Abstract:
Methods and apparatus for delivering precise amounts of fluid under pressure into cardiac tissue for the purpose of facilitating ablation of the tissue along a desired lesion line. One method injects fluid under pressure through a discharge orifice in a needle-less injection device. The injected fluid can be a cytotoxic fluid and/or a highly conductive fluid injected in conjunction with radio frequency ablation to create an ablative virtual electrode. The injected fluid can provide deeper and narrower conduction paths and resulting lesions. Radio frequency ablation can be performed at the same time as the fluid injection, using the injection device as an electrode, or subsequent to the fluid injection, using a separate device. In some methods, the injected fluid is a protective fluid, injected to protect tissue adjacent to the desired lesion line. Fluid delivery can be endocardial, epicardial, and epicardial on a beating heart. The present methods find one use in performing maze procedures to treat atrial fibrillation.

Description:
RELATED APPLICATIONS 
     The present application is a divisional of U.S. patent application Ser. No. 10/356,909, filed on Feb. 3, 2003, now U.S. Pat. No. 7,118,566 which claims the benefit of U.S. provisional patent application Ser. No. 60/381,217, filed on May 16, 2002, titled DEVICE AND METHOD FOR ABLATION OF CARDIAC TISSUE, herein incorporated by reference in its entirety. The present application is related to commonly assigned U.S. patent application Ser. No. 10/356,868, filed on Feb. 3, 2003, titled DEVICE AND METHOD FOR ABLATION OF CARDIAC TISSUE. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates generally to the field of devices for cardiac surgery, and more specifically to devices for ablation of cardiac tissue. 
     BACKGROUND OF THE INVENTION 
     The present invention is directed toward treatment of tachyarrhythmias, which are heart rhythms in which one or more chambers of the heart exhibit an excessively fast rhythm. In particular, the present invention is directed toward treatment of tachycardias, which are due to the presence of ectopic foci within the cardiac tissue or due to the presence of aberrant condition pathways within the cardiac tissue. 
     There are many medical treatments that involve instances of cutting, ablating, coagulating, destroying, or otherwise changing the physiological properties of tissue. These techniques can be used beneficially to change the electrophysiological properties of tissue. For example, ablation of cardiac tissue can be used to cure various cardiac conditions. Normal sinus rhythm of the heart begins with the sinoatrial node (or “SA node”) generating a depolarization wave front. The impulse causes adjacent myocardial tissue cells in the atria to depolarize, which in turn causes adjacent myocardial tissue cells to depolarize. The depolarization propagates across the atria, causing the atria to contract and empty blood from the atria into the ventricles. The impulse is next delivered via the atrioventricular node (or “AV node”) and the bundle of HIS (or “HIS bundle”) to myocardial tissue cells of the ventricles. The depolarization of these cells propagates across the ventricles, causing the ventricles to contract. This conduction system results in the described, organized sequence of myocardial contraction leading to a normal heartbeat. 
     Sometimes aberrant conductive pathways develop in heart tissue, which disrupt the normal path of depolarization events. For example, anatomical obstacles in the atria or ventricles can disrupt the normal propagation of electrical impulses. These anatomical obstacles (called “conduction blocks”) can cause the electrical impulse to degenerate into several circular wavelets that circulate about the obstacles. These wavelets, called “reentry circuits,” disrupt the normal activation of the atria or ventricles. 
     The aberrant conductive pathways create abnormal, irregular, and sometimes life-threatening heart rhythms, called arrhythmias. An arrhythmia can take place in the atria, for example, as in atrial tachycardia, atrial fibrillation or atrial flutter. The arrhythmia can also take place in the ventricle, for example, as in ventricular tachycardia. 
     The lesions used to treat atrial fibrillation, are typically long and thin and are carefully placed to interrupt the conduction routes of the most common reentry circuits. More specifically, the long thin lesions are used to create a maze pattern that creates a convoluted path for electrical propagation within the left and right atria. The lesions direct the electrical impulse from the SA node along a specified route through all regions of both atria, causing uniform contraction required for normal atrial transport function. The lesions finally direct the impulse to the AV node to activate the ventricles, restoring normal atrioventricular synchrony. Several surgical approaches have been developed with the intention of treating atrial fibrillation. One particular example is known as the “maze procedure,” as is disclosed by Cox, J L et al. in “The surgical treatment of atrial fibrillation. I. Summary” Thoracic and Cardiovascular Surgery 101(3), pp. 402-405 (1991); and also by Cox, J L in “The surgical treatment of atrial fibrillation. IV. Surgical Technique”, Thoracic and Cardiovascular Surgery 101(4), pp. 584-592 (1991), both of which are incorporated by reference herein in their entireties. In general, the “maze” procedure is designed to relieve atrial arrhythmia by restoring effective atrial systole and sinus node control through a prescribed pattern of incisions about the tissue wall. In the early clinical experiences reported, the “maze” procedure included surgical incisions in both the right and the left atrial chambers. However, more recent reports predict that the surgical “maze” procedure may be substantially efficacious when performed only in the left atrium, such as is disclosed in Sueda et al., “Simple Left Atrial Procedure for Chronic Atrial Fibrillation Associated With Mitral Valve Disease” (1996), which is incorporated herein by reference in its entirety. 
