Abstract:
Myocardial revascularization catheters and methods are provided herein. Catheters in accord with the present invention may include an outer shaft and an inner shaft where the inner shaft may be slidably and rotatably disposed in the outer shaft and the distal movement of the inner shaft may be arrested by the engagement of stops and catches located within the inner and outer shaft Methods in accord with the current invention may include providing a therapeutic, providing a radiopaque contrast media, injecting the therapeutic through a lumen into the myocardium of the heart, and injecting the radiopaque contrast media through a lumen into myocardium of the heart. In this example, the location of the injection the radiopaque material may be chosen to indicate the injection point of the injection of the therapeutic.

Description:
FIELD OF THE INVENTION  
         [0001]    The present invention is related generally to medical devices. More specifically, the present invention is related to devices associated with delivery of genes or therapeutic substances.  
         BACKGROUND OF THE INVENTION  
         [0002]    A number of techniques are available for treating heart disease and diseases of other organs percutaneously. Examples of such techniques include delivery of genes and therapeutic substances, including the delivery of genes and therapeutic substances for percutaneous myocardial revascularization (PMR). This procedure is performed to increase blood perfusion through the myocardium of a patient. For example, in some patients, the number of lesions in coronary vessels is so great or the location so remote in the patient vasculature that restoring blood flow to the heart muscle is difficult. Percutaneous myocardial revascularization (PMR) has been developed as an alternative to techniques which are directed at bypassing or removing lesions. PMR is performed by boring holes directly into the myocardium of the heart. Positive results have been demonstrated in some human patients receiving PMR treatments. These results are believed to be caused in part by blood flowing from within a heart chamber through patent holes formed by PMR to the myocardial tissue. Suitable PMR holes have been proposed to be burned by laser, cut by mechanical means, and burned by radio frequency devices. Increased blood flow to the myocardium is also believed to be caused in part by the heating response to wound formation, specifically, the formation of new blood vessels in response to the newly created wound.  
           [0003]    Several aspects of PMR procedures could be improved upon. One area for improvement is in the preparation of PMR injection catheters for use by the treating physician. In particular, at present, the PMR device maybe flushed with a drug to prime the distal needle by flushing the drug through the needle and into a container. This preparation can be awkward and may leave a container of biologically active material which may require further processing. Another aspect which may be further optimized lies in the attachment of the needle to the distal region of the PMR catheter tube. In particular, forces may act upon the needle during both the advancement and retraction of the needle within the heart wall, urging the needle undesirably both into and out of the tube. Improved methods of securing the needle to the tube would be desirable.  
           [0004]    During a PMR treatment, a physician may be attempting to treat a three-dimensional space using a catheter having a distal bend. In particular, the physician may be attempting to treat the heart chamber side, anterior, and posterior wall regions. This may presently be difficult to visualize under fluoroscopy as current marking systems for shafts may make interpretation of the catheter distal region orientation somewhat ambiguous. The heart chamber wall thickness can vary depending on the chamber and wall region being treated. In particular, the left ventricle wall is thinner in the posterior region relative to the anterior region. Improved devices for variable depth, yet controlled penetration of the heart walls, would be advantageous. As multiple sites of the heart chamber wall are penetrated, a system for tracking the treated versus untreated regions would also be desirable.  
         SUMMARY OF THE INVENTION  
         [0005]    The present invention includes improved devices and methods for performing PMR procedures. One device allows for improved preparation of PMR catheters used to inject a drug or therapeutic substance into the heart wall. One such device includes a PMR device distal region or hood disposed within the neck of a vial for receiving the drug. The vial can be used to receive the drug while the drug is being flushed through the PMR device and needle to prepare the PMR device for use. One vial has a neck and shoulder region for receiving and retaining the distal region of a PMR injection device. A no-leak gasket defines one wall of an inner cavity within one such vial.  
           [0006]    The vial is preferably formed of a transparent or translucent material for observing the injection of the drug into the vial. In one embodiment, the vial cavity includes a drug-neutralizing agent. The agent allows the drug to be neutralized after receiving the drug. A neutralizing agent can provide improved safety, should the integrity of the vial be breached. The drug-neutralizing vial allows a biologically active drug to be flushed through the catheter with the vial being disposed of in a normal waste stream such as a wastebasket, rather than requiring special handling.  
