Patent Application
20050059931
The present invention relates generally to intravascular drug delivery to localized and semi-localized regions. The invention includes a catheter device having one or more occluding devices, preferably balloons, associated therewith.
Methods for localized and semi-localized drug delivery are disclosed in Yock et al. U.S. Pat. No. 6,346,098, which is incorporated by reference, in its entirety, herein. The aforesaid Yock et al. patent describes several ways in which a pressurized system can be used to accomplish retrograde perfusion, alone or in conjunction with other modalities, e.g., energy, to cause disruption or increased porosity in a localized region of the wall of a blood vessel whereby an agent, e.g., a therapeutic substance, is caused to pass through the wall of a blood vessel to produce the desired effect in the tissue surrounding the localized delivery site. Angiogenesis and myogenesis are two particularly desirable uses of the Yock et al. method. Given the desirability of the effective use of that method, there remained a need for apparatus which would improve the effectiveness of the method and for improvements in the method itself.
It is also noted that Corday et al. U.S. Pat. Nos. 4,689,041 and 5,033,998 make use of a catheter having an occluding balloon at its distal end for retrograde venous injection of fluids into a blockaded region of the heart which has become inaccessible by reason of an occluded artery. The method of Corday et al. involves placing the balloon into the coronary sinus and directing fluid retrograde into all veins of the heart. Since the objective of Corday et al. is to deliver cardioplegic solution to the entire heart, the described system would appear to be suited for its purpose. However, it would not be useful to achieve the objectives of Yock et al. U.S. Pat. No. 6,346,098 which are centered on localized and semi-localized delivery through the wall of a blood vessel.
The patent to Glickman, U.S. Pat. No. 5,919,163, which is incorporated herein by reference, describes the use of a double balloon catheter to isolate a tumor for chemotherapy treatment.
The apparatus of the present invention includes a catheter system for delivery of an agent, where the catheter system has one or more occluding devices, preferably balloons, which function to isolate a region within a blood vessel whereby the delivery of an agent through the blood vessel wall will take place only in the localized or semi-localized region. In one embodiment of this catheter system, at least two members, each of which may be a catheter, are used to carry an occluding device to the desired location in the blood vessel. At least one of the catheters preferably has two or more regions of variable stiffness. In this embodiment, the catheter system preferably comprises a telescoping assembly of two catheters, each provided with an occlusion device whereby the length of the isolated region may be varied. The occlusion device may be an inflatable member such as a balloon. In this event, the catheter provided with an inflatable occlusion device may be provided with an inflation lumen, which communicates with the inflatable occlusion device.
The first, or distal, inner catheter includes a distal occlusion device and is configured to move within a lumen of a second, or proximal, outer catheter having a proximal occlusion device. A desired agent can be delivered to the isolated space between the two occlusion devices from an open distal end of the outer catheter, and then infused into the localized region. In an additional embodiment, a separate lumen can be provided for infusion, preferably located within the inner catheter. In either embodiment, the sizing of the infusion lumen will depend on the infusion flow rate desired.
Many of the catheter embodiments described herein can be used to infuse an agent into regions of differing size. Depending on the particular application as well as the anatomy of the vasculature, infusion can occur to either a localized region or a larger, semi-localized region, both of which are located external to the blood vessel. For example, one location where localized delivery of the agent can occur is in a continuous blood vessel segment isolated by occlusion devices and without side branches. When the fluid pressure of the agent within the isolated space of the vessel reaches a high enough level, the vessel walls can become disrupted and allow the agent to pass through the walls and into the localized region surrounding the vessel.
Alternatively, one location where semi-localized delivery of the agent can occur is in a blood vessel segment having numerous smaller side branches or connecting vessels. These smaller vessels can limit the potential collateral escape of the agent by restricting flow of the agent to such a degree that the desired infusion pressure can be reached. Once the pressure is great enough, the smaller vessels can become disrupted, and in some case even burst, allowing the infusion agent to pass through and into the surrounding tissue or interstitium. By delivering and infusing the agent through each of these smaller vessels, a much larger, semi-localized region can be reached. This can be desirable in certain applications because it allows infusion of more of the agent over a wider area.
The catheter system of the present invention may use a coaxial or dual-lumen construction for the outer catheter and may use a tri-lumen construction for the inner catheter. In one embodiment, the system is provided with a pressure monitoring lumen in the distal catheter. This lumen extends distally along the length of the inner catheter and has a distal end, which is provided with a port, which opens into the space outside of the catheter at a location proximal to the distal occlusion device. When the two catheters are placed axially within a blood vessel, the port at the distal end of the pressure monitoring lumen is located between the two occlusion devices. The proximal end of the pressure monitoring lumen can be coupled with a pressure sensor and used to monitor pressure in the space between the two occlusion devices.
In still another embodiment, the system can be constructed such that the outer catheter with the proximal occlusion device is placed first using a guide wire and/or malleable stylet, such that this catheter acts as a guide for the inner catheter having the distal occlusion device. In certain applications, it is desirable for the outer catheter to be placed in the coronary sinus and certain physical characteristics are desirable for this purpose. These characteristics include a reinforced shaft which can transmit torque in its proximal region, which does not enter the vasculature (e.g., approximately 50 cm). The distal end is more flexible thereby enabling tracking into the venous anatomy. Additionally, the outer catheter shaft can have a pre-formed curve in its distal region, so that the catheter can be pointed in the proper direction to facilitate making a turn into the coronary sinus. A dilator can be used to substantially straighten the pre-formed curve if desired. Alternatively, the catheter shaft can be substantially straight and used in conjunction with a stylet to facilitate navigation within the coronary sinus.
The present invention also includes a system in which the inner catheter and the outer catheter are placed such that the inner catheter is placed first and acts as a rail over which the outer catheter may be advanced. In one embodiment thereof, before introducing either catheter, a guide wire is placed within the vessel and the inner catheter is advanced with the aid of the guide wire. In another embodiment thereof, the guide wire is integrated with the inner catheter and can be advanced into the vessel without the aid of an additional guiding device. The integrated guide wire can be coupled to the distal end of the inner catheter and can extend distally therefrom. The guide wire can also be curved to facilitate navigation within the vasculature. In another embodiment, the distal end of the guide wire is covered by and coupled with an atraumatic distal tip of the inner catheter.