     When modifying the electrophysiological properties of cardiac tissue by ablation, or by other means of destroying tissue to create lesions, physicians must carefully place the lesions. Otherwise, tissue will be unnecessarily destroyed. In addition, the heart is in close proximity to nerves and other nervous tissue and the destruction of this tissue will result in severe harm to the patient. Anatomical methods are used to locate the areas to be ablated or otherwise modified. In other words, the physician locates key structures such as the mitral valve annulus and the pulmonary veins. Lesions are typically formed that block propagations near these structures. Additional lesions are then formed which connect these lesions and complete the so-called “maze pattern.” However, the exact lesion pattern, and number of lesions created, can vary from patient to patient. 
     The surgical “maze procedure” as performed in the left atrium generally includes forming vertical incisions from the two superior pulmonary veins and terminating in the region of the mitral valve annulus, traversing the inferior pulmonary veins en route. An additional horizontal line also connects the superior ends of the two vertical incisions. Thus, the atrial wall region bordered by the pulmonary vein ostia is isolated from the other atrial tissue. In this process, the mechanical sectioning of atrial tissue eliminates the precipitating conduction to the atrial arrhythmia by creating conduction blocks within the aberrant electrical conduction pathways. 
     Injection of alcohol into heart tissue has also been employed to ablate cardiac tissue. Alcohol may be delivered to blood vessels supplying the tissue to be ablated, as described in “Transcoronary Chemical Ablation of Arrhythmias”, by Nellens et al, Pace Vol. 15, pages 1368-1373, September 1992. Alternatively, alcohol can be delivered directly to the tissue to be ablated by means of a needle inserted through a catheter, as described in “Chemical Ablation by Subendocardial Injection of Ethanol via Catheter—Preliminary Results in the Pig Heart”, by Weismuller et al, European Heart Journal, Volume 12, pages 1234-1239, 1991. 
     Although successful at treating AF, the surgical maze procedure is quite complex and is currently performed by only a few skilled cardiac surgeons in conjunction with other open-heart procedures. Tools that could reliably duplicate the Maze incisions by other means (e.g. radio frequency, laser, microwave, ultrasound energy) will reduce the time and invasiveness required for the maze procedure and make it more accessible to more surgeons. Problems faced by these methods, however, include (a) the creation of continuous, linear lesions in the atria for the prevention of atrial fibrillation, (b) minimization of clotting and thromboembolism, (c) the effect of heat loss due to circulating blood, (d) minimization of lesion width and minimization of atrial debulking, (e) conforming to an irregular myocardial thickness, (f) adaptability to a variety of lesion geometries and (g) usefulness from either the endocardial surface of an open heart, or the epicardial surface of a beating heart. 
     SUMMARY OF THE INVENTION 
     The present invention includes devices and methods for ablation of cardiac tissue in which a hand-held, needle-less injector is used to deliver precise amounts of liquid under pressure into cardiac tissue for purposes of ablation of the tissue along a desired lesion line. The liquids can be cytotoxic, protective, and/or conductive and can optionally be used in conjunction with RF current ablation and/or photochemically activated. The injection under pressure can deeply and narrowly ablate cardiac tissue, and can transmurally ablate cardiac tissue entirely through the myocardium when delivered from either the epicardial or the endocardial surface. The needle-less injector device can be a modification of those used for mass vaccinations. 
     In one embodiment of the invention, the fluid that is injected into the tissue is photo-chemically activated. Light energy can be applied slightly before, during, or after injection of the fluid into the tissue. The distal head of the injection device can incorporate fiber optic electrodes capable of transmitting the appropriate wavelength of energy to the tissue to activate the cytotoxic property of the fluid. Photo-chemically activated fluids are well known, having been used in chemotherapy. 
     One needle-less, tissue ablative, injector device includes a cylindrical housing having a lumen within for containing a fluid, an electrically conductive distal surface operably coupled to the housing for contacting tissue, and at least one discharge orifice near the electrically conductive surface and in fluid communication with the fluid lumen. The device can also include a pressure applicator in communication with the fluid lumen for imparting sufficient pressure to the fluid lumen to inject the fluid into the myocardium from the epicardial or endocardial surface. A pressure applicator switch operably coupled to the pressure applicator can impart pressure to eject fluid through the discharge orifice when the pressure applicator switch is activated. An electrical connector in electrical continuity with the tissue contacting surface can provide ablative electrical energy to the tissue contacting surface. 
     Some needle-less tissue ablative injector devices also include a radio-frequency current source electrically coupled to the device electrical connector. Other needle-less injector devices include a fluid supply connector coupled to the fluid lumen. The pressure applicator can include a reciprocating piston slidably disposed within at least part of the fluid lumen. In some devices, a spring urges the piston distally. In other devices, a gas pressure source acts on the piston to move the piston distally. The distal motion of the piston within the fluid lumen can impart high pressure to the fluid in the lumen, forcing the fluid out the discharge orifice and into the tissue. 