           [0007]    One set of devices provides improved needle attachment to drug delivery tubes. One improved drug delivery tube has an outer tube defining a lumen therein. A needle may be disposed within the distal end of the tube. The needle can have a distal, sharp tube region for insertion into the heart wall, as a well as a wider, more proximal region having outward protrusions for engaging or biting into the drug delivery tube inner wall. One device has a wide flange for abutting the drug delivery tube distal end, thereby limiting the proximal travel of the needle into the drug delivery tube lumen. One drug delivery tube also has a bonding hole which can be used to inject an adhesive to further secure the needle within the drug delivery. tube distal region. The improved securing of the needle to the drug delivery tube can act to prevent the needle from being distally pulled from the tube.  
           [0008]    During insertion of the needle into the heart wall, forces can act to urge the needle into the tube. Upon retraction of the needle from the heart wall, forces may act to pull the needle distally from the tube. Both the outward protrusions, the flange, and the added adhesive can act to better secure the needle to the drug delivery tube. One embodiment includes outward barbs biting into the drug delivery tube, while another embodiment uses a series of helically disposed screw threads to engage the tube wall. A preferred embodiment uses outward protruding elements which engage the inner wall, while another embodiment uses inwardly protruding elements engaging the outer wall of the tube distal region.  
           [0009]    Another aspect of the invention provides improved visualization of the catheter shaft orientation under fluoroscopy. One embodiment utilizes asymmetrically disposed radiopaque markers on the shaft distal region to enable the treating physician to determine whether the catheter distal region is pointed at right angles to the treating physician or is pointed toward or away from the treating physician. One embodiment has the radiopaque marker being asymmetrically distributed with respect to a plane bisecting a longitudinal axis of the catheter tube distal region. Another embodiment further includes the radiopaque marker being asymmetrically distributed with respect to length over the catheter distal region. One marker includes an annular ring portion and a straight leg portion lying along the length of one side of the tube. Yet another embodiment includes an annular shell or ring portion and an annular arc leg portion extending along a length from the annular shell or ring portion. The radiopaque markers may be disposed on either the proximal or the distal side of any bend in the catheter shaft. A preferred use of the radiopaque marker band is on a guide catheter used to guide a PMR therapeutic tip to the heart wall.  
           [0010]    In yet another aspect of the invention, radiopaque marker segments are asymmetrically distributed such that the rotation of the tube relative to the treating physician may be determined under fluoroscopy. One embodiment uses opposing annular shells on opposing sides of a tube where the annular shells are shifted longitudinally relative to each other. The asymmetrically disposed shells are thus asymmetric both with respect to a plane bisecting a longitudinal central access and with respect to a plane transversely bisecting a catheter shaft.  
           [0011]    In still another aspect of the invention, marker bands are provided a distance apart which approximates the desired inter-treatment site spacing along the heart wall. A method can be performed using this aspect of the invention, whereby a therapeutic substance is delivered at treatment sites which are observed under fluoroscopy to be spaced apart approximately the distance between marker bands. Any distortion or magnification of the distances between marker bands will approximately be matched by distortions between treatment sites.  
           [0012]    The present invention also includes a PMR device for allowing precise, variable depth needle penetration of the heart wall. One device includes at least one inner stop affixed to a rotatable inner needle. The device also can have one or more stops disposed inwardly from an outer tube, the outer tube having the inner needle rotatably disposed within. The inner needle can be longitudinally advanced until the inner stop abuts an outer stop, thereby inhibiting further distal movement of the inner needle. If greater penetration is desired, the inner shaft can be rotated, thereby swinging the inner stop clear of the first encountered outer stop, allowing the inner stop to proceed further distally until a subsequent outer stop is encountered. This aspect of the invention allows a single device to be used, yet provides multiple, preset, precise penetration depths. This may be of particular use where the thickness of the heart wall varies over different regions of the heart chamber wall.  
           [0013]    Yet another aspect of the invention provides for injection of drug and contrast media into the heart wall. Injection of contrast media near the injection site of a drug allows the treating physician to visualize under fluoroscopy which areas of the heart wall have been treated and which have not yet been treated. One device provides a contrast media injection needle disposed side-by-side with a drug delivery needle. One embodiment allows the two side-by-side needles to be retracted and advanced together. The needles can be distally straight, arcuate, or one arcuate and one straight. Another embodiment provides a drug and contrast media injection device having a pair of needles one being coaxially disposed within the other. The innermost needle can be used to inject drug deep into the heart tissue, while the more outer, coaxially disposed needle may be used to inject contrast media to the heart wall, thereby marking the site of treatment. One embodiment utilizes a sharp, cutting end to inject contrast media. Another embodiment uses a less sharp, less cutting end, for injecting a contrast media into the heart wall tissue using pressure, rather than cutting.  
