AU652377B2 - Miniature steroid eluting pacing lead electrode - Google Patents

Description

SOPI 'DATE'07/01/92 INTER AOJP DATE 13/02/92

INTERNA';

APPLN. ID 82248 91

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PCT NUMBER PCT/US91/04122 fREATY (PCT) (51) International Patent Classification 5 (11) International Publication Number: WO 91/19533 A61N 1/05 Al (43) International Publication Date: 26 December 1991 (26.12.91) (21) International Application Number: PCT/US91/04122 (81) Designated States: AT (European patent), AU, BE (European patent), CA, CH (European patent), DE (Euro- (22) International Filing Date: 11 June 1991 (11.06.91) pean patent), DK (European patent), ES (European patent), FR (European patent), GB (European patent), GR (European patent), IT (European patent), JP, LU (Euro- Priority data: pean patent), NL (European patent), SE (European pa- 539,102 15 June 1990 (15.06.90) US tent).

(71) Applicant: MEDTRONIC, INC. [US/US]; 7000 Central Published Avenue Minneapolis, MN 55432 With international search report.

Before the expiration of the time limit for amending the (72) Inventors: STOKES, Kenneth, B. 7657 Unity Avenue claims and to be republished in the event of the receipt of Minneapolis, MN 55432 LINDEMANS, Fred amendments.

Grootveldstaat 14, NL-6141 LT Limbricht t (74) Agents: RISSMAN, John, A. et al.; Medtronic, Inc., 7000i Central Avenue Minneapolis, MN 55432 ,J (54) Title: MINIATURE STEROID ELUTING PACING LEAD ELECTRODE (57) Abstract A small diameter, unipolar or bipolar, atrial or ventricular transvenous or epimyocardial pacing lead with a porous, platinized, steroid eluting cathode electrode exhibiting an effective surface area in the range of 0.1 to 4.0 mm 2 preferably 0.6 to mm 2 provides low stimulation thresholds in the range of 0.5 volts, 0.5 milliseconds, very high pacing impedance (800 to 2,000 relatively low polarization, good to excellent sensing, and adequately low source impedance. The high pacing impedance prolongs the longevity of pacing pulse generators and allows for the miniaturization of their components. The low thresholds allow large safety factors at low applied voltages, which also contribute to increased battery longevity.

vc WO 91/19533 PCT/US91/04122 -1- MINIATURE STEROID ELUTING PACING LEAD ELECTRODE.

BACKGROUND OF THE INVENTION Field of the Invention This invention relates generally to chronically implanted medical electrode leads and, in particular, to cardiac pacing leads with an electrode structure which minimizes chronic pacing thresholds and drain on the pacing pulse generator power source.

Description of the Prior Art The safety, efficacy and longevity of an implanted pacemaker system depends (in part) on the performance of its pacing lead(s), the electronic circuits of the pacemaker pulse generator, the integrity of the pulse generator and the capacity and reliability of the pulse generator power source. These inter-related components of the pacemaker i system optimally are matched in a fashion that accommodates ever increasing demands on the modes of operation and function of the system in conjunction with an overall reduction in its size, an increase in its longevity and an increased expectation in the reliability of the entire system. During the past thirty years, the technology of cardiac pacing has significantly advanced, with implantable pacemakers displaying an ever increasing variety of pacing modalities, substantially broadening the indications for pacemaker use. In conjunction with this advancement, there has been extensive research and development effort expended to optimize the performance of pacing leads and their reliability.

In the past ten years, substantial improvements in reliable stable chronic pacemaker stimulation and sensing thresholds have been achieved which in turn have allowed the i WO 91/19533 PCT/US91/04122 -2development of smaller and longer-lived pacemakers that can be used with those leads with excellent safety margins and reliability. As new circuits are developed with lower "overhead" current drains, however, and as the circuits increase in complexity to allow for ever increasing pacemaker capabilities in their programmable functions, modes and memory, the longevity of the device depends increasingly more on the characteristics of the lead. In addition, implanters prefer that pacing lead bodies be made ever thinner, to occupy less space in the venous system, without diminishing or detracting from the mechanical strength and integrity of the lead body.

In the early days of cardiac pacing, very high geometric surface area electrodes were employed with bulky and short-lived pacemaker pulse generators. Early investigators including Dr. Victor Parsonnet advanced designs of pacing electrodes for achievement of low polarization and low thresholds while presenting a relatively small effective surface area for the delivery of a stimulating impulse in designs known as differential current density (DCD) of the type shown in U.S. Patent No.

3,476,116. The DCD electrode (like all pacing electrodes of that time) suffered excessive chronic tissue inflammation and instability and was not pursued commercially.

Subsequent researchers, including Dr. Werner Irnich explored in considerable detail the electrode-tissue interface and sought to arrive at an optimum exposed electrode surface area for both stimulation thresholds and sensing. Dr. Irnich in "Considerations in Electrode Design For Permanent Pacing" published in Cardiac Pacina; Proceedings of the Fourth International SymPosium of Cardiac Pacing Thalen, Ed.) 1973, pages 268-274, argued that the field strength required to stimulate varies as E 4 WO 91/19533 PCT/US91/04122 -3v r d] 2 where v equals r applied voltage (threshold, r equals electrode radius and d equals fibrous capsule thickness. He further argues that the mean value for d equals about 0.7 mm, regardless of electrode radius. Therefore, the smaller the electrode radius the lower threshold (assuming E is a constant) until r equals d. When r<d, thresholds rise again. Dr. Irnich had concluded that the exposed hemispherical electrode at the tip of the lead should have a radius in the order of 0.7 to 1.0 mm which would result in an exposed surface area of 3 6 mm 2 However, Dr. Irnich went on in his article to propose a somewhat different design employing wire hooks designed to penetrate the myocardium to hold the electrode in position. These active fixation wire hook electrodes never achieved popularity and were supplanted by passive fixation tined and active fixation screw-in endocardial pacing leads.