     Needle-less injector devices can also include a distal tip coupled to the device distal region and can have at least one discharge orifice disposed in the tip. The tip can include a fluid lumen coupling the device fluid lumen and the tip discharge orifices, with the tissue contacting surface located on the tip, such that fluid can be injected through at least two discharge orifices simultaneously. In some devices the tip is removable. 
     Other needle-less injector devices also include an electrical switch electrically coupled to the electrical connector for controllably providing radio frequency energy to the tissue, with the electrical switch being coupled to the pressure applicator switch. Devices can have a two-position trigger configured to first change the state of the pressure applicator switch, and subsequently change the state of the electrical switch. The two-position trigger can cause conductive fluid to be injected into the tissue, followed by application of ablative electrical energy deeply into the tissue, conducted in part by the injected conductive solution. 
     In one aspect of the invention, a needle-less injector is used to repeatedly penetrate cardiac tissue with fluid under pressure and to deliver a cytotoxic agent into the cardiac tissue. The cytotoxic agent is used to “draw” a lesion on the myocardium by the repeated injection of cytotoxic fluid while moving the tip of the device along the desired lesion pattern. Because of the repeated and rapid injection, the surgeon can complete the lesion pattern rapidly. In some devices, a manually operated switch on the housing of the device activates the pressure applicator as desired by the operator and repeatedly injects fluid under pressure from the device. The fluid pressure can be adjusted to control the depth at which the cytotoxic fluid is delivered to the tissue. The imparted fluid pressure can enable the cytotoxic fluid to be injected into the tissue so that it extends transmurally, through the entire thickness of the tissue. The fluid can be bulk loaded into a fluid reservoir in the device for multiple injections or can be loaded into a “single shot” lumen and repeatedly replenished from an external fluid source. The fluid delivery can be performed endocardially, and/or epicardially on a stopped heart, and/or epicardially on a beating heart. 
     In yet another aspect of the invention, a device as described above is utilized in combination with radio frequency ablation. The device tissue contacting surface can be connected to one pole of a radio frequency generator while the other pole of the generator is connected to a large indifferent electrode. 
     In still another aspect of the present invention, the injection head includes two electrodes to create a bipolar ablation device. The electrodes can reside on the surface or penetrate the tissue, using needles for example. The distal ablation head is small in some embodiments, having discrete point or short linear electrodes and only one or a small number of injection orifices. In other embodiments, the ablation head includes longer linear electrodes and a larger number of injection orifices. 
     Rather than a cytotoxic agent, the high-pressure device can deliver a conductive liquid such as a saline solution that creates an ablative virtual electrode when delivered into the tissue through high pressure. The device is advanced along a desired lesion line on the tissue as the fluid is injected into the tissue. Delivery of the conductive liquid and the ablative radio frequency energy can be synchronized to form the virtual electrode and ablate the tissue along the desired lesion line. 
     In another aspect of the invention, a device as described above is utilized in combination with a conventional radio frequency ablation device such as the Cardioblate® pen sold by Medtronic, Inc. Rather than a cytotoxic agent, pressure injection delivers a conductive liquid such as a hypertonic saline solution to the tissue. The device is advanced along a desired lesion line on the tissue as the fluid is injected into the tissue. Delivery of the conductive liquid is made into the tissue along the desired lesion line. The conductive tip of the Cardioblate pen is subsequently drawn along the desired lesion line while applying radio frequency energy to the tissue. The hypertonic saline solution that creates a low impedance electrical pathway to ground such that the resultant lesion is deeper and narrower than would normally result from the use of the conventional radio frequency ablation device. 
     In yet another aspect of the invention, a device as described above is utilized in order to deliver a protective fluid in order to protect certain areas of cardiac tissue, such as tissue near vessels and valves. For example, a hypotonic fluid can be used as a protective fluid in order to increase the electrical impedance of the tissue to be protected relative to the surrounding tissues, essentially insulating the protected tissue from the electrical current of the radio frequency ablation device. This aspect of the invention can be combined with one or more of the other aspects of the invention in which a conductive liquid is delivered to a first portion of cardiac tissue along a desired lesion line and a protective fluid is delivered to a second portion of cardiac tissue spaced apart from the desired lesion line. This can be readily accomplished by a device having a plurality of spaced-apart discharge orifices with centrally located orifices delivering the conductive liquid and other orifices on one or both sides of the centrally located orifices delivering the protective fluid. As the radio frequency ablation device, such as the Cardioblate pen, is advanced along the desired lesion line, a narrower and deeper lesion will result with this technique. 