In another embodiment of the present invention, an additional occlusion device can be provided with the inner catheter so that the inner catheter has both a distal and a proximal occlusion device enabling the inner catheter to be used without the outer catheter. This embodiment can be used to isolate a small, fixed, axial region of the blood vessel. An infusion lumen is provided within the inner catheter and connected to an aperture located between the two occlusion devices such that the desired infusion agent can be delivered to this isolated region. If the outer catheter is used, occlusion can be performed using one of the occlusion devices on the inner catheter and the occlusion device on the outer catheter.
In certain applications, the catheter system of the present invention can be used to deliver an agent to a semi-localized or localized region of the body with only one occlusion device. In one example embodiment, the inner catheter includes an axially indented occlusion device, which is preferably a balloon, that can create an isolated region of the blood vessel corresponding to the shape of the indentation. When the balloon is inflated, it contacts the entire circumference of the blood vessel along an axial length, except for the region of the blood vessel adjacent where the indented portion is located. The isolated region corresponds to where the indented portion of the balloon does not contact the vessel wall. The axial indentation is preferably located in the middle section of the balloon. A portion of the indentation preferably contacts the inner catheter such that an aperture can be provided in the inner catheter to deliver the infusion agent to the isolated region and into the localized region of the body.
This embodiment can also be used to deliver the agent to a semi-localized region of the body. For instance, the axial indentation of the balloon can be aligned within the blood vessel such that the region of the blood vessel adjacent to the indented portion of the balloon includes a communicative junction with a second blood vessel, i.e., an opening for blood to flow into or out of a second blood vessel. This second blood vessel preferably branches into a plurality of smaller vessels that form a flow restricting configuration that limits any potential collateral escape and allows the agent to be delivered at a pressure sufficient to infuse the agent through the numerous smaller vessels and into the larger, semi-localized region.
In other embodiments, a substantially isolated region is created using only one occlusion device located on the outer catheter. These embodiments are preferable in applications where the vessel where infusion is to occur has a flow restricting configuration that limits any potential collateral escape of the agent. The occlusion device on the outer catheter is expandable to occlude the vessel and create a substantially isolated blood vessel region defined by the downstream, or proximally located occlusion device and the upstream, or distally located flow restricting configuration of the vessel. The agent can then be delivered to the isolated region through an infusion means located distal to the occlusion device.
In an example embodiment of a catheter system having one occlusion device, the outer catheter can include an inner tubing, middle reinforced tubing and an outer tubing. The outer tubing can include a first occlusion balloon that is expandable to create a substantially isolated blood vessel region. The middle tubing is preferably coupled with the outer tubing and extends within the outer tubing. The space between the middle tubing and the outer tubing defines a first lumen configured to pass an inflation medium to the first occlusion balloon. The inner tubing is preferably coupled with the middle tubing and extends within the middle tubing. The space between the middle tubing and the inner tubing defines a second lumen configured to deliver an infusion agent to an open distal end of the middle tubing. The space within the inner tubing defines a third lumen configured to monitor pressure within the isolated blood vessel region.
The catheter system of the present invention can also include a pressure regulator for regulating the pressure of an infusion agent in the isolated blood vessel region. The pressure regulator can be incorporated in an injection device, or it can be coupled between an injection device and the catheter system. The pressure regulator can be an accumulator type pressure regulator or can regulate the allowable fluid flow rate directly, such as with a valve and the like. The pressure regulator can also use fluid pressure feedback from the infusion site to regulate the fluid flow rate at the injection device.
Infusion pressure can be regulated in at least two ways. Infusion pressure can be regulated passively, e.g., by including a biased reservoir that controls flow through a regulator at the input or output of the catheter system based on the fluid pressure within the reservoir. Infusion pressure can also be regulated actively, e.g., by monitoring the infusion pressure at the infusion site with a fluid pressure feedback and using this feedback pressure to control flow through the regulator located at the input to the catheter system. At least partial passive pressure regulation is preferable in order to prevent the fluid pressure at the infusion site from exceeding a maximum desired pressure that might injure the patient.
The balloons are preferably fabricated from a compliant material and have a variable diameter depending on inflation volume and/or pressure. Such materials include elastic polymers such as elastomeric polyurethane, silicone polymers, synthetic rubbers such as polyneoprene, neoprene and polybutylene, thermoplastic elastomers and other elastic materials well known to those skilled in the art. The balloons can be configured with any desired shape, such as spherical or cylindrical.
Radio opaque markers may be added to one or both catheters to mark desired points on catheters, e.g., the distal region of each catheter and/or the proximal position of the distal occlusion device. Also, radio opaque dye can be injected through the annular space during placement of the catheter. The use of radio opaque markers or dye will help catheter positioning and accurate measurement of the infusion space. Furthermore, radio opaque dye can be introduced with the agent, or prior to delivery of the agent, to monitor the infusion of the agent into the localized or semi-localized region.
The present invention also provides numerous methods for infusing an agent to a localized or semi-localized region of the body. These methods are capable of use with each of the various embodiments of the catheter system described above.
FIGS. 1A-B illustrate schematic views of example embodiments of the catheter system of the present invention.
FIGS. 2A-B illustrate the regions of one example embodiment of the outer catheter, which have different stiffnesses.
FIGS. 8A-B illustrate an alternate example embodiment in which an integrated guide wire and inner catheter are provided with an expandable occlusion device.
FIGS. 11A-C illustrate the catheter system with an example embodiment of the inner catheter.
FIGS. 12A-B illustrate additional example methods of delivering an infusion agent using the catheter system of the present invention.
FIGS. 13A-C illustrate cross-sectional views of the catheter system with another example embodiment of the inner catheter.
FIGS. 15A-C illustrate the catheter system with additional example embodiments of the outer catheter.
FIGS. 17, 18A-C, 19A-C, 20A-C, 21, 22, 23A-B, 24A-D and 25A-B illustrate example embodiments of a pressure regulator which may be used in conjunction with the present invention.
As can be seen from FIGS. 1A-B, one example embodiment of the present invention comprises two catheters, each of which is provided with an occlusion device. The catheter system is constructed such that it can pass over guide wire 1. Inner catheter 2 carries distal occlusion device 3. Similarly, outer catheter 4 carries proximal occlusion device 5. One of skill in the art will readily recognize that any occlusion device can be used with the present invention and, accordingly, the present invention is not limited to any particular type or style of occlusion device. Here, occlusion devices 3 and 5 are balloons. Occlusion balloons can be shaped according to the needs of the application. In
This construction facilitates deployment of the distal region of the catheter through the coronary sinus into distal venous branches of the patient, which is desirable when treatment will be for purposes of angiogenesis or myogenesis. In a preferred embodiment of the present invention, cells which will promote angiogenesis or myogenesis are delivered to a localized region of the heart.