In a later paper, "Acute Voltage, Charge and Energy Thresholds as Functions of Electrode Size for Electrical Stimulation of the Canine Heart", by F.W. Lindemans and A.N.E. Zimmerman; Cardiovascular Research, Vol. XIII, No. 7, pp. 383-391, July, 1979, the author demonstrates that an electrode radius of about 0.5 mm is optimal in the acute situation. However, it was recognized that the benefits of a small electrode surface area would be lost when the fibrous capsule gets thicker than about 0.5 mm (as Irnich also states), and for that reason (and others stated in the article), electrodes of such small surface area could not be used chronically.

Dr. Seymour Furman had also studied the relationship of electrode size and efficiency of cardiac stimulation and presented a ball-tip/exposed spaced coil electrode and a small hemispheric electrode in his article entitled "Decreasing Electrode Size and Increasing Efficiency of

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gi* WO 91/19533 PCT/US91/04122 -4- Cardiac Stimulation" in Journal of Surgical Research, Volume 11 Number 3, March, 1971, pages 105-110. Dr. Furman concluded that the practical lower limit of electrode surface area was in the range of 8 mm 2 observing that impedance increased as an inverse function of the surface area.

Electrodes of many shapes including cylindrical, balltip, corkscrew, ring tip and open cage or "bird cage" configurations were pursued with exposed electrode surface areas tending toward 8 mm 2 in the mid 1970's.

More recently, various investigators have emphasized materials and their relationship to the considerations involved in optimizing electrode design. For example, the Medtronic U.S. Patent No. 4,502,492 discloses a low polarization, low threshold electrode design of the early to mid 1980's which was commercialized as the "Target Tip®" pacing leads in numerous models including Models 4011, 4012, 4511 and 4512. The tip electrode of the Target Tip® leads was generally hemispherical and provided with circular grooves. The electrode was fabricated of platinum, coated over its external surface with a plating of platinum black.

The combination of the relatively low electrode surface area and platinum black contributed to state-of-the-art thresholds in that time period. Other manufacturers marketed porous platinum mesh (Cardiac Pacemakers, Inc.), totally porous sintered (Cordis Corporation), glassy and vitreous carbons (Siemens), and laser drilled metal (Telectronics Ppty. Ltd.) electrodes in that same time period.

A considerable breakthrough in the development of low threshold electrode technology occurred with the invention of the steroid eluting porous pacing electrode fof Stokes U.S. Patent No. 4,506/680 and related Medtronic U.S. Patent Nos. 4,577,642, 4,606,118 and 4,711,281, all incorporated 4 WO 91/19533 pCT/US91/04122 herein by reference. The electrode disclosed in the '680 patent was constructed of porous, sintered platinum or titanium, although carbon and ceramic compositions were mentioned. Within the electrode, a plug of silicone rubber impregnated with the sodium salt of dexamethasone phosphate or the water soluble forms of other glucocorticosteroids was placed in a chamber. The silicone rubber plug allowed the release of the steroid through the interstitial gaps in the porous sintered metal electrode to reach the electrodetissue interface and prevent or reduce inflammation, irritability and subsequent excess fibrosis of the tissue adjacent to the electrode itself. The porous steroid eluting electrodes presented a source impedance substantially lower compared to similarly sized solid electrodes and presented significantly lower peak and chronic pacing thresholds than similarly sized solid or porous electrodes. Those two advantages of steroid eluting electrodes allowed the use of relatively small surface arra electrodes of about 5.5 mm 2 (CAPSURE® SP Model 5023, 5523 leads sold by Medtronic, Inc.) to raise the pacing impedance without sacrificing the ability to sense heart activity.

The smaller electrode size permitted by the '680 patent invention resulted in higher current density during stimulation pulses, provided more efficient stimulation of the heart tissue with lower current drain from the implanted pacemaker power source. In addition, the localized nature of the drug treatment minimized the systemic assimilation of the drug and avoided undesirable side effects for the patient.

The 8 mm 2 surface area CAPSURE® steroid eluting lead Models 4003, 4503, 4004, and 4504 sold by Medtronic, Inc. I have enjoyed remarkable commercial success to the present time. However, many physicians are not taking full I advantage of prope:ties of the electrode to save battery k~ l~ly, WO 91/19533 PCT/US91/04122 -6current and, therefore, longevity attainable by programming pacemaker pulse voltage to a safety margin level above the thresholds afforded by these leads. The quest to provide even lower stimulation thresholds and improved sensing and otherwise increase the performance and reliability of the pacing leads continues. One objective is to achieve markedly lower stimulation thresholds and to convince the physicians to accept and program lower voltage stimulation pacing pulses.