     In still another aspect of the invention, a device as described above is utilized in order to deliver an ink or dye to the cardiac tissue in order to identify the position of the lesion line on the cardiac tissue and to identify portions of tissue along the lesion line where the lesion has been completed. For example, the ink or dye can be added to the cytotoxic fluid in order to identify portions of tissue that have received the cytotoxic fluid, and to insure that those portions create a complete lesion along the desired lesion line. Alternatively, the ink or dye can be added to the conductive liquid in order to identify the portions of tissue that have been ablated by the radio frequency energy of a virtual electrode. The completeness of the lesion line is again indicated by the presence of the ink or dye. Alternatively, the ink or dye can be added to the conductive liquid in order to identify the position of the desired lesion line so that the Cardioblate pen or other radio frequency ablation device can be guided along the line that has been established by the delivery of the conductive fluid. In yet another aspect, the ink or dye can be thermochromic such that it changes color when heated to a temperature, which indicates that a lesion has been formed by the application of radio frequency energy. Typically, temperatures above about 50 to 55 degrees C. are required to cause cell death in an ablative lesion made by radio frequency ablation and the thermochromic material would preferably change color in that temperature range. 
     Other means to drive fluid into tissue can also be used with the present invention. One method includes the use of ultrasound, for example high intensity focused ultra sound (HIFU), to drive a fluid, for example saline, into the tissue. With the addition of a secondary energy source to the device, photophoresis or iontophoresis can be used to help drive fluid into the tissue. If desired, photophoresis and/or iontophoresis may be used alone to drive fluid into the tissue, since photophoresis and/or iontophoresis do not themselves require high-pressure injection. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a side, schematic view of a needle-less injector device according to the present invention. 
         FIG. 2  is an end view of a linear array nozzle having multiple discharge orifices according to the present invention. 
         FIG. 3  is a longitudinal, cross-sectional view of the linear array nozzle of  FIG. 2 . 
         FIG. 4  is a transverse, cross-sectional view of a bi-polar injection nozzle having short linear electrodes. 
         FIG. 5  is a bottom view of the bi-polar injection nozzle of  FIG. 4 . 
         FIG. 6  is a transverse, cut-away view of a bi-polar injection nozzle having numerous injection orifices and elongate electrodes. 
         FIG. 7  is a diagrammatic, longitudinal cross-sectional view of a needle-less injector device having a spring loaded pressure applicator. 
         FIG. 8  is a fragmentary, longitudinal cross-sectional detail view of the needle-less injector device of  FIG. 7 . 
         FIG. 9  is a highly diagrammatic, longitudinal cross-sectional view of a needle-less injector device having a high pressure, gas-pressurized applicator. 
         FIG. 10  is a schematic view of the heart showing various maze lesions that can be formed according to the invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The following detailed description should be read with reference to the drawings, in which like elements in different drawings are numbered identically. The drawings, which are not necessarily to scale, depict selected embodiments and are not intended to limit the scope of the invention. Several forms of the invention have been shown and described, and other forms will now be apparent to those skilled in art. It will be understood that embodiments shown in drawings and described below are merely for illustrative purposes, and are not intended to limit the scope of the invention as defined in the claims, which follow. 
       FIG. 1  is a schematic view of a needle-less fluid injector device  20  having generally a distal end  26 , a proximal end  27 , and a handle  36 . Needle-less fluid injector  20  includes a barrel or housing  22  having a fluid lumen  24  within. Fluid lumen  24  can terminate distally in a discharge orifice or port  28  and be in fluid communication with a pressure applicator  30 . Pressure applicator  30  can include any suitable device for imparting high pressure to the fluid in fluid lumen  24 . A pressure applicator trigger  32  may be seen coupled to pressure applicator  30  via a pressure control linkage  34 . When depressed, pressure applicator trigger  32  can initiate the rapid application of pressure to fluid lumen  24  by pressure applicator  30 . 
     Needle-less fluid injector  20  can also include an optional electrical connector  40 . Electrical connector  40  can be any suitable electrical connector, including banana plug connectors, screw terminals, spade lugs, jacks, or jack receptacles, as well as other electrical connectors well-known to those skilled in the art. Electrical connector  40  is preferably electrically coupled to tissue contacting surface  29 . 
       FIG. 1  illustrates a radio frequency source electrical connector  42  that is electrically coupled to electrical connector  40 . Electrical connector  42  can be coupled via an electrical line  44  to an electrical trigger or switch  46 . Electrical trigger or switch  46  is coupled to a radio frequency energy source  50  via another electrical line  48 . In some embodiments, electrical switch  46  is external to needle-less fluid injector device  20 , for example, a foot switch. In other embodiments, electrical switch  46  is carried on or contained in needle-less fluid injector device  20 . In some embodiments, depressing pressure applicator trigger  32  also triggers electrical switch  46 . In one device, pressure applicator trigger  32  is a two-position trigger, having a first position for triggering the application of pressure to inject fluid into tissue, followed by a second position for administering ablative radio frequency energy to the tissue now having the injected fluid within. 
     Fluid can be injected into tissue through discharge orifice  28  while the tissue is contacted by tissue contacting surface  29 . Tissue contacting surface  29  can be electrically conductive and in electrical continuity with electrical connector  40 . Tissue contacting surface  29  can be part of a distal nozzle region disposed about discharge orifice  28  in some embodiments, and be electrically coupled to electrical connector  40 . In another set of embodiments, discharge orifice  28  is coupled to a tip. In this embodiment, the tip itself bears the tissue contacting surface and contains a fluid discharge orifice for injecting fluid under pressure into the tissue. 
