second balloons, and further adapted such that occluded blood is detourable to the jugular vein or the superior vena cava by using pumping means or the like in order to secure blood transport from the inferior vena cava to the heart.
  • the pump apparatus for maintaining a flow in said bypass and perfusion circuits, said pump apparatus comprises:
  • bypass pump which is couplable to the extracorporeal parts of the bypass circuit, for pumping the blood in said bypass circuit
  • a perfusion pump which is couplable to the extracorporeal part of the perfusion circuit, for pumping a perfusion fluid in said perfusion circuit; and (3) means for establishing a negative relative pressure at the perfusion circuit outlet at the organ.
  • the perfusion control apparatus is couplable to the pump apparatus and is devised to control the operation of said pumps such that the outflow of fluid from the organ exceeds the inflow of fluid into the organ in the perfusion circuit due to a net volume contribution of blood from the systemic circulation entering the isolated organ.
  • FIG. 1 shows a general block diagram of the system according to the invention
  • Figure 2 shows a schematic drawing of a liver connected to the system for retrograde perfusion according to one embodiment of the invention
  • Figure 3 shows a schematic drawing of a liver connected to the system for retrograde perfusion according to another embodiment of the invention
  • Figure 4 shows a schematic drawing of an embodiment of a catheter with a disk like catheter devised for the occlusion of the inferior vena cava
  • Figure 5 shows a schematic drawing of another embodiment of a catheter with a disk like balloon in combination with a second ballon devised for the occlusion of the inferior vena cava below the hapatic veins.
  • the invention is a method and a system for performing perfusion of an essentially isolated organ in order to perfuse said organ with a perfusion fluid, which may contain a therapeutic agent.
  • the perfusion can either be performed in antegrade or in retrograde.
  • Antegrade perfusion means that the flow of the perfusion fluid in the perfused organ is of the same direction as the normal systemic blood flow and retrograde means that the perfusion flows are redirected compared to the normal blood flow in the perfused organ.
  • retrograde perfusion provides certain advantages that will be explained below.
  • Fig 1 shows an organ 101 having a main blood input vessel 120 and a main blood output vessel 122. The normal direction of the blood flow is illustrated by thick arrows and perfusion fluid direction by thin arrows.
  • bypass catheter means comprising bypass inlet 111 and outlet 112 conduits or lumens, are percutaneously introduced into the blood vessels to establish a bypass path.
  • the conduits are placed such that the distal opening 118 of the bypass inlet lumen 111 is placed upstream the occlusive seal 106, and such that the distal opening 110 of the bypass inlet lumen is placed downstream the second occlusive seal 108.
  • the proximal ends of the bypass conduits are connected to a bypass pump 126 devised for pumping blood in the bypass path formed by the bypass lumens.
  • Perfusion catheter means comprising perfusion inlet 1 14 and outlet 1 16 conduits or lumens, are percutaneously introduced into the blood vessels to establish a perfusion circuit.
  • the perfusion conduits are placed such that the distal opening 113 of the perfusion outlet lumen 116 is placed between the output of the organ and the occlusive seal 106, and the distal opening of the perfusion inlet lumen 114 is placed between the input of the organ and the occlusive seal 108.
  • the proximal end of the inlet perfusion lumen 1 14 is coupled via a perfusion fluid pump 124, e.g. a roller pump, coupled to a perfusion fluid reservoir 132 containing a perfusion fluid.
  • the perfusion fluid pump is devised to pump perfusion fluid from the reservoir at a controllable pressure or flow rate.
  • the proximal end of the outlet perfusion lumen 116 is coupled to means 134 for establishing a negative relative pressure, e.g. a suction pump in the form of a roller pump or other kinds of pumps.
  • a negative relative pressure e.g. a suction pump in the form of a roller pump or other kinds of pumps.
  • a control apparatus 128 coupled to the pumping means and provided with a control command input 130 is also shown in Fig 1.
  • the control apparatus is devised to control the operation of the pumps such that the outflow of fluid from the organ exceeds the inflow of fluid into the organ in the perfusion circuit due to a net volume contribution of blood from the systemic circulation entering the isolated organ.
  • Embodiments of the perfusion system further includes different parameter sensors for sensing e.g. flow rate, pressure, temperature and the like.
  • a set of catheters is, according to one preferred embodiment of the method and the system of the present invention, placed as described above when the patient is under anaesthetic.
