Microjoule electrical discharge catheter for thrombolysis in stroke patients

A micro-catheter system utilizing a microjoule pulsed electrical discharge between first and second electrodes in a recessed lumen at the catheter's working end for creating a cavitating volume of electrolytic fluid composition including a pharmacologic agent. The expansion and collapse of media at a high repetition rate creates acoustic waves that propagate distally from the working end of the micro-catheter to disrupt thrombus. The expansion and collapse of such cavitation bubbles "jet" the pharmacologic agent at a controlled velocity into the acoustically-disrupted thrombus to further depolymerize the thrombus. The catheter system includes a computer-controller for independent modulation of (i) all aspects of pharmacologic agent delivery, and (ii) all parameters of electrical discharge to "tailor" the combined acoustic wave effects and pharmacologic agent effects to dissolve thrombus rapidly and efficiently.

BACKGROUND OF THE INVENTION
 1. Field of the Invention
 The invention relates to a micro-catheter device utilizing .mu.J electrical
 discharges for the dissolution of thrombus in blood vessels, and more
 particularly for such treatments in the small diameter circulatory
 arteries of the brain in victims of stroke. It further relates to a
 technique for electroacoustic wave propagation against thrombus
 contemporaneous with high-velocity projection or jetting of pharmacologic
 agents against thrombus, the combination of acoustic wave or mechanical
 effects with pharmacologic thrombolysis being adapted to cause rapid
 dissolution or depolymerization of fibrin in thrombus.
 2. Description of the Related Art
 In the treatment of thrombus in a blood vessel, either in cardiac patients
 or stroke victims, conventional treatment is the intravenous
 administration of pharmacologic agents, such as t-PA (tissue plasminogen
 activator), streptokinase or urokinase. In such intravenous drug
 deliveries, the probability of success may be less than about 50 percent,
 and the success rates are limited by the fact that agents are not
 delivered directly to the site of the thrombus.
 To ablate thrombus in an invasive procedure, various energy-based catheters
 have been developed, for example utilizing laser and ultrasound energy
 delivery systems. A disadvantage of such approaches is that the catheter's
 diameter may be too large, and the catheter's flexibility may be limited,
 thus preventing the catheter's working end from reaching the thrombus site
 in the small circulatory arteries of the patient's brain. Another
 disadvantage of such catheters is the technique associated with
 positioning the catheter's working end in close proximity to thrombus
 prior to energy delivery to have the desired effect. For example, in using
 a pulsed laser catheter for the ablation or photo-disruption of thrombus,
 the pioneering technique relied on the steady advance of the working end
 through the target lesion while continuously emitting pulsed laser energy.
 The laser's photonic energy is absorbed by the thrombus if the working end
 is positioned properly. Investigators found that such laser treatment
 could cause excessive thermal effects and damage vessel walls. More
 recently, the original laser-catheter technique has been modified to a
 "pulse-and-retreat" approach to reduce thermal effects. In other words,
 the laser pulses are commenced for a brief "session" just before the
 working end reaches the target lesion, and then the pulsing is paused for
 about 60 seconds before advancing the working end for another lasing
 "session ". The pause is adapted to allow for cooling of the vessel walls
 and dissipation of any gas bubbles in blood caused by the pulsed laser
 treatment. The disadvantages of such pulse-and-retreat" techniques are
 that they are time-consuming, it is difficult to effectively position the
 working end in relation to the thrombus prior to the initial lasing
 session, and it is even more difficult to position the working end prior
 to follow-on lasing "sessions". (See, e.g., Topaz, et al., "Acute Results,
 Complications, and Effect of Lesion Characteristics on Outcome With the
 Solid-State, Pulsed Wave, Mid-Infrared Laser Angioplasty System", Lasers
 in Surg. & Med. 22:228-239 (1998). Further, some such laser angioplasty
 treatments generally rely on photothermal absorption within the high water
 content of the thrombus itself to disrupt the thrombus. It would be
 preferable to not deliver such excessive thermal effects to intraluminal
 fluids and to the thrombus. In using ultrasound catheters for blood clot
 disruption, it is believed that an ultrasonic "radiator" comprising a
 piezoelectric crystal or elongate tuned member cannot easily be
 miniaturized to the size need for the brain's circulatory arteries and
 still deliver significant acoustic power. (C.function.. U.S. Pat. No.