       FIG. 2  illustrates a linear array nozzle  60  for injecting fluid under pressure into tissue from several discharge orifices or ports simultaneously. Linear array nozzle  60  includes generally a body  66 , a tissue contacting surface  62 , and several discharge orifices  64 .  FIG. 3  illustrates linear array nozzle  60  from the side, shown in longitudinal cross-section. Linear array nozzle  60  may be seen to also include a manifold  68  for distributing fluid amongst the discharge orifices as well as a threaded connector  70  for connecting to a discharge orifice on a needle-less fluid injector, for example, needle-less fluid injector  20  of  FIG. 1 . In use, linear array nozzle  60  can be applied to the tissue such that the several discharge orifices  64  are aligned along the desired lesion line. The fluid can then be injected at numerous sites along the desired lesion line at once, speeding the lesion-creating process. 
       FIGS. 4 and 5  illustrate a bi-polar injection nozzle  72  that can be used without an external indifferent electrode. Bi-polar injection nozzle  72  includes a non-conductive body  73  having a fluid lumen  74  within and terminating in a fluid injection orifice  76 . Orifice  76  is disposed within a tissue contacting surface  77 . Nozzle  72  also includes a tissue proximity sensor  71  mounted in tissue contacting surface  77 . Tissue proximity sensor  71  can be used to sense the presence of tissue to ensure that nozzle  72  is disposed near the tissue before ejection of fluid and/or application of RF energy are allowed. Tissue sensor  71  can be a sensor that measures impedance, capacitance, pressure, or other properties, and can be a mechanical sensor in some embodiments. As used herein, the term “tissue sensor or tissue proximity sensor” refers to a sensor that senses the presence of tissue, but may also sense other surfaces and still be considered a tissue sensor. In one example, a mechanical or solid state pressure switch would trigger on any applied pressure, and would still be considered a tissue sensor. The tissue sensor can be used to control or bias a relay or gate to require that the nozzle be pressed against something or near something in order for fluid to be injected and/or RF energy applied. A suction pod or vacuum orifice  69  is also shown on tissue contacting surface  77 . In one embodiment, one or more vacuum pods are present on, and can even encircle the nozzle. The vacuum pods can be coupled to a vacuum lumen (not shown in  FIG. 4 ). The vacuum pods can aide in holding the nozzle firmly against the tissue. Holding the nozzle steady and making sure the nozzle is disposed against the tissue can reduce any irritation that might be caused by ejecting fluid while moving the nozzle. 
     Tissue contacting surface  77  of nozzle  72  also includes a first polarity electrode  78  and a second polarity electrode  79 . Electrodes  78  and  79  can be either relatively short linear electrodes as illustrated in  FIG. 5 , point electrodes, or elongate electrodes intended for use with multiple orifices. 
       FIG. 6  illustrates a bi-polar, linear array nozzle  82 , having a non-conductive body  83  housing a fluid lumen  85 . Lumen  85  feeds several nozzle supply lumens  88  that in turn supply fluid discharge orifices  86  positioned along a tissue contacting surface  87 . Nozzle  82  includes a stem or shoulder region  84  that can be threaded or otherwise configured for attachment to a fluid injection device. The tissue contacting surface  87  of nozzle  82  includes two, opposite polarity electrodes, arranged on opposite sides of the linear array of orifices  86 , one of the electrodes, electrode  90 , is illustrated in  FIG. 6 . Electrode  90  is disposed within a nozzle region  89 . Electrode  90  is an elongate electrode, extending along the numerous discharge orifices  86 . In one embodiment of the invention, nozzle  82  is between about 5 and 7 centimeters long, and has between about 4 and 8 discharge orifices. Nozzle  82  can be used without an external indifferent electrode, and can be used to inject multiple tissue locations simultaneously. In another embodiment, not requiring separate illustration, a second manifold is provided to supply some of discharge orifices  86 . In one example, a first manifold supplies orifices near stem  84  and the second manifold supplies orifices further from stem  84 . In one example of use, an ablative fluid is injected from a centrally located orifice and a protective fluid is injected from orifices located on one or both sides of the central orifice. 
       FIG. 7  illustrates another needle-less injector  120 , having a spring-loaded, mechanical pressure applicator. Needle-less injector  120  includes a distal end region  122 , a proximal end region  124 , a handle  126 , a housing or barrel  130 , and a distal tip  123 . Tip  123  includes a fluid discharge orifice or port  164  and a tissue-contacting surface  162 . Optionally; tip  123  can be electrically conductive. Tip  123  can be connected to conductor  106 , which is electrically coupled to an electrical connector  168 . External radio frequency (RF) ablation energy sources can be connected to electrical connector  168 . Needle-less injector  120  includes a fluid lumen  140  for containing the fluid to be injected. Fluid lumen  140  can be coupled to a supply lumen  160  which can in turn be coupled to a check valve  158 . Check valve  158  can be supplied by a fluid loading port  156 . In some embodiments, a distal check valve  159  is disposed between fluid lumen  140  and fluid discharge orifice  164 . A piston  150  may be seen in fluid communication with fluid lumen  140 . 
