Source: http://www.google.com/patents/US20050137671?dq=6,606,102
Timestamp: 2016-06-25 09:48:02
Document Index: 183008102

Matched Legal Cases: ['art 250', 'art 250', 'art 250', 'art 250', 'art 250', 'art 250', 'art 250']

Patent US20050137671 - His bundle mapping, pacing, and injection method and lead - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inPatentsA cardiac rhythm management system includes a lead assembly for intracardiac mapping, pacing, and drug delivery. The lead assembly includes an implantable endocardial lead having a proximal end for connection to an implantable cardiac rhythm management device and a distal end for disposal in an intracardiac...http://www.google.com/patents/US20050137671?utm_source=gb-gplus-sharePatent US20050137671 - His bundle mapping, pacing, and injection method and leadAdvanced Patent SearchPublication numberUS20050137671 A1Publication typeApplicationApplication numberUS 10/745,302Publication dateJun 23, 2005Filing dateDec 23, 2003Priority dateDec 23, 2003Also published asUS7245973, US8078287, US20070233216Publication number10745302, 745302, US 2005/0137671 A1, US 2005/137671 A1, US 20050137671 A1, US 20050137671A1, US 2005137671 A1, US 2005137671A1, US-A1-20050137671, US-A1-2005137671, US2005/0137671A1, US2005/137671A1, US20050137671 A1, US20050137671A1, US2005137671 A1, US2005137671A1InventorsLili Liu, Randy Westlund, Steven GirouardOriginal AssigneeLili Liu, Randy Westlund, Girouard Steven D.Export CitationBiBTeX, EndNote, RefManPatent Citations (20), Referenced by (83), Classifications (4), Legal Events (4) External Links: USPTO, USPTO Assignment, EspacenetHis bundle mapping, pacing, and injection method and lead
DETAILED DESCRIPTION [0030] In the following detailed description, reference is made to the accompanying drawings which form a part hereof, and in which is shown by way of illustration specific embodiments in which the invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and it is to be understood that the embodiments may be combined, or that other embodiments may be utilized and that structural, logical and electrical changes may be made without departing from the spirit and scope of the present invention. The following detailed description provides examples, and the scope of the present invention is defined by the appended claims and their equivalents. [0031] It should be noted that references to “an”, “one”, or “various” embodiments in this disclosure are not necessarily to the same embodiment, and such references contemplate more than one embodiment. [0032] This document discusses, among other things, a cardiac rhythm management (CRM) system including an implantable endocardial lead assembly allowing delivery of electrical therapy, chemical therapy, and biological therapy to an intracardiac region in or about the His bundle. However, it is to be understood that the present methods and apparatuses may be employed to deliver electrical therapy, chemical therapy, and/or biological therapy to other internal organs or regions of a person, including, but not being limited to, other intracardiac regions. After an AV block resulted from an injury to the AV node and/or the His bundle, pacing and drug therapies are delivered to the intracardiac region in or about the His bundle to prevent the His bundle degeneration, prevent the remodeling of the ventricular walls, and maintain a normal or at least tolerable hemodynamic performance. The implantable endocardial lead assembly includes a lead and a mapping stylet for locating of the intracardiac region by electrophysiological mapping, and subsequently, delivering drug and/or electrical therapies to the located intracardiac region. After the intracardiac region has been stabilized and/or conditioned by the drug and/or electrical therapy, a biological therapy is delivered to the intracardiac region to restore the ventricular rhythm that provides for a desirable hemodynamic performance. [0033] The drug therapy includes delivering a pharmaceutical substance to the intracardiac region in or about the His bundle. In one embodiment, the drug therapy conditions the His bundle to facilitate the biological therapy. In one specific embodiment, the pharmaceutical substance prevents the degeneration of the His bundle that occurs when AV conduction is absent. In another embodiment, the drug therapy, or an additional drug therapy, is delivered subsequent to the biological therapy to enhance the biological therapy. The pharmaceutical substance includes one or more chemical agents. In one example, a growth factor is delivered to promote vessel growth in the intracardiac region, thereby increasing blood supply to that region. [0034] The electrical therapy includes His bundle pacing, i.e., delivering cardiac pacing pulses to the intracardiac region in or about the His bundle. In one embodiment, the His bundle pacing conditions the intracardiac region to facilitate the biological therapy. In one specific embodiment, the His bundle pacing prevents the degeneration of the His bundle and maintains its normal electrical conduction characteristics. In one embodiment, the His bundle pacing enhances the drug therapy. In a further embodiment, the His bundle pacing is delivered subsequent to the biological therapy to enhance the biological therapy. Additionally, the His bundle pacing maintains or improves hemodynamic performance of the heart, such as increasing stroke volume and ventricular synchrony, at least until the biological therapy is successful. The maintained hemodynamic performance prevents ventricular remodeling and creates a physiological environment facilitating the biological therapy. The pacing mode for the His bundle pacing is selected from all available single chamber, dual chamber, and multi-chamber pacing modes, based on the need and the circumstances of a particular patient. In one embodiment, VVI or VVIR mode pacing is delivered to the intracardiac region with the His bundle treated as a ventricular pacing site. In another embodiment, in which a normal sinus rhythm is present, an atrial tracking pacing mode, such as VDD, VDDR, DDD, and DDDR, is applied with the His bundle treated as a ventricular pacing site. Other standard and custom pacing modes may also be applied, depending on the need and circumstances of each individual patient. [0035] The biological therapy includes delivering a therapeutic biological substance to the intracardiac region in or about the His bundle. In one embodiment, the therapeutic biological substance includes a biologic pacemaker. In another embodiment, the therapeutic biological substance develops into a biologic pacemaker in the intracardiac region. The therapeutic biological substance includes