|Publication number||US20070129761 A1|
|Application number||US 11/599,882|
|Publication date||Jun 7, 2007|
|Filing date||Nov 14, 2006|
|Priority date||Apr 8, 2002|
|Also published as||US8620423, US8948865, US20100174282, US20110257564, US20140107539, US20150157398, WO2008070413A2, WO2008070413A3|
|Publication number||11599882, 599882, US 2007/0129761 A1, US 2007/129761 A1, US 20070129761 A1, US 20070129761A1, US 2007129761 A1, US 2007129761A1, US-A1-20070129761, US-A1-2007129761, US2007/0129761A1, US2007/129761A1, US20070129761 A1, US20070129761A1, US2007129761 A1, US2007129761A1|
|Inventors||Denise Demarais, Hanson Gifford|
|Original Assignee||Ardian, Inc.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Referenced by (44), Classifications (20), Legal Events (1)|
|External Links: USPTO, USPTO Assignment, Espacenet|
The present application is a continuation-in-part application of each of the following co-pending U.S. patent applications:
(1) U.S. patent application Ser. No. 10/408,665, filed on Apr. 8, 2003 (published as U.S. Patent Publication 2003/0216792 on Nov. 20, 2003), which claims the benefit of U.S. Provisional Patent Application Nos. 60/442,970, filed Jan. 29, 2003; 60/415,575, filed Oct. 3, 2002; and 60/370,190, filed Apr. 8, 2002.
(2) U.S. patent application Ser. No. 11/133,925, filed on May 20, 2005, which is a continuation of U.S. patent application Ser. No. 10/900,199, filed on Jul. 28, 2004 (now U.S. Pat. No. 6,978,174), which is a continuation-in-part of U.S. patent application Ser. No. 10/408,665, filed on Apr. 8, 2003.
(3) U.S. patent application Ser. No. 11/189,563, filed Jul. 25, 2005, which is a continuation-in-part of U.S. patent application Ser. No. 11/129,765, filed on May 13, 2005, which claims the benefit of U.S. Provisional Patent Application Nos. 60/616,254, filed Oct. 5, 2004; and 60/624,793, filed Nov. 2, 2004.
(4) U.S. patent application Ser. No. 11/266,993, filed on Nov. 4, 2005.
(5) U.S. patent application Ser. No. 11/363,867, filed Feb. 27, 2006, which (a) claims the benefit of U.S. Provisional Application No. 60/813,589, filed on Dec. 29, 2005 (originally filed as U.S. application Ser. No. 11/324,188), and (b) is a continuation-in-part of each of U.S. patent application Ser. No. 11/189,563, filed on Jul. 25, 2005, and U.S. patent application Ser. No. 11/266,933, filed on Nov. 4, 2005.
(6) U.S. patent application No. 11/504,117 filed on Aug. 14, 2006.
All of the foregoing applications, publication and patent are incorporated herein by reference in their entireties.
All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.
The present invention relates to methods and apparatus for neuromodulation. In some embodiments, the present invention relates to methods and apparatus for treating heart arrhythmia, such as atrial fibrillation.
Heart arrhythmia are conditions affecting the electrical system of the heart, causing irregular heart rhythms. Arrhythmia may originate in the atria or the ventricles of the heart, and they may induce tachycardia (fast heart rate) or bradycardia (slow heart rate). Atrial tachycardia include atrial fibrillation, atrial flutter, supraventricular tachycardia and Wolff-Parkinson-White syndrome. The irregular heart rhythm experienced during atrial fibrillation or other heart arrhythmia may reduce the volume of blood pumped by the heart and/or may put a patient at an elevated risk for stroke. Ventricular tachycardia include ventricular tachycardia, ventricular fibrillation and long QT syndrome. Bradycardia include sick sinus and conduction block. Pre-existing heart conditions, such as high blood pressure, valvular disease, coronary artery disease and cardiomyopathy, may trigger heart arrhythmia by lowering blood supply to the heart, damaging heart tissue and/or other mechanisms.
Bradycardia may, for example, be treated with a pacemaker. Medical practitioners commonly treat tachycardia, such as atrial fibrillation, via electrical cardioversion with an external defibrillator. An implantable cardioverter defribrillator additionally or alternatively may be utilized. Medical practitioners also may utilize anti-arrhythmics to control the patient's heart rhythm. Furthermore, they may recommend that a patient take anti-coagulants, such as warfarin or aspirin, to thin the blood and reduce a risk of blood clot formation. Serious tachycardia may be treated via ablation of targeted regions of the heart that impede aberrant electrical signals via a band of scar tissue. Patients who have undergone such ablation procedures may require a pacemaker to maintain a regular heart rhythm.