     A shaft  134  is shown in  FIG. 7 , having a proximal hexagonal cross-sectional portion  136  and a more distal threaded portion  138 . A rotatable knob  128  can be disposed about shaft hexagonal portion  136 . Shaft  134  can extend through a split-nut  144  coupled to a split-nut actuator  142 . Split-nut actuator  142  can be maintained in a closed, thread engaging position by a biasing spring  143 . Shaft  134  extends further distally through a compression spring  152 , with shaft  134  being coupled to piston  150  near the shaft distal region. Mechanical elements referenced but not discussed with respect to  FIG. 7  are shown and discussed with respect to  FIG. 8 . 
       FIG. 8  illustrates the mechanical actuating elements of needle-less injector  120  in more detail. A retention rack  154  may be seen coupled at its distal end to piston  150 . Retention rack  154  may be seen to have a plurality of teeth  155 . A piston retainer  146  may be seen pivotally mounted about pivot  174  and having a pawl  170  for engaging retention rack  154  as well as a more proximal cam or actuator end  172 . A keeper spring  148  may be seen biasing pawl  170  to engage retention rack teeth  155 . A trigger  132  may also be seen, mounted about a pivot  131  and having a manually operable portion  135  and an actuator portion  133  disposed near an actuator end  141  of split-nut actuator  142 . 
     The operation of needle-less injector device  120  can be visualized with respect to  FIGS. 7 and 8 . In use, needle-less injector device  120  can be “cocked” by proximally retracting shaft  134 , thereby compressing spring  152  and proximally retracting piston  150  to create fluid containing space within fluid lumen  140 . In devices having check valve  159 , check valve  159  can prevent air from being pulled into fluid lumen  140 . A fluid supply tube can be coupled to fluid loading port  156 , and fluid forced through check valve  158  and supply lumen  160  into fluid lumen  140 . Check valve  158  can later prevent fluid from being ejected out through fluid loading port  156 , rather than into the tissue as desired. 
     Shaft  134  can be proximally retracted in various ways in various embodiments. In the embodiment illustrated in  FIG. 7 , knob  128  can be rotated. Knob  128 , having a hexagonal shaped internal opening to mate to the outside of shaft hexagonal portion  136 , can apply torque to shaft  134  and thereby rotate shaft  134 . The rotating shaft  134  threaded portion  138  passes through split-nut  144 , with the nut being in the closed, thread engaging position. Knob  128  can thus be rotated to proximally retract shaft  134  by engaging the internal threads of split-nut  144 . In some embodiments, the functionality of knob  128  is either assisted or replaced by a motor-driven element for rotatably engaging shaft  134 . In some embodiments, teeth  155  on retention rack  154  may be angled to allow the proximal retraction of shaft  134  while engaged by pawl  170 . In other embodiments, trigger  132  may be pulled while retracting shaft  134 . With shaft  134  in a proximally retracted position, and fluid lumen  140  containing fluid, the device is prepared to inject fluid. 
     Trigger manually operable portion  135  can be pulled, thereby urging trigger actuator end  133  against split-nut actuator end  141 , to urge split-nut actuator  142  against biasing spring  143 . Split-nut actuator  142  thus opens split nut  144  to disengage shaft threaded portion  138 , leaving retention rack teeth  155  engaged by pawl  170 . As trigger  132  is further depressed, trigger actuator end  133  can engage piston retainer cam region  172  to pivot piston retainer  146  about pivot  174  and thereby disengage pawl  170  from teeth  155 . Spring  152  can now drive piston  150  against the fluid contained within fluid lumen  140  to force the fluid through discharge orifice  164 . In other embodiments, knob  128  can be replaced by a lever-cam device, for rapidly retracting shaft  134  in a single motion. 
     In embodiments utilizing only a cytotoxic fluid, and not utilizing radio frequency (RF) ablation, a device performing the functions of needle-less injector device  120  may be sufficient to form a lesion along the desired lesion line. In embodiments utilizing RF ablation, an external RF ablation source can be connected to electrical connector  168  to supply tissue-contacting surface  162  with radio frequency ablation energy. In some devices, an external trigger or switch is used to control the application of radio frequency ablation energy to the tissue. In other embodiments, an electrical switch can be operably coupled to trigger  132 , such that the action of trigger  132  triggers both the fluid injection and the application of radio frequency ablating energy to the tissue. The application of radio frequency energy to the tissue can be slightly delayed to allow the injection of fluid into the tissue prior to the application of the radio frequency energy. 