one or more of cells, matrices, and gene products. More specifically, the therapeutic biological substance includes, but is not limited to, one or more of exogenous cells, a cloned pacemaker channel, cloned α or β subunits of the endogenous human pacemaker current (HCN2 or other HCN types), and stem cells containing HCN channel genes. Examples of such biological therapy are discussed in Qu et al., J. Physiol., 526(3), 561-69 (2000), Qu et al., Circ. Res., 89(1), e8-14(2001), Yu et al., Circ. Res., 88(12), e84-87 (2001), and Shi et al., Circ. Res., 85(1), e1-6 (1999) [0036] Throughout this document, unless otherwise indicated, “intracardiac region” refers to the intracardiac region in or about the His bundle (AV bundle) or bundle branches. The drug therapy, electrical therapy, and biological therapy can be administrated each alone, in any combination, and/or in any order or sequence, depending on the particular need and conditions of an individual patient. [0037] FIGS. 1A-D illustrate various embodiments of an implantable endocardial lead assembly. The lead assembly includes a steerable stylet 120 suitable for locating the His bundle by electrophysiological mapping, a hollow needle 134 suitable for intracardiac injection of the therapeutic biological substance, and an implantable endocardial pacing lead 100 (shown by its various embodiments including lead 100A and 100B). Lead 100 includes a lumen 114 accommodating a portion of stylet 120 or a portion of needle 134. Lumen 114 allows a stylet distal end 124 or a needle distal end 138 to reach the intracardiac region through lead 100. In this document, unless indicated otherwise, the term “distal end” refers to the portion of lead 100, stylet 120, or needle 134 that is to be disposed in the intracardiac region, and the term “proximal end” refers to the opposite end of lead 100, stylet 120, or needle 134. [0038] FIG. 1A is an illustration of portions of lead 100A, which is one embodiment of lead 100. Lead 100A is a screw-in, unipolar endocardial lead providing an electrical connection between the intracardiac region and an implantable CRM device. Lead 100A includes an elongate lead body 102 having a lead distal end 108A and a lead proximal end 116. At or near lead distal end 108A, lead 100A includes an electrode 104, a fixation helix 106, and an osmotic drug collar 110. At lead proximal end 116, lead 100A includes a terminal pin 118. A conductor 112A electrically and mechanically connects electrode 104 and terminal pin 118. Lumen 114 extends throughout lead 100A and has a proximal opening at lead proximal end 116 and a distal opening at lead distal end 108A. It accommodates at least a portion of a flexible elongate object, and allows an end portion of that flexible elongate object to enter the proximal opening and exit from the distal opening. In one embodiment, the implantable CRM device includes a pacemaker. Electrode 104 allows the pacemaker to sense cardiac electrical activities from and delivering pacing pulses to the intracardiac region. [0039] Lead 100A includes a conductor 112A formed by a multifilar wire coiled around a major portion of lumen 114 and connecting electrode 104 and terminal pin 118. In one embodiment, fixation helix 106 is mechanically connected to electrode 104. In a further embodiment, fixation helix 106 is also electrically connected to electrode 104, and is therefore a part of electrode 104. In one embodiment, fixation helix 106 is a retractable fixation. It advances or retracts in a rotating motion when terminal pin 118 is being rotated. The rotation is translated to fixation helix 106 through conductor 112A. [0040] FIG. 1B is an illustration of portions of lead 100B, which is another embodiment of lead 100. As illustrated in FIG. 1B, lead 100B is a bipolar lead providing for two separate electrical connections between the intracardiac region and an implantable CRM device. Terminal pin 118 for lead 100B includes two separate conductive portions that allow electrodes 104 and 105 to connect to the implantable CRM device separately. Lead 100B includes a first conductor 112A and a second conductor 112IB. First conductor 112A is formed by a multifilar wire coiled around a major portion of lumen 114 and connecting electrode 104 and a first conductive portion of terminal pin 118. Second conductor 112B is formed by another multifilar wire coiled around a major portion of first conductor 112A and connecting electrode 105 and a second conductive portion of terminal pin 118. A tubular insulation layer 103 separates conductors 112A and 112B. In one embodiment, fixation helix 106 is mechanically and electrically coupled to conductor 112A, and includes a conductive tip forming electrode 105. In one embodiment, fixation helix 106 is a retractable fixation. It advances or retracts in a rotating motion when terminal pin 118 is being rotated. The rotation is translated to fixation helix 106 through conductor 112A. [0041] Lumen 114 in lead 100 (100A or 100B) accommodates one of a portion of stylet 120 and a portion of needle 134, for the purposes of allowing access to the intracardiac region by stylet distal end 124 or needle distal end 138, respectively. In one embodiment, lumen 114 has a substantially uniform diameter throughout its length. [0042] Drug collar 110 is incorporated into the distal end of lead 100 (distal end 108A of lead 100A or distal end 108B of lead 100B) and delivers the pharmaceutical substance including the one or more chemical agents. In one embodiment, drug collar 110 includes a drug reservoir containing the pharmaceutical substance and a means for controlled delivery of the pharmaceutical substance. In another embodiment, drug collar 110 includes the means for controlled delivery of the pharmaceutical substance, and the implantable CRM device includes the drug reservoir, which is in fluid communication with drug collar 110 via a passageway within and extending through lead 100. In one embodiment, the means for controlled delivery includes an osmotic membrane such that the pharmaceutical substance is delivered by way of osmosis. One example of a drug delivery system including the drug reservoir containing the pharmaceutical substance and the means for controlled delivery of the pharmaceutical substance is discussed in U.S. patent application Ser. No. 10/246,249, “DEVICES AND METHODS TO STIMULATE THERAPEUTIC ANGIOGENESIS FOR ISCHEMIA AND HEART FAILURE,” filed on Sep. 18, 2002, assigned to Advanced Cardiovascular Systems, Inc., which is incorporated herein by reference in its entirety. [0043] Examples of additional details about lead 100 such as lead 100A or 100B are discussed below with reference to FIGS. 6A, 6B, and 7. [0044] FIG. 1C