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0014]    [0014]FIG. 1 is a fragmentary, side, cutaway view of a myocardial revascularization preparation system including a drug neutralizing vial and a myocardial revascularization drug delivery catheter in the process of being prepared for use by flushing a drug through the injection needle into the drug-neutralizing vial;  
         [0015]    [0015]FIG. 2 is a fragmentary, longitudinal, cross-sectional view of a drug delivery catheter distal portion having a needle disposed within a tube, the needle having barbs for engaging the tube inner wall to improve needle retention;  
         [0016]    [0016]FIG. 3 is a fragmentary, longitudinal, cross-sectional view of a drug delivery catheter distal portion having a needle disposed within a tube, the needle having threads for engaging the tube inner wall to improve needle retention;  
         [0017]    FIGS.  4 A- 4 C are perspective views of a prior art catheter shaft having an annular radiopaque band;  
         [0018]    FIGS.  5 A- 5 C are perspective views of a catheter shaft having an asymmetric radiopaque marker;  
         [0019]    FIGS.  5 D- 5 E are transverse, cross-sectional views taken through the catheter of FIGS.  5 A- 5 C;  
         [0020]    FIGS.  6 A- 6 C are perspective views of a catheter having an asymmetric radiopaque marker;  
         [0021]    FIGS.  6 D- 6 E are transverse, cross-sectional views taken through the catheter of FIGS.  6 A- 6 C;  
         [0022]    [0022]FIG. 7 is a perspective view of a catheter shaft having an asymmetric, radiopaque marker disposed proximal of a bend;  
         [0023]    FIGS.  8 A- 8 H are plan views of a catheter shaft having an asymmetric radiopaque marker in varying degrees of rotation;  
         [0024]    [0024]FIGS. 9A and 9B are perspective views of a guide catheter shaft including radiopaque marker bands having an inter-band distance corresponding to a desired myocardial revascularization treatment site spacing;  
         [0025]    [0025]FIG. 10 is a fragmentary, longitudinal cross-sectional view of a PMR catheter having multiple stops for controlling needle penetration;  
         [0026]    FIGS.  11 A- 11 C are fragmentary, longitudinal cross-sectional views of a PMR catheter having side-by-side needles for injection of a drug and a radiopaque fluid; and  
         [0027]    FIGS.  12 A- 12 B are fragmentary, longitudinal cross-sectional views of PMR devices having coaxially disposed drug and dye delivery lumens. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0028]    [0028]FIG. 1 illustrates a myocardial revascularization drug delivery preparation assembly  30  including a drug receiving vial  32  and a drug delivery catheter  42  inserted into vial  32 . Drug delivery catheter  42  includes a tube  44  having a lumen  46  therethrough. Catheter  42  includes a distal portion  54  having an injection device or needle  50  in fluid communication with lumen  46 . Catheter  42  further includes a distal hood  48 , illustrated in an expanded state. Drug injection needle  50  is illustrated penetrating through a self-sealing, no-leak gasket  40 . Gasket  40  can be disposed within vial  32  in an annular seat  52 , as shown.  
         [0029]    Drug receiving vial  32  includes a wall  38 , which is preferably formed of a transparent or translucent material, allowing both an expelled drug and catheter needle to be viewed through the vial wall. Vial  32  includes a cavity  34  having a drug-neutralizing agent  36  disposed within cavity  34 . Vial  32  includes a neck region  58  for receiving catheter distal portion  54 . In one embodiment, vial  32  further includes a shoulder or contour region  56  for engaging catheter distal hood  48 . In some embodiments, vial shoulder  56  and catheter hood  48  are cooperatively sized such that shoulder  56  engages hood  48  even when hood  48  is in a non-expanded state. Hood  48  is preferably sufficiently compliant so as to allow retraction of hood  48  through vial neck region  58  after preparing the catheter. Vial shoulder  56  can also flex to contain hood  48 .  
         [0030]    In use, drug delivery catheter preparing system  30  can be provided substantially as illustrated in FIG. 1. Catheter  42  can be provided either separate from, or already engaged within, vial neck region  58 . When catheter  42  is to be prepared, catheter  42  distal portion  54  can be inserted into vial neck region  58 , if not already so disposed. Catheter  42  can be further advanced, forcing needle  50  through gasket  40 , and into cavity  34 . With needle  50  inserted through gasket  40 , the drug to be delivered can be flushed through needle  50  into cavity  34 , preferably mixing with a neutralizing agent. In this way, the drug to be delivered can be loaded into catheter  42 , preparing the catheter for use. The excess drug can be contained within cavity  34 , which may be desirable where the drug is potentially harmful or must be isolated for other reasons. Catheter  42  can be retracted from vial  32  when needed. Gasket  40  is preferably formed of a self-sealing material, such that a seal is re-formed after needle  50  is withdrawn. In embodiments having a drug-neutralizing agent, the contents of the vial will be harmless, even if the vial integrity is compromised. After preparing, vial  32  can be disposed of in a proper manner. In some embodiments, vial  32 , containing either a harmless or a neutralized drug, may be disposed of in a wastebasket, with no special handling required.  
