(12) United States Patent
`March
`
`USOO6200259B1
`US 6,200,259 B1
`(10) Patent No.:
`Mar. 13, 2001
`(45) Date of Patent:
`
`(54) METHOD OF TREATING
`CARDOWASCULAR DISEASE BY
`ANGIOGENESIS
`
`(76) Inventor: Keith L. March, 13800 Oakwood Ct.,
`Carmel, IN (US) 46032
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`(*) Notice:
`
`(21) Appl. No.: 09/325,229
`(22) Filed:
`Jun. 3, 1999
`(51) Int. Cl." ................................................. A61B 17/52
`(52) U.S. Cl. ................................................................... 600/9
`(58) Field of Search ............................................. 600/9-15
`(56)
`References Cited
`U.S. PATENT DOCUMENTS
`
`3,890.953 * 6/1975 Kraus et al..
`3,915,151 * 10/1975 Kraus.
`3,921,620 * 11/1975 Nakayama.
`4,266,532 * 5/1981 Ryaby et al. .
`5,401.233
`3/1995 Erickson et al. ....................... 600/14
`5,524,624 * 6/1996 Tepper et al..
`5,723,001
`3/1998 Pilla et al. ............................. 607/68
`OTHER PUBLICATIONS
`Bassett, “Fundamental and Practical Aspects of Therapeutic
`Uses of Pulsed Electromagnetic Fields (PEMFs), " Critical
`Reviews in Biomedical Engineering, vol. 17 Issue 5 (1989),
`pp. 451-522.
`Norton, “Pulsed Electromagnetic Field Effects on Chondro
`blast Culture,” Reconstr. Surg. Traumat., Vol 19 (Karger,
`Basel 1985), pp. 70-86.
`Detlavs et al., “Experimental study of the effects of radiof
`requency electromagnetic fields on animals with Soft tissue
`wounds,” The Science of the Total Environment, 180 (1996),
`pp. 35-42.
`
`
`
`Lin et al., “Effects of Pulsing Electromagnetic Fields on the
`Ligament Healing in Rabbits,” J. Vet. Med. Sci.54(5) (1992),
`pp. 1017-1022.
`Coats, “Pulsed electromagnetic-(short-wave) energy
`therapy,” Br. J. Sp. Med., vol. 23, No. 4 (1989), pp. 213–215.
`Glassman et al., “Effect of External Pulsing Electromagnetic
`Fields on the Healing of Soft Tissue,” Annals of Plastic
`Surgery, vol. 16, No. 4 (Apr. 1986), pp. 287–295.
`Watkins, “Healing of Surgically created defects in the equine
`Superficial digital flexor tendon: Effects of pulsing electro
`magnetic field therapy on collagen-type transformation and
`tissue morphologic reorganization, Am. J. Vet. Res., Vol. 4,
`No. 10 (Oct. 1985), pp. 2097–2103.
`Yen-Patton et al., “Endothelial Cell Response to Pulsed
`Electromagnetic Fields: Stimulation of Growth Rate and
`Angiogenesis. In Vitro,” Journal of Cellular Physiology, 134
`(1988), pp. 37–46.
`* cited by examiner
`Primary Examiner Max Hindenburg
`(57)
`ABSTRACT
`A System and method for treating cardiovascular disease
`utilizes electromagnetic fields (EMF) applied by non
`invasive or minimally invasive procedures. The EMF is
`applied to existing vascular Structure to modulate blood flow
`and blood vessel growth in the patient. In one embodiment,
`a structure of electromagnetic coils is placed about a desired
`treatment Zone to apply an EMF to the Zone on the order of
`10'-10 T. For cardiac angiogenesis, coils can be positioned
`on the anterior chest wall and on the back at the level of the
`heart. Various coil configurations are contemplated to yield
`appropriate field intensities at the treatment Zone. In another
`embodiment, coils can be implanted within the patient and
`placed within or overlying the treatment Zone. An EMF
`dosage plan can be developed for the patient and Specific
`treatment Zone incorporating Several aspects, Such as fre
`quency components, the use of a carrier frequency, pulse
`shape, duty cycle, and total time exposure to the EMF.
`9 Claims, 7 Drawing Sheets
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`1
`METHOD OF TREATING
`CARDIOVASCULAR DISEASE BY
`ANGIOGENESIS
`
`The present invention is directed to a method for treating
`cardiovascular disease by promoting growth of collateral
`vessels to increase blood flow to target organs and tissues.