is an illustration of an embodiment of stylet 120. Stylet 120 is a steerable mapping stylet including a mapping electrode 126 at stylet distal end 124, a connector 132 at stylet proximal end 130, a conductor 128 electrically connecting mapping electrode 126 and connector 132, and a nonconductive shell 122 insulating at least a major portion of conductor 128. In one embodiment, mapping electrode 126, connector 132, and conductor 128 include a single conductor. Stylet 120 includes an insulated conductor with both distal and proximal ends exposed to allow electrical connection. That is, mapping electrode 126 includes a non-insulated portion of conductor 128 at about stylet distal end 124, and connector 132 includes another non-insulated terminal portion of conductor 128 at about stylet proximal end 130. [0045] Examples of material of which nonconductive shell 122 is made include, but are not limited to, silicone, polyurethane, Teflon, and polytetrafluoroethylene (PTFE). Examples of material of which conductor 128 and connector 132 are each is made include, but are not limited to, stainless steel and alloys of nickel, titanium, cobalt, etc. Examples of material of which electrode 126 is made include, but are not limited to, one or more of platinum and iridium alloy. [0046] FIG. 1D is an illustration of an embodiment of a needle 134. Needle 134 is a hollow needle that allows for intracardiac injection of the pharmaceutical and/or therapeutic biological substance. Needle 134 includes a needle tip 140 at needle distal end 138, a needle connector 146 at needle proximal end 144, a flexible needle body 136 connecting needle tip 140 and needle connector 146, and a needle lumen 142 extending throughout needle 134 to allow passage of the pharmaceutical and/or therapeutic biological substance. In one embodiment, needle 134 includes a radiopaque marker 139 at needle distal end 138 to allow monitoring of the location of needle tip 140 inside a body using fluoroscopy. [0047] In one embodiment, needle tip 140 is constructed of, by way of example, but not but way of limitation, one of stainless steel, stainless steel alloys, and nitinol. Needle body 136 is constructed of, by way of example, but not by way of limitation, one of Teflon, polyethylene terephthalate (PET), and polyurethane. Needle tip 140 includes a non-cutting tip, such as a conical tip, that is designed to avoid damages to lumen 114 of lead 100. [0048] In one embodiment, needle lumen 142 has a substantially uniform diameter throughout its length. The diameter of needle lumen 142 is sufficient for the passage of the pharmaceutical and/or therapeutic biological substance. [0049] FIG. 2A is an illustration of an embodiment of an implantable endocardial lead assembly 252, including lead 100 and stylet 120, and portions of an environment in which it is used. In the drawing of this document, lead 100 includes a pacing lead such as lead 100A and lead 100B, and lead distal end 108 includes the distal end portion of lead 100, such as lead distal end 108A of lead 100A and lead distal end 108B of lead 100B, as discussed above with reference to FIGS. 2A and 2B. Lead assembly 252 is used for locating the His bundle in a heart 250 by electrophysiological mapping. The mapping allows the electrical therapy and the drug therapy to be delivered directly to the His bundle by accurately locating it. In FIG. 2A, lumen 114 of lead 100 accommodates a portion of stylet 120. Lead distal end 108 is disposed in a heart 250 near the His bundle. Stylet 120 is steered to move forward and backward relative to lead 100, through lumen 114 of lead 100, such that mapping electrode 126 is disposed outside of lead distal end 108 in a plurality of sites within the intracardiac region. [0050] FIG. 2B is an illustration of an embodiment of an apparatus for locating the His bundle by electrophysiological mapping using lead assembly 252. The electrophysiological mapping includes a process of seeking a site where an electrical impulse as recorded from that site displays a known timing, amplitude, and/or morphological relationship with that electrical impulse as recorded from a known site. FIG. 2B illustrates an embodiment in which the His bundle is located by recording a His bundle electrogram as well as atrial and/or ventricular electrogram. The atrial and/or ventricular electrograms are used as references for the timing, amplitude, or morphological relationship between an event in the His bundle electrogram and the same event in the atrial and/or ventricular electrograms. In one specific embodiment, the drug and electrical therapies are delivered after an AV node ablation in a patient suffering atrial fibrillation. The His bundle is located by mapping before the ablation, when the AV conduction is still intact, and the His bundle can be located based on the known or expected conduction intervals between the atrium and the His bundle and between His bundle and the ventricle. In another specific embodiment, the His bundle is located subsequent to an AV block based on a retrograde Purkinje fibers-His bundle conduction. [0051] In FIG. 2B, a mapping system includes lead assembly 252 (including lead 100 and stylet 120), an atrial lead 254 having at least one electrode in RA, and a ventricular lead 256 having at least one electrode in RV. Stylet 120, atrial lead 254, and ventricular lead 256 are connected to a cardiac signal monitor 260 that senses electrograms. One specific example of cardiac signal monitor 260 includes PRUCKA Cardio Lab EP System (model C-Lab Pro-800, GE Marquette Medical System). Cardiac signal monitor 260 includes a display 262 to present an RA electrogram 264A sensed via atrial lead 254, a His bundle electrogram 264B sensed via stylet 120, and an RV electrogram 264C sensed via ventricular lead 256. RA electrogram 264A includes events 266A indicative of RA depolarizations, referred to as RA events. RV electrogram 264C includes events 266C indicative of RV depolarizations, referred to as RV events, which are triggered by the electrical impulses which cause events 266A and are conducted through the His Bundle to the RV. His bundle electrogram 264B includes events 266B indicative of the AV conduction of the electrical impulses which cause events 266A, as recorded at the location of mapping electrode 126. In one embodiment, His bundle electrogram 264B includes A, H, and V waves. The A waves correspond to the RA depolarizations sensed by mapping electrode 126. The V waves correspond to the RV depolarizations sensed by mapping electrode 126. The H waves are events 266B. As illustrated in FIG. 2B, A, H, and V waves are identifiable by using the simultaneously displayed RA electrogram 264A and/or RV