 5,318,014 to Carter titled "Ultrasonic Ablation/Dissolution Transducer").
 What is needed is a micro-catheter and working end: (i)that can be
 miniaturized to easily introduce into 1 mm. to 3 mm. brain circulatory
 arteries either independently or over a guidewire; (ii) that has a lumen
 together with pharmacologic agent dosimetry control means for controlled
 delivery of such agents directly to the thrombus site; (iii) that has
 pharmacologic agent pressure delivery means for creating pressure
 gradients for such agent delivery into the working end and against
 thrombus, (iv) that carries acoustic-energy generation means for
 delivering acoustic energy against thrombus; (v) that includes control
 systems for modulating all parameters of both pharmacologic agent delivery
 pressure and acoustic energy propagation; (vi) that protects the
 endothelium and vessel walls from thermal damage; (vii) that protects the
 endothelium and vessel walls from acoustic damage while at the same time
 dissolving thrombus; (viii) that can be activated in a continuous mode
 while advancing the working end toward and through the thrombus to require
 less precision in the imaging component of a thrombolysis procedure; (ix)
 that utilizes a non-complex energy source such as electrical discharge
 instead of a laser source or an ultrasound generator; and (x) that
 provides a system with disposables that are simple and inexpensive to
 manufacture.
 SUMMARY OF THE INVENTION
 In general, the invention comprises a micro-catheter system that utilizes
 pulsed electrical discharges between first and second electrodes in a
 novel arrangement in a recessed bore of the catheter's working end. The
 microjoule discharges are adapted to expand gas bubbles that rapidly
 collapse into a cavitating volume of an electrolytic fluid composition
 including a pharmacologic agent AG introduced into the working end from a
 computer-controlled source. The expansion and collapse of such gas bubbles
 at a high repetition rate will create acoustic waves that propagate
 distally from the working end of the micro-catheter to disrupt thrombus.
 The expansion and collapse of such cavitation bubbles also will project or
 "jet" the pharmacologic agent at a controlled velocity into the
 acoustically disrupted thrombus to further depolymerize the thrombus
 allowing it to flow though the patient's circulatory system.
 The catheter system includes a computer-controller and various subsystems
 that allow for independent modulation of (i) all aspects of pharmacologic
 agent delivery, and (ii) all parameters of electrical discharge to
 "tailor" the combined acoustic wave effects and pharmacologic agent
 effects to dissolve thrombus rapidly since the passage of time is critical
 in treating victims of stroke. It is believed that there are wide
 variations in thrombus size, location and other patient-specific
 characteristics that will require many different treatment parameters,
 which are offered by the control systems of the invention. With respect to
 pharmacologic agent delivery, the system allows modulation of the dose of
 pharmacologic agent, the pressure or velocity of agent propagation into
 thrombus, and the timing of agent introduction relative to the actuation
 acoustic waves for disrupting the thrombus. With respect to the electrical
 discharge source, the computer controller and software can independently
 modulate voltage, peak power per pulse, discharge pulse length, the energy
 profile within each discharge pulse, and the timing between discharge
 pulses resulting in a set or variable discharge pulse rate.