         [0031]    Catheter  42  can be used to inject various drugs or other therapeutic substances into the myocardium. Examples of therapeutic substances include small molecular drugs, proteins, genes and cells which could promote angiogenesis, protect tissues (i.e., cardiac protection), or promote tissue regeneration. Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factors (FGFs) are believed suitable for use with the present invention. Carriers for the therapeutic agents of the present invention can include polymers, angiopoietins, biodegradable and biostable hydrogels, and dissoluble polymers. Adhesives suitable for binding the present invention include fibrin glues and cyanoacrylates which may also be included with the therapeutic substance to improve the desired response. Drug injection catheters referred to in the remainder of the present patent application, and- drugs similarly referenced, may include the injection and use of the aforementioned therapeutic substances.  
         [0032]    Catheter  42 , as well as subsequently referenced drug injection catheters or myocardial revascularization catheters, can include catheters such as those described in co-pending U.S. patent application Ser. No. 09/271,045, filed Mar. 17, 1999, entitled TRANSMYOCARDIAL REVASCULARIZATION CATHETER AND ASSEMBLY; and U.S. patent application Ser. No. 09/184,220, filed Nov. 2, 1998, entitled PERCUTANEOUS MYOCARDIAL REVASCULARIZATION GROWTH FACTOR MEDIUMS AND METHOD, herein incorporated by reference. In particular, guide catheters described according to the present invention may be used to guide these previously referenced devices, and others, to target sites in the myocardium.  
         [0033]    [0033]FIG. 2 illustrates the distal portion of a drug delivery catheter  60  which, in a preferred use, can be used for a procedure such as myocardial revascularization. Drug delivery catheter  60  includes a tube  62  having a wall  64  defining a drug delivery lumen  66  within. Catheter  60  has a distal region  68 ; terminating in a distal end  76 . Disposed within catheter tube  62  is a drug delivery needle  78 , including generally a wider, proximal portion  80 , and a narrower, distal portion  82 . Distal portion  82  includes an elongate tube  83  terminating in a sharp end  84 . Needle wide proximal portion  80 , in the embodiment illustrated, includes a plurality of wider protrusions  88  spaced apart from each other by a plurality of narrower regions  90 . Protrusions  88 , in a preferred embodiment, include sharp tips or barbs  86  for engaging and gripping tube wall  64 .  
         [0034]    As can be seen in FIG. 2, outward protrusions or barbs  86  may form a plurality of deformations  69  where the barbs dig into tube wall  64 . In a preferred embodiment, barbs  86  have at least a slight inclination toward the distal direction, such that retraction of needle  78  from tube  62  is more difficult than insertion of needle  78  into tube  62 . In a preferred embodiment, drug delivery catheter  60  includes a distal flange  72  which can serve to limit travel of needle  78  into drug lumen  66 . In the embodiment illustrated, flange  72  abuts tube distal end  76  and has a hole  74  therethrough for receiving needle distal tube portion  83 . In one embodiment, tube  62  includes a bonding hole  70  through tube wall  64  for receiving adhesive. Adhesive can be injected through hole  70  for improving the adherence of needle wide portion  80  to tube distal region  68 .  
         [0035]    In one use, drug delivery catheter  60  can be advanced through the vasculature and into a heart chamber wall. After injection of a drug through drug lumen  66 , drug delivery catheter  60  can be retracted, thereby retracting needle distal end  84 . In a situation where the heart wall grips needle distal tube portion  83 , barbs or protrusions  86  can serve to resist the distally directed force attempting to retain needle  78 .  