electrogram 264C as references. Stylet 120 provides for sensing of electrogram 264B in several sites in the general area where His bundle is likely located. In one embodiment, several pairs of conduction intervals are measured, with respect to the several sites, between adjacent events 266A and 266B, and between adjacent events 266B and 266C. The His bundle, or the site for delivering the intended pacing and drug therapy, is located by identifying one pair of the conduction intervals that agrees with the expected RA-His bundle conduction interval and His Bundle-RV conduction interval. In another embodiment, several conduction intervals are measured, with respect to the several sites, between adjacent events 266B and 266C. The His bundle, or the site for delivering the intended pacing and drug therapy, is located by identifying one of the conduction intervals that agrees with the expected His bundle-RV conduction interval. In one specific embodiment, an AV conduction interval is measured between RA and RV. In an alternative embodiment, ventricular lead 256 is disposed in heart 250 with at least one electrode in LV. All the embodiments discussed with respect to RV are applicable with RV substituted by LV. In one specific embodiment, an AV conduction interval is measured between RA and LV. In one embodiment, amplitudes of events 266B measured at the several sites are compared for locating or confirm the location of the His bundle. The one of the several sites associated with the largest events 266B amplitude is considered in or closest to the His bundle. [0052] The atrium-His bundle conduction interval is generally expected to be about 60 ms to 120 ms. The His bundle-ventricle conduction interval is generally expected to be about 35 ms to 55 ms. [0053] FIG. 3 is an illustration of an embodiment of a CRM system including lead 100 connected to an implantable device 370 that provides for a pacing therapy. Implantable device 370 communicates with an external system 372 via a telemetry link 374. Implantable device 370 includes a cardiac pacemaker. In one embodiment, implantable device further includes a defibrillator. In one embodiment, external system 372 includes a programmer. In another system, external system 372 includes an advanced patient monitoring system such as discussed in U.S. patent application Ser. No. 10/323,604, “ADVANCED PATIENT MANAGEMENT FOR DEFINING, IDENTIFYING AND USING PREDETERMINED HEALTH-RELATED EVENTS,” filed on Dec. 18, 2002, assigned to Cardiac Pacemakers, Inc., the specification of which is incorporated herein by reference in its entirety. [0054] After the site for delivering the drug and/or electrical therapies is located, fixation helix 106 of lead 100 is screwed in to that site by rotating terminal pin 118, and stylet 120 is removed from lead 100. Lead 100 is then connected to implanted device 370 to allow the His bundle pacing. If the pacing mode used for the His bundle pacing requires RA sensing and/or pacing, atrial lead 254 remains connected to heart 250 and is also connected to implantable medical device 370. If the pacing mode used for the His bundle pacing requires RV or LV sensing and/or pacing, ventricular lead 256 remains connected to heart 250 and is also connected to implantable medical device 370. [0055] In one embodiment, implantable device 370 includes a single chamber pacemaker capable of delivering VVI mode pacing (with the His bundle treated as a ventricular pacing site). In one further embodiment, implantable device 370 also includes a physiological sensor, such as an accelerometer or a respiration sensor, to support a rate adaptive pacing in the VVIR mode. In one embodiment, implantable device 370 includes a dual chamber or multi-chamber pacemaker capable of delivering either single chamber pacing such as VVI mode pacing or dual/multi-chamber pacing such as VDD and DDD mode pacing. In one further embodiment, implantable device 370 also includes a physiological sensor, such as an accelerometer or a respiration sensor, to support a rate adaptive pacing in pacing modes such as VVIR, VDDR, and DDDR. In one embodiment, the pacemaker includes other standard or custom pacing modes, to be selected based on the need and the circumstances of each individual patient. [0056] The drug therapy is delivered by osmotic drug collar 110 at the distal end of lead 100. This includes releasing the pharmaceutical substance to the area surrounding osmotic drug collar 110, i.e., the intracardiac region in or near the His bundle. In one embodiment, the drug therapy enhances the therapeutic effect of the electrical therapy in conditioning the heart to facilitate an anticipated biological therapy. In another embodiment, the electrical therapy enhances the therapeutic effect of the drug therapy. [0057] FIG. 4A is an illustration of an embodiment of an implantable endocardial lead assembly 458, including lead 100 and needle 134, and portions of an environment in which it is used. Lead assembly 458 is used for delivering the biological therapy to the intracardiac region in or about the His bundle. The delivery of the biological therapy includes injecting the biologic substance through needle 134. After the His bundle is located by the electrophysiological mapping, lead 100 is fixed to the site to which the drug therapy and/or the electrical therapy, as well as the biological therapy, are delivered. To inject the biological substance, needle 134 is advanced through lumen 114 of lead 100 until needle tip 140 extends beyond lead distal end 108 of lead 100 to enter cardiac tissue. In one embodiment, the needle tip is advanced to a predetermined point that is visible under fluoroscopy. In another embodiment, lead 100 and/or needle 134 include a needle stop structure to limit the extent to which needle tip can be extended beyond lead distal end 108. The biologic substance is then injected into needle proximal end 144 and forced through needle 134 to enter the intracardiac site. [0058] FIG. 4B is an illustration of an embodiment of an apparatus for delivering the biological therapy using lead assembly 458, including lead 100 and needle 134. In one embodiment, after the intracardiac region is treated by the drug and/or electrical therapies, the biological therapy is delivered to the intracardiac region surrounding lead distal end 108 of lead 100. In one embodiment, lead 100 is temporarily disconnected from implantable device 370 for the delivery of the biological therapy. Needle 134 is then advanced through lumen 114 until needle tip 140 penetrates into the tissue of the intracardiac region. Needle connector 144 is connected to a biological therapy administrator 480 from which the biological substance is delivered. In