As shown in
In a preferred embodiment of the present invention, the inner catheter 2 is slidably associated with outer catheter 4 such that the space between balloon 3 and balloon 5 can be varied according to the circumstances of the desired treatment. Published U.S. patent application 2002/0188253, which is incorporated herein by reference, discloses a dual balloon system in which the catheters are slidable with relation to each other to thereby vary the space between the balloons as desired.
One of skill in the art will readily recognize that the placement of balloon 5 and the lengths of each region 10, 11 and 12 can be varied based on the needs of the individual application. For instance, an application may be very susceptible to pinch off in which case balloon 5 can be placed on the relatively stiff proximal region 10. Also, an application may require relatively smaller distance between balloons 3 and 5. In this case, balloon 5 can be placed on softer region 12 so long as the inflation pressure and the region durometer hardness is not such as to cause outer catheter 4 to collapse. Also, balloon 5 can be placed on the relatively stiff proximal region 10 and the relative lengths of each region 10 and 11 can be shortened, so long as the catheter retains sufficient track-ability to allow advancement into the target region of the patient.
In
In the embodiments of
The infusion pressure in the isolated blood vessel region is preferably measured with the pressure monitoring lumen 15. However, the infusion pressure can also be calculated from the pressure in main lumen 13 when the agent is being delivered, based on the flow rate, viscosity of solution, flow resistance of the catheters 2 and 4 and assuming steady state flow. If the pressure is measured in this manner, the pressure monitoring lumen 15, illustrated in
All of the catheters shown herein may be circular in cross section or may have other shapes such as elliptical or irregular.
Two conventional methods could be employed to advance a catheter to the target vessel. In the first method, a guide wire is first advanced to the target vessel and then the catheter is advanced over the guide wire. In order to do this, the catheter must have an open distal end. However, if there is not a smooth tapered transition between the guide wire and the open end, then the open end can skive, or scratch, the interior of the blood vessels as the catheter is advanced. In the second method, a guide wire is first advanced to the target vessel and then a guiding catheter is advanced over the guide wire into proximity with the target vessel. The guide wire is then removed and the catheter is advanced within the guiding catheter to the target vessel. Again, there is a risk of skiving because the guiding catheter must have an open distal end to be advanced along the guide wire. FIGS. 8A-B and 9 illustrate example embodiments of the catheter system of the present invention that improve over these conventional systems and methods.
Also shown is outer catheter 4, which has a coaxial configuration and is deployed over inner catheter 2, also in a coaxial configuration. Outer catheter 4 includes inner tubing 19A and outer tubing 19B configured in a coaxial manner. Outer catheter 4 also includes occlusion device 5, which is depicted as a balloon in this embodiment. Lumen 13 is located within inner tubing 19A and is preferably used to deliver the desired infusion agent through open distal end 34. Annular lumen 18 is located between inner tubing 19A and outer tubing 19B and is preferably used to transmit the inflation medium to balloon 5. Balloon 5 can also be integrally coupled with outer catheter 4 in a manner similar to that described above.
Atraumatic tip 40 is located at the distal end of guide wire 32. Atraumatic tip 40 is softer than guide wire 32 and facilitates introduction of guide wire 32 into the blood vessel in an atraumatic fashion. In the example embodiment depicted here, atraumatic tip 40 is a springform tip. Springform tip 40 is preferably a coiled wire placed over a tapered end of guide wire 32 and can be optionally used as a radio opaque marker. The distal end 99 of outer catheter 4 is preferably beveled to reduce the risk of skiving. Here, infusion of the agent occurs in the localized region surrounding the isolated segment of vessel 98. However, it should be noted that the presence of one or more additional, side-branching vessels forming a flow restricting configuration in the isolated region of vessel 98 can allow infusion to occur in a larger semi-localized region.
In FIGS. 8A-B, the coupling of inner catheter 2 to guide wire 32 eliminates the clinical step of inserting the inner catheter 2 over a previously inserted guide wire, which simplifies the overall medical procedure. Here, both the inner catheter 2 can be inserted directly and navigated to the desired location with the aid of integrated guide wire 32. In addition, there is no open distal end of inner catheter 2 that can skive the interior of the blood vessels.
In
Next, at 704, occlusion device 3 associated with inner catheter 2 is positioned distally from the distal end of outer catheter 4. Then, at 706, occlusion devices 3 and 5 are expanded such that the blood vessel is occluded by occlusion device 3 in a first location and occluded by occlusion device 5 in a second location proximal to the first location. The two occlusion devices 3 and 5 can be expanded in any order or simultaneously as desired. Finally, at 708, an agent is delivered to the region of the blood vessel located between the two expanded occlusion devices 3 and 5 at a pressure sufficient to infuse the agent into a localized or semi-localized region of the body.
Integration of inner catheter 2 with guide wire 32 creates numerous advantages and gives the catheter system of the present invention added flexibility in implementation. However, inner catheter 2 can be provided in multiple other configurations, each providing additional advantages and added flexibility in the implementation of the catheter system. For instance, the catheter system can be configured to occlude small fixed lengths of a target blood vessel, e.g., by adding a second occlusion device to inner catheter 2. FIGS. 11A-C depict example embodiments of the catheter system where inner catheter 2 is provided with two occlusion devices, distal occlusion device 50 and proximal occlusion device 52. This configuration is preferably used to occlude and isolate a relatively short, fixed length of a blood vessel region between the two devices 50 and 52. In this embodiment, occlusion devices 50 and 52 are balloons and are spaced closely together for applications requiring infusion in a very limited fixed space, for instance on the order of 5 millimeters (mm). Occlusion balloon 5 on outer catheter 4 is left uninflated during occlusion by devices 50 and 52.
The infusion agent is preferably transmitted through guide wire lumen 17 (not shown) of inner catheter 2, and delivered from an aperture, or skive 54 that is located between balloons 50 and 52. Guide wire 1 is preferably removed from within guide wire lumen 17 before infusion takes place.
Because occlusion is accomplished using only the two occlusion devices 50 and 52 located on inner catheter 2, applications using this embodiment can optionally eliminate outer catheter 4 and perform occlusion with only inner catheter 2. However, in some applications, the added ability to also occlude a variable length of the vessel may be desired, in which case both outer catheter 4 and inner catheter 2 are used.