         [0036]    Another drug delivery catheter  100  is illustrated in FIG. 3, having a needle  114  disposed within a tube  102 . Tube  102  includes a tube wall  104  having an inner surface  108  and an outer surface  107 . Tube  102  includes a distal region  110 , a distal end  112 , and a lumen  106  disposed therethrough. Needle  114  includes a distal tip region  116  ending distally in a sharp distal end  118 . Needle  114  also includes a proximal needle portion  118  including a plurality of threads  120  which are spaced .apart and have narrower regions  121  disposed between threads  120 . Needle  114  includes a needle lumen  124  extending through needle  114  and having a proximal throat region  126 . Throat  126  can improve the flow characteristics of fluid through the needle. Needle threads  120  may be seen to engage or bite into tube wall  104 . In the embodiment illustrated, threads  120  are disposed on the outside of needle  114 , and engage inner surface  108  of tube wall  104 . In another embodiment, not requiring illustration, the proximal portion of the needle extends over tube  104 . In this embodiment, threads are disposed inward within the needle lumen and engage tube outer surface  107 , rather than the inner surface. Needle  114  can be secured to tube  102  by advancing needle  114  into tube lumen  106  and rotating  114 , thereby screwing needle  114  into tube lumen  106 . Threads  120  thus secure needle  114  to tube  102  and resist the distally directed forces attempting to urge needle  114  out of tube  102 .  
         [0037]    [0037]FIGS. 4A through 4C illustrate a prior art catheter shaft  130  having a bend  134  and extending to a distal end  132 . Catheter shaft  130  has an annular band  136  which includes a radiopaque material. FIG. 4A is a side view, viewing catheter shaft  130  from an angle of about ninety degrees (90°) away from a straight-on end view looking directly along the central longitudinal axis. FIG. 4B illustrates catheter  130  viewed from an angle of less than ninety degrees (90°) off the center longitudinal axis. FIG. 4B illustrates catheter shaft  130  where distal end  132  is pointed more toward the viewer than away. FIG. 4C illustrates catheter shaft  130  being pointed more away from than toward the viewer. FIGS. 4B and 4C illustrate that annular radiopaque band  136  looks somewhat elliptical, and looks about the same, whether viewed from the front or the back. Annular band  136  thus looks the same when catheter shaft distal end  132  is pointed toward or away from the viewer. Annular radiopaque band  136  gives no indication under fluoroscopy of the direction the catheter shaft distal end is pointed. This is a less than optimal attribute of annular radiopaque band  136 , when used in an application such as myocardial revascularization, where the catheter shaft may be rotated and translated in all directions.  
         [0038]    [0038]FIGS. 5A through 5E illustrate a catheter shaft  140  having an asymmetric radiopaque marker. Catheter shaft  140  includes a bend  141  disposed proximal of a distal end  142 . Catheter  140  includes an asymmetric radiopaque marker  144  including a first, annular or ring portion  146  extending radially about the catheter and disposed transversely to the catheter longitudinal axis, and a second, straight portion  148 , extending along one side of shaft  140  toward distal end  142 . FIG. 5A illustrates a side view of catheter shaft  140 . The view of FIG. 5A is taken from about ninety degrees (90°) away from a straight-on end view, a view which would look directly along the central longitudinal axis. FIG. 5B illustrates a view of catheter shaft  140  with shaft distal end  142  pointed more toward the viewer than away. FIG. 5C illustrates catheter shaft  140  having distal end  142  pointed more away from the viewer than toward the viewer. As can be seen from inspection of FIGS. 5B and 5C, marker  144  appears differently when the catheter distal end is pointed away from the viewer compared to pointing toward the viewer. The asymmetric marker band  146  thus provides an indication under fluoroscopy of whether the catheter is pointed away from, or toward the viewer.  
         [0039]    [0039]FIG. 5D illustrates the asymmetric nature of radiopaque marker  144 . FIG. 5D, taken through annular ring portion  146 , shows a more proximal slice through catheter shaft  140 . FIG. 5E, taken through a more distal portion of catheter  140 , illustrates marker  144  having straight leg portion  148  only on one side. It may be seen from FIGS. 5A through 5E that a plane bisecting the central longitudinal axis of catheter shaft  140 , will have differing, asymmetrical portions of radiopaque marker on either side of the bisecting plane. In particular, the markers on either side of the bisecting plane are not mirror images of each other. It may also be seen that marker  144 , when compared proximal end to distal end, is asymmetric along its length. In particular, radiopaque marker  144  does not have a distal portion which is a mirror image of its more proximal portion.  