one embodiment, biological therapy administrator 480 includes a syringe. [0059] In one embodiment, the purpose of delivering the biological therapy is to develop a biologic pacemaker in the intracardiac region in or about the His bundle in heart 250. This biologic pacemaker generates electrical impulses in a way similar to the SA node. The His bundle conducts the electrical impulses from the biologic pacemaker to the right bundle branch (RBB) and left bundle branch (LBB). The RBB and LBB then conduct the electrical impulses to the RV and LV, respectively, resulting in the synchronized contraction of the ventricles. [0060] In one embodiment, after the delivery of the biological therapy, a drug therapy and/or an electrical therapy is delivered using the CRM system illustrated in FIG. 3. In one embodiment, after the delivery of the biological therapy, the CRM system remains in the patient and continues to deliver the drug and/or electrical therapies to the patient. The drug and/or electrical therapies enhance the biological therapy by stimulating the injected biological substance and by maintaining an intracardiac environment facilitating the development of the biologic pacemaker. [0061] FIG. 5 is a flow chart illustrating a method for treating heart 250 using combined drug, electrical, and biological therapies. The method includes delivering the drug, electrical and/or biological therapies to the intracardiac region in or about the His bundle. An electrophysiological mapping is performed to locate the intracardiac region at 500. In one embodiment, the intracardiac region is located by using, for example, the apparatus illustrated in FIG. 2B, before an AV node ablation. Mapping electrode 126 is placed in a plurality of sites accessible with lead assembly 252. One site suitable for delivering the drug, electrical, and biological therapies, either being in the His bundle or the closest to the His bundle, is selected based on the amplitude and/or the timing of the electrical impulses recorded for each of the plurality of sites. [0062] The drug therapy is delivered to the located intracardiac region at 510. In one embodiment, a pharmaceutical substance is delivered from osmotic drug collar 110 at lead distal end 108 of lead 100. The pharmaceutical substance treats the intracardiac region to facilitate the biological therapy. [0063] The electrical therapy is delivered to the located intracardiac region at 520. In one embodiment, the electrical therapy includes His bundle pacing. In one embodiment, pacing pulses are delivered from implantable device 370 via lead 100. [0064] The biological therapy is delivered to the located intracardiac region at 530. In one embodiment, a biological substance is delivered with lead assembly 458, i.e., through needle 134 advanced to the intracardiac region through lumen 114 of lead 100. [0065] The drug, electrical, and biological therapies can be performed in different orders and may each be repeated after interruption, depending on each individual patient's needs and specific circumstances. In other words, steps 510, 520, and 530 in FIG. 5 do not denote any particular order or sequence. For example, before the biological therapy, the drug therapy and the electrical therapy can be delivered to condition the tissue to facilitate the biological therapy. After the biological therapy is delivered, the drug therapy and the electrical therapy can be delivered to enhance the biological therapy. [0066] FIGS. 6A and 6B are detailed illustrations of one embodiment of the distal end of a bipolar pacing lead 600 as a specific embodiment of lead 100B. The design and construction of lead 600, including its detailed components, are generally applicable for lead 100A, with necessary modifications. FIG. 6A illustrates lead distal end 608 when lead 600 is in a retracted position. FIG. 6B illustrates a lead distal end 608 when lead 600 is in an extended position. As illustrated in FIGS. 6A and 6B, lead 600 includes a tip electrode and a ring electrode. The tip electrode includes a fixation helix 606, an electrode base 672, and an electrode collar 678 connecting fixation helix 606 and electrode base 672. Electrode base 672 and electrode collar 678 each have a tubular structure forming a portion of lumen 614. Fixation helix 606 allows lead distal end 608 to be affixed to the intracardiac region. Electrode base 672 is mechanically connected to conductor a 612A, such that when conductor 612A rotates, the electrode base 672 translates along an axis 660 of lead 600. In a further embodiment, electrode base 672 is formed of an electrically conductive material, such as metal, and is electrically connected to conductor 612A. Disposed about electrode base 672 are external threads 676, which allow electrode base 672 to rotate and translate fixation helix 606. Electrode base 672 is coupled with an outer threaded shell 674. The ring electrode includes electrode 675, which is electrically connected to a conductor 612B. An inner insulation 677 electrically insulates conductors 612A and 612B from each other. A lead body 602 provides for an outer insulation for the conductors. [0067] In one embodiment, components of the tip and ring electrodes are all made of conductive materials such as metals. Examples of material of which fixation helix 606 is made include, but are not limited to, stainless steel, platinum-iridium, and titanium. Examples of material of which electrode base 672 is made include, but are not limited to, stainless steel alloys. Examples of material of which electrode collar 678 is made include, but are not limited to, stainless steel and platinum-iridium alloys. Examples of material of which electrode 675 is made include, but are not limited to, platinum-iridium alloys. [0068] Lead 600 includes a drug collar 610 for delivering a pharmaceutical substance including the one or more chemical agents. In one embodiment, drug collar 610 includes a drug reservoir containing the pharmaceutical substance and a means for controlled delivery of the pharmaceutical substance. In another embodiment, drug collar 610 includes the means for controlled delivery of the pharmaceutical substance. Lead 600 includes a passageway providing for fluid communication between drug collar 610 and the implantable medical device to which lead 610 is connected. [0069] Lead body 602 forms the outer shell for a major portion of lead 600. Examples of material of which the outer shell is made include, but are not limited to, silicone and polyurethane. [0070] In one embodiment, conductors 612A and 612B each include a coiled multifilar wire. Examples of material of which the coiled multifilar wire is made include, but are not limited to, stainless