The occlusion device in the first location can be either occlusion device 50 or occlusion device 52 if occlusion device 52 is positioned distally from the distal end of outer catheter 4. The occlusion device in the second location can be either occlusion device 5 or the proximally located occlusion device 52 if that device is positioned distally from the distal end of outer catheter 4 and not used to occlude the vessel in the first location. Finally, at 858, an agent is delivered in the region of the blood vessel located between the two expanded occlusion devices at a pressure sufficient to infuse the agent into a localized or semi-localized region of the body.
In the embodiments previously discussed within the Detailed Description section, occlusion of the blood vessel is accomplished using at least two occlusion devices. In contrast to these embodiments, the embodiments described in the following discussion and depicted in FIGS. 13A-B and 15A-C allow occlusion of at least a portion of a blood vessel region with only one occlusion device. It is important to note that even though the nomenclature “inner” and “outer” catheter is retained in discussing these embodiments, each embodiment is capable of operation with only one of either the inner or outer catheters, depending on the needs of the particular application.
FIGS. 13A-C depict an example embodiment where inner catheter 2 is configured to occlude a portion of a blood vessel region by using one axially indented balloon 58 having a side indent 59 in a middle section of cylindrically-shaped balloon 58.
An aperture, or skive, 54 can be placed in region 102 where the indented portion of balloon 58 is coupled with inner catheter 2. Aperture 54 is preferably in fluid communication with the guide wire lumen 17 of inner catheter 2 such that a desired infusion agent can be infused into the isolated region. This allows selective infusion-of a very small region 57 in a directional manner. In other words, only region 57 of vessel 98, isolated in both the axial and radial directions, is exposed to the infusion agent. This is in contrast to the previously described embodiments where infusion takes place at a portion of the blood vessel isolated only in the axial direction, allowing exposure to the infusion agent around the entire circumference of the blood vessel. Valve 56 can also be included for sealing the distal end of inner catheter 2. Balloon 58 is inflated with an inflation medium transmitted through lumen 16 and into balloon 58 via aperture 55. Although not shown, an additional aperture can be placed in region 102. This aperture can provide fluid communication with an additional lumen disposed within inner catheter 2, and can be used to monitor pressure in the isolated space adjacent to indent 59.
For instance, in
Because these embodiments in FIGS. 13A-C allow infusion using only the one occlusion balloon 58 located on inner catheter 2, outer catheter 4 is not required and can be optionally eliminated from the catheter system. As noted above, although catheter 2 is referred to as “inner” catheter 2, the term “inner” is retained for purposes of providing clarity and cohesiveness with the embodiments discussed throughout the application. It should be understood that catheter 2 can be used alone, or in combination with outer catheter 4 as desired. Accordingly, use of the term “inner” does not limit the present invention to only embodiments using both the inner and outer catheters.
Furthermore, it may be desirable to position catheter 2 such that indented portion 59 is adjacent to an opening in the blood vessel wall that connects the blood vessel containing catheter 2 with a second blood vessel. Preferably, the second blood vessel branches into a plurality of smaller vessels that form a flow restricting configuration that restricts flow to a degree that allows the agent to be delivered at a pressure sufficient to infuse the agent to the semi-localized region.
Next, at 904, occlusion device 58 is expanded such that the blood vessel is occluded by occlusion device 58 and the portion of occlusion device 58 not located in indented area 59 is in contact with the inner surface of the blood vessel. Then, at 906, an agent is delivered in the region of the blood vessel adjacent to indented portion 59 of occlusion device 58 and not in contact with indented portion 59 at a pressure sufficient to infuse the agent into a localized or semi-localized region of the body. Preferably, if valve 56 is used, the pressure exerted by the agent on valve 56 during delivery causes valve 56 to seal.
Similar to the embodiments described with regard to FIGS. 13A-C, the example embodiment depicted in FIGS. 15A-C allows both the creation of an isolated blood vessel region with only one occlusion device and the independent monitoring of pressure during infusion to the isolated region. Here, the sole occlusion device is located on outer catheter 4 and is preferably used to isolate the entire axial length of a blood vessel region and not in a directional manner within a radially limited portion of a blood vessel. This embodiment can be used in applications where the distal portion of the targeted vessel has a flow restricting configuration, limiting any potential downstream escape of the infusion agent. The flow restricting configuration restricts flow to the extent that the desired infusion pressure can be achieved.
Middle tubing 60 preferably includes a reinforcement, such as metal braiding and the like, for strengthening and stiffening outer catheter 4. Middle tubing 60 and inner tubing 62 are preferably coaxial, with the distal end of middle tubing 60 located proximal to the distal end of inner tubing 62. The annular space between middle tubing 60 and inner tubing 62 defines annular lumen 64. Lumen 64 is preferably used for transmission of the desired infusion agent to the infusion site. Vented cone region 68 is preferably located at the transition between the distal end of middle tubing 60 and inner tubing 62. Here, vented, or slotted, cone region 68 is a transition between the exterior of inner tubing 62 and the distal end of middle tubing 60, which acts as a smooth transition between middle tubing 60 and inner tubing 62 and reduces the risk of skiving the interior of the blood vessel. Also, the distal end of outer tubing 72 is beveled to reduce the risk of skiving. In an alternative embodiment, vented cone region 68 can be coupled with inner tubing 62 and the distal end of outer tubing 72. Cone region 68 also preferably includes one or more openings, vents or slots 69 for infusion, as depicted in
Outer catheter 4 can include two or more regions of varying stiffness, for example the relatively stiff proximal region 10, softer intermediate region 11 and still softer distal region 12 as well as any curved or bent region for facilitating navigation. Outer catheter 4 can also include pressure monitoring lumen 15 (not shown), if lumen 66 in inner catheter 2 is not used as such. In addition, outer catheter 4 can include proximal occlusion balloon 5, located on outer tubing 72 and preferably in intermediate region 11 shown in
FIGS. 15A-C depict one example embodiment of outer catheter 4 that can be used to occlude a blood vessel having a flow restricting configuration. It should be noted that in addition to this embodiment, other example embodiments of outer catheter 4 can also be used, such as the embodiment depicted in
As discussed above, outer catheter 4 can be used in a blood vessel with a flow restricting configuration at the upstream end of the vessel.
One target application includes the infusion of an agent within the anterior interventricular vein (AIV) of the heart for the purposes of angiogenesis or myogenesis.