         [0040]    [0040]FIG. 6A illustrates a catheter  160  having a radiopaque marker  164  which is asymmetric and includes a first, annular arc shell portion  166 , and a second, annular ring portion  168 . In FIG. 6A, it may be seen that a plane bisecting the central longitudinal axis of catheter  160  would have an asymmetry with respect to the marker about the bisecting plane. In particular, the right and left halves of catheter  160  are not mirror images of each other. In FIG. 6A, catheter distal end  160  is pointed directly at the viewer. In FIG. 6B, catheter  160  is directed such that catheter distal end  162  is pointed ninety degrees (90°) away from the viewer, directly to the side. In FIG. 6C, catheter  160  is pointed one hundred eighty degrees (180°) away from the viewer, toward the back. Comparison of FIGS. 6A through 6C illustrates that marker  164  appears differently depending whether catheter distal end  162  is pointed toward the viewer, to the side of the viewer, or away from the viewer. FIG. 6D shows a transverse cross-section taken through radiopaque annular shell  166 . Annular arc shell  166  extends along the length of the catheter and substantially parallel to the central longitudinal axis, similar in some respects to straight segment  140  of FIGS. 5A through 5E, but wider. FIG. 6E shows a transverse cross-section taken through marker  164  through annular ring  168 . The asymmetry about the bisecting plane may be seen in FIGS. 6D and 6E, as well. Radiopaque marker  164  may also be seen to be asymmetric about a transverse bisecting plane. In particular, the top half of marker  164  in FIG. 6A is not the mirror image of a bottom half of marker  164  in FIG. 6A.  
         [0041]    In comparing FIGS. 5A through 5C and  6 A through  6 C, it may be seen that both embodiments, when viewed from an angle orthogonal to a plane containing the shaft on either side of the bend, have an asymmetric marker having two portions. The first portion lies substantially within a plane transverse to the center longitudinal axis. The second portion lies substantially within a plane that contains the center longitudinal axis. One embodiment has the marker disposed proximal of the bend, while the other embodiment has the marker disposed distal of the bend. One embodiment indicates shaft rotation proximal of the bend directly and infers the orientation of the segment distal of the bend. Another embodiment indicates shaft rotation distal of the bend directly and infers the orientation of the segment proximal of the bend. The other embodiment, not requiring illustration, has both the markers of FIGS. 5A through 5C and  6 A through  6 C on the same shaft.  
         [0042]    [0042]FIG. 7 illustrates a catheter shaft  200  having a radiopaque marker  201  including a first portion  206  and a second portion  208 . Catheter  200  has a bend  202  and a distal end  204 . In the embodiment illustrated, catheter  200  has a lumen  210  extending therethrough. As can be seen from inspection of FIG. 7, a plane bisecting the center longitudinal axis through catheter shaft  200  would bisect radiopaque marker  201  into two halves  206  and  208 , with the halves being asymmetric relative to the bisecting plane. In particular, first marker portion  206  and second marker portion  208  are not mirror images of each other with respect to a bisecting plane sending through the central axis. Radiopaque marker  201  is also not symmetrical with respect to a transverse bisecting plane. The asymmetry causes marker  201  to appear differently depending on the rotation of the tube with respect to a viewer. In particular, marker  201  will appear differently under fluoroscopy depending on the degree to which the catheter is rotated about its central, longitudinal axis proximal of bend  202 .  
         [0043]    [0043]FIG. 8A illustrates a catheter shaft  220  somewhat similar to catheter shaft  200  of FIG. 7. Catheter shaft  220  has a distal end  224 , a first or left marker portion  226 , and a second or right marker portion  228 . Together, first and second marker portions  226  and  228  form an asymmetric marker  230  which is asymmetric about a bisecting plane extending through the center longitudinal axis of catheter shaft  220 . In FIG. 8A, catheter shaft  220  is rotated such that catheter distal end  224  is disposed at an angle of zero degrees (0°) relative .to the viewer. Catheter shaft distal end  224  is directed directly at the viewer. FIG. 8B illustrates catheter shaft  220  rotated at a forty-five degree (45°) angle relative to the viewer, yet still remaining in a somewhat forward disposition. Similarly, FIG. 8C illustrates catheter  220  rotated at ninety degrees (90°) relative to the viewer, and FIG. 8D has the catheter pointed at a one hundred thirty five degree (135°) angle away from the viewer. FIG. 8E illustrates catheter shaft  220  being pointed directly away from the viewer, followed by FIG. 8F, which illustrates the same catheter pointing away from the viewer, but at an angle of two hundred twenty five degrees (225°). FIG. 8G illustrates catheter shaft  220  being rotated sufficiently to point two hundred seventy degrees (270°) relative to the line of view, toward the side. Finally, FIG. 8H illustrates catheter shaft  220  being pointed three hundred fifteen degrees (315°) away from its initial location, pointing mainly toward the viewer, but at a slight angle to the left.  