steel, stainless steel alloy MP35N, titanium, and tantalum. [0071] In one embodiment, a steroid collar 662 is disposed within lead distal end 608 of the lead 600. Steroid collar 662 includes a steroidal substance that releases into the intracardiac region after lead distal end 608 is placed in that region. The steroidal substance reduces inflammation that is a response to the invasion of lead 600 into the intracardiac region. [0072] Outer threaded shell 674 includes internal threads 682. As the electrode base 672 rotates, external threads 676 engage with internal threads 682 and translate electrode base 672 along axis 660. In one embodiment, lead 600 includes a stop to prevent fixation helix 606 from over-extension. In one embodiment, a stop 670 on internal threads 682 blocks the rotation of external threads 676. Once external threads 676 reach stop 670, electrode base 672 can no longer be rotated and translated. This prevents fixation helix 606 from being over-extended into the tissue of the intracardiac region. In one embodiment, a stop 666 is formed on an outer shell 680 to block the movement of electrode collar 678. [0073] In one embodiment, outer threaded shell 674 and/or outer shell 680 are each formed of polyetheretherketone (PEEK). In one embodiment, outer threaded shell 674 is formed of PEEK 150G, which has a low melt viscosity. For PEEK 150G, the melt viscosity ranges from about 0.12-0.18 KNs/m2, and the tensile strength is greater than or equal to 90 MPa. In another embodiment, outer threaded shell 674 is formed of PEEK 450G, which has a standard melt viscosity. For PEEK 450G, the melt viscosity ranges from about 0.38-0.50 KNs/m2, and the tensile strength is greater than or equal to 90 MPa. PEEK allows outer threaded shell 674 to be molded, extruded, or machined for tighter tolerances or providing precision structures. PEEK is a tough rigid thermoplastic material that is biocompatible. [0074] Proximate to lead distal end 608 of lead 600 is a fluoroscopy ring 664, as a radiopaque marker disposed about fixation helix 106. In one embodiment, as fixation helix 606 is extended out from lead 600, electrode collar 678 translates toward fluoroscopy ring 664 until abutting a portion fluoroscopy ring 664, at which point the fixation helix 606 is fully extended. Electrode collar 678 and fluoroscopy ring 664 allow viewing, under fluoroscopy, of whether fixation helix 606 is fully extended. [0075] In one embodiment, outer shell 680 provides a stop for the translation of electrode collar 678. Outer shell 680 is coupled with outer threaded shell 674. In one embodiment, epoxy 668 is disposed between outer threaded shell 674 and outer shell 680. In one embodiment, epoxy 668 includes a blend of two different epoxies. The two different epoxies include EPOTEK� 353ND and EPOTEK� 353ND-T made by Epoxy Technology. They are mixed in the ratio of 1 part EPOTEK�353ND to 1.75 parts EPOTEK� 353ND-T. Epoxy 668 is cured at a temperature of 150� C. for one hour. [0076] FIG. 7 is a detailed illustration of one embodiment of a lead proximal end 716 of lead 600 (as a specific embodiment of lead 100B). Lead proximal end 716 includes a terminal pin 718, which is mechanically and electrically coupled to conductor 612A. Terminal pin 718 provides the electrical connection between implantable device 370 and the tip electrode of lead 600 though conductor 612A. A connective crimp tube 787 reinforces the connection between terminal pin 718 and conductor 612A. As terminal pin 718 is rotated, conductor 612A rotates, thereby rotating electrode base 672, electrode collar 678, and fixation helix 606. Terminal pin 718 has a tubular structure that forms a proximal portion of lumen 614. [0077] Lead 600 further includes an outer terminal ring 796 that is electrically coupled to conductor 612B through a conductive collar 789 to provide the electrical connection between implantable device 370 and the ring electrode (675) of lead 600 though conductor 612B. An insulator sleeve 798 is disposed over at least a portion of terminal pin 718, to insulate terminal pin 718 from outer terminal ring 796. In one embodiment, sleeve 798 rotates with outer terminal ring 796. In one embodiment, sleeve 798 is coupled to terminal pin 718 with a snap-fit connection. In another embodiment, sleeve 798 is also coupled to outer terminal ring 796 with a snap-fit connection. In one embodiment, sleeve 798 includes a shoulder 790. Shoulder 790 is engaged with a recess 794 of terminal pin 718, and prevents terminal pin 718 from moving axially. In one embodiment, shoulder 790 includes an annular shoulder disposed about the circumference of sleeve 798, which allows terminal pin 718 to rotate relative to outer terminal ring 796. The annular shoulder engages within an annular recess disposed within the circumference of terminal pin 718. In another embodiment, sleeve 798 further includes at least one recess 788 disposed adjacent to shoulder 790. Recess 788 receives a shoulder 786 of terminal pin 718. In another embodiment, sleeve 798 further includes a stop 792 for outer terminal ring 796. Terminal pin body 791 provides increased axial strength to the connection between lead 600 and implantable device 370. [0078] Terminal pin 718 and outer terminal ring 796 are each made of conductive materials such as metals. Examples of material of which terminal pin 718 is made include, but are not limited to, stainless steel, titanium, and platinum-iridium. Examples of material of which terminal ring 796 is made include, but are not limited to, stainless steel, titanium, and platinum-iridium. [0079] Sleeve 798 is formed of non-conductive material. In one embodiment, sleeve 798 is formed of PEEK. In one embodiment, sleeve 798 is formed of PEEK 150G. In another embodiment, sleeve 798 is formed of PEEK 450G. The PEEK allows sleeve 798 to be molded, extruded, or machined for tighter tolerances or providing precision structures. [0080] Lumen 614 extends along axis 600 throughout lead 600, and has a substantially circular cross-section perpendicular to axis 600. As illustrated in FIGS. 6A, 6B, and 7, lumen 614 is formed directly by the tip electrode of lead 600, conductor 612, and terminal pin 718. Lumen 614 has a distal opening at lead distal end 608 and a proximate opening at lead proximal end 616. In one embodiment, the substantially circular cross-section has a substantially uniform diameter throughout lead 600. The diameter is of a size allowing passage of stylet 120 and needle 134 (one at a time). [0081] Generally, metals used for components of lead 600, as illustrated in FIGS. 6A. 6B, and 7, include, but are not limited to, stainless steel, titanium, niobium, platinum-iridium alloys, other alloys such