DETAILED DESCRIPTION OF THE INVENTION
 1. Type "A" Embodiment of Micro-Catheter
 Referring to FIG. 1, the present invention comprises a micro-catheter
 system 5 having a body diameter of from 0.5 mm. to 2.5 mm. (not limiting
 adapted for insertion into and through blood vessels as small as 1 mm. for
 accessing the site of thrombus in circulatory arteries of the brain of a
 stroke patient. In FIG. 1, the working end 10 of micro-catheter 5 is shown
 that carries an electrode arrangement with first and second electrodes 12A
 and 123 for pulsed electrical discharges therebetween. The electrical
 discharges are adapted to develop and expand gas bubbles BB that collapse
 into a cavitating volume CV within an electrolytic fluid composition EF
 including a pharmacologic agent AG introduced into the working end. The
 expansion and collapse of such gas bubbles at a repetition rate creates
 acoustic waves that propagate distally to disrupt or disintegrate
 thrombus. (The terms disrupt, disintegrate and fragment in relation to
 thrombus may be used interchangeably in this disclosure and are defined as
 meaning the reduction of a thrombus mass into a particulate-sized
 composition that will flow along with blood through the patient's
 circulatory system). The rapid expansion of such gas bubbles further
 develops pressure gradients in the cavitating volume of the electrolytic
 fluid EF to thus project or "jet" the cavitating volume CV at suitable
 velocities relative to the working end 10 and against and into
 acoustically-disrupted thrombus.
 The catheter body or sleeve 14 is elongate and has any suitable length
 along centerline 15 (FIG. 1). The catheter body 14 is of any suitable
 extruded plastic catheter material or other braided or composite material
 known in the art. FIG. 1 shows first (proximal) electrode indicated at 12A
 along centerline 15 in distal catheter core 16 that is carried at recessed
 dimension RD from the distalmost end or perimeter 18 of catheter body 14.
 One or more fluid flow passageways 19 are provided through or around core
 16 for allowing electrolytic fluid composition EF and pharmacologic agent
 AG flow therethrough. Catheter core 16, as can be seen in FIG. 1, has a
 concave-shape 20 facing distally for reasons described below. Second
 (distal) electrode 12B is shown as extending around the inner portion of
 walls 22 around the distal portion of the catheter's lumen 25, or more
 particularly, the distal recessed lumen portion indicated at 25A. It
 should be appreciated that second electrode 12B may comprise one or more
 separate electrode elements around the distal portion or end of catheter
 body 14.
 Referring still to FIG. 1, it can be seen that the concave-shape indicated
 at 20 may be of any suitable radius r given the small dimension of
 recessed lumen portion 25A and of catheter body 14. It should be
 appreciated that the radius r of concavity (e.g., the concavity may be
 almost flat or flat) is less important than the fact that concavity 20 is
 recessed in lumen portion 25A a particular recessed dimension RD which
 ranges from a maximum of about 10.0 mm. to a minimum of about 0.5 mm. More
 preferably, the recessed dimension RD ranges from a maximum of about 5.0
 mm. to a minimum of about 1.0 mm. The recessed core 16 (which carries
 first electrode 12A) together with recessed lumen 25A are adapted to serve
 several purposes that are described next, and in additional relevant
 detail in Section 2 concerning the technique of the invention. The
 electrical discharge between the first and second electrodes causes
 several energy "effects", each of which must be modulated to achieve
 dissolution of thrombus while at the same time not damaging the
 endothelium EN or vessel walls 28 (see FIG. 2A). The energy "effects"
 resulting from a single electrical discharge, or preferably a sequence of
 pulsed discharges, in an electrolytic fluid medium in which the working
 end is immersed are: (i) the electro-mechanical (or hydraulic) effects
 which result in acoustic waves propagating within intraluminal fluids of a
 vessel; (ii) electro-thermal effects in the electrolytic fluid; and (iii)
 cavitation and propagation of fluids at high acceleration rates and fluid
 flow velocities away from the site of the electrical discharge.
 A first purpose for core 16 being recessed dimension RD is to provide means
 for directing acoustic wave propagation. Referring to FIG. 2A, acoustic
 waves WV are generated by the expansion and collapse of a gas bubble BB in
 contact with electrode 12A at the time of an electrical discharge. As will
 be described below, acoustic waves of a suitable frequency, either pulsed
 or continuous, can disrupt or fragment thrombus (c.function.. U.S. Pat.