The kidneys may play a role in atrial fibrillation, as well as other heart arrhythmia or other cardio-renal diseases. Numerous academic studies have noted an increase in sympathetic nerve activity during atrial fibrillation. The functions of the kidneys can be summarized under three broad categories: (a) filtering blood and excreting waste products generated by the body's metabolism; (b) regulating salt, water, electrolyte and acid-base balance; and (c) secreting hormones to maintain vital organ blood flow. Without properly functioning kidneys, a patient may suffer water retention, reduced urine flow and an accumulation of waste toxins in the blood and body.
Applicants have previously described methods and apparatus for treating renal and/or cardio-renal disorders by applying energy or neuromodulatory agents, either directly or indirectly, to neural fibers that contribute to renal function. Such energy may, for example, comprise a monopolar or bipolar electric field, a thermal or non-thermal electric field, a pulsed or continuous electric field, a stimulation electric field, a beam of high intensity focused ultrasound, a thermal cooling energy and/or a thermal heating energy. See, for example, Applicants' co-pending U.S. patent application Ser. Nos. 11/129,765, filed on May 13, 2005; 11/189,563, filed on Jul. 25, 2005; 11/363,867, filed on Feb. 27, 2006; 11/368,836, filed on Mar. 6, 2006; and 11/504,117, filed on Aug. 14, 2006. Additional methods and apparatus for achieving renal neuromodulation, e.g., via localized drug delivery (such as by a drug pump or infusion catheter) or via use of a stimulation electric field, etc, are described, for example, in co-owned and co-pending U.S. patent application Ser. No. 10/408,665, filed Apr. 8, 2003, as well as U.S. Pat. No. 6,978,174.
The energy or neuromodulatory agents may be delivered to the neural fibers that contribute to renal function from apparatus positioned intravascularly, extravascularly, intra-to-extravascularly or a combination thereof. Furthermore, the energy or neuromodulatory agents may be delivered to neural fibers innervating a single kidney, or they may be delivered bilaterally to neural fibers innervating both kidneys. In some embodiments, the energy may initiate denervation or other renal neuromodulation substantially athermally at least in part via irreversible electroporation or via electrofusion. In other embodiments, the energy may thermally induce the denervation or other renal neuromodulation via ablation or other mechanisms. Renal neuromodulation may reduce renal sympathetic nerve activity.
In view of the foregoing, it would be desirable to provide novel methods and apparatus for treating heart arrhythmia.
Several embodiments of the present invention will be apparent upon consideration of the following detailed description, taken in conjunction with the accompanying drawings, in which like reference characters refer to like parts throughout, and in which:
The present invention provides methods and apparatus for treating heart arrhythmia via modulation of neural fibers that contribute to renal function. The neuromodulation may be achieved, for example, via (a) a monopolar or bipolar electric field, (b) a thermal or a non-thermal electric field, (c) a continuous or a pulsed electric field, (d) a stimulation electric field, (e) localized drug delivery, (f) a high intensity focused ultrasound field or beam, (g) thermal techniques, (h) substantially athermal techniques, and/or (i) combinations thereof. Such neuromodulation may, for example, effectuate irreversible electroporation or electrofusion, ablation, necrosis and/or inducement of apoptosis, alteration of gene expression, action potential blockade or attenuation, changes in cytokine up-regulation and other conditions in target neural fibers. Heart arrhythmia that potentially may be treated by the present invention include, but are not limited to, atrial arrhythmia, ventricular arrhythmia, tachycardia, bradycardia, atrial tachycardia, atrial fibrillation, atrial flutter, supraventricular tachycardia, Wolff-Parkinson-White syndrome, ventricular tachycardia, ventricular fibrillation, long QT syndrome, sick sinus, conduction block and combinations thereof.