`BACKGROUND OF THE INVENTION
`The major component of morbidity and mortality attrib
`utable to cardiovascular disease occurs as a consequence of
`the partial or complete blockage of vessels carrying blood in
`the coronary vascular System and in peripheral vasculature.
`When Such vessels are occluded, various clinical Syndromes
`may result from death of tissue previously nourished by the
`occluded vessels or inability of the vessels to transport
`Sufficient blood Supply to regions requiring high blood
`consumption and accompanying nutrients. In Some
`individuals, blood vessel occlusion is partially compensated
`by the natural process of angiogenesis, in which new con
`duits are formed to replace the function of the impaired
`vessels. These new conduits, called “collateral” vessels, may
`facilitate restoration of blood flow to the deprived tissue,
`thereby constituting “natural bypasses' around the occluded
`vessels. However, Some individuals are unable to generate
`Sufficient collateral vessels to manage the consequences of
`diminished blood flow from cardiovascular disease.
`At present, blood vessel occlusions are usually treated by
`mechanically enhancing blood flow or by medical reduction
`of oxygen demands in the involved tissueS or organs.
`Mechanical enhancements are provided most commonly by
`(1) employing Surgical techniques that attach autologous or
`Synthetic vascular conduits proximal and distal to the areas
`of occlusion, thereby providing bypass grafts, or (2) revas
`cularization by various means to physically enlarge the
`vascular lumen at the site of occlusion. These procedures
`involve Such devices as balloons, endovascular knives
`(atherectomy), endovascular drills, and the like. The Surgical
`approach is accompanied by Significant morbidity and even
`mortality, while the angioplasty-type processes are compli
`cated by recurrent stenoses in 25-35% of cases. Successful
`mechanical revascularization depends, inter alia, on acces
`Sibility of the occluding Stenosis to Such procedures. Clearly,
`there remains a pressing need for means to Stimulate angio
`genesis to provide collateral blood flow by non-invasive or
`minimally invasive procedures.
`SUMMARY OF THE INVENTION
`This invention employs electromagnetic fields (EMF)
`applied by non-invasive or minimally invasive procedures to
`modulate blood vessel growth in human or animal vascula
`ture. In positive modulation, external application of energy
`fields Stimulates progressive collateralization by artificially
`inducing or enhancing biochemical and cellular responses in
`the tissues permeating the target fields. In this manner, blood
`flow is restored to coronary and other organ Systems, periph
`eral vasculature and muscle vascular beds through an accel
`erated formation and/or maturation of newly-generated and
`enlarged vessels that bypass partially or entirely occluded
`vasculature by induced angiogenesis.
`From a clinical perspective, the choice to use Such non
`invasive revascularization would be particularly appropriate
`(1) in patients without reasonable options for mechanical
`revascularization because of inaccessible location of the
`Stenosis, diffuse vascular disease, or poor overall medical
`condition for Surgical or even endovascular intervention; (2)
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`as an adjunct to Surgical or endovascular interventions, in
`which the anatomy of the patient’s blood vessels precluded
`revascularization of all ischemic regions (i.e., incomplete
`revascularization using other modalities); (3) as an adjunct
`to the application of other mechanical Stimuli Such as laser
`channel formation (transmyocardial laser revasularization)
`which have been found to reduce Symptoms of ischemia; (4)
`as an adjunct to the administration or direct application of
`genetic or growth factor agents also intended to facilitate
`vascular growth or angiogenesis; and (5) in patients with
`ischemic disease and attendant Symptoms who are not yet
`appropriate candidates for the above interventions, thereby
`favoring a non-invasive procedure and making possible
`earlier therapy attended by virtual absence of morbidity.
`Potential forms of energy fields include electromagnetic
`fields that are pulsed over a wide range of frequencies,
`intensities and pulsed waveform shapes (PEMF). Electro
`magnetic fields may also be generated in a continuously
`oscillating, nonpulsed manner, thus providing a sinusoidal
`waveform. Specific combinations of these variables deliver
`a range of biological effects that can be tailored to desired
`results. Other energy forms, including pulsed or
`continuously-generated microwave-radiated energy and
`ultrasonic energy, may be applied. In the case of PEMF,
`application involves placement of coils around the regions
`of tissues in which collateralization is desired. One approach
`is to embed the coils in a cloth wrap, which may be worn as
`a garment Surrounding the body area of interest. For cardiac
`applications, a Vest-type garment may be fabricated. For
`peripheral applications a wrap, i.e., either around the leg or
`arm, can be designed to deliver the desired field to the
`affected organ or tissue.