 No. 5,424,620 to Rosenschien titled "Ablation of Blood Thrombi By Means of
 Acoustic Energy"). The extension of recessed lumen portion 25A distally
 from electrode 12A is adapted to initially confine the expansion and
 collapse of gas bubbles to the working end. Such confinement within the
 walls 22 around lumen 25A thus direct all hydraulic forces and acoustic
 wave forms WV generally axially and distally along axis 15 as indicated in
 FIG. 2A. In other words, the propagation of such waves within intraluminal
 fluids (e.g., blood or an introduced fluid) will be generally "along" the
 vessel walls 28 instead of more directly against the vessel walls. Such an
 axial propagation of wave forms WV is important because damage to the
 endothelium EN or perforation of the vessel wall could result in a
 life-threatening complication. The "along-the-lumen" acoustic wave
 propagation that is provided by the working end 10 of the invention is to
 be contrasted with the prior art ultrasound catheter of FIG. 2B in which
 the exposed "radiator" may propagate acoustic waves at more direct angles
 against the vessel walls and thus have a higher probability of damaging
 the endothelium EN or bursting the vessel wall.
 A second purpose for core 16 and first electrode 12A being recessed
 dimension RD is to provide thermal-effect dissipation means to eliminate
 the possibility of tissue damage from thermal effects caused by the
 electrical discharge. It is an objective of the invention to dissolve
 thrombus without relying on thermal energy being applied to the thrombus
 itself. For this reason, the extended lumen portion 25A of the above
 described dimensions is provided to largely confine thermal effects to the
 introduced electrolytic fluid composition EF (or blood) between electrodes
 12A and 12B. Thus, thermal effects will not be in close proximity to the
 endothelium EN or vessel walls 28. Referring to FIGS. 3A-3C,
 representations of isotherms 29a-29c are shown within and around working
 end 10 in electrolytic fluid EF and indicate temperature levels in the
 fluid in which the working end 10 is immersed. The views of FIGS. 3A-3C
 are at various arbitrary microsecond (.mu.s) intervals after an electrical
 discharge between electrodes 12A and 12B. The temperature levels within
 the isotherms 29a-29c are arbitrarily labeled with the darkest shading
 indicating a "tissue-ablative" temperature range, the medium shading being
 a temperature range creating "negligible tissue trauma", and the lightest
 shading being a temperature range that has "no effect" on tissue. FIG. 3A
 represents fluid EF within at the time of an electrical discharge (at
 time=T.sub.ZERO) showing the superheating of the electrolyte to about
 100.degree. C. in contact with electrode 12A and the formation of a gas or
 cavitation bubble BB which comprises the highest temperature zone and
 which would ablate the endothelium EN if in contact with it. FIG. 3B
 represents the effect of the discharge a few .mu.s later (at time=T.sub.+1
 a.u. where a.u. is an arbitrary unit of time) at which time the cavitation
 bubble BB would collapse into a volume of smaller cavitating bubbles (not
 shown; hereafter cavitating volume CV) with the superheated area expanding
 and moving away from electrode 12A caused by pressures related to the
 bubble expansion and collapse. FIG. 3C represents the effect of the
 electrical discharge a few .mu.s later (at time=T.sub.+2 a.u.) wherein the
 superheated region has moderated in temperature as the cavitating volume
 CV expands further and is projected distally from the working end of the
 catheter. Thus, it can be seen in FIG. 3C that the endothelium EN and
 vessel walls 28 can be protected from thermal effects by confining the
 electrolytic fluid EF when superheated to recessed lumen portion 25A. By
 the time that the electrolytic fluid EF is ejected from the lumen portion
 25A, it is believed that the dimension RD of lumen 25A will allow for
 cooling of the cavitating volume to a non-damaging temperature. For this
 reason, a time-temperature gradient can be developed which will show a
 dissipation-of-temperature zone indicated at shaded region D.sub.T wherein
 the temperature of the fluid EF would be cooled below the threshold level
 that would damage tissue. As will be described below in the technique of
 the invention, all energy delivery parameters (voltage, current, discharge
 rate, electrolytic level of fluid, etc.) will be tested in various
 combinations to place D.sub.T zone at a suitable location at or about the
 distal end 18 of the catheter.