  • the sys tem comprises catheters which are placed as in the following description of the method.
  • a first catheter, having a lumen and an occlusive seal, is thus placed with a distal end on the venous side of the organ in as close proximity to the organ as possible.
  • Said first catheter is the outlet from the organ to the perfusion circuit.
  • a second catheter having a lumen and an occlusive seal, is placed with a distal end on the arterial side of the organ, said catheter being the inlet to the organ in the perfusion circuit.
  • a third catheter having a lumen, is placed with a distal end on the side where blood normally enters said organ, which side usually is arterial, and upstream the occlusive seal of said second catheter.
  • a fourth catheter having a lumen, is placed with a distal end downstream the occlusive seal of said first catheter in the main output blood vessel of the organ. The proximal ends of said first and second catheter are connected to form an, at least partially, extracorporeal perfusion circuit into which the organ to be perfused is connected.
  • catheter three and four are connected to form an, at least partially, extracorporeal bypass circuit through which the blood in the systemic circulation is bypassed said essentially isolated organ.
  • the catheters are extracorporeally connected through tubing, which in one embodiment is isolated in order to preserve the appropriate temperature. Both circuits are connected to pumps for pumping. When all catheters are in place, the systemic blood circulation through said organ is blocked and the circulation is started in the bypass circuit and perfusion circuit, respectively.
  • the perfusion fluid in the perfusion circuit is connected to a supply for therapeutic agent.
  • Leakage from the perfusion circuit is, in one embodiment of the invention, controlled by adding a substance to the perfusion fluid, which substance can be detected in the systemic blood circulation.
  • a substance for example could a carrier medium dye, which is directly visible by imaging, be used as an initial control of the perfusion circuit.
  • Another substance for example a radio marked substance is added together with the therapeutic agent and intermittently analysed blood samples from peripheral circulation or continuously controlled by an extra-corporeal meter capable of measuring radioactivity a blood vessel.
  • the invention can be used for repeated local treatments of various organs, i.e. organs which mainly have well defined input and output blood vessels such as kidney, liver, pancreas, bladder and pelvis.
  • organs which mainly have well defined input and output blood vessels such as kidney, liver, pancreas, bladder and pelvis.
  • the invention is particularly advantageous with retrograde perfusion of an essentially isolated organ, which type of perfusion is preferred in cases when there is a considerable fraction of the blood flow which does not enter or leave the organ through the main input and output blood vessels, for example in case of the liver.
  • Each treatment can proceed a period of time during which the body can manage without having the systemic blood circulation in contact with the perfused organ.
  • the perfusion circuit is normally filled up with uncontaminated fluid, for example blood which may have been drawn from the patient at an earlier time or taken from another blood supply, in order to secure that drugs used for treatment do not spread systemically.
  • FIG. 2 An embodiment of the invention applied on a liver in a human patient is schematically shown in Fig 2.
  • the perfusion is in this example carried out in retrograde on an isolated liver 280.
  • the flow direction in catheters is illustrated by thin arrows and the normal direction of the systemic blood flow by thick arrows.
  • a first catheter 202 having a perfusion lumen 204 and an occlusive seal 210, is placed in the inferior vena cava 282 of the patient such that the seal is placed close to but upstream, below in Fig 2, the hepatic veins 284 and the distal end opening 206 of the lumen 204 is positioned downstream said occlusive seal 210 preferably at level with the hepatic veins.
  • the first catheter 202 is for example introduced via vena femoralis and is preferrably devised to be placed in vena cava inferior by means of an introducer having a maximum outer diameter of 14 French, the occlusive seal of said first catheter being devised to be capable of efficiently sealing off vena cava inferior upstream the hepatic veins.
  • Fig 4 shows a detailed view of an example of a catheter suitable for entering to the inferior vena cava via the superior vena cava.
  • This catheter is provided with an occlusive balloon 402 with a disk like shape devised to seal off the portion of the inferior vena cava between the hepatic veins and the entrance to the heart with a minimal extension in the axial direction.
  • the ballon 402 is positioned adjacent the front end of the catheter.