When the neuromodulatory methods and apparatus are applied to renal nerves and/or other neural fibers that contribute to renal neural functions, it is expected that the neuromodulation can directly or indirectly increase urine output, decrease plasma renin levels, decrease tissue (e.g., kidney) and/or urine catecholamines (e.g., norepinephrine), increase urinary sodium excretion, and/or control blood pressure. Furthermore, the neuromodulatory effects may reduce renal sympathetic nerve activity, which may reduce the load on the heart and/or may provide a systemic reduction in sympathetic tone to reduce the patient's susceptibility to heart arrhythmia, such as atrial fibrillation. Applicants believe that these or other changes may prevent or treat heart arrhythmiaor a host of other renal or cardio-renal conditions, such as congestive heart failure, hypertension, acute myocardial infarction, end-stage renal disease, contrast nephropathy, other renal system diseases, and/or other renal or cardio-renal anomalies. The methods and apparatus described herein could be used to modulate efferent or afferent nerve signals, as well as combinations of efferent and afferent nerve signals.
In several embodiments, bilateral renal neuromodulation is effectuated by modulating neural fibers that contribute to renal function of both the right and left kidneys. Bilateral renal neuromodulation may provide enhanced therapeutic effect in some patients compared to unilateral renal neuromodulation (i.e. modulation of neural fibers innervating a single kidney). In some bilateral embodiments, concurrent modulation of neural fibers that contribute to both right and left renal function may be achieved. In other bilateral embodiments, the modulation of the right and left neural fibers may be sequential. Bilateral or unilateral renal neuromodulation may be continuous or intermittent, as desired.
When utilizing an electric field to achieve desired neuromodulation, the electric field parameters may be altered and combined in any combination, as desired. Such parameters can include, but are not limited to, voltage, field strength, power, pulse width, pulse duration, the shape of the pulse, the number of pulses and/or the interval between pulses (e.g., duty cycle), etc. For example, suitable field strengths can be up to about 10,000 V/cm, and the field may be continuous or pulsed. When pulsed, suitable pulse widths can be of any desired length, for example, up to about 1 second. Suitable shapes of the electrical waveform include, for example, AC waveforms, sinusoidal waves, cosine waves, combinations of sine and cosine waves, DC waveforms, DC-shifted AC waveforms, RF waveforms, square waves, trapezoidal waves, exponentially-decaying waves, or other combinations of wave shapes. When pulsed, the field may include at least one pulse, and in many applications the field includes a plurality of pulses. Suitable pulse intervals include, for example, intervals less than about 10 seconds. These parameters are provided as suitable examples and in no way should be considered limiting. The electric field (or other energy modality or neuromodulatory agent) may achieve desired neuromodulation thermally or substantially athermally.
To better understand the structures of the devices described herein, and the methods of using such devices, for renal neuromodulation in the treatment of heart arrhythmia, it is instructive to examine the renal anatomy in humans.
B. Selected Embodiments of Methods for Neuromodulation
With reference now to
Similarly, the lengthwise or longer dimensions of tissues overlying or underlying the target nerve are orthogonal or otherwise off-axis (e.g., transverse) with respect to the longer dimensions of the nerve cells. Thus, in addition to aligning an electric field with the lengthwise or longer dimensions of the target cells, the electric field may propagate along the lateral or shorter dimensions of the non-target cells (i.e., such that the electric field propagates at least partially out of alignment with non-target smooth muscle cells SMC). Therefore, as seen in
An electric neuromodulation system placed within and/or in proximity to the wall of the renal artery may propagate an electric field having a longitudinal portion that is aligned to run with the longitudinal dimension of the artery in the region of the renal nerves RN and the smooth muscle cells SMC of the vessel wall so that the wall of the artery remains at least substantially intact while the outer nerve cells are destroyed, fused or otherwise affected. Monitoring elements may be utilized to assess an extent of, e.g., electroporation or temperature change, induced in renal nerves and/or in smooth muscle cells, as well as to adjust electric field parameters to achieve a desired effect.
C. Illustrative Schematic Diagrams of Steps and Potential Mechanisms by which Renal Neuromodulation May Treat Heart Arrhythmia
With reference to
As seen in
Applicants believe that these or other changes might prevent or treat heart arrhythmia or a host of other renal or cardio-renal conditions, such as heart failure, hypertension, acute myocardial infarction, end-stage renal disease, contrast nephropathy, other renal system diseases, and/or other renal or cardio-renal anomalies for a period of months, potentially up to six months or more. This time period may be sufficient to allow the body to heal, thereby alleviating a need for subsequent re-treatment. Alternatively, as symptoms reoccur, or at regularly scheduled intervals, the patient may return to the physician for a repeat therapy. The methods and apparatus described herein could be used to modulate efferent or afferent nerve signals, as well as combinations of efferent and afferent nerve signals.