This region is “substantially” isolated because although some fluid or infusion agent can still pass through flow restricting configuration 97, enough flow is restricted such that the desired pressure for infusion through the wall of AIV 92 can be achieved. While other embodiments refer to isolating a continuous blood vessel segment using multiple occlusion devices, it should be noted that it is not necessary to completely occlude or isolate the vessel for infusion to occur. A blood vessel segment is sufficiently occluded and isolated if the occlusion devices limit the potential collateral escape of the agent enough to allow the desired infusion pressure to be achieved.
Preferably, a catheter system using only one occlusion device, such as outer catheter 4 as depicted in FIGS. 15A-C, is used to perform infusion within AIV 92. However, other outer catheters can also be used, such as outer catheter 4 as depicted in FIGS. 2A-B. Furthermore, this embodiment is not limited to catheter systems using only one catheter and one occlusion device. Catheter systems using two or more catheters and occlusion devices, such as the catheter system depicted in FIGS. 1A-B, can also be used if desired.
In this preferred embodiment, a guide wire is used in order to properly position outer catheter 4. The guide wire is preferably introduced to coronary sinus 96 at step 1002, either directly or through other surrounding vasculature, and navigated through great cardiac vein 94 into AIV 92 at step 1004. Alternatively, outer catheter 4 can be navigated to through coronary sinus 96 directly, with a curved or bent distal region as depicted in FIGS. 2A-B. Also, a shaped stylet can be placed within lumen 66 and used, either instead of or in combination with the curved region, to facilitate navigation of outer catheter 4 within coronary sinus 96.
Once the guide wire is in place, at step 1006, outer catheter 4 is preferably routed over the guide wire using lumen 66 and positioned within AIV 92 in proximity with the desired infusion site. In one embodiment, navigation is facilitated by the use of radio opaque markers located on outer catheter 4. Once in position, at step 1008 balloon 5 is expanded to occlude AIV 92 and create the substantially isolated region between the expanded occlusion device 5 and flow restricting configuration 97. The infusion agent is then transmitted through lumen 64 and delivered to the substantially isolated region via apertures 69 on vented cone region 68 at step 1010. Delivery of the infusion agent continues in order to increase the fluid pressure within the substantially isolated region to the desired pressure for infusion through the wall of AIV 92 at step 1012 and into a localized region of the body.
The pressure of the infusion agent may be such that infusion occurs into a semi-localized region of heart primarily through the walls of the tributaries defining flow restricting configuration 97 of AIV 92. Once the infusion pressure reaches the desired level, these tributaries become disrupted and porous, and even in some cases burst, thereby allowing the infusion agent to be infused through the walls of the tributaries and into the surrounding tissue at step 1012. While some injury to AIV 92 is preferable in order to allow infusion to occur through the wall of the vessel, fluid pressure within the infusion site is preferably regulated to ensure that only minor injury takes place.
The devices of the present invention may be provided with a pressure regulator to maintain a desired infusion pressure, or to prevent fluid pressure from exceeding a maximum desired pressure in order to maintain a safe environment for the patient. Typically, an infusion pressure at the infusion site of 100-200 mmHg is desired, but greater or lesser pressures may be employed. The pressure regulator can usefully be attached to the input side of the catheter system between the infusion port on the catheter and a syringe or other means used to infuse the desired agent under pressure. The pressure regulator can also be attached to the output side of the catheter system between the pressure feedback and the atmosphere (or a reservoir). The regulator can also be incorporated directly into the syringe or infusion device. The desired pressure at the regulator may be calculated from the desired pressure at the infusion site according to engineering principles well known to those skilled in the art. Several embodiments of pressure regulators useful with the catheter system of the present invention are illustrated in
In this embodiment, a pressure feedback is used to regulate pressure. The pressure feedback is preferably in fluid communication with the isolated blood vessel segment to give a high degree of accuracy in regulation. Here, the pressure feedback is provided by a pressure monitoring lumen, such as pressure monitoring lumen 15, which is coupled to infusion feedback chamber 306 via infusion feedback port 307. The fluid pressure in infusion feedback chamber 306 controls valve 304 and regulates flow accordingly.
Valve 304 includes spool 316 coupled to diaphragms 312 and 314. Spool 316 has through-hole 318 that is preferably aligned with lumen 303 when the spool 316 is centered within the housing 302. Spool 316 is configured to slide laterally within housing 302 such that the misalignment of through-hole 318 can provide increased resistance to fluid flow until it seals lumen 303 completely. Diaphragms 312 and 314 are coupled to spool 316 on opposite sides of lumen 303. Diaphragm 312 is located within infusion feedback chamber 306 and diaphragm 314 is located in an opposing chamber 322. Preferably, both diaphragms 312 and 314 are of equal strength to help maintain spool 316 in an equilibrium position when no other pressures or biases are applied. Here, spool 316 is shown partially misaligned.
When fluid is injected through pressure regulator 100 via lumen 303, the fluid pressure at the target site within the body is fed back to pressure regulator 100 at infusion pressure feedback chamber 306. As the pressure within chamber 306 increases past a predetermined level, a lateral force is exerted on diaphragm 312 causing spool 306 to move laterally away from chamber 306 and begin to seal lumen 303.
The predetermined level is at least partially determined by the bias applied by bias member 320. Bias member 320 is coupled with spool 316 and configured to apply a lateral force in a direction opposite to the fluid pressure force exerted by infusion feedback chamber 306. Spool 316 will only move away from chamber 306 when the fluid pressure force in chamber 306 exceeds the force applied by bias member 320 and diaphragms 312 and 314, in addition to any frictional or gravitational resistances to movement. When the pressure in chamber 306 causes great enough deflection in spool 316, lumen 303 is sealed entirely. Preferably, stop 324 is included to prevent bias member 320 from moving spool 316 too far laterally such that through-hole 318 becomes misaligned with lumen 303 when the fluid pressure in chamber 306 is below the predetermined level. Also, a vent aperture 330 is placed in housing 302 such that the air of other medium within chamber 322 can flow into and out of chamber 322 as required when spool 316 moves.
In this embodiment, bias member 320 is a spring, however, any bias member can be used according to the needs of the application. Because compression coil springs tend to increase in force as the spring is compressed, an increasing amount of force is required to seal lumen 303 entirely in an embodiment that uses a compression coil spring as bias member 320. The threshold point as well as the fluid pressure necessary to seal the lumen 303 entirely can be varied by selecting a bias member 320 with the appropriate compressive and expansive strengths. The bias applied by bias member 320 can also be adjusted by adjustment device 325.