  • a lumen is provided for passing liquid to the balloon for balloon expansion, and a further lumen is provided for passing liquid from the distal end of the catheter to one or several openings 404.
  • a second catheter 212 having a bypass lumen 213 and an occlusive seal 216, is placed in the inferior vena cava 282 of the patient such that the seal 216 is placed between the heart 286 and the hepatic veins 284 and the distal end opening 214 of the bypass lumen 213 ends on the proximal side of the occlusive seal 216.
  • the second catheter 212 is introduced via vena cava superior 283 and is devised to be placed in vena cava inferior 282 by means of an introducer having a maximum outer diameter of 14 French, the occlusive seal of said second catheter being capable to efficiently seal off vena cava inferior between the hepatic veins 284 and the heart 286 without blocking any of the hepatic veins.
  • a third catheter 220 is placed in vena porta 288. The third catheter is devised to be placed in vena porta percutaneously and trans-hepatically by means of an introducer with a maximum outer diameter of 12 French.
  • the third catheter is provided with an introducer 222, having an introducer lumen 224 with distal 226 and proximal 228 end openings and being devised to operate .as a perfusion lumen, a bypass lumen 230 with distal 232 and proximal 234 end openings and an occlusive seal 236.
  • the third catheter is devised such that the occlusive seal is positioned between said distal end opening of the bypass lumen and said distal end opening of the introducer lumen during operation of the system.
  • Vena porta 288 branches into several veins before it enters the liver and the seal 236 of said third catheter 220 must be placed upstream these branches.
  • the vena porta is difficult to enter due to its position between the liver and the intestinal parts. According to the invention vena porta is therefore entered through the liver, which due to its structure is relatively undamaged.
  • a fourth catheter 240 is placed in the hepatic artery 290.
  • the fourth catheter is provided with a perfusion inlet lumen 242 with distal 244 and proximal 246 end openings and an occlusive seal 248, said distal end opening being positioned distally of the occlusive seal.
  • the fourth catheter 240 is devised to be placed in the hepatic artery 290 by means of an introducer with a maximum outer diameter of 5 French, the occlusive seal of said fourth catheter being capable to efficiently seal off the hepatic artery.
  • a fifth catheter 250 is placed in vena cava inferior 282 upstream the occlusive seal 210 of the first catheter 202.
  • the fifth catheter is provided with a bypass lumen 252 with distal 254 and proximal 256 end openings, and is devised to be placed in vena cava inferior by means of an introducer having a maximum outer diameter of 14 French.
  • a partially extracorporeal bypass circuit is formed by connecting the proximal end opening 256 of the lumen of said fifth and the proximal end opening 234 of the bypass lumen of said third catheter to a bypass pump 260.
  • the bypass pump 260 e.g. a roller pump, is further coupled to the proximal end opening 218 of the bypass lumen of said second catheter.
  • the venous blood from the lower parts of the body is taken out through the fifth catheter and is, together with the venous blood from the intestines taken out through the lumen of the third catheter, reentered into the systemic blood circulation above the liver 280 through the second catheter 212.
  • a partially extracorporeal perfusion circuit is formed by connecting the proximal end opening 228 of the introducer lumen of said introducer 222 of said third catheter with a perfusion fluid reservoir 268 via means for establishing a negative relative pressure, e.g. a pump perhaps in the form of a roller pump.
  • the proximal end opening 208 of the lumen of the first catheter 202 and the proximal end opening 246 of the lumen of the fourth catheter are connected to the reservoir 268 via a pump 264, e.g a roller pump.
  • the perfusion fluid is pumped from the reservoir into the hepatic veins 284 and the hepatic artery 290, and to the reservoir from vena porta.
  • the portal vein (vena porta) is advantageous to use for establishing a negative relative pressure at the perfusion outlet of the liver, since it is surrounded and strengthened by a relatively rigid structure which prevents the portal vein from collapsing.
  • this feature does not occur in the vessels entering or leaving the organ to be perfused, it is conceivable to provide, at the perfusion outlet opening of a catheter, a structure devised to prevent the vessel from collapsing, for example in the form of a stent.
  • FIG 3 Another embodiment of the invention applied on a liver in a human patient is schematically shown in Fig 3.
  • the perfusion is also in this example carried out in retrograde on an isolated liver 280.
  • the flow direction in catheters is illustrated by thin arrows and the normal direction of the systemic blood flow by thick arrows.