`The structure of coils contained within Such garments or
`wraps can provide for Simple homogeneous, “flat field
`distributions in three-dimensional Space, or may be config
`ured to focus on fields with greater intensity localized near
`the target area.
`The number of wire loops comprising a single coil, or
`each of Several coils, and the electric power used to power
`these wire loops, should be Such that the peak intensity of the
`field within the region of interest is on the order of 10-10
`T.
`These applications of energy fields may be utilized not
`only as primary therapy but in conjunction with mechanical
`approaches to revascularization or following Standard
`Surgical/endovascular or angioplasty approaches. For
`example, where Such revascularization is partially but inad
`equately achieved by Standard techniques, externally-based
`fields provide an opportunity for complementary revascu
`larization of target areas.
`Apparatus for delivering the desired electromagnetic
`Stimulation to target areas taught herein are readily adapted
`from well-reported (FMF) technology relating to the skeletal
`System. Principles of design are to be found, for example, in
`U.S. Pat. Nos. 5,401233, 4,266,532, 3,890,953 and 3,915,
`151. This applies not only to the basic structure employed in
`the delivery System but also for the ranges of parameters, as
`discussed herein. Of particular interest for its comprehensive
`coverage of electromagnetic therapy is Bassett, “Fundamen
`tal and Practical Aspects of Therapeutic Uses of Pulsed
`Electromagnetic Fields (PEMFs).” Critical Reviews in Bio
`medical Engineering, 17:451, Issue 5 (1989). Also of inter
`est in refining parameters based on target location and
`environment, are the following: Norton, “Pulsed Electro
`magnetic Field Effects on Chondroblast Culture,” Reconstr.
`Surg. Tramaut., 19:70 (1985); Detlays et al., “Experimental
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`Study of the Effects of Radiofrequency Electromagnetic
`Fields on Animals With Soft Tissue Wounds,” Sci. of Total
`Environ., 180:35 (1996); Lin et al., “Effects of Pulsing
`Electromagnetic Fields on the Ligament Healing in Rabbits,
`J. Vet. Med. Sci. 54(5):1017 (1992); Goats, “Pulsed
`Electromagnetic-(short-wave) Energy Therapy,” Br. J. Sp.
`Med. 23:213; Glassman et al., “Effect of External Pulsing
`Electromagnetic Fields on the Healing of Soft Tissue.”
`Annals of Plast. Surg. 16(4):287 (April 1986); Watkins et al.,
`“Healing of Surgically Created Defects in the Equine Super
`ficial Digital Flexor Tendon: Effects of Pulsing Electromag
`netic Field Therapy on Collagen-type Transformation and
`Tissue Morphologic Reorganization,” Am. J. Vet. Res.
`46(10):2097 (1985), and Zoltan, “Electrical Stimulation of
`Bone: An Overview,” Seminars in Orthopaedics 1(4):242
`(1986).
`The use of PEMF and local application of ultrasonic
`energy have been described as providing enhancement of
`fusion rates of bony fractures, as well as accelerating rates
`of wound healing. U.S. Pat. No. 5,524,624. Such procedures
`have shown significant promise in diabetes, tobacco use, or
`other conditions which appear to deter natural bone healing
`or wound healing responses. They have, however, Suggested
`no extension of the electromagnetic phenomenon in circum
`stances where positive or negative modulation of angiogen
`esis can provide dramatic opportunities for addressing prob
`lems of (1) occlusions in the coronary and other organ
`Systems and peripheral vasculature, and (2) blood-dependent
`tumorous tissues.
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`DESCRIPTION OF THE FIGURES
`FIGS. 1A-1C are diagrammatic representations of
`anterior, Side and posterior views of a human heart and torSo
`with anterior and posterior coils in accordance with one
`embodiment of the present invention.
`FIGS. 2A-2C are diagrammatic representations of
`anterior, Side and posterior views of a human heart and torSo
`with an anterior coil only in accordance with a further
`embodiment of the present invention.