D. Illustrative Embodiments of Systems and Additional Methods for Neuromodulation
With reference to
The electric field generator 50 is located external to the patient. The generator, as well as any of the embodiments of electrodes described herein, may be utilized with any embodiment of the present invention for delivery of an electric field with desired field parameters. It should be understood that embodiments of field delivery electrodes described hereinafter may be electrically connected to the generator even though the generator is not explicitly shown or described with each embodiment.
The electrode(s) 212 can be individual electrodes that are electrically independent of each other, a segmented electrode with commonly connected contacts, or a continuous electrode. A segmented electrode may, for example, be formed by providing a slotted tube fitted onto the electrode, or by electrically connecting a series of individual electrodes. Individual electrodes or groups of electrodes 212 may be configured to provide a bipolar signal. The electrodes 212 may be dynamically assignable to facilitate monopolar and/or bipolar energy delivery between any of the electrodes and/or between any of the electrodes and an external ground pad. Such a ground pad may, for example, be attached externally to the patient's skin, e.g., to the patient's leg or flank. In
Referring now to
The intravascular embodiment of
The positioning element 304 may comprise an impedance-altering element that alters the impedance between electrodes 306 a and 306 b during the e-field therapy, for example, to better direct the e-field therapy across the vessel wall. This may reduce an applied voltage or a total energy required to achieve desired renal neuromodulation. Applicants have previously described use of an impedance-altering element, for example, in co-pending U.S. patent application Ser. No. 11/266,993, filed Nov. 4, 2005. When the positioning element 304 comprises an inflatable balloon, the balloon may serve as both a centering element for the electrodes 306 and as an impedance-altering electrical insulator for directing an electric field delivered across the electrodes, e.g., for directing the electric field into or across the vessel wall for modulation of target neural fibers. Electrical insulation provided by the element 304 may reduce the magnitude of applied voltage or other parameters of the electric field necessary to achieve desired field strength or thermal effects at the target fibers.
The electrodes 306 can be individual electrodes (i.e., independent contacts), a segmented electrode with commonly connected contacts, or a single continuous electrode. Furthermore, the electrodes 306 may be configured to provide a bipolar signal, or the electrodes 306 may be used together or individually in conjunction with a separate patient ground pad for monopolar use. As an alternative or in addition to placement of the electrodes 306 along the central shaft of catheter 302, as in
In use, the catheter 302 may be delivered to the renal artery RA as shown, or it may be delivered to a renal vein or to any other vessel in proximity to neural tissue contributing to renal function, in a low profile delivery configuration, for example, through a guide catheter. Once positioned within the renal vasculature, the optional positioning element 304 may be expanded into contact with an interior wall of the vessel. A thermal or non-thermal electric field that is continuous or pulsed is then generated by the field generator 50, transferred through the catheter 302 to the electrodes 306, and delivered via the electrodes 306 across the wall of the artery. The e-field therapy modulates the activity along neural fibers that contribute to renal function, e.g., at least partially denervates the kidney innervated by the neural fibers. This may be achieved, for example, via irreversible electroporation, electrofusion and/or inducement of ablation, necrosis or apoptosis in the nerve cells. In many applications, the electrodes are arranged so that the electric field is aligned with the longitudinal dimension of the renal artery to facilitate modulation of renal nerves with little effect on non-target smooth muscle cells or other cells.
When utilizing intravascular e-field apparatus to achieve neuromodulation, in addition or as an alternative to central positioning of the electrode(s) within a blood vessel, the electrode(s) optionally may be configured to contact an internal wall of the blood vessel. Wall-contacting electrode(s) may facilitate more efficient transfer of an electric field across the vessel wall to target neural fibers, as compared to centrally-positioned electrode(s). In several embodiments, the wall-contacting electrode(s) may be delivered to the vessel treatment site in a reduced profile configuration, then expanded in vivo to a deployed configuration wherein the electrode(s) contact the vessel wall. In other embodiments, the electrode(s) may also be at least partially contracted to facilitate retrieval of the electrode(s) from the patient's vessel.