as elgiloy and nickel/titanium alloys. Non-metal materials used for components of lead 600, as illustrated in FIGS. 6A. 6B, and 7, include, but are not limited to, silicone, polyurethane, polydimethyls, siloxanes, and PEEK. [0082] Other embodiments of the detailed structure and elements of lead 600 are available by adopting and/or modifying existing lead structures and elements to include lumen 614. Examples of such existing lead structures and elements are discussed in U.S. Pat. No. 6,141,594, “SINGLE PASS LEAD AND SYSTEM WITH ACTIVE AND PASSIVE FIXATION ELEMENTS,” U.S. Pat. No. 6,463,334, “EXTENDABLE END RETRACTABLE LEAD,” U.S. patent application Ser. No. 10/264,494, “EXTENDABLE AND RETRACTABLE LEAD HAVING A SNAP-FIT TERMINAL CONNECTOR,” filed Oct. 4, 2002, all assigned to Cardiac Pacemakers, Inc., which are incorporated herein by reference in their entirety. [0083] It is to be understood that the above detailed description is intended to be illustrative, and not restrictive. Other embodiments will be apparent to those of skill in the art upon reading and understanding the above description. The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. Patent CitationsCited PatentFiling datePublication dateApplicantTitleUS5336252 *Jun 22, 1992Aug 9, 1994Cohen Donald MSystem and method for implanting cardiac electrical leadsUS5634899 *Jan 4, 1994Jun 3, 1997Cortrak Medical, Inc.Simultaneous cardiac pacing and local drug delivery methodUS5755766 *Jan 24, 1997May 26, 1998Cardiac Pacemakers, Inc.Open-ended intravenous cardiac leadUS6086582 *Mar 13, 1997Jul 11, 2000Altman; Peter A.Cardiac drug delivery systemUS6236887 *Jul 9, 1997May 22, 2001Impulse Dynamics N.V.Drug-device combination for controlling the contractility of musclesUS6345204 *Sep 14, 2000Feb 5, 2002Cardiac Pacemakers, Inc.Single pass lead having retractable, actively attached electrode for pacing and sensingUS6358247 *Mar 2, 1999Mar 19, 2002Peter A. AltmanCardiac drug delivery systemUS6363286 *Sep 24, 1999Mar 26, 2002Cardiac Pacemakers, Inc.High impedance electrode assemblyUS6416510 *Oct 13, 1999Jul 9, 2002Biocardia, Inc.Drug delivery catheters that attach to tissue and methods for their useUS6547787 *Oct 13, 1999Apr 15, 2003Biocardia, Inc.Drug delivery catheters that attach to tissue and methods for their useUS6560489 *Jan 8, 2001May 6, 2003Em Vascular, Inc.Therapeutic device and method for treating diseases of cardiac muscleUS6810286 *Mar 5, 2001Oct 26, 2004Medtronic, IncStimulation for delivery of molecular therapyUS6909920 *Apr 27, 2001Jun 21, 2005Medtronic, Inc.System and method for positioning an implantable medical device within a bodyUS6931286 *Apr 25, 2003Aug 16, 2005Medtronic, Inc.Delivery of active fixation implatable lead systemsUS20010044619 *Apr 8, 1998Nov 22, 2001Peter A. AltmanCardiac drug delivery system and method for useUS20020058981 *Dec 28, 2001May 16, 2002Cardiac Pacemakers, Inc.High impedance electrode assemblyUS20030093104 *Sep 25, 2002May 15, 2003Bonner Matthew D.Methods and apparatus for providing intra-pericardial accessUS20030109914 *Apr 23, 2002Jun 12, 2003Randy WestlundCoronary vein leads having an atraumatic TIP and method thereforUS20050267557 *Jul 1, 2005Dec 1, 2005Cardiac Pacemakers, Inc.Extendable and retractable lead having a snap-fit terminal connectorUS20060030810 *Oct 5, 2005Feb 9, 2006Cardiac Pacemakers, Inc.Devices and methods to stimulate therapeutic angiogenesis for ischemia and heart failure* Cited by examinerReferenced byCiting PatentFiling datePublication dateApplicantTitleUS7400931Sep 18, 2002Jul 15, 2008Cardiac Pacemakers, Inc.Devices and methods to stimulate therapeutic angiogenesis for ischemia and heart failureUS7460914Oct 5, 2005Dec 2, 2008Cardiac Pacemakers, Inc.Devices and methods to stimulate therapeutic angiogenesis for ischemia and heart failureUS7630761Nov 4, 2005Dec 8, 2009Cardiac Pacemakers, Inc.Method and apparatus for modifying tissue to improve electrical stimulation efficacyUS7647124Apr 27, 2007Jan 12, 2010Medtronic, Inc.Delivery catheterUS7729782Nov 15, 2005Jun 1, 2010Medtronic, Inc.Delivery catheterUS7764995Jul 27, 2010Cardiac Pacemakers, Inc.Method and apparatus to modulate cellular regeneration post myocardial infarctUS7840263Feb 27, 2004Nov 23, 2010Cardiac Pacemakers, Inc.Method and apparatus for device controlled gene expressionUS7860581Oct 31, 2005Dec 28, 2010St. Jude Medical AbImplantable lead with a stimulating electrode and a mapping electrode that is electrically disconnectableUS7981065Jul 19, 2011Cardiac Pacemakers, Inc.Lead electrode incorporating extracellular matrixUS8005544Jun 26, 2008Aug 23, 2011Cardiac Pacemakers, Inc.Endocardial pacing devices and methods useful for resynchronization and defibrillationUS8005549Sep 15, 2008Aug 23, 2011Medtronic, Inc.Medical electrical leadUS8005550Aug 23, 2011Medtronic, Inc.Medical electrical leadUS8010191Aug 30, 2011Cardiac Pacemakers, Inc.Systems, devices and methods for monitoring efficiency of pacingUS8010192Aug 30, 2011Cardiac Pacemakers, Inc.Endocardial pacing relating to conduction abnormalitiesUS8014861Sep 6, 2011Cardiac Pacemakers, Inc.Systems, devices and methods relating to endocardial pacing for resynchronizationUS8050756Jun 26, 2008Nov 1, 2011Cardiac Pacemakers, Inc.Circuit-based devices and methods for pulse control of endocardial pacing in cardiac rhythm managementUS8060219Nov 15, 2011Cardiac Pacemakers, Inc.Epicardial patch including isolated extracellular matrix with pacing electrodesUS8209035Jun 26, 2012Cardiac Pacemakers, Inc.Extendable and retractable lead having a snap-fit terminal connectorUS8255063Nov 11, 2008Aug 28, 2012Biotronik Crm Patent AgIntracardial electrode line and cardiac stimulatorUS8285376Oct 9, 2012Cardiac Pacemakers, Inc.Ventricular pacingUS8290586Oct 16, 2012Cardiac Pacemakers, Inc.Methods, devices and systems for single-chamber pacing using a dual-chamber pacing deviceUS8326423Jun 26, 2008Dec 4, 2012Cardiac Pacemakers, Inc.Devices and methods for steering electrical stimulation in cardiac rhythm managementUS8346358Jan 1, 2013Cardiac Pacemakers, Inc.Pacemaker which reestablishes or keeps the physiological electric conduction of the heart and a method of applicationUS8364267Jan 29, 2013Boston Scientific Neuromodulation CorporationFixation of implantable pulse generatorsUS8406899Mar 16, 2012Mar 26, 2013Cardiac Pacemakers, Inc.Bundle of his stimulation systemUS8423139Jun 26, 2008Apr 16, 2013Cardiac Pacemakers, Inc.Methods, devices and systems for cardiac rhythm management using an electrode arrangementUS8428715Apr 23, 2013Cardiac Pacemakers, Inc.Methods for treating the physiological electric conduction of the heartUS8437848Oct 10, 2008May 7, 2013Cardiac Pacemakers, Inc.Apparatus for treating the physiological