`FIGS. 3A-3C are diagrammatic representations of
`anterior, Side and posterior views of a human heart and torSo
`with coil having a bent Oval configuration in accordance
`with another embodiment of the present invention.
`FIGS. 4A-4C are diagrammatic representations of
`anterior, Side and posterior views of a human heart and torSo
`with an anterior coil and a larger posterior coil in accordance
`with yet another embodiment of the present invention.
`FIGS. 5A-5C are diagrammatic representations of
`anterior, Side and posterior views of a human heart and torSo
`with two sets of coils in accordance with an alternative
`embodiment of the present invention.
`FIGS. 6A-6C are diagrammatic representations of
`anterior, Side and posterior views of a human heart and torSo
`with coils vertically positioned adjacent the pericardial Sac
`in accordance with an additional embodiment of the present
`invention.
`FIGS. 7A-7C are diagrammatic representations of
`anterior, Side and posterior views of a human heart and torSo
`with coils horizontally positioned adjacent the pericardial
`Sac in accordance with an additional embodiment of the
`present invention.
`GENERAL DESCRIPTION
`It is important, in the application of electromagnetic fields
`to facilitate or prevent angiogenesis, that the body's region
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`of interest be Subjected to an essentially homogeneous
`electrical field for maximum efficacy and Safety. This means
`that the treatment field should have specific spatial and
`temporal characteristics. To achieve this focused treatment
`environment with deep tissue penetration, pulsed EMF is
`preferred.
`Spatial Characteristics
`An apparatus is designed to deliver PEMF with the
`appropriate Spatial characteristics for treatment of the region
`of focus in three dimensions. For example, the field must be
`Sufficiently homogeneous with respect to biological effects
`throughout the cardiac Volume in the case of coronary
`angiogenesis or other target areas.
`A degree of Spatial Specificity is assured by the fact that
`ischemic tissues possess increased Sensitivity to a variety of
`proangiogenic Stimuli. Accordingly, regions of the muscle or
`Surrounding organs which are not actively ischemic by
`virtue of limited blood flow would not be expected to
`respond to PEMF as readily as ischemic tissues. In ischemic
`tissues, a variety of other receptor and growth factor gene
`expressions occur in response to the ischemia, thereby
`conferring enhanced Sensitivity on the field. High resolution
`of the Spatial characteristics of the field to restrict exposure
`to target tissues are usually not necessary. Instead, it is
`sufficient that adequate field amplitude be directed to the
`target region to provide a Stimulus that is greater than a
`threshold required to yield a desired biologic response.
`One approach for providing the desired PEMF signal to
`the target tissue Volume, either including the heart, or
`peripheral musculature, is the use of paired (Helmholtz)
`coils which are placed in a parallel configuration Separated
`by a distance approximately similar to the diameter of the
`coils, So that the Space between the coils encompasses the
`target volume for treatment. The coils are then energized
`Simultaneously. This arrangement results in a Substantially
`homogeneous field within the target Volume, which will thus
`produce biologically significant effects therein. For cardiac
`angiogenesis, coils would be positioned on the anterior chest
`wall and on the back, at the level of the heart.
`FIG. 1 depicts a human torso containing a heart. FIG. 1A
`shows anterior 1 and posterior 2 coils as described, with
`diameters slightly larger than cardiac Silhouette 3, and
`Similar to the anterior-posterior distance between the two
`coils. FIG. 1B, with the arm raised, demonstrates that the
`anterior 1 and the posterior 2 coils are placed So as to
`encompass the cardiac region in the Volume Subtended by
`the two coils. FIG. 1C shows posterior coil 2, again with
`diameter Similar to that of anterior coil 1 and to the distance
`Separating the two coils. FIG. 1B also shows a pulse
`generator box 4, consisting of a power Supply, an appropriate
`circuitry designed to generate pulses to energize the coils,
`and an amplifier apparatus as necessary to amplify these
`pulses to the desired energies. Also shown in FIG. 1B are
`leads 5 running from the pulse generator/amplifier circuitry
`box 4 to the paired coils 1 and 2. The generator box 4 and
`leads 5 are present but not shown in FIGS. 2-7.