As seen in
After delivery of the electric field, the electrode 306 a′ may be returned to a contracted profile to facilitate removal of the apparatus 300 from the patient. For example, the positioning element 304 may be collapsed (e.g., deflated), and the electrode 306 a′ may be contracted by withdrawing the catheter 302 within the guide catheter 303. Alternatively, the electrode may be fabricated from a shape-memory material biased to the collapsed configuration, such that the electrode self-collapses upon collapse of the positioning element.
In addition to extravascular and intravascular neuromodulation systems, intra-to-extravascular neuromodulation systems may be provided having, e.g., electrode(s) that are delivered to an intravascular position, then at least partially passed through/across the vessel wall to an extravascular position prior to delivery of e-field therapy. Intra-to-extravascular positioning of the electrode(s) may place the electrode(s) in closer proximity to target neural fibers during the e-field therapy compared to fully intravascular positioning of the electrode(s). With reference to
ITEV e-field system 320 comprises a catheter 322 having (a) a plurality of proximal electrode lumens terminating at proximal side ports 324, (b) a plurality of distal electrode lumens terminating at distal side ports 326, and (c) a guidewire lumen 323. The catheter 322 preferably comprises an equal number of proximal and distal electrode lumens and side ports. The system 320 also includes proximal needle electrodes 328 that may be advanced through the proximal electrode lumens and the proximal side ports 324, as well as distal needle electrodes 329 that may be advanced through the distal electrode lumens and the distal side ports 326.
Catheter 322 comprises an optional expandable positioning element 330, which may comprise an inflatable balloon or an expandable basket or cage. In use, the positioning element 330 may be expanded prior to deployment of the needle electrodes 328 and 329 in order to center the catheter 322 within the patient's vessel (e.g., within renal artery RA). Centering the catheter 322 is expected to facilitate delivery of all needle electrodes to desired depths within/external to the patient's vessel (e.g., to deliver all of the needle electrodes approximately to the same depth). In
As illustrated in
The proximal electrodes 328 can be connected to field generator 50 as active electrodes and the distal electrodes 329 can serve as return electrodes. In this manner, the proximal and distal electrodes form bipolar electrode pairs that align the e-field therapy with a longitudinal axis or direction of the patient's vasculature. As will be apparent, the distal electrodes 329 alternatively may comprise the active electrodes and the proximal electrodes 328 may comprise the return electrodes. Furthermore, the proximal and/or the distal electrodes may comprise both active and return electrodes. Any combination of active and distal electrodes may be utilized, as desired.
When the electrodes 328 and 329 are connected to field generator 50 and are positioned extravascularly, and with positioning element 330 optionally expanded, e-field therapy may proceed to achieve desired neuromodulation. After completion of the e-field therapy, the electrodes may be retracted within the proximal and distal lumens, and the positioning element 330 may be collapsed for retrieval. ITEV e-field system 320 then may be removed from the patient to complete the procedure. Additionally or alternatively, the system may be repositioned to provide e-field therapy at another treatment site, for example, to provide bilateral renal neuromodulation.
It is expected that e-field therapy, as well as other methods and apparatus of the present invention for neuromodulation (e.g., localized drug delivery, high intensity focused ultrasound, thermal techniques, etc.), whether delivered extravascularly, intravascularly, intra-to-extravascularly or a combination thereof, may, for example, effectuate irreversible electroporation or electrofusion, ablation, necrosis and/or inducement of apoptosis, alteration of gene expression, action potential blockade or attenuation, changes in cytokine up-regulation and other conditions in target neural fibers. In some patients, when such neuromodulatory methods and apparatus are applied to renal nerves and/or other neural fibers that contribute to renal neural functions, applicants believe that the neuromodulatory effects induced by the neuromodulation may increase urine output, decrease plasma renin levels, decrease tissue (e.g., kidney) and/or urine catecholamines (e.g., norepinephrine), increase urinary sodium excretion, and/or control blood pressure.
Neuromodulation in accordance with the present invention optionally is achieved without completely physically severing, i.e., without fully cutting, the target neural fibers. However, it should be understood that such neuromodulation may functionally sever the neural fibers, even though the fibers may not be completely physically severed.
Apparatus and methods described herein illustratively are configured for percutaneous use. Such percutaneous use may be endoluminal, laparoscopic, a combination thereof, etc.