  • a first catheter 302 is placed in vena cava inferior, said first catheter having a perfusion lumen 304 with distal 306 and proximal 308 end openings and a first occlusive seal 310 being positioned distally of said distal end opening and a second occlusive seal 312 being positioned proximally of said distal end opening 306.
  • the first catheter 302 is devised to be placed in vena cava inferior 282 by means of an introducer having a maximum outer diameter of 14 French, the first occlusive seal of said first catheter being capable to efficiently seal off vena cava inferior between the heart 286 and the hepatic veins 284, and the second occlusive seal of said first catheter being capable to efficiently seal off vena cava inferior 282 below the hepatic veins 284.
  • An embodiment of a double balloon catheter devised in accordance with the inventive concept is shown in Fig 5. This catheter 501 is provided with a disk like balloon 502 close to the distal end of the catheter.
  • the disk like balloon is as specified above specifically designed to have an extension in the radial direction that is suitable for occluding the inferior vena cava between the hepatic veins and the inferior vena cava while having a minimal extension in the axial direction.
  • a second balloon 504 of a more ordinary type is provided a distance, e.g. 5-20 cm, closer to the proximal end of the catheter and is devised to occlude the inferior vena cava below the hepatic veins.
  • One or more openings 506 are provided between the two occluding balloons for passing a liquid through a lumen from or to the proximal end of the catheter dependent on if liquid is sucked or infused.
  • an opening 508 positioned at the proximal side of the second balloon is connected via a lumen to an opening 509 positioned at the distal side of the first balloon and devised for bypassing blood from the inferior vena cava upstream of the second balloon to the right atrium of the heart downstream the first balloon.
  • the catheter is also provided with lumens for passing liquid to the balloons in order to expand them for exclusion.
  • a second catheter 320 is placed in vena cava inferior, said second catheter having a bypass lumen 321 with distal 322 and proximal 324 end openings.
  • the second catheter 320 is devised to be placed in vena cava inferior by means of an introducer having a maximum outer diameter of 14 French.
  • a third catheter 330 is placed in vena porta 288, the third catheter being provided with an introducer 332, having an introducer lumen 334 with distal 336 and proximal 338 end openings and being devised to operate as a perfusion lumen, said catheter having a bypass lumen 340 with distal 342 and proximal 344 end openings and an occlusive seal 346, said third catheter being devised such that the occlusive seal is positioned between said distal end opening of the bypass lumen and said distal end opening of the introducer lumen during operation of the system.
  • the third catheter 330 is devised to be placed percutanously and trans hepatically in vena porta by means of an introducer with a maximum outer diameter of 12 French, the occlusive seal of said third catheter being devised to be capable of efficiently sealing off vena porta.
  • a fourth catheter 348 is placed in the hepatic artery 290, said fourth catheter having a perfusion inlet lumen 350 with distal 352 and proximal 354 end openings and an occlusive seal 356, said distal end opening being positioned distally of the occlusive seal.
  • the fourth catheter 348 is devised to be placed in the hepatic artery by means of an introducer with a maximum outer diameter of 5 French, the occlusive seal of said fourth catheter being capable to efficiently seal off the hepatic artery
  • a fifth catheter 360 is placed is placed in the inferior vena cava upstream or below the occlusive seal 312 of the first catheter 302.
  • the fifth catheter is merely provided with a bypass lumen 362 with distal 364 and proximal 366 end openings.
  • Fig 3 is coupled in an analougue with the embodiment of Fig 2.
  • a second catheter 212 having a bypass lumen 213 and an occlusive seal 216, is placed in the inferior vena cava 282 of the patient such that the seal 216 is placed between the heart 286 and the hepatic veins 284 and the distal end opening 214 of the bypass lumen 213 ends on the proximal side of the occlusive seal 216.
  • the second catheter 212 is introduced via vena cava superior 283 and is devised to be placed in vena cava inferior 282 by means of an introducer having a maximum outer diameter of 14 French, the occlusive seal of said second catheter being capable to efficiently seal off vena cava inferior between the hepatic veins 284 and the heart 286 without blocking any of the hepatic veins.
  • a third catheter 220 is placed in vena porta 288.
  • the third catheter is devised to be placed in vena porta percutaneously and trans-hepatically by means of an introducer with a maximum outer diameter of 12 French.