The impedance of the lead as a whole is a function of the resistance of the lead conductor and the electrode tip as well as the effective impedance of the electrode-tissue interface. An inefficient way or means to raise impedance is to increase the resistance of the conductors. This wastes current as heat. It is preferable to decrease lead current drain with more efficient control of the electrodetissue interface impedance. This can be done by reducing the geometric surface area of the cathode. However, it is commonly believed that small electrodes are inefficient at sensing natural depolarizations of the cardiac tissue. This is not necessarily true, however. The amplitude of the intrinsic cardiac depolarization signals (typically the ventricular QRS and/or atrial P-wave complexes) is essentially independent of electrode size, as measured on a high, megohm range input impedance oscilloscope. The problem is that the sense amplifiers of modern pulse generators have comparatively lower input impedance typically about 35kn. The impedance of the QRS or P-wave signal (or "source impedance") increases as the electrode 24 surface area decreases. Thus, a 5 mm 2 polished electrode will produce QRS or P-waves with about 5kn source impedance.

According to Kirchof's law, the attenuation of the signal in the generator's amplifier is 1/(1 Zin/Zs) where Zin is the input impedance of the amplifier and Zs is the source

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WO 91/19533 PCT/US91/04122 -7impedance of the signal to be sensed. Thus, a 5kn signal into a 35kf amplifier will have its amplitude reduced by 1/(1 35/5) 12.5%. In marginal cases, this may make the difference between being able to sense properly or not being able to sense. Therefore, it is important to keep the source impedance low, preferable to attenuate less than of the cardiac signal, that is, Zs 1800n, for a 35 kn amplifier.

Thus, there is a trade-off with geometric surface area of the cathode electrode between the demands for low current drain and adequate sensing. In addition, it is desirable to achieve relatively low polarization effects so that they do not distort the electrogram of evoked or intrinsic cardiac depolarizations or leave a postpulse potential of sufficient magnitude to be mistakenly sensed as a QRS or P-wave by the amplifier.

STU-LY OF THE I E- It is thus an object of the present invention reduce the effective surface area of pacing electrodeso a point well below the presently accepted dimension o increase pacing impedance without increasing thr olds and without negatively impacting sensing capabi ies.

The present invention prov es a body-implantable lead for the delivery of an elec ic stimulus to a desired body site, particularly the rial or ventricular chambers of a patient's heart. T* s lead presents a very high (greater or equal to 800 o0 pacing impedance with low peak and chronic thresholds ow source impedance and excellent sensing in a size o pproximately 1.5 mm exposed geometric (or ma oscopic) surface area. Specifically, the lead of the present invention possesses an electrode with an exposed >^--gooo c area in thz r-ange of 0.1 4.0 un, t-'TI 7a SUMMARY OF THE INVENTION The present invention provides a body implantable lead comprising: a) an electrical conductor having a proximal end and a distal end; b) insulating sheath means for covering said conductor between said proximal and distal ends thereof; c) electrical connector means coupled to said proximal end of said conductor for electrically connecting said lead to a pulse generator; d) electrode means electrically coupled to said distal end of said electrical conductor for conducting electrical energy to and from said body tissue site desired to be stimulated and sensed, said electrode means comprising a body of a porous metallic or other conductive material with high microscopic surface area in proportion to macroscopic surface area, mounted to a distal end of a conductive pin and extending radially from said conductive pin, a proximal end of said pin being coupled to said distal end of said electrical conductor; and e) drug dispensing means mounted around said pin, proximal to said porous body, within said insulating sheath, for storing a drug to be dispensed while allowing dispensing of said drug through said porous body to counter undesirable interactions between said lead and said body site.

iii al i C WO 91/19533 PCT/US 1/04122 preferably between 0.6 and 3.0 mm 2 with about 1.0 mm 2 providing optimum performance. The lead has a pac g impedance of 1400 260 ohms, a source impedan of about 1650 410 ohms in both chambers of the hea The lead of the present invention constitutes a pac*g lead having a spherical, hemispheric or disk shape exposed distal tip electrode of approximately 1 mil eter in diameter fabricated of platinized poro platinum (or other porous electrode material), loade with glucocorticosteroid. In at least one embodiment, e electrode is attached to the distal end of a pac' g lead of about 1.0 mm or 3 to 4 French in overall diam er.

Both e ocardial and epicardial leads may be fabricated in accor .ce with the teachings of the present invention.

another aspect of the present invention, DCD e ctrode technology may be successfully employed with a steroid eluting release device and with apertures in the l--rutnnge G9 Q r1 9m.-- BRIEF DESCRIPTION OF THE DRAWTNGS These and other objects and advantages of the present invention may be fully understood and appreciated in conjunction with the attached drawings and the following detailed description of the preferred embodiments where the same numerals are employed to denote the same or similar features throughout: Figure 1 shows a side plan view of an endocardial, unipolar, ball-tip electrode pacing lead according to the present invention; Figure 2 shows a cross-sectional view of the ball-tip electrode of the lead shown in Figure 1; Figure 3 shows an end plan view of the distal tip of the electrode of the lead shown in Figure 1; WO 91/19533 PCF/US91/04122 -9- Figure 4 shows a cross-sectional view of the distal portion of an endocardial, unipolar, DCD electrode pacing lead, according to the present invention; Figure 5 shows an end plan view of the distal tip of the DCD electrode of the lead shown in Figure 4; Figure 6 shows a cross-sectional view of the distal tip portion of a further endocardial, bipolar, cylindrical tip electrode pacing lead according to the present invention; Figure 7 shows an end plan view of the distal tip electrode of the lead shown in Figure 6; Figure 8 shows a cross-sectional view of the distal tip portion of a further embodiment of the ball-tip electrode according to the present invention; Figure 9 shows a cross-sectional view of the distal electrode of a modified DCD electrode according to the present invention; Figure 10 shows a plan view of the distal portion of a bipolar epicardial pacing lead according to the present invention; Figure 11 shows a cross-sectional view of t!,e distal tip portion of the electrode, preferably employed in the epicardial electrode of Figure Figure 12 depicts graphically the performance of the exposed electrodes of the present invention with steroid elution against electrodes of the same size and configuration without steroid eiution; and, Figure 13 depicts graphically the performance of a DCD electrode of the present invention with steroid elution against a test DCD electrode of the same size and configuration without steroid elution.