       FIG. 9  illustrates a gas pressure operated needle-less fluid injector  220 . Needle-less injector device  220  may be seen to extend from a distal region  202  to a proximal region  204  and have a handle  236 . Needle-less injection device  220  includes a distal tip  208  having a fluid discharge orifice  228  and a distal tissue-contacting surface  206 . Distal tip  208  may be seen contacting tissue  221 . Needle-less injection device  220  also includes a barrel or housing  210  having a fluid chamber or fluid lumen  234  within. Fluid lumen  234  may be seen coupled to a check valve  270 , which is in turn coupled through a supply lumen  271  to a fluid coupling  273 . Fluid coupling  273  may be seen connected to an external fluid source  272 . 
     A high-pressure gas source or cylinder  280  may be seen within handle  236 . High pressure gas source  280  is coupled to a valve body  282  having a valve channel  286  therethrough reversibly blocked by a valve stem or plug  288 . Valve plug  288  is coupled to a tension biasing spring  290  to maintain the valve plug in the closed position. A trigger  232  may be seen including a lever arm  235  pivotally mounted about pivot point  233 . Lever arm  235  is coupled to valve plug  288  through a rod  292 . Valve body  282  is a coupled to a piston  262  through a gas channel  270 . Piston  262  can be slidably and sealingly disposed within fluid lumen  234 . 
     Needle-less injection device  220  can also include an electrical line  296  coupled to distal tip  208  at  297  and to tissue contacting surface  206 . Electrical line  296  is also connected to a lumen contacting electrode  295 . Devices can have the electrical source in contact with the tissue contacting surface, a conductive fluid within the fluid lumen, or both. Electrical line  296  is coupled through an electrical switch  237  to a second electrical line  241  which is in turn electrically coupled to an electrical connector  240 . Electrical connector  240 , as previously discussed with respect to connector  40  of  FIG. 1 , can be any suitable connector for coupling tip  208  to an external RF energy ablation source. Electrical switch  237  can be disposed near trigger lever arm  235  so as to be closable by trigger action from trigger  232 . In some embodiments, trigger  232  is configured to release high-pressure gas against piston  262  in a first degree of movement, and to close electrical switch  237  with a second, greater degree of movement. This two-position trigger allows the initial injection of fluid into myocardial tissue followed by the subsequent delivery of radio frequency current into the already-injected tissue. 
     In use, fluid can be supplied by fluid source  272 , through fluid coupling  273 , and through check valve  270  into fluid lumen  234 , thereby forcing piston  262  proximally away from distal tip  208 , and filling fluid lumen  234  with fluid. Distal tip  208  can be disposed against tissue  221  and trigger  232  depressed to a first position, moving valve plug  288  out of valve channel  286  to allow high pressure gas to flow from high pressure gas source  280  through gas channel  270  to drive piston  262  against fluid contained in fluid lumen  234 . The driving piston  262  thus forces fluid out of fluid lumen  234 , through fluid discharge orifice  228 , and into tissue  221 . Trigger  232  can then be depressed to a second, more depressed position to close electrical switch  237 , providing radio frequency ablative energy to tissue contacting surface  206 . Ablative electrical energy can thus be provided to the tissue region recently injected with fluid. As previously discussed, the fluid can be a conductive fluid, thus forming a virtual electrode in the tissue. 
     Many presently available vaccination guns can be used to practice one aspect of the present invention. Specifically, applicants believe that presently available vaccination guns can be used to inject cytotoxic fluids into the myocardial tissue as well as other tissues to be injected with cytotoxic fluids. Presently available vaccination guns may also be used by modifying the guns to provide ablative, radio frequency energy at or near the distal, tissue contacting surface or tip. Some vaccination guns can be modified by adding an electrical connector electrically coupled to the conductive, distal tip. An external radio frequency energy source can then be connected to the gun electrical connector to practice the ablative, radio frequency energy aspect of the present invention to form tissue legions in the target tissue. 
     The depth of penetration of the fluid injected can be adjusted to match the target tissue thickness and the desired degree of penetration. In myocardial applications, it may be desirable to have the fluid penetrate at least about halfway through the tissue thickness without penetrating entirely through the tissue thickness. In some methods, the fluid pressure can be set to effect transmural penetration. The penetration depth can be controlled by adjusting the pressure applied by the pressure applicator. In mechanical embodiments of the present invention, the pressure may be adjusted by varying the degree of compression supplied to a spring within the needle-less injector device. In gas-operated embodiments, the pressure may be varied by regulating the gas pressure supplied at the piston. In one embodiment of the invention, an ultrasonic transducer can be mounted near the device distal end to provide an indication of tissue thickness near the tip, and the fluid penetration depth set as a function of the indication of tissue thickness. 
     The cytotoxic agents referred to in the present application are agents that have cytotoxic properties and can be delivered as injectable liquids or as liquid suspensions. Preferably, a cytotoxic substance has potent cytotoxic properties that destroy cell function without affecting protein structure and scaffolding. The cytotoxic agent also preferably has limited and controllable diffusion properties through extracellular spaces. Also, the cytotoxic agent preferably has a fleeting effect such that the compound washes out of the systemic circulation quickly. Alkylating agents such as cytotoxin or melphalan or their active metabolites are preferred. 