FIGS. 18A-C illustrate a preferred example embodiment of an active pressure regulator 100 useful with the catheter system of the present invention. Preferably, this embodiment incorporates the infusion pressure to actively regulate fluid flow. Here, pressure regulator 100 includes housing 602 with lumens 604 and 606. Preferably, the injection device (not shown) is coupled with a fluid input (not shown) to lumen 604 and the catheter system (not shown) is coupled with a fluid output (not shown) of lumen 604, such that fluid can flow from the injection device, through lumen 604 and into the catheter system. Lumen 604 is preferably composed of a flexible tube, such that lumen 604 can be pinched off, or sealed, by an externally applied force.
Piston 613 is movably disposed within housing 602 such that the motion of piston 613 applies pressure to and seals flexible tube 604. Piston 613 includes bias receiving member 614 and fluid pressure receiving member 615, which are located within cavities 621 and 623, respectively. Members 614 and 615 are coupled together with struts 619, which move within cavities 622. Pinching member 618 is coupled with fluid pressure receiving member 615 and located adjacent to flexible tube 604. Pinching member 618 has a wedge shaped portion configured to contact flexible tube 604 and facilitate the sealing, or pinching off, of lumen 604.
In this embodiment, a pressure feedback is used to actively regulate pressure. The pressure feedback preferably provides fluid communication with the isolated blood vessel segment to give a high degree of accuracy in regulation. Here, the pressure feedback is provided by a pressure monitoring lumen, such as pressure monitoring lumen 15 (not shown), which is coupled to fluid cavity region 628 via fluid input 608. Fluid cavity region 628 is sealed on one side by flexible diaphragm 612. Flexible diaphragm 612 is located adjacent to face 616 of fluid pressure receiving member 615. As the fluid pressure within cavity 628 increases past a predetermined level, diaphragm 612 flexes outward and moves piston 613 in direction 611. The movement of piston 613 causes pinching member 618 to at least partially seal lumen 604. Once the fluid pressure in cavity 628 becomes great enough, lumen 604 is entirely sealed by pinching member 618.
Also illustrated in
The bias force applied by bias member 620 at least partially determines the predetermined level at which piston 613 moves. In a preferred embodiment, the predetermined level where piston 613 begins to move in direction 611 is equal to the bias force applied by bias member 613 plus any frictional and gravitational resistances to movement acting upon piston 613 in direction 601. The bias force applied by bias member 620 can be adjusted by adjustment device 626.
FIGS. 19A-C illustrate another example embodiment of an active pressure regulator 100 useful with the catheter system of the present invention. Again, this embodiment preferably incorporates the infusion pressure to actively regulate fluid flow.
In this embodiment, a pressure feedback is used to actively regulate pressure. The pressure feedback preferably provides fluid communication with the isolated blood vessel segment to give a high degree of accuracy in regulation. Here, the pressure feedback is provided by a pressure monitoring lumen, such as pressure monitoring lumen 15 (not shown), which is preferably coupled with inflatable balloon 644 at input 648. Inflatable balloon 644 is located adjacent to lever arm 658, which is pivotably coupled with frame 640 at pivot point 656. Lever arm 658 includes pinching member 660, which extends outward towards flexible tube 642. As the fluid pressure at the isolated blood vessel segment increases past a predetermined level, balloon 644 begins to inflate and rotate lever arm 658 towards flexible tube 642. The rotation of lever arm 658 causes pinching member 660 to pinch off, or seal, flexible tube 642. The degree to which lumen 642 is sealed is directly related to the amount of inflation of balloon 644. Balloon 644 is preferably coupled with lever arm 658 such that as the fluid pressure begins to drop and cause balloon 644 to deflate, lever arm 658 is rotated in the opposite direction and at least partially unseals lumen 642. Thus, the rate of fluid injection into the catheter system can be actively regulated by the fluid pressure feedback provided to balloon 644. Balloon 644 can also include a valve 662 for releasing any undesired any air or gas from balloon 644. In this embodiment, valve 662 is a stop cock.
The use of lever arm 658 provides mechanical advantages in the mechanical relation between rotation of the arm and sealing lumen 642. By placing the pinching member 660 near pivot point 656 and applying force with balloon 644 along substantially the entire length of arm 658, the amount of leverage needed to seal lumen 642 decreases. Also, the addition of multiple pinching members can increase the sensitivity of regulator 100.
FIGS. 20A-C illustrate another example embodiment of an active pressure regulator 100 useful with the catheter system of the present invention. Preferably, this embodiment incorporates the infusion pressure to actively regulate fluid flow.
In this embodiment, a pressure feedback is used to actively regulate pressure. The pressure feedback is preferably in fluid communication with the isolated blood vessel segment to give a high degree of accuracy in regulation. Here, the pressure feedback is provided by a pressure monitoring lumen, such as pressure monitoring lumen 15 (not shown), which is preferably coupled with cavity 678 via fluid input 679. Flexible diaphragm 680 preferably forms a wall of cavity 678, located adjacent to face 677 of body member 675. Body member 675 is located on a first side of flexible tube 671. Pinching member 676 extends from body member 675 to a second side of lumen 671 that is opposite the first side such that lumen 671 is located between pinching member 676 and body 675.
As the fluid pressure within cavity 678 increases past a predetermined level, diaphragm 680 flexes outward and moves piston 674 in direction 690. The movement of piston 674 causes pinching member 676 to at least partially seal lumen 671. Once the fluid pressure in cavity 678 becomes great enough, lumen 671 is entirely sealed by pinching member 676.
Also illustrated in
Groove 693 in housing 670 is provided to allow the movement of piston 674 in directions 690 and 691.
The bias force applied by bias member 681 can at least partially determine the predetermined level at which piston 674 moves. In a preferred embodiment, the predetermined level where piston 674 begins to move in direction 690 is equal to the bias force applied by bias member 681 plus any frictional and gravitational resistances to movement acting upon piston 674 in direction 691.
In the above discussion, various embodiments are presented that use a member to pinch a flexible lumen in order to restrict the flow of fluid through that lumen. It should be noted that in certain applications, the fluid passing through the lumen can be an agent comprised of a biological cells. In these applications, the design and construction of the various pinching members and flexible lumens should take into account the risk of pinching the flexible lumen in such a way that the cells are ruptured.
Also included within housing 950 is cam 954. Cam 954 is movably disposed within housing 950 in cavity 962. Cam 954 is coupled with bias element 960, which is in turn coupled with housing 950 within cavity 962. Cam 954 has two opposing sides 951 and 953. Side 951 is located adjacent to balloon 952. Opposite side 953 has pinching member 955 extending outwards towards flexible tube 956. Flexible tube 956 can optionally include an inner jacket 957 and a harder, outer jacket 958, in which case an opening 959 in outer jacket 958 is preferably provided and aligned with pinching member 955 to allow pinching member 955 to contact inner jacket 957.