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WO 91/19533 PCT/US91/04122 DETAILED DESCRIPTION OF THE DRI-WINGS Before describing the specific features of the preferred embodiments of the present invention certain matters should be defined. First of all, the practice of the present invention contemplates the employment of a steroid or other drug with an electrode possessing a mechanism for allowing the drug to be eluted through and/or around the electrode in order to reach the endocardial or myocardial cells in the vicinity of the tip of the pacing lead in order to reduce, if not eliminate entirely, the acute and chronic inflammation occasioned by the cellular foreign body and physical irritation response to the tip of the lead. As described in the aforementioned Stokes' patents, the electrode is preferably fabricated of body compatible electrically conducting material with or without specific steroid eluting passages but generally with a porous structure either throughout the body of the electrode or at its surface. The porosity of the electrode surface or body provides a large surface area for sensing whereas the overall dimension or shape of the exposed electrode defines a comparatively smaller surface area for stimulation. The porous structure thus presents a microscopic (or "fractal") large surface area tor sensing and a macroscopic or geometrically measured very small surface area for stimulation. Acceptable electrode materials and the associated fabrication techniques employed to achieve the micro-porous structure, as well as the porosity of that structure are all set forth in the aforementioned prior art patents and in the Richter et al U.S. Patent No. 4,773, 433, the Heil et al U.S. Patent No. 4,819, 661, the Thoren et al U.S. Patent No. 4,149;542, the Robblee U.S. Patent No.

4,677,989, the Heil et al U.S. Patent 4,819,662, the Mund et i fdistal end of said electrical conductor; and e) drug dispensing means mounted around said pin, /2 WO 91/19533 PCr/US91/04122 -11al U.S. Patent No. 4,603,704, the Skalsky et al U.S. Patent No. 4,784,161, and the Szilagyi U.S. Patent No. 4,784,160 and other patents and literature in the prior art.

Furthermore, the present invention may be practiced in the context of electrode structures that have heretofore been referred to as conventional exposed electrodes and the DCD electrode structures of the type shown in the aforementioned Parsonnet patent. In this regard, it will be observed in the following description of the preferred embodiments that electrodes of the present invention may be fabricating having characteristics of both the conventional and the DCD electrode structures. Dr. Parsonnet, in his early work on the DCD electrode, sought to reduce the polarization overvoltage (shown in Figure 2 of his '116 patent) and the resulting postpulse polarization voltages which made and still make it difficult to distinguish the heart's P-waves or R-waves from those postpulse polarization voltages within 5 to 100 milliseconds after the delivery of the stimulus. In the practice of the present invention, the electrodes may be internalized in the DCD manner or externalized in the conventional manner. In the DCD context, the macroscopic surface area through which current is emitted during stimulation is defined by the aperture area presented to the cells in the vicinity of the tip of the pacing lead. The large, microscopic surface area is effected, as shown in Figure 4 of the Parsonnet '116 patent, by the conductor coil within the distal portion of the lead j body. In the present invention, the conductor coil may be rendered textured or porous by one or more of the aforementioned techniques, and steroid is eluted as described further herein below. Figure 1 illustrates a plan view of an exposed electrode constructed in accordance with the present invention. The lead includes an elongated lead body 10 covered by an insulative sleeve 12. Insulative

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WO 91/19533 PCT/US91/04122 -12sleeve 12 may be fabricated of any flexible biocompatible and biostable insulator especially silicone rubber or polyurethane. At the proximal end of the lead, terminal assembly 14 is adapted to couple the lead to an implantable pacemaker pulse generator. Terminal assembly 14 is provided with sealing rings 16 and a terminal pin 18, all of a type known in the art. An anchoring sleeve 20 (shown partially in cross-section) slides over lead body 10 and serves as a point for suturing the lead body to body tissue at the insertion point of the lead into the vein or tissue in a fashion known in the art. Anchoring sleeve 20 and terminal assembly 14 may be conveniently fabricated of silicone rubber.

The lead shown in Figure 1 further includes a stylet guide 11 and stylet assembly 13 coupled to the terminal pin 18 for imparting stiffness to the lead during the insertion and placement of the lead transvenously into either the right ventricle or the right atrium of the heart. The stylet guide and stylet assembly are discarded after use and before connection of the terminal pin 18 to a pacemaker pulse generator.

At the distal end of the lead 10, a tine protector is shown (in cross-section) protecting the tines until the lead is used. Tines 26 are employed to passively retain the tip electrode 22 in position against the endocardium as is well known in the pacing art.