 A third purpose for working end core 16 being recessed by dimension RD is
 to provide fluid-velocity dissipation means for reducing the velocity of
 fluid jetting from working end 10 to a suitable velocity that will not
 "cut" tissue. The extended lumen portion 25A is provided as a region of
 confinement within the device in which the acceleration in propagation of
 the cavitating volume CV is slowed such that it will not contact the
 endothelium EN at any particular high velocity that would cut the
 endothelium. It should be understood that the velocity of propagation of
 the cavitating volume CV (including pharmacologic agent AG) relates to (i)
 the pressure under which the fluid is introduced, and (ii) the expelling
 forces created by the expansion and collapsed of gas bubbles. Further, the
 jetting velocity of the cavitating volume into the interface of
 intraluminal fluid (blood) makes somewhat unpredictable the actual distal
 movement of the cavitating volume CV. In any event, the velocity of
 propagation of the cavitating volume CV is different from the speed of
 propagation of acoustic waves WV therein which propagate across the
 interface between the introduced fluid EF and the pre-existing
 intraluminal fluids (blood). The objective of the working end of the
 present invention is to create a flow velocity in the cavitating volume,
 which includes the introduced pharmacologic agent AG, to engulf the
 thrombus instantly after the acoustic waves have struck and disrupted the
 thrombus. At the same time, the flow velocity must not be so high as to
 cut tissue. As is well known in field of laser-tissue interactions, such
 soft tissue cutting occurs when short laser pulses causes the explosive
 expansion of media absorbing photonic energy in close proximity to tissue,
 or within fluids in the tissue surface itself, thus creating cavitation
 within the media or tissue. In such laser-tissue interactions, any soft
 tissue proximate to the expansion and collapse of such bubbles will be
 disrupted or "cut". A similar cutting process could occur with the fast
 electrical discharge between electrodes 12A and 12B of the working end 10
 disclosed herein if any such tissues were proximate to first electrode
 12A. Since the objective of the present invention is to not cut tissue, it
 is necessary to insure that thrombus T and the vessel walls 28 are
 maintained at a particular desired distance from the cavitating volume CV
 and its distal projection at particular velocities. As shown in FIG. 4,
 the velocity of propagation V.sub.P of the cavitating volume or agent AG
 is generally indicated by wave forms WV. The distance between wave forms
 indicates velocity, or the distance traveled per arbitrary unit of time,
 which diminishes as distance increases from the location of bubble
 formation at electrode 12A. FIG. 4 thus indicates that initial V.sub.P
 close to electrode 12A will diminish to lesser V.sub.P ' just beyond the
 distalmost end 18 of the catheter. It can be thus understood that
 electrode 12A and extended lumen portion 25A are provided to insure that
 tissue is not in close proximity to a cavitating volume CV when it is
 traveling or jetting distally at initial V.sub.P which could cut tissue.