  • the third catheter is provided with an introducer 222, having an introducer lumen 224 with distal 226 and proximal 228 end openings and being devised to operate as a perfusion lumen, a bypass lumen 230 with distal 232 and proximal 234 end openings and an occlusive seal 236.
  • the third catheter is devised such that the occlusive seal is positioned between said distal end opening of the bypass lumen and said distal end opening of the introducer lumen during operation of the system.
  • Vena porta 288 branches into several veins before it enters the liver and the seal 236 of said third catheter 220 must be placed upstream these branches.
  • the vena porta is difficult to enter due to its position between the liver and the intestinal parts. According to the invention vena porta is therefore entered through the liver, which due to its structure is relatively undamaged.
  • a fourth catheter 240 is placed in the hepatic artery 290.
  • the fourth catheter is provided with a perfusion inlet lumen 242 with distal 244 and proximal 246 end openings and an occlusive seal 248, said distal end opening being positioned distally of the occlusive seal.
  • the fourth catheter 240 is devised to be placed in the hepatic artery 290 by means of an introducer with a maximum outer diameter of 5 French, the occlusive seal of said fourth catheter being capable to efficiently seal off the hepatic artery.
  • a fifth catheter 250 is placed in vena cava inferior 282 upstream the occlusive seal 210 of the first catheter 202.
  • the fifth catheter is provided with a bypass lumen 252 with distal 254 and proximal 256 end openings, and is devised to be placed in vena cava inferior by means of an introducer having a maximum outer diameter of 14 French.
  • the extra-corporeal parts of the bypass and perfusion circuits consist mainly of tubing which is connected to the proximal ends of the catheters through per se known connections.
  • these connections are e.g. luer lock conncetions, but other types of connections such as screw connections are conceivable.
  • the liver By sealing off the flow of blood as described above the liver is essentially isolated from the systemic circulation. Although, there is still a number of minor arteries and veins which still connect the organ to the rest of the body 200.
  • the circuits are filled with fluid in order to ensure that air does not enter the body through the circuits. Circulating the blood past the liver in the bypass circuit is achieved by pumping. The pressure of the venous blood in the lower parts of the body and in vena porta is not high enough to press the blood all the way to the outlet of the perfusion circuit.
  • the same portions of the vessels as described above are occluded.
  • a perfusion fluid is instead injected into the portal vein through the sheath of the catheter introduced into the portal vein. Blood mixed with perfusion fluid is sucked from the portion of inferior vena cava between the occluding balloons.
  • the flow is reversed as compared to the above described embodiment.
  • a perfusion fluid reservoir is connected to the perfusion lumens.
  • the perfusion fluid is withdrawn from the perfused organ by establishing a negative relative pressure at the perfusion outlet from the organ
  • a negative relative pressure is in a simple embodiment achieved by arranging a relative difference in height between the reservoir and the perfused organ, e.g. by means of a vertically movable mounting of the reservoir.
  • a more active suction is for example achieved by pumping or by lowering the pressure above the fluid in the perfusion fluid reservoir.
  • Therapeutic agents to be used for treatment of the perfused liver is entered into the perfusion circulation through the perfusion fluid reservoir.
  • the perfusion circuit is filled with uncontaminated fluid and the organ is filled with this clean blood before the occlusive seals are unsealed and the circulation is turned off.
  • heating equipment devised to heat the fluid in the perfusion circuit
  • an oxygenator devised to oxygenate the fluid in perfusion circuit
  • Embodiments of the system of the present invention includes means for exchanging the fluid in the perfusion circuit after finsihed treatment, such means are for example a T-valve in the perfusion circuit tubing, which valve is connected to a supply of uncontaminated fluid.
  • the circulation in the perfusion and the bypass circuits is in preferred embodiments maintained and controlled by means of a perfusion apparatus comprising two pumps, a perfusion fluid reservoir and a control apparatus.
  • a heart-lung machine may, when operated by a very skilled person however also, be used as perfusion apparatus.
  • the system further comprises a substance to be added to the perfusion fluid for enabling control of potential leakage to the systemic circulation and/or a substance to be added to the fresh blood or the perfusion fluid for enabling control of the exchange of perfusion fluid with fresh blood.