       FIG. 10  illustrates some possible generally linear lesion patterns  110  that are capable of interrupting conductive pathways  112  and  114 . The lesion patterns can be made as described above or in combination with a conventional radio frequency ablation device such as the Cardioblate pen sold by Medtronic, Inc. (not shown). Rather than a cytotoxic agent, a device delivers a conductive liquid such as a hypertonic saline solution to the tissue. The device is advanced along a desired lesion line  110  on the tissue as the high-pressure fluid is forced into the tissue. Delivery of the conductive liquid is made into the tissue along the desired lesion line  110 . The conductive tip of the Cardioblate pen can then be drawn along the desired lesion line  110  while applying radio frequency energy to the tissue. The hypertonic saline solution creates a low impedance electrical pathway from the conductive tip to the ground electrode such that the resultant lesion is deeper and narrower than would normally result from the use of the conventional radio frequency ablation device. 
     A protective fluid can also be used when making the linear lesions  110  in order to protect certain areas of cardiac tissue, such as tissue near vessels and valves like the pulmonary veins  116 . For example, a hypotonic fluid can be used as a protective fluid in order to increase the electrical impedance of the tissue to be protected relative to the surrounding tissues, essentially insulating the protected tissue from the electrical current of the radio frequency ablation device. Alternatively, the protective fluid can be a thermally protective fluid such as a chilled fluid, which protects tissue adjacent to the intended lesion from being overheated. This aspect of the invention can be combined with one or more of the other aspects of the invention in which a conductive liquid is delivered to a first portion of cardiac tissue along a desired lesion line and a protective fluid is delivered to a second portion of cardiac tissue spaced apart from the desired lesion line. This can be readily accomplished by a device having a plurality of spaced-apart discharge orifices with centrally located orifices delivering the conductive liquid and other orifices on one or both sides of the centrally located orifices. As the radio frequency ablation device, such as the Cardioblate pen, is advanced along the desired lesion line a narrower and deeper lesion would result with this technique. 
     Also, the device as described above can be utilized in order to deliver an ink or dye to the cardiac tissue in order to identify the position of the lesion line  110  on the cardiac tissue and to identify portions of tissue along the lesion line  110  where the lesion has been completed. For example, the ink or dye can be added to the cytotoxic fluid in order to identify portions of tissue which have received the cytotoxic fluid and that those portions create a complete lesion along the desired lesion line. Alternatively, the ink or dye can be added to the conductive liquid in order to identify the portions of tissue, which has been ablated by the radio frequency energy of a virtual electrode. Again the completeness of the lesion line is indicated by the presence of the ink or dye. Alternatively, the ink or dye can be added to the conductive liquid in order to identify the position of the desired lesion line so that the Cardioblate pen or other radio frequency ablation device can be guided along the line that has been established by the delivery of the conductive fluid. Dyes such as those used for tattoos are believed suitable, as are some tissue dyes. Toluene blue and methylene blue are examples of dyes believed suitable for use in the present invention. 
     In yet another aspect, the ink or dye can be thermochromic such that it changes color when heated to a temperature, which indicates that a lesion has been formed by the application of radio frequency energy. Typically, temperatures above about 50 to 55 degrees C. are required to cause cell death in an ablative lesion made by radio frequency ablation and the photochromic material would preferably change color in that temperature range. 
     In still another aspect, the injected fluid can include a viscosity enhancing agent or fluid added to reduce or retard fluid diffusion after delivery. Reducing the diffusion of a cytotoxic and/or conductive fluid can reduce the width of the resulting lesion. Reducing the diffusion of a protective fluid can maintain the protective fluid in a desired position adjacent the cytotoxic and/or conductive fluid, to serve its protective function. Viscous fluids such as dextrose or glycerol may be added to increase the viscosity of a delivered fluid. The viscous fluids or agents can provide a fluid viscosity of at least about twice that of water. 
     In still another aspect, the delivery of ionized fluids may be enhanced via a small current applied across two electrodes, i.e., iontophoresis. For example, a small current applied between the conductive distal tip  208  of needle-less injection device  220  and the ground electrode can enhance the movement within tissue of ionized fluid delivered from the fluid discharge orifice  228 . As an alternative to a mono-polar configuration, a bi-polar configuration could be used. For example, a small current may be applied between electrode  78  of nozzle  72  and electrode  79  of nozzle  72 . As described above, electrodes  78  and  79  can be either relatively short linear electrodes as illustrated in  FIG. 5 , point electrodes, or elongate electrodes intended for use with multiple fluid discharge orifices. Positive ions may be introduced into tissue from the positive pole or electrode, or negative ions from the negative pole or electrode. The use of iontophoresis can markedly facilitate the transport of certain ionized molecules. 
     It will be appreciated by those skilled in the art that while the invention has been described above in connection with particular embodiments and examples, the invention is not necessarily so limited, and that numerous other embodiments, examples, uses, modifications and departures from the embodiments, examples and uses are intended to be encompassed by the claims attached hereto. The entire disclosure of each patent and publication cited herein is incorporated by reference, as if each such patent or publication were individually incorporated by reference herein.