 Still, thombus T contacted by the cavitating volume CV at diminished
 velocity V.sub.P ', in addition to being subjected to acoustic wave forces
 sufficient to fragment thombus T, will be engulfed in chemical lysis
 effect of the pharmacologic agent AG within the cavitating volume CV as
 described below. For this reason, a time-velocity gradient can be
 developed to identify a dissipation-of-velocity zone indicated at shaded
 region D.sub.V wherein the velocity of electrolyte or agent jetting would
 be below the threshold level that would "cut" tissue. The discharge
 parameters (voltage, current, discharge rate, electrolytic level of fluid,
 etc.) will be tested in combinations to place D.sub.V zone at a suitable
 distance from the distal end 18 of the catheter
 A fourth purpose for the recessed dimension RD of core 16 is to provide a
 confinement zone or discharge interaction zone DIZ in which the inner
 surfaces of walls 22 around recessed lumen portion 25A are adapted to
 capture the introduced electrolytic fluid EF between electrodes 12A and
 12B. By this means of largely capturing the electrolytic fluid EF
 momentarily before it intermixes with the pre-existing intraluminal
 fluids, it is possible to accurately predict and model the effects of the
 electrical discharge since the electrolytic characteristics of the
 electrolytic fluid EF can be predetermined. This is to be contrasted with
 a situation in which no means would be provided for confining a known
 electrolyte between the electrodes and the discharge would occur in blood
 or a mixture of blood and introduced fluids, in which case the effects
 would be unpredictable.
 A fifth purpose for working end core 16 being recessed by dimension RD is
 to provide electrical discharge confinement means for reducing the
 threshold energy levels required to induce cavitation bubble
 formation--that is, to increase energy efficiency. It is postulated that
 the threshold for bubble generation per electrical discharge (and thus
 acoustic wave propagation) will be in the range of about 1 .mu.J to 50
 .mu.J which may be significantly less than used in laser-based catheters
 developed for angioplasty purposes. (As described below, a somewhat
 broader range of .mu.J energy delivery is disclosed to perform the
 technique of the invention). It is believed that the faces of walls 22
 around recessed lumen portion 25A and the capture of the expanding bubble
 volume will create additional pressures on the bubble formation and thus
 lower the threshold energy discharge requirement, in contrast to a
 situation in which no such confinement was provided.
 Referring to FIGS. 1 and 5, first proximal electrode 12A is coupled to the
 distal end of conductive wire or element 30A that extends through lumen 25
 of catheter body 14. The recessed catheter core 16 is bonded or molded in
 place within lumen 25 of the catheter with electrode 12A molded or inset
 therein. To catheter distal core 16 may be any suitable insulated material
 such as a plastic or glass-type compound. First electrode 12A, as can be
 seen in FIG. 1, has a significantly reduced cross-section portion 33 such
 that the exposed electrode surface portion 35 that is exposed to a
 discharge in recessed lumen 25A has a very small diameter d (e.g., ranging
 in diameter from about 5 microns to 25 microns or equivalent
 cross-section). The exposed surface area 35 preferably is from about 0.05
 mm.sup.2 to 0.5 mm.sup.2 and thus causes the energy discharge to be
 focused about a very small surface area within the discharge interaction
 zone DIZ FIG. 1 shows that wire 30A with insulation 36 may be carried
 loosely and lumen 25 of catheter sleeve 14 making the catheter simple to
 fabricate. Current-carrying wire 30A may be any suitable conductive
 material, for example platinum, copper, gold, etc. In FIG. 1, it can
 further be seen that the medial portion of catheter body 14 has wall
 portion 44 with current-carrying flat wire 30B embedded therein which
 extends to second electrode 12B. The thickness of wall 44 may be any
 suitable dimension. Wires 30A and 30B may be any diameter from about the
 10 to 200 microns in diameter or equivalent cross-section. The axial
 dimension between first electrode 12A and second electrode 12B ranges
 between about 0.1 mm. and 10.0 mm., along with a lumen cross-section
 indicted at C in FIG. 1 ranging between 0.2 mm. and 2.0 mm. in diameter or
 equivalent cross-section thus creating a particularly dimensioned
 discharge interaction zone DIZ.