Bias element 960 applies a bias force to maintain cam 954 in position. When the fluid pressure in balloon 952 reaches a predetermined level, balloon 952 begins to inflate and move cam 954 and pinching member 955 towards flexible tube 956 and cause pinching member 955 to at least partially seal tube 956. As the fluid pressure within balloon 952 increases, balloon 952 continues to expand and cause pinching member 955 to increasingly seal flexible tube 956. The predetermined level at which balloon 952 begins to inflate can be dependent on numerous factors including the material elasticity of balloon 952, the bias force applied by bias member 960, frictional forces and the like.
Furthermore, the amount of movement or deflection of cam 954 necessary to completely seal tube 956 can be adjusted with adjustment device 976. Adjustment device 976 preferably adjusts plate 974 both towards and away from flexible tube 956 in order to increase and decrease, respectively, the amount of movement needed by cam 954 to seal tube 956. In this embodiment, adjustment device 976 is a screw knob that screwably adjusts plate 974. Adjustment device 976 can optionally include a visible indicator to indicate the fluid pressure necessary to seal tube 956 at each position of device 976.
Plate 29 is coupled to spring element 30 which may be a coil, leaf or other type of spring. A coil spring is illustrated. The spring is also coupled to the shell 31 of the pressure regulator. Pressure is regulated by the counter forces of the pressure of the fluid in cavity 25 and the pressure exerted by spring 30. When the pressure in cavity 25 exceeds the desired pressure, diaphragm 27 will be brought into contact with plate 29 and the spring force in spring 30 will counter undesired over pressurization in cavity 25.
To inject an infusion agent in a pressure regulated manner, an injection device such as a syringe (not shown) can be coupled with fluid input 216 while the catheter system (not shown) can be coupled to fluid output 218. The injection device can then be used to inject the infusion agent into the catheter system through pressure regulator 100. In this embodiment, the position of piston 206 is determined by the pressure exerted by bias member 214, diaphragm 210 and the fluid pressure in outlet chamber 204, which is primarily a result of the amount of force exerted by the injection device to inject fluid into outlet chamber 204 by way of through-hole 208.
Once the fluid pressure in outlet chamber 204 becomes equal to or greater than the pressure of bias member 214, a threshold point is reached, and piston 206 deflects towards plunger 212. As piston 206 approaches plunger 212, the resistance to fluid flow increases. Once the pressure applied by diaphragm 210 becomes great enough, valve 205 closes and prevents further fluid flow into the catheter system.
The amount of travel of piston 206, the deflectability of diaphragm 210, the compressive and expansive pressures applicable by bias member 214, the location of plunger 212 as well as the resistance to deflection incurred by any seal 220 located on piston 206, are all variables that should be considered in the design of pressure regulator 100. Preferably, the resistance to movement created by seal 220 and the positioning of piston 206 are not substantial relative to the pressure applied by bias member 214 and diaphragm 210. Pressure regulator 100 can be further configured with an adjustment device for allowing valve 205 to seal at varying fluid pressures. Here, the depth of plunger 212 is adjustable by coupling plunger 212 with inlet chamber 202 via a rotatable threaded knob.
When the pressure feedback fluid pressure acting on piston 236 becomes greater that the counteracting pressure exerted by bias member 238, the threshold point is reached and piston 236 is deflected away from plunger 240. Because valve 234 is a needle valve in this embodiment, the pressure is reduced as piston 236 moves away from plunger 240. Also, as in the above embodiment, pressure regulator 100 can optionally include adjustment device 242 for adjusting the point at which valve 234 seals. Also shown is seal 239 coupled with piston 236. Seal 239 provides some resistance to movement by piston 236, preferably this resistance is not substantial relative to the bias applied by bias member 238. Piston 236 could be replaced by a diaphragm as shown in
FIGS. 24A-D and 25A-B illustrate additional example embodiments of a passive pressure regulator 100 useful with the catheter system of the present invention. As opposed to the previous embodiments, which regulate fluid pressure by directly adjusting the allowable flow, these pressure regulators 100 regulate pressure by accumulating excess fluid to maintain the pressure at an acceptable level.
In the embodiment illustrated in FIGS. 24A-D, passive pressure regulator 100 is incorporated directly into injection device 400. Injection device 400 can be any device configured to inject an infusion agent into the catheter system and, in this embodiment, injection device 400 is a syringe. Syringe 400 includes housing 402 for holding a fluid an outputting the fluid through fluid output 404. Syringe 400 also includes plunger 406 slidably coupled with the housing 402, plunger 406 configured to force the fluid out of fluid output 404 in a conventional manner known to those of skill in the art.
In the preferred embodiment, pressure regulator 100 is incorporated within plunger 406. Here, pressure regulator 100 includes slidable piston 410 housed within the plunger body 408. Piston 410 is coupled with bias member 412 that is configured to apply pressure to piston 410 in direction 414, thereby maintaining piston 410 in an extended state as illustrated in
As noted above, in embodiments using a compression coil spring for bias member 412, the compressive force applied by spring 412 in direction 414 varies based on the extent to which spring 412 is compressed. Accordingly, because of the different levels of compression, the point where spring 412 begins to return piston 410 to the extended state will generally be greater than the threshold point required for piston 410 to initially retract.
Also, if plunger 406 is depressed very rapidly, the fluid pressure within housing 402 will spike, or increase rapidly and cause piston 410 to retract. The fluid pressure in housing 402 will then decay as the depression of plunger 406 slows, or as piston 410 returns to the extended state. There is a time delay for this pressure spike to travel through the catheter system to the infusion site, and the infusion site may experience only a reduced pressure spike or even none at all. This embodiment can therefore provide insulation to pressure spikes as well as regulation of the fluid pressure at the infusion site.
In this embodiment, injection device 400 also includes seal 418 at the base of plunger body 408 for sealing off housing 402. Piston 410 includes O-ring seal 420 for sealing the inner cavity of plunger body 408 from fluid within housing 402. Also, injection device 400 can optionally include adjustment device 422 for adjusting the threshold point. In this embodiment, adjustment device 422 is a threaded knob screwably coupled with plunger body 408. As the knob 422 is screwed into plunger body 408, bias member 412 is compressed and the threshold point becomes larger. However, in order to reduce the complexity of injection device 400 in actual applications, pressure regulator 100 can be configured to provide the proper compressive forces without the need for additional adjustment device 422.