The lead assembly 10 of Figure I includes a multifiler conductor coil extending from the terminal pin 18 to the tip electrode 22. Figure I depicts a unipolar lead and it should be understood that the present invention may be implemented in a bipolar lead design employing a second conductor extending from a second exposed cylindrical terminal surface area-near the proximal end of the lead to an exposed ring electrode spaced 8 mm from the distal tip WO 91/19533 PCT/US91/04122 -13electrode 22 as is well known in the art. The 8 mm spacing is necessary because the current sense amplifier bandpass center frequency is about 25-30 Hz. Closer spacings are possible if the sense amplifier bandpass center frequency is shifted to higher values accordingly, and if higher gains are used.

Referring now to Figure 2, it shows in cross section a view of the distal lead portion of the preferred embodiment of the electrode of the present invention and its connection to the lead conductor 28. In Figure 2, the distal electrode 22 is depicted as a porous platinum ball covered with platinum black at the end of a metal pin 23 of platinum extending from the tip electrode 22 to the distal end of the conductor coil 28. The conductor coil 28 is attached to the proximal end of the pin by crimping at point 34 of crimping member 36 at the time of manufacture. Silicone adhesive may be used at point 32 to seal the assembly against leakage of blood into the conductor coil. The insulative sheath 12 is shown placed over the crimping member as well as the tine assembly 38 which is fit between the distal end of the insulative sheath 12 and the crimping member 54. A steroidsilicone rubber compound ring 40 is located proximal from the electrode ball.

Referring now to Figure 3, the end view of the ball-tip electrode 22, tines 26 and tine assembly 38 is shown. The ball-tip distal electrode 22 is constructed as shown in Figures 2 and 3 to present a circular, hemispheric or 1 spherical exposed macroscopic surface area in the range A between 0.1 and 4.0 square mm 2 The ball-tip electrode 22 is fabricated of porous, sintered platinum having a porosity in the range of .5 to 100 microns, employing "splat" powder in the sintering process.

The porous platinum electrode is electroplated with platinum black and the porosity, together with the platinum 4

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rf WO 91/19533 PCI/US91/04122 -14black coating is intended to reduce source impedance and polarization. The silicone backing sleeve 40 forms a monolithic controlled release device (MCRD), as it is loaded with an anti-inflammatory agent, a steroid dexamethasone sodium phosphate. The steroid also is deposited within the pores of the porous platinum electrode 22 by application of a solution of 200 mg U.S.P.

dexamethasone sodium phosphate dissolved in 5.0 cc isopropanol and 5.0 cc distilled or deionized water as described in the aforementioned Stokes' patents. The MCRD weight and composition as well as the electrode surface area are critical to the electrode's overall performance. The small geometric macroscopic electrode size is intended to produce very high pacing impedance. The porous surface configuration together with platinum black electroplating and steroid contribute to a microscopically large surface area for low polarization, low source impedance and low thresholds. The porous surface also facilitates the retention of steroid and adhesion of the platinum black to the electrode surface. Referring now to Figures 4 and they depict a DCD electrode fabricated in accordance with the teachings of the present invention. A platinized coil of platinum wire is crimped to conductor coil 28 using crimp sleeve 52 and crimp core 58. Silicone rubber adhesive 54 may be used to provide a seal to assure that blood does not leak into the conductor coil. The polymeric insulation tubing 12 extends to the end or just beyond the end of platinized coil 50. Three or four symmetrically placed tines 26 are placed close to the distal orifice or aperture 56. The aperture 56 of the tubing 12 presents a circular hole of 0.1 to 4.0 mm 2 about 0.62 mm 2 as shown. The lumen of the platinized coil is filled with a solution of 200 mg dexamethasone sodium phosphate in 5 cc water and 5 cc isopropanol. The solvents are allowed to evaporate, leaving El I_1 I il WO 91/19533 PCr/US91/04122 a coating of steroid on the coils. The steroid loaded MCRD is located at the proximal end of the platinized coil.

The exposed surface of the platinized coil 50 must be large enough, preferably 2 50 mm 2 to produce low polarization.

Past DCD electrodes required that the distal lumen be filled with conductive saline prior to insertion into the vein. This is not required with the steroid loaded lead, because the steroid acts as a wetting agent, allowing blood to fill the lumen as the lead is pushed down the vein.

In operation, charge transfer from electronic to ionic conduction occurs at the interface of the platinized coil and the blood or fibrotic tissue that eventually fills the lumen. Because this surface is large, polarization losses are low. Electric current is conducted through the blood and fibrotic tissue to the heart muscle to provide stimulation. Because the aperture 56 is small, acute thresholds are low and pacing impedance is high. The steroid controls inflammation in the surrounding tissue and helps to prevent or reduce chronic threshold rise.

Referring now to Figures 6 and 7, they depict an alternative design of the bipolar, endocardial pacing lead of the present invention, and in particular, a modified electrode assembly of the present invention. The lead of Figure 6 is constructed in similar fashion to the lead of Figures 1-3 and, to the extent possible, the same numerals will be employed to describe the same or equivalent elements of these two embodiments of the lead. The principal differences between Figures 1-3 and Figures 6 and 7 are that the lead of Figures 6 and 7 is bipolar, possessing a ring electrode 60 spaced from tip electrode 22', the tine elements 26 are constructed somewhat differently and the quadrafiler conductor coil 28 comprises two pair of bifiler, commonly wound, separately insulated conductors, each respectively connected to one of the two electrodes. Thus, m. -I -I WO 91/19533 PCT/US91/04122 -16at point 62, two of the conductor wires are attached to the ring electrode 60, and at point 64 the remaining two conductor wires contact the pin 23 and crimp sleeve 36 which is crimped against the coils 64 at point 34. The pin 23 extends through the steroid impregnated ring The tip electrode 22' is fabricated of the same materials and treated in the same fashion as the tip electrode 22 of the embodiment of Figures 1-3. Figures 6 and 7 thus illustrate a bipolar embodiment of the pacing lead of the present invention.