 FIG. 5 is a schematic view of the catheter system 5 showing electrical
 discharge source 50 and the electrolytic fluid composition EF and
 pharmacologic agent AG delivery system 60 that are connected to working
 end 10 and lumen 25 at a catheter handle portion (not shown) by means
 known in the art. Typically, the fluid composition EF including agent AG
 are intermixed to provide a known electrolytic component (i.e., with known
 resistivity (Ohms/cm.), heat capacity (J/g.), etc.). The fluid delivery
 system 60 includes a manual control or preferably is controlled by a
 computer-controller known in the art and indicated at 65 to release the
 fluid from a reservoir operatively connected to the catheter handle. As
 can be seen in FIG. 5, the computer controller 65 coupled to the fluid
 delivery system 60 allows independent modulation of all elements of
 electrolytic fluid EF delivery through subsystems, including: (i) the dose
 of pharmacologic agent AG per volume of fluid EF; (ii) the electrolytic
 component (current-resisting or sensitizing composition yields resistivity
 of fluid EF in Ohms/cm.) of the fluid EF; (iii) the particular pressure of
 flow of fluid EF through the catheter and working end; and (iv) the timing
 of fluid EF introduction relative to the actuation of a pre-determined
 sequence of electrical discharges from electrical discharge source 50.
 The electrical discharge source 50 of the invention also is shown in FIG. 5
 and is based on a thyratron switch 66 that can enable a very fast
 discharge of capacitor 68. After the thyratron is switched on, and
 following a very short rise time, an electrical discharge pulse will be
 generated between first electrode 12A and second electrode 12B that
 results from the discharge of the capacitances through the electrolytic
 fluid EF that has flowed into distal lumen portion 25A and in which the
 discharge interaction zone DIZ is thus immersed. The electrical discharge
 source 50 and the wires 30A and 30B will have some capacitance which will
 result in the voltage at the electrodes 12A and 12B to be somewhat less
 than the starting voltage at capacitor 66. Still referring to FIG. 5, with
 the thyratron 66 switched off, the capacitor 68 will charge back to its
 potential through a second resistor and through the electrolytic fluid in
 which discharge interaction zone DIZ and working end 10 is still immersed.
 The electrical discharge source 50 is further is coupled to computer
 controller 65 that may be programmed with suitable software 70 to
 independently modulate all parameters of energy levels and timing the
 electrical discharge, including: (i) voltage, current and peak electrical
 power per pulse; (ii) the length of a discharge pulse; (iii) the profile
 of energy within each discharge pulse, and (iv) the timing between
 discharge pulses resulting in a set or variable discharge pulse rate. FIG.
 5 shows that a digital oscilloscope 75 is between electrodes 12A and 12B
 to register the voltage and current pulses in association with computer
 controller 65.
 2. Technique of Use of Type "A" Embodiment of Micro-Catheter
 In use, the patient would be prepared in the usual manner and working end
 10 of catheter 5 would be introduced to the site of the thrombus T in the
 blood vessel under any suitable imaging or angiography system. Referring
 to FIG. 6A, under such imaging, the working end 10 of the catheter would
 be advanced to within about 10 mm. or less from the location of thrombus
 T.
 Next, referring to FIG. 6B, the controller 65 would be actuated (at
 time=T.sub.ZERO) to deliver a predetermined dose of electrolytic fluid EF
 and pharmacologic agent AG through lumen 25 at a pre-selected pressure
 into recessed lumen portion 25A at the working end 10 of the catheter. The
 composition of electrolytic fluid EF (e.g., saline solution) and
 pharmacologic agent AG would have been determined prior to treatment by
 modeling as described above. The pharmacologic agent AG is selected from a
 class of suitable thrombolytic agents known on the art, for example,
 including t-PA, streptokinase and urokinase.