         [0044]    As can be seen from inspection of FIGS. 8A through 8H, catheter marker  230  appears differently under fluoroscopy depending on the rotation of the marker relative to the viewer. In particular, the marker is asymmetrically disposed on the catheter shaft such that rotation of the catheter about its longitudinal center axis appears different, relative to a fixed viewer orthogonal to the longitudinal axis of the catheter shaft. Marker  201  thus enables a viewer using fluoroscopy to determine the angle of rotation of the catheter shaft about its longitudinal axis. This can prove useful in a myocardial revascularization procedure, where turning the catheter in varying degrees can be important, as the degree of rotation may correspond to the location of holes formed in the heart chamber wall.  
         [0045]    [0045]FIG. 9A illustrates a catheter shaft  240  having a bend  242  and a distal end  244 . Catheter shaft  240  further has a first radiopaque marker band  246  and a second radiopaque marker band  248  disposed at a known distance “D1” apart. In a preferred embodiment, marker bands  246  and  248  are disposed at a distance apart of between about 1-2 cm. FIG. 9B illustrates catheter  240  being rotated toward and to the left of the viewer. A treatment catheter  250  may be seen to extend from catheter shaft distal end  244 . Treatment catheter  250  may be-seen to have a therapeutic tip  252 . A first treatment site  254  is represented by an “X” in FIG. 9B. As illustrated in FIG. 9B, therapeutic tip  252  has been moved to a distance of about “D2” from first treatment site  254 . In the embodiment illustrated, therapeutic tip  252  is about to treat a second site  256 , where the inter-site distance, D2, is substantially equal to the D1 distance. The marker bands may thus be used as a scale to accurately space the treatments sites in the heart chamber wall. The marker bands, being spaced apart about the same distance as the desired treatment spacing, will be subject to the same magnifications and/or distortions under fluoroscopy. This means that even if the distance between the markers appears distorted under fluoroscopy, the distance between target sites will likewise be distorted by about the same amount.  
         [0046]    [0046]FIG. 10 illustrates a PMR catheter  280  including an inner needle  282  rotatably disposed within an outer tube  284 . Inner needle  282  includes a shaft  286 , and can terminate distally in a sharp needle tip  288 . Outer tube  284  includes a tube wall  290 , and has a distal flange or hood  292 . A hole  293  is disposed within distal flange  292  for receiving needle tip  288 . In the embodiment illustrated, inner needle  282  has an inner stop  294  secured to inner shaft  286 . Inner stop  294  is secured to inner shaft  286  such that rotating the inner shaft rotates the inner stop. In this embodiment, outer tube  284  has outer stops  295 ,  296 , and  297  secured at various longitudinal and angular locations along tube wall  290 . As can be seen from inspection of FIG. 10, inner stop  294 , if advanced further distally, will encounter outer stop  295  which will limit the distal travel of needle tip  288 . It may also be seen that rotating inner shaft  286  by ninety degrees (90°) will allow inner stop  294  to clear outer stop  294  and proceed distally further. In an embodiment where inner stop  294  has a hemispherical configuration, rotating inner shaft  286  by one hundred eighty degrees (180°) would allow needle tip  288  to travel distally, yet be stopped by outer stop  296 , again requiring one hundred eighty degree (180°) rotation to allow further distal travel of the needle tip. Thus, twisting the inner shaft can allow the depth of penetration to be controlled. In some embodiments, the inner and outer stops are formed of radiopaque material, allowing the degree of penetration to be observed under fluoroscopy. Having staggered stops, as illustrated in FIG. 10, allows the penetration depths to be accurately controlled from the proximal end of the catheter. This may be of particular importance in PMR procedures due to the varying thickness of the heart wall.  
         [0047]    [0047]FIG. 11A illustrates a PMR device  400  extending from a proximal region  402  to a-distal region  404  and having a distal flange  410 . PMR device  400  includes an outer tube  408  defining an outer lumen  412  within and slidably containing an inner tube  414  having a first lumen  416  and a second lumen  418  disposed within. In one embodiment, the two lumens are formed within a multi-lumen extrusion of inner tube  414 . In another embodiment, the two lumens  416  and  418  are defined by separate tubes which are joined together along their length. First lumen  416  may have a fluid injected through a first manifold port  420  disposed in proximal region  402  extending through a first access tube  417  which can define first lumen  416  in the proximal region. First lumen  416  extends distally to a first injection needle  426  which may be seen to have an arcuate distal region  427 . Similarly, second lumen  418  may be seen to extend from a second manifold port  422 , through a second proximal tube  419 , extending distally to a second fluid injection needle  428 . In the embodiment illustrated, first injection needle  426  is curved, while second injection needle  428  is substantially straight in the distal region.  