In addition, injection device 400 can include direct pressure scale 424 located on piston 410 and aligned with a marking on piston 410. This pressure scale 424 can be used to determine the fluid pressure being applied either within housing 402 or within the isolated blood vessel region.
FIGS. 25A-B illustrate additional accumulator-type embodiments of passive pressure regulator 100. In
As stated above, one preferred use of the catheter system of the present invention is with the methods of Yock et al. U.S. Pat. No. 6,346,098 which are centered on localized and semi-localized delivery of an infusion agent through the wall of a blood vessel. Because blood vessel structure can vary widely, the catheter systems and methods used to isolate and seal the vessel must vary accordingly. For instance, because the physiologic venous pressures are much lower than arterial pressures, veins tend to be more compliant and have much thinner walls than arteries. Therefore, an expanded occlusion device will tend to distend, or stretch, the walls of the vein to a greater degree than would occur within an artery. Also, venous walls exert less resistance to expansion, and therefore the force exerted by the venous wall against the occlusion device is less than the force that would be exerted by an arterial wall. The lesser force allows fluids to pass between the occlusion device and the venous wall more easily and makes occlusion more difficult, especially when infusion pressures in the range of 100-200 mmHg, and even up to 400 mmHg are sought. Simply increasing the diameter of an expanded occlusion device may lead to injury and rupture of the vein.
In order to adequately occlude and isolate a venous blood vessel region with balloons 3 and 5, the balloons 3 and 5 preferably achieve nominal diameters of between 0.25 and 6 atmospheres (atm) of pressure, either fluid or air pressure, where higher pressures result in higher occlusion forces against the walls. The nominal diameter can vary according to the needs of the individual application. Experimental studies have shown that nominal diameters substantially in the range of 6-8 millimeters (mm), such as 6.0, 6.5 and 8.0 mm, all can provide optimal trade-off between occlusion force and expansion of the venous walls. The nominal diameter will vary according to the size of the targeted blood vessel region.
In addition, the balloons are preferably configured to expand in diameter by 1-2 mm with the addition of 2-3 atm of fluid pressure. This allows the use of one balloon 3 or 5 in multiple venous diameters. If balloons 3 and 5 are too non-compliant (e.g., nylon, Polyethylene, Polyethylene Terephthalate) they may not be adjustable for vessel size as indicated above. If the balloons are too compliant (e.g. silicone rubber, latex, low-durometer Polyurethane) they may not provide enough occlusive force at their nominal diameters. Experimentation and simulation results have found that high durometer elastomeric materials, such as 55D Polyurethane, provide an optimal or near-optimal trade-off between compliant and non-compliant materials.
In addition to the material composition and fluid pressure factors, the balloon geometry should also be considered for proper occlusion. Preferably, balloons 3 and 5 have a cylindrical shape instead of a spherical shape in order to maximize the sealing area, or working length, with the wall. By increasing the working length, a higher infusion pressure can be achieved without creating dangerously high pressures to the venous walls. The working length can be chosen based on the needs of the application, such as the need to balance the required infusion pressure with the desire to achieve the smallest balloon diameter possible to facilitate handling. Preferably, the working length of balloons 3 and 5 are in the range of 1-2 centimeters (cm) although longer or shorter lengths can be used as desired.
The catheter system described herein can be furnished to a user, such as a medical professional, in the form of a kit. The kit preferably includes inner catheter 2, outer catheter 4, pressure regulator 100, an agent and instructions for use. The kit can include any number of guide wires, such as 0.014″, 0.018″ and 0.035″ guide wires and the like. The kit can also include radio opaque dye or markers for facilitating navigation of the catheter or guide wire. The radio opaque dye can be optionally mixed with the agent if desired and if it does not significantly inhibit the therapeutic or diagnostic qualities of the agent.
The kit can be further customized for a desired application. For instance, in a preferred embodiment the catheter system is inserted into the AIV of a patient to treat angiogenesis or myogenesis. A kit customized for use in this application can also include one or more stylets or dilators, configured to aid in advancing the catheter system in the patient's vasculature. In the case where outer catheter 4 is shaped or curved to facilitate navigation within the vasculature, the dilator can be used to straighten out outer catheter 4.
If either inner catheter 2 or outer catheter 4 require additional shaping to facilitate navigation, a stylet can be used. One or more stylets can be provided for different anatomies, each stylet being customized to facilitate navigation into a target vessel. The stylet can be configured according to the needs of the application, by adjusting the stiffness, shape and/or composition of the stylet. In one example embodiment, the stylet is flexible enough to straighten while being inserted into the body, yet is stiff enough to maintain the desired shape while within inner catheter 2 or outer catheter 4 and the vasculature. The stylet can also be malleable such that it can be configured directly to the anatomy prior to use. This stylet can be hollow such that it can be advanced over a guide wire and can also be optionally composed of a shape memory material. In one example embodiment, a teflon-coated non-annealed stylet is used. However, other configurations and hardnesses can also be used.
Also, pressure regulator 100 can be customized to regulate the pressure in a user friendly manner, for instance without the need for adjustment of the threshold point or without the need for monitoring a pressure scale by the user. Furthermore, the occlusion devices can be sized and configured for the target blood vessels within the coronary sinus. Integrated guide wire 32 can optionally be provided in combination with inner catheter 2. Kits can be customized for any application using the present catheter system, and the kits are not limited solely to the treatment of angiogenesis or myogenesis and are also not limited to use within the coronary sinus.
In the foregoing specification, the invention has been described with reference to specific embodiments thereof. It will, however, be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention. For example, the reader is to understand that the specific ordering and combination of process actions described herein is merely illustrative, and the invention can be performed using different or additional process actions, or a different combination or ordering of process actions. For example, this invention is particularly suited for applications involving the infusion of an agent in an isolated blood vessel, but can be used in any application involving blood vessel isolation. As a further example, each feature of one embodiment can be mixed and matched with other features shown in other embodiments. Features and processes known to those of ordinary skill in the art of catheter systems may similarly be incorporated as desired. Additionally and obviously, features may be added or subtracted as desired. Accordingly, the invention is not to be restricted except in light of the attached claims and their equivalents.
This application is a continuation-in-part of U.S. application Ser. No. 10/664,171, filed Sep. 16, 2003, which is fully incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 10664171 | Sep 2003 | US |
| Child | 10783217 | Feb 2004 | US |