Turning now to Figure 8, it discloses a further balltip electrode 22'' attached to a pin 23 extending back to a similar connection with a coiled wire conduc.tor (not illustrated). The tip electrode 22'' is virtually fully exposed as is a portion of the distal end of the steroid eluting MCRD 40'. Thus the electrode depicted in Figure 8 illustrates an extreme example of the exposed "nanotip" concept of the present invention and may be employed in either endocardial or epi/myocardial lead designs where the tip electrode may penetrate myocardial tissue. The exposed surface of the MCRD 40' thus allows for steroid elution in a path in both through and around the spherically shaped electrode 22 Turning now to Figure 9, it depicts a still further embodiment of the distal portion of the electrode of the present invention. The electrode of Figure 9 is a modification of the electrode depicted in Figures 1 to 3 except that, unlike the electrode depicted in Figure 8, the I ball-tip electrode 22'" is fully retracted within the distal portion of the tine bearing member 38. The inside diameter of the lead tip, that is the inside diameter of the tine element 38, is preferably .040 inches which equals a 0.8 mm 2 orifice. Only, a hemispheric portion of the surface Ii WO 91/19533 PCT/US91/04122 -17of the ball electrode is exposed in this embodiment of the invention.

The aforementioned embodiments of the present invention are all illustrated as endocardial pacing leads wherein the electrode or lead tip may or may not be designed to pass through the endocardium and into the myocardium of the heart. In substitution for the tined fixation mechanisms shown, any of the endocardial lead embodiments may be provided with active screw-in fixation mechanisms.

Figures 10 and 11 depict a further embodiment wherein the concept of the present invention is embodied in a bipolar epicardial pacing lead wherein the tip electrode is mounted on a stem 70 extending from a platform 72 of an epicardial lead body 74 to penetrate into the myocardium. While not specifically shown, the epicardial lead of Figure 10 may be affixed in place by fixation hooks or screws (partially shown at 78) or sutures. The specific configuration of the electrode may take the form of any of the electrodes 22 previously described with the exception that the outer surface or tubular member of the extension 70 may need to be stiff enough to allow the tip electrode to penetrate the epicardial membrane. It will be understood, furthermore, that the epicardial version of the lead of the present invention may further incorporate a DCD design within body 74 or 70 of the type shown, for example, in the aforementioned Parsonnet '116 patent.

However, preferably the tip electrode and stem are constructed as shown in Figure 11. The stem preferably comprises a hollow metal tube 80 having an MCRD 40 located at any point therein between the tip electrode and the point where the tube is mechanically and electrically connected to the conductor coil (not shown) within housing 74. The tip electrode is attached to the tip of tube 80, and the exterior of the tube 80 is a«

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r: WO 91/19533 P(J/US91/04122 -18insulated by outer tube 12. The steroid in the MCRD elutes through the porous tip electrode The bipolar mesh electrode 76 shown in Figure 10 may also be soaked with steroid in same fashion as tip electrode The epicardial lead may al.o be constructed in unipolar fashion substituting a porous fabric for metallic mesh electrode 76 to allow fixation to the epicardium by fibrotic tissue ingrowth. Said unipolar leads may also be fixed to the heart by sutures, obviating the need for the fabric mesh. Such leads may otherwise possess the features of Medtronic U.S. Patent No. 4,010,758 and designs discussed in a paper by K. Stokes, "Preliminary Studies on a New Steroid Eluting Epicardial Electrode", PACE. Vol. 11., pp. 1797 1803, November, 1988, incorporated herein by reference.

The electrodes of each of the foregoing embodiments may be fabricated by coating machined electrode blanks or by dipping the end of pin 23 (of Figures 1-3 and 6--10) into a binder, then dipping it into a fluidized bed of platinum splat powder, which adheres to the pin 23 in a generally ball shape, and then sintering the powder. The electrode of Figure 11 may be constructed by applying a mixture of the binder and splat powder to the opening of the tube 80 and then sintering it in situ.

The previously described embodiments of the present invention are illustrative of the construction and features of the very small diameter tip electrodes and pacing leads of the present invention. As previously indicated, the prior art had progressed to the point where the lower limit for effective macroscopic surface areas was believed to be within the range between 5.5 mm2 and 8 mm 2 Studies that we have conducted with steroid free, small macroscopic surface area porous electrodes in both the exposed and DCD

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WO 91/19533 PCT/US91/04122 -19configuration confirmed the expectation and findings of the aforementioned prior investigators in the field.

In regard to exposed electrodes of the present invention with steroid compared to those electrodes without steroid, the difference in stimulation thresholds is striking. Figure 12 depicts the results of a paired study in canines of the ventricular "nanotip" leads with and without steroid over an 8 week study period. The stimulation thresholds show a marked rise for the leads without steroid as compared to those leads with steroid.