Landscapes

  • Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oncology (AREA)
  • External Artificial Organs (AREA)
  • Media Introduction/Drainage Providing Device (AREA)

Abstract

L'invention porte sur un système non chirurgical de perfusion, en particulier du foie (101) comprenant: un cathéter de dérivation s'introduisant par voie percutanée dans un vaisseau sanguin de l'organe et conçu pour dériver le flux sanguin au-delà de l'organe; un cathéter de perfusion s'introduisant également par voie percutanée dans un vaisseau sanguin et conçu pour conduire le fluide de perfusion dans l'organe; des obturateurs (106, 108) séparant le circuit de dérivation du circuit de perfusion; un dispositif de pompage comprenant une pompe (126) de dérivation; une pompe de perfusion; des moyens établissant une dépression relative à la sortie de perfusion de l'organe; et un appareil (128) commandant la pompe pour que le débit de sortie de perfusion de l'organe dépasse celui d'entrée compte tenu de l'apport net de sang de la circulation systémique pénétrant dans l'organe isolé.
PCT/JP1999/006320 1998-11-12 1999-11-12 Systeme de perfusion WO2000029046A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU11793/00A AU1179300A (en) 1998-11-12 1999-11-12 Perfusion system

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP35998098A JP2004135688A (ja) 1998-11-12 1998-11-12 血管用バルーンカテーテル
JP10/359980 1998-11-12

Publications (2)

Publication Number Publication Date
WO2000029046A2 true WO2000029046A2 (fr) 2000-05-25
WO2000029046A3 WO2000029046A3 (fr) 2000-11-09

Family

ID=18467288

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1999/006320 WO2000029046A2 (fr) 1998-11-12 1999-11-12 Systeme de perfusion

Country Status (3)

Country Link
JP (1) JP2004135688A (fr)
AU (1) AU1179300A (fr)
WO (1) WO2000029046A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102100570A (zh) * 2011-02-17 2011-06-22 浙江大学 一种肝门阻断装置
EP2498858A1 (fr) * 2009-11-09 2012-09-19 Delcath Systems, Inc. Systèmes et méthodes de traitement homéostatique de maladie des organes par administration locale d'agents thérapeutiques
WO2024016168A1 (fr) * 2022-07-19 2024-01-25 上海诺英医疗器械有限公司 Système de perfusion intelligent

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100473432C (zh) * 2006-12-30 2009-04-01 中国人民解放军第三军医大学第一附属医院 肝段定位导管
JP6905220B2 (ja) * 2017-03-08 2021-07-21 国立大学法人 大分大学 バルーン位置確認システム

Citations (6)

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US4192302A (en) 1978-09-12 1980-03-11 Boddie Arthur W Hepatic isolation and perfusion circuit assembly
US4714460A (en) 1983-07-29 1987-12-22 Reynaldo Calderon Methods and systems for retrograde perfusion in the body for curing it of the disease or immume deficiency
US4883459A (en) 1983-07-29 1989-11-28 Reynaldo Calderon Retrograde perfusion
EP0364799A2 (fr) 1988-10-21 1990-04-25 Delcath Systems, Inc. Traitement de cancer
US5746717A (en) 1993-03-30 1998-05-05 Aigner; Karl R. Balloon catheter and device for perfusion with the balloon catheter
US5817046A (en) 1997-07-14 1998-10-06 Delcath Systems, Inc. Apparatus and method for isolated pelvic perfusion

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US4655746A (en) * 1985-12-02 1987-04-07 Target Therapeutics Catheter device
DE3705637A1 (de) * 1987-02-21 1988-09-29 Bissendorf Peptide Gmbh Vorrichtung zur entfernung von lokal applizierten wirkstoffen gegen solide tumoren
US5458574A (en) * 1994-03-16 1995-10-17 Heartport, Inc. System for performing a cardiac procedure

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4192302A (en) 1978-09-12 1980-03-11 Boddie Arthur W Hepatic isolation and perfusion circuit assembly
US4714460A (en) 1983-07-29 1987-12-22 Reynaldo Calderon Methods and systems for retrograde perfusion in the body for curing it of the disease or immume deficiency
US4883459A (en) 1983-07-29 1989-11-28 Reynaldo Calderon Retrograde perfusion
EP0364799A2 (fr) 1988-10-21 1990-04-25 Delcath Systems, Inc. Traitement de cancer
US5746717A (en) 1993-03-30 1998-05-05 Aigner; Karl R. Balloon catheter and device for perfusion with the balloon catheter
US5817046A (en) 1997-07-14 1998-10-06 Delcath Systems, Inc. Apparatus and method for isolated pelvic perfusion

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2498858A1 (fr) * 2009-11-09 2012-09-19 Delcath Systems, Inc. Systèmes et méthodes de traitement homéostatique de maladie des organes par administration locale d'agents thérapeutiques
EP2498858A4 (fr) * 2009-11-09 2013-08-28 Delcath Systems Inc Systèmes et méthodes de traitement homéostatique de maladie des organes par administration locale d'agents thérapeutiques
CN102100570A (zh) * 2011-02-17 2011-06-22 浙江大学 一种肝门阻断装置
WO2024016168A1 (fr) * 2022-07-19 2024-01-25 上海诺英医疗器械有限公司 Système de perfusion intelligent

Also Published As

Publication number Publication date
JP2004135688A (ja) 2004-05-13
AU1179300A (en) 2000-06-05
WO2000029046A3 (fr) 2000-11-09

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