electric conduction of the heartUS8538521Aug 25, 2011Sep 17, 2013Cardiac Pacemakers, Inc.Systems, devices and methods for monitoring efficiency of pacingUS8543203Aug 17, 2011Sep 24, 2013Cardiac Pacemakers, Inc.Endocardial pacing devices and methods useful for resynchronization and defibrillationUS8565880Apr 26, 2011Oct 22, 2013Cardiac Pacemakers, Inc.His-bundle capture verification and monitoringUS8606369Jun 1, 2010Dec 10, 2013Medtronic, Inc.Delivery catheterUS8634933Apr 15, 2011Jan 21, 2014Cardiac Pacemakers, Inc.Active fixation leads and method of assemblyUS8666493Jan 28, 2013Mar 4, 2014Boston Scientific Neuromodulation CorporationFixation of implantable pulse generatorsUS8688234Dec 18, 2009Apr 1, 2014Cardiac Pacemakers, Inc.Devices, methods, and systems including cardiac pacingUS8761880Feb 24, 2012Jun 24, 2014Cardiac Pacemakers, Inc.His capture verification using electro-mechanical delayUS8812105Oct 26, 2011Aug 19, 2014Cardiac Pacemakers, Inc.Circuit-based devices and methods for pulse control of endocardial pacing in cardiac rhythm managementUS8812106May 2, 2013Aug 19, 2014Cardiac Pacemakers, Inc.Apparatus for treating the physiological electric conduction of the heartUS8825155Sep 1, 2011Sep 2, 2014Cardiac Pacemakers, Inc.Systems, devices and methods relating to endocardial pacing for resynchronizationUS8825159Nov 29, 2012Sep 2, 2014Cardiac Pacemakers, Inc.Devices and methods for steering electrical stimulation in cardiac rhythm managementUS8838238Oct 4, 2012Sep 16, 2014Cardiac Pacemakers, Inc.Ventricular pacingUS8880169Aug 24, 2011Nov 4, 2014Cardiac Pacemakers, Inc.Endocardial pacing relating to conduction abnormalitiesUS8903489Oct 12, 2012Dec 2, 2014Cardiac Pacemakers, Inc.Methods, devices and systems for single-chamber pacing using a dual-chamber pacing deviceUS8929997Dec 16, 2013Jan 6, 2015Cardiac Pacemakers Inc.Active fixation leads and method of assemblyUS8934969Sep 16, 2013Jan 13, 2015Cardiac Pacemakers, Inc.Systems, devices and methods for monitoring efficiency of pacingUS9008768Apr 15, 2013Apr 14, 2015Cardiac Pacemakers, Inc.Methods, devices and systems for cardiac rhythm management using an electrode arrangementUS9031648Sep 17, 2013May 12, 2015Cardiac Pacemakers, Inc.Endocardial pacing devices and methods useful for resynchronization and defibrillationUS9227054Nov 25, 2014Jan 5, 2016Cardiac Pacemakers, Inc.Active fixation leads and method of assemblyUS20040186546 *Sep 18, 2002Sep 23, 2004Evgenia MandrusovDevices and methods to stimulate therapeutic angiogenesis for ischemia and heart failureUS20050192637 *Feb 27, 2004Sep 1, 2005Girouard Steven D.Method and apparatus for device controlled gene expressionUS20060030810 *Oct 5, 2005Feb 9, 2006Cardiac Pacemakers, Inc.Devices and methods to stimulate therapeutic angiogenesis for ischemia and heart failureUS20070106202 *Nov 4, 2005May 10, 2007Cardiac Pacemakers, Inc.Method and apparatus for modifying tissue to improve electrical stimulation efficacyUS20070112405 *Nov 15, 2005May 17, 2007Williams Terrell MDelivery catheterUS20080027526 *Jul 27, 2006Jan 31, 2008Cardic Pacemakers, Inc.Lead comprising a drug region shared by more than one electrodeUS20080288040 *Oct 31, 2005Nov 20, 2008Johan EckerdalImplantable Lead with a Stimulating Electrode and a Mapping Electrode that is Electrically DisconnectableUS20080319500 *Jun 26, 2008Dec 25, 2008Qingsheng ZhuSystems, Devices and Methods Relating to Endocardial Pacing for ResynchronizationUS20080319501 *Jun 26, 2008Dec 25, 2008Qingsheng ZhuSystems, Devices and Methods for Monitoring Efficiency of PacingUS20090005830 *Jun 26, 2008Jan 1, 2009Qingsheng ZhuEndocardial Pacing Relating to Conduction AbnormalitiesUS20090005832 *Jun 26, 2008Jan 1, 2009Qingsheng ZhuCircuit-Based Devices and Methods for Pulse Control of Endocardial Pacing in Cardiac Rhythm ManagementUS20090071686 *Sep 15, 2008Mar 19, 2009Medtronic, Inc.Medical electrical leadUS20090076577 *Sep 15, 2008Mar 19, 2009Medtronic, Inc.Medical electrical leadUS20090076578 *Sep 15, 2008Mar 19, 2009Medtronic, Inc.Medical electrical leadUS20090076579 *Sep 15, 2008Mar 19, 2009Medtronic, Inc.Medical electrical leadUS20090076580 *Sep 15, 2008Mar 19, 2009Medtronic, Inc.Medical electrical leadUS20090138060 *Nov 11, 2008May 28, 2009Thomas DoerrIntracardial electrode line and cardiac stimulatorUS20090192555 *Jul 30, 2009Boston Scientific Neuromodulation CorporationFixation of implantable pulse generatorsUS20090259272 *Apr 15, 2009Oct 15, 2009Reddy G ShantanuBundle of his stimulation systemUS20100305579 *Dec 2, 2010Medtronic, Inc.Delivery catheterEP2065071A1 *Oct 29, 2008Jun 3, 2009BIOTRONIK CRM Patent AGIntracardial electrode line and cardiac stimulatorEP2526997A1 *Apr 15, 2009Nov 28, 2012Cardiac Pacemakers, Inc.Bundle of His stimulation systemWO2007053065A1 *Oct 31, 2005May 10, 2007St. Jude Medical AbImplantable lead with a stimulating electrode and a mapping electrode that is electrically disconnectableWO2007059376A1 *Nov 1, 2006May 24, 2007Medtronic, Inc.Delivery catheterWO2009035708A1 *Sep 15, 2008Mar 19, 2009Medtronic, Inc.Medical electrical profiled leadWO2009035709A1 *Sep 15, 2008Mar 19, 2009Medtronic, Inc.Medical electrical profiled leadWO2009035710A3 *Sep 15, 2008Jun 4, 2009Gregory A BoserMedical electrical lead with jacketed conductive elementsWO2009035711A3 *Sep 15, 2008Jun 4, 2009Gregory A BoserMedical electrical lead with jacketed conductive elementsWO2009035712A1 *Sep 15, 2008Mar 19, 2009Medtronic, Inc.Medical electrical profiled leadWO2009035713A3 *Sep 15, 2008Sep 3, 2009Medtronic, Inc.Medical electrical leadWO2009129313A2 *Apr 15, 2009Oct 22, 2009Cardiac Pacemakers, Inc.Bundle of his stimulation systemWO2009129313A3 *Apr 15, 2009Jan 21, 2010Cardiac Pacemakers, Inc.Bundle of his stimulation systemWO2011146191A1 *Apr 18, 2011Nov 24, 2011Cardiac Pacemakers, Inc.Active fixation leads and method of assemblyWO2012125273A3 *Feb 24, 2012Feb 28, 2013Cardiac Pacemakers, Inc.His capture verification using electro-mechanical delayWO2015106378A1 *Jan 14, 2014Jul 23, 2015无锡慧思顿科技有限公司Multifunctional medical mems microprobe* Cited by examinerClassifications U.S. Classification607/122International ClassificationA61N1/05Cooperative ClassificationA61N1/0568European ClassificationA61N1/05N2DLegal EventsDateCodeEventDescriptionJun 7, 2004ASAssignmentOwner name: CARDIAC PACEMAKERS, INC., MINNESOTAFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:LIU, LILI;WESTLUND, RANDY;GIROUARD, STEVEN D.;REEL/FRAME:014703/0473;SIGNING DATES FROM 20040430 TO 20040604Oct 23, 2007CCCertificate of correctionDec 16, 2010FPAYFee paymentYear of fee payment: 4Dec 24, 2014FPAYFee paymentYear of fee payment: 8RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData provided by IFI CLAIMS Patent Services