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4i i I 1,111-1 W091/9533PCT/US91/04122 WO 91/19533 The actual data from the paired "nanotip" ventricular canine study is set forth in Tables I and II as follows: TABLE I PAIRED VENTRICULAR, DATA Implant Time 0.5ms Threshold (v) 0.5 ms Pacing Impedance (n) No With No (Weeks) N Steroid Steroid Steroid 0 1 2 3 4 8 0. 32±. 05 53 1.3±.51 1.2±.35 1.3±.56 1.2±.64 0.30±. 08 0. 52±. 09 0.52±. 15 0.57±. 15 0. 45±. 07 0. 45±. 07 13 00±2 00 87 0±14 0 78 0±3 2 0 1000±2 10 97 0±200 1200±43 0 With Steroid 13 00±3 00 950±17 0 88 0±52 0 1100±180 1160±33 0 99 0±48 L- ib_ L-PL Cc r i C Yi L 1IIII1SIIII~I

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WO 91/19533 PC/US91/04122 -21- TABLE II PAIRED VENTRICULAR DATA Implant R-Wave Amplitude (mV) R-Wave (Slew Rate) Source Imped.(n) No With No (Weeks) N Steroid Steroid Steroid S Time With teroid 4 38±3.9 29±7.6 (18.4±1.9) 6.7±4.2) 1 4 26±4.9 (4.1±.16) 3 25±5.7 (4.1±.77) 3 26±6.9 (4.2±.38) 2 25±9.9 (4.1±.85) 29±5.7 (4.1±2.2) 27±2.2 (4.3±1.5) 28±2.9 (5.0±1.8) 28±2.8 (5.7±0) 1400±330 1100±190 1100±290 1000±200 1150±210 1200±430 1450±510 975±171 1200±270 1300±210 1350±490 2 27±4.2 (4.9±.28) 31±1.4 1000±0 In our studies without steroid, the DCD electrodes having apertures of 0.1 to 0.2 mm 2 and probably up to mm 2 do not work. They go to exit block and stay there. A DCD electrode having a 0.6 mm 2 aperture without steroid exhibits a threshold rise of from 0.5 volts to over 8 volts in three weeks as exhibited in the graph of Figure 13.

However, with steroid, the same size DCD electrode exhibits a chronic threshold rise of from 0.5 volts to approximately 0.8 volts over a 12 week implant time as shown in the lower curve of Figure 13.

~LF -L -I

W

)91/19533 PCT/US91/04122 -22- In regard to the performance of the DCD electrodes the data from the studies conducted in dogs are presenfted in the following Tables III and IV.

TABLE III 0.6 mm 2 APERTURE STEROID ELUTING DCD ELECTRODE AS A FUNCTION OF IMPLANT TIME IN CANINES (N Implant 0.5ms Pacing R/P-Wave R/P- Wave Time Threshold Impedance Amplitude .0 Source Impedance (My) (s) Slew Rate s) (Weeks) (v) VENTRI CLE 0 1 0.

0.7±.

0.67±. 38 0. 87±. 62 0. 57 12* 0.45±.23 1300±570 29±5.9 85±.50 1000±320 25±2.9 48 1000±670 28±1.9 131 1000±610 29±3.8 1300± 1300±617 28±3.9 1200± 990±580 28±3.6 1100±' 0.82±.57 1200±380 28±4.2 22 50±7 90 14 00±500 00±860 4 740 4. 4± 680 5. 5± 670 4. 4± 13 00±420 5. 4±1. 2 4. 83 7 3 1.8 2.6 2.7 4 8* 4. 6±2 .7 0 .34 1. 2±.

62 0. 33 0. 84±. 45 0. 28±. 08 0. 47±. 09 *N =4

ATRIUM

±.08 2900±220 13±3.6 3100±580 69 1400±210 6.2±2.0 1700±210 1600±190 7.6±2.4 2100±280 1.9 1700±100 9.0±3.9 2200±420 2.2±1.

1700±110 8.2±2.7 1900±250 1.8±1.

1600±210 8.5±3.4 1800±270 2.6±1.

1600±240 8.5±3.3 1700±0 2.5±1.

4. 4±1. 9 1. 4±1. 2 5 3 5 4 3 8 8 12* 9 is 2.

.4 WO 91/19533 W091/9533PCT/US91/04122 -23- TABLE IV PAIRED DCD THRESHOLDS AND PACING IMPEDANCES Implant Time Exposed Electrode Area (m2) 0.5ms Thresholds(v) Pacing Impedance (f) No With Steroid Steroid No With Steroid Steroid (Weeks) 0 0 0.15 0.62 1 0.15 6.9 1 1 0.62 2 1 0.15 2 1 0.62 3 1 0.15 3 1 0.62 4 1 0.15 4 1 0.62 0.8 0.5 ±.3 >10 2.4 6.1 5.0 >10 6.5 9.6 8.1 2.1 0.6 ±.07 ±3 17000 1.2 7.8 1.4 3.8 2.2 3.3 1.7 19000 3( 3300 50 ±2500 39000 0000 4300 15 3400 4000 .000 26000 3300 3500 38000 3800 4400 16000 33000 5400 3400 WO 91/19533 PC/US91/04122 -24- In regard to the myocardial electrodes of the type shown particularly in Figures 10 and 11, animal implant data of 1.5 mm 2 macroscopic surface area electrodes with and without steroid is presented in the following Tables V and

VI.