Although the embodiments of
Furthermore, although the embodiments of
It may be desirable to achieve bilateral renal neuromodulation. Bilateral neuromodulation may enhance the therapeutic effect in some patients as compared to renal neuromodulation performed unilaterally, i.e., as compared to renal neuromodulation performed on neural tissue innervating a single kidney. For example, bilateral renal neuromodulation may further reduce clinical symptoms of heart arrhythmia, and/or of congestive heart failure, hypertension, acute myocardial infarction, contrast nephropathy, renal disease and/or other cardio-renal diseases.
As seen in
With the guidewire and the guide catheter positioned in the right renal artery, the catheter 302 of the apparatus 300 may be advanced over the guidewire and through the guide catheter into position within the artery. As seen in
Expansion of element 304 may center or otherwise position the electrodes 306 within the vessel and/or may alter impedance between the electrodes. With apparatus 300 positioned and deployed as desired, e-field therapy may be delivered, e.g., in a bipolar fashion across the electrodes 306 to achieve renal neuromodulation in neural fibers that contribute to right renal function, e.g., to at least partially achieve renal denervation of the right kidney. As illustrated by propagation lines Li, the electric field may be aligned with a longitudinal dimension of the renal artery RA and may pass across the vessel wall. The alignment and propagation path of the electric field is expected to preferentially modulate cells of the target renal nerves without unduly affecting non-target arterial smooth muscle cells.
As seen in
Next, the catheter 302 may be re-advanced over the guidewire and through the guide catheter into position within the left renal artery, as shown in
As discussed previously, bilateral renal neuromodulation optionally may be performed concurrently on fibers that contribute to both right and left renal function.
In one example, separate arteriotomy sites may be made in the patient's right and left femoral arteries for percutaneous delivery of the two catheters 302. Alternatively, both catheters 302 may be delivered through a single femoral access site, either through dual guide catheters or through a single guide catheter.
As will be apparent, intra-to-extravascular apparatus alternatively may be utilized for bilateral renal neuromodulation. Such bilateral renal neuromodulation may be performed sequentially, concurrently or a combination thereof. For example, ITEV e-field system 320 of
Additional methods and apparatus for achieving renal neuromodulation, e.g., via localized drug delivery (such as by a drug pump or infusion catheter) or via use of a stimulation electric field, etc, also may utilized. Examples of such methods and apparatus have been described previously, for example, in co-owned and co-pending U.S. patent application Ser. No. 10/408,665, filed Apr. 8, 2003, and in U.S. Pat. No. 6,978,174, both of which have been incorporated herein by reference.
Delivering the therapy through the conduits 402 a and 402 b may achieve bilateral renal neuromodulation. Such therapy delivery may be conducted concurrently or sequentially, as well as continuously or intermittently, as desired, in order to provide concurrent or sequential, continuous or intermittent, renal neuromodulation, respectively.
In one embodiment, the element 400 comprises an implantable neurostimulator or a pacemaker-type device, and the conduits 402 comprise electrical leads that are coupled to the neurostimulator for delivery of an electric field, such as a pulsed or continuous electric field, a stimulation electric field, a thermal or non-thermal electric field, to the target neural fibers. In another embodiment, the element 400 comprises an implantable drug pump, and the conduits 402 comprise drug delivery catheters for delivery of neuromodulatory agent(s) or drug(s) from the pump to the target neural fibers. In yet another alternative embodiment, electrical techniques may be combined with delivery of neuromodulatory agent(s) to achieve desired renal neuromodulation.
In an alternative embodiment of the apparatus of
Although preferred illustrative variations of the present invention are described above, it will be apparent to those skilled in the art that various changes and modifications may be made thereto without departing from the invention. It is intended in the appended claims to cover all such changes and modifications that fall within the true spirit and scope of the invention.
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|Cooperative Classification||A61B2018/00577, A61B18/04, A61B2018/0022, A61B2018/00434, A61B2018/00511, A61N1/36017, A61N1/36114, A61N1/05, A61N1/32, A61N1/0551, A61B18/1492, A61F7/007, A61N7/02, A61M5/00|
|European Classification||A61N1/36E2, A61N1/36, A61N1/05, A61N1/32|
|Feb 9, 2007||AS||Assignment|
Owner name: ARDIAN, INC., CALIFORNIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:DEMARALS, DENISE;GIFFORD, II, HANSON;REEL/FRAME:018925/0101;SIGNING DATES FROM 20070110 TO 20070111