         [0048]    In one embodiment, first lumen  416  is used to inject radiopaque fluid, while second lumen  418  is used to inject a drug as part of the PMR procedure. In another embodiment, first lumen  416  is used to inject a drug, while second lumen  418  is used to inject a radiopaque material. In this latter embodiment, the straight needle  428  can be used to inject radiopaque material at the center of a circular pattern formed by the repeated injection of a drug through first needle  426 . Injection of the radiopaque fluid allows the treating physician to visualize under fluoroscopy which areas of the heart wall have already been treated with the drug.  
         [0049]    [0049]FIG. 11B illustrates a distal PMR device region  434 , similar to distal region  404  of FIG. 11A, and having similar proximal regions, but -having a different configuration for the two distal needles. In the embodiment illustrated, the PMR device distal region includes outer tube  408 , inner tube  414 , and first and second lumens  416  and  418 , as in FIG. 11A. First needle  426  has arcuate region  427 . In this embodiment, a second needle  430  is illustrated, also having arcuate distal segment  432 . In this embodiment, both first and second needles have arcuate distal regions. FIG. 11C illustrates distal region  434  of FIG. 1B, shown in a retracted configuration. First needle  426  and second needle  430  may be seen to be retracted within outer tube  408 .  
         [0050]    [0050]FIGS. 12A and 12B illustrate other embodiments of PMR device distal regions, with the proximal regions not requiring illustration and having somewhat similar designs to those of FIG. 11A. FIG. 12A illustrates a PMR device  440  including a distal region  444  and having a distal atraumatic flange  446 . PMR device  440  includes an outer tube  448  defining an outer lumen  450  within. Outer lumen  450  includes within an intermediate or first tube  452  defining an intermediate or first lumen  454  within. Intermediate lumen  454  includes within an inner or second tube  456  defining an inner or second lumen  458  within. Intermediate lumen tube  452  extends distally and terminates in a distal injection tip  462 . Second or inner tube  456  extends distally, terminating in a distal injection tip  463 .  
         [0051]    In one embodiment, first lumen  454  is used to inject a drug through needle  462 . In this embodiment, second or intermediate lumen  458  is used to inject a radiopaque dye through second or intermediate needle  463 . In the embodiment illustrated in FIG. 12A, intermediate tube  452  can be slidably disposed within the outer tube  444 , and can have inner tube  456  slidably disposed within. In another embodiment, the functions of the first and second lumens are reversed relative to the aforementioned embodiment. In this embodiment, inner needle  463  is used to inject dye, while intermediate needle  462  is used to inject a drug. Injecting a radiopaque dye or contrast media allows the treating physician to observe which areas of the heart wall have been treated and which have not been treated, under fluoroscopy.  
         [0052]    [0052]FIG. 12B illustrates a PMR device  480  including a distal region  484  and having a distal atraumatic flange  486 . A first material may be injected through a proximal manifold port, through a first lumen  492  defined within a first or intermediate tube  490 . The first material or fluid may be injected through intermediate tube  490 , being injected into tissue through a first distal tip  494 . A second material or fluid may be injected through a second or inner manifold port, flowing through an inner lumen  500  defined within an inner tube  498 . The second media may be injected distally into tissue through a inner distal tip  502 .  
         [0053]    In the illustrated embodiment, tube  490  is fixed relative to outer tube  484 , while inner tube  498  can be slidably disposed with respect to tube  490 . In this embodiment, radiopaque contrast media may be injected at approximately the same site as a drug delivered in a PMR procedure. In one embodiment, a drug is injected through inner tip  502 , while a contrast media is injected through tip  494 . In another embodiment, contrast media is injected through tip  502 , while a drug or other therapeutic substance is delivered through the outer distal tip  494 . In the embodiment illustrated in FIG. 12B, outer distal tip  494  is relatively rounded at the end, with pressure being used to force material into the heart wall, rather than relying primarily on needle penetration. PMR device  480  also allows injection of contrast media near the site of drug injection. This allows the treating physician to observe the location of sites treated by PMR under fluoroscopy, distinguishing the treated sites from the untreated areas.  
         [0054]    Numerous advantages of the invention covered by this document have been set forth in the foregoing description. It will be understood, however, that this disclosure is, in many respects, only illustrative. Changes may be made in details, particularly in matters of shape, size, and arrangement of parts without exceeding the scope of the invention. The invention&#39;s scope is, of course, defined in the language in which the appended claims are expressed.