TABLE V MYOCARDIAL 1.5 mm ELECTRODES CANINE VENTRICULAR STIMULATION Implant Time (Weeks) 0 1 2 3 4 8 12 0.5ms Thresholds With No Steroid Steroid (N 4) (N 3) 0.50±.10 0.86+.40* 0.50±.11 0.451.12 0.47±.22 0.45+.12 0.47±.17 0.35±.10 1.4 ±.40 1.9 ±.28 1.1 +.55 0.83±.32 0.63±.12 0:.70 10 0.5ms Pacing With Steroid (N 4) 4400±4500 1400± 350 1600± 210 1600± 150* 1600± 210 1400± 160 1200± 270 Impedance(n) No Steroid (N 3) 3800±2100 1300± 180 1600± 300 2150±1200 1300± 550 1300± 430 1500± 260**

I

8 N 3 L

I

WO 91/19533 PCr/US91/04122 N 2 TABLE VI MYOCARDIALJ 1.5 mm 2

ELECTRODES

CANINE VENTRICULAR SENSING R-Wave Source Impedance (n2) Implant Time (Weeks) Amnplitudes (mv) 0 1 2 3 4 8 12 With Steroid (N 4) 17±4 .3 17±5. 7 17±7.8 18±7.9 18±8.0 24±7.1 19±8. 3 No Steroid (N 3) 23 ±13 19±1.0 20±3 6 23±5. 0 22±4 7 23±5.3 24±5.9 With Steroid (N 4) 39 00±12 00 2400± 460 2500± 450 2600± 330 2400± 220 19 00± 96 1800± 220 No Steroid (N 3) 7 60 0±1500 34 00± 510 3 600±1500 2900± 590 3000± 600 23 00± 610 2400± 870 LI I ~r 111 WO 91/19533 PCT/US91/04122 -26- Thus it can be seen that the very small "nanotip", exposed and DCD electrodes of the present invention satisfy the aforementioned desirable characteristics of a pacing lead, that has low stimulation thresholds very high pacing impedance (800 2500 ohms) relatively low polarization, good to excellent sensing, and adequately low source impedance. The high pacing impedance prolongs the longevity of pacing pulse generators and allows for the miniaturization of their components. The low thresholds allow large safety factors at low applied voltages, which also contribute to increased battery longevity.

While the embodiments of the present invention have been described in particular application to cardiac pacing, it will be understood that the invention may be practiced in other electrode technologies where the aforementioned characteristics are desirable, including neurological and muscle stimulation applications. Moreover, the miniaturization of the electrodes afforded by the present invention may advantageously allow the clustering of two or more electrode structures at the tip of a stimulation/sensing lead or probe. While not specifically illustrated above, the present invention may advantageously be implemented in tip electrode configurations of the type illustrated in Sleutz et al U.S. Patent No. 4,662,382 in order to provide practical closely spaced bipolar stimulation and sensing.

The invention has been described in detail with particular reference to the preferred embodiments thereof, but it will be understood that variations and modifications can be effected within the scope of the following claims.

li_

Claims (14)

1. A body implantable lead comprising: a) an electrical conductor having a proximal end and a distal end; b) insulating sheath means for covering said conductor between said proximal and distal ends thereof; c) electrical connector means coupled to said proximal end of said conductor for electrically connecting said lead to a pulse generator; d) electrode means electrically coupled to said distal end of said electrical conductor for conducting electrical energy to and from said body tissue site desired to be stimulated and sensed, said electrode means comprising a body of a porous metallic or other conductive material with high microscopic surface area in proportion to macroscopic surface area, mounted to a distal end of a conductive pin and extending radially from said conductive pin, a proximal end of said pin being coupled to said distal end of said electrical conductor; and e) drug dispensing means mounted around said pin, proximal to said porous body, within said insulating sheath, for storing a drug to be dispensed while allowing dispensing of said drug through said porous body to counter undesirable interactions between said lead and said body site.

2. A lead according to claim 1, wherein said electrode means is formed of porous metallic or other conductive materials from the class of materials consisting A essentially of platinum, palladium, titanium, tantalum, rhodium, iridium, carbon, vitreous carbon, and alloys, oxides and nitrites of such metals or other conductive materials. NI 28

3. A lead according to claim 1, wherein said drug dispensing means comprises a fluid permeable polymer body located within said insulating sheath means, said polymer body containing a water soluble form of said drug.

4. A lead according to claim i, wherein said drug is a water soluble form of an anti-inflammatory drug.

A lead according to claim 4, wherein said drug is a glucocorticosteroid.

6. A lead according to claim 4, wherein said drug is the sodium salt of dexamethasone phosphate.

7. A lead according to claim 1, wherein said exposed macroscopic surface area is in the range of between 0.10 2 and 2.0mm

8. A lead according to claim 1, wherein said exposed macroscopic surface area is generally hemispherical in shape.

9. A lead according to claim i, wherein: said drug dispensing means is situated in a position in relation to said porous electrode portion to provide for the delivery of said drug only through said porous body to said body tissue site.

A lead according to claim 1, wherein said porous body is generally circular in cross section.

11. A lead according to claim 10, wherein said porous body is generally spherical.

12. A lead according to claim 1, wherein said porous body extends radially between said conductive pin and said insulating sheath.

13. A lead according to claim 1, wherein said drug dispensing means extends distal to said insulating sheath.

14. A lead according to claim 1, wherein said porous body is located within said insulating sheath. N 4 L I\ i I 29 A body implantable lead as hereinbefore described with reference to the accompanying drawings. DATED this 27 day of June 1994 MEDTRONIC, INC. Patent Attorneys for the Applicant: F.B. RICE CO. ?1 I f.1 j