 Now referring to FIG. 6C, at a certain time later (ranging from about a ms
 to 1 second) hereafter identified as an arbitrary unit of time a.u., the
 electrical discharge source 50 is actuated. FIG. 6B thus represents
 time=T.sub.+1 a.u. when a first electrical discharge crosses the gap
 between first electrode 12A and second electrode 12B which superheats the
 electrolytic fluid EF in contact with surface area 35 of electrode 12A. In
 a matter of nanoseconds or less, the discharge forms a cavitation bubble
 BB that expands in diameter from a few microns to about 500 microns or the
 size of the lumen. The expansion of the bubble within recessed lumen
 portion 25A will develop pressure waves or acoustic waves that will
 propagate distally within working end 10 and then through intraluminal
 fluid (e.g., blood) to strike the thrombus T as was illustrated in FIG.
 2A). It is believed that the acoustic waves WV will resonate within the
 thrombus to thus disrupt or disintegrate the thrombus as shown in FIG. 6C.
 As also is shown in FIG. 6C, the expansion of the bubble BB causes the
 electrolytic fluid EF and agent AG to be ejected distally from the working
 end 10.
 FIG. 6D at time=T.sub.+2 a.u. represents the ejection or jetting of fluid
 EF and agent AG further to engulf the disintegrated or
 acoustically-disrupted thrombus T. It is believed that agent AG will be
 ejected distally with the velocity being enhanced by concave surface 20
 such that the velocities within lumen 25A will range from about 1 to 25
 m/s. As also shown in FIG. 6D, it is postulated that the energy parameters
 can be modulated to produce cavitation bubbles resulting from the collapse
 of initial bubble BB, and fluid velocities, that will dissipate entirely
 at distances ranging from about 0.1 mm. to 5.0 mm. from the distal end 18
 of the catheter which would meet the objective of the invention. Not shown
 in FIG. 6D are follow-on pulsed electrical discharges that will repeat the
 process of acoustic wave generation and pharmacologic agent AG jetting. By
 this combination technique, it is believed that pressure waves WV against
 the thrombus T followed by the immersion of remaining thrombus in the
 cavitating pharmacologic agent AG will dissolve the thrombus T rapidly and
 efficiently to a particulate dimension that will flow through the
 patient's blood vessel system. It is believed such a combination technique
 will offer better thrombolytic results than possible with the use of
 energy-delivery alone, or the use of pharmacologic agents alone. The
 system disclosed herein is adapted to be tested with modulation of all
 electrical discharge parameters to define the optimal pulse rate for
 acoustic waves to disrupt thrombus, and the locations of dissipation zones
 as defined above to control fluid jetting velocities and thermal effects.
 Modeling suggests that the pulse energy that is optimal for thrombolysis,
 both for acoustic wave generation and fluid propagation is from about 5
 .mu.J to about 500 .mu.J at pulse discharge repetition rates from about 1
 Hz to 1 kHz. More preferably, the discharge repetition rates range from
 about 10 Hz to 500 Hz. Still more preferably, the discharge repetition
 rates range from about 50 Hz to 100 Hz.
 It should be appreciated that slight variations in the technique are
 intended to fall within the scope of the invention, such as introducing
 the electrolytic fluid and pharmacologic agent AG under pressure from 1 to
 30 seconds before actuating the electrical discharge to thus develop
 thrombolytic effects in advance of the acoustic wave propagation. Any
 sequence of such agent thrombolysis and electroacoustic waves are intended
 to fall within the scope of the inventive technique. While the invention
 is particularly adapted for small diameter circulatory arteries in the
 brain, it should be appreciated that the catheter may be used to dissolve
 thrombus in any part of the patient's circulatory system.
 It should be appreciated that catheter wall 44 may be provided with a lumen
 or other means known in the art for over-the-wire introduction of the
 working end 10 when a guidewire is used. Although particular embodiments
 of the present invention have been described above in detail, it will be
 understood that this description is merely for purposes of illustration.
 Specific features of the invention are shown in some drawings and not in
 others, and this is for convenience only and any feature may be combined
 with another in accordance with the invention. Further variations will be
 apparent to one skilled in the art in light of this disclosure and are
 intended to fall within the scope of the appended claims.