`Where less field homogeneity is required for the treatment
`of the target Volume, a single coil on the anterior or posterior
`Surface of the thorax may be used. Such a coil provides a
`field of an intensity that decreaseS as the distance from the
`Surface of the coil increases. This simpler approach is
`feasible because it has been determined that the biological
`effects of PEMF are relatively amplitude-insensitive. In that
`case, the decrement and intensity distance from the coil may
`be comparatively unimportant to achieve the desired effect.
`FIG.2 depicts a single coil 1, placed on the anterior aspect
`of the chest, again with diameter So it would be greater than
`that of the cardiac Silhouette.
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`To enhance focus of PEMF intensity in the cardiac region,
`an asymmetric configuration comprising a bent oval
`wrapped from the anterior thorax along the left Side of the
`body may be used to encompass within its field a geometric
`Space that includes the heart.
`FIG.3 depicts a bent oval configuration for the single coil
`1, which provides a wrap extending from the anterior view
`in FIG. 3A, around the left aspect of the thorax as seen in
`FIG. 3B, and onto the back as in FIG. 3C, thus encompass
`ing the heart Volume within its bent shape.
`Another means for enhancing field focus is to provide
`intensity and Specificity in the cardiac region by a compara
`tively Small anterior coil and a comparatively large posterior
`coil, causing the more anteriorly-located heart to receive the
`greater intensity of field Strength.
`FIG. 4 demonstrates a comparatively small anterior coil 1
`positioned over the heart, thus providing for an increase in
`the Volume-Specific field intensity in the anterior aspect of
`the thorax, closer to the location of the cardiac volume. FIG.
`4C also shows this Smaller coil 1 placed anteriorly and a
`larger coil 2 placed posteriorly. FIG. 4B further shows larger
`coil 1, which produces a diminished field intensity as the
`back is approached.
`Enhanced PEMF effects in the cardiac region in compari
`Son to other areas of the thorax may also be provided by
`intermittent application of a PEMF using anterior and poS
`terior coils alternating with PEMF employing left and right
`sided coil placements. Here, the fields with alternate inter
`action from the anterior-posterior and the Side-to-side
`direction provide a convergence of both fields upon the
`cardiac Volume. TissueS on the left or right or anterior and
`posterior to the heart would receive leSS intense fields
`because they would not be at the intersection of the "field
`cylinders.”
`FIG. 5 shows two pairs of coils, with an anterior 6 and
`posterior 7 pair of coils, respectively, in the anterior and
`posterior views in FIGS. 5A and 5C, and a left/right pair of
`coils 8 seen both from the front and back in FIGS. 5A and
`5C. The left coil is best seen in FIG. 5B. These would be
`energized So that the anterior/posterior pair would initially
`create a field, alternating with a field created between the left
`and right pair of coils. Accordingly, the tissue Volume that
`would receive the maximal energy exposure would be the
`cardiac Volume occurring at the interSection of the cylinders
`described by the two coil pairs in FIGS.5A and 5C. FIG. 6
`shows a pair of coils implanted either within or overlying the
`pericardial Sac for maximal spacial proximity to the cardiac
`tissue.
`Enhanced spatial localization of the PEMF to the region
`of the heart may also be achieved while limiting exposure of
`other tissues by use of a Single coil, or one or both of a pair
`of coils placed in the body by Surgical or minimally-invasive
`methods. One or more Such cells are placed in geometric
`proximity to the cardiac Structure. Such coils would prefer
`ably be in opposition to the heart Surface, either outside or
`inside the pericardial Space. In this way, the heart Structures
`would receive the maximum geometrically feasible local
`ization as compared to the adjacent thoracic structures.
`FIG. 6 shows coils 8 and 9 placed in a vertical plane, seen
`both from the anterior and back views in FIGS. 6A and 6C,
`as well as in FIG. 6B.
`Further shaping of the PEMF field in three dimensions is
`possible by utilizing Structures of variable permeability to
`the electromagnetic fields placed as Specific shields on the
`thoracic body wall, in conjunction with coils similarly
`placed. These shields, consisting of thin (1-100 micron)
`layers of material incorporating ferromagnetic or other simi
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`lar materials, would be placed between the coil Surfaces and
`the body wall. Selective placement of such shields makes it
`possible to focus the field intensity on the desired tissue
`Volume while diminishing its intensity in other regions.
`FIG. 7 depicts an alternative positioning for implanted
`coils to be placed within or overlying the pericardial Sac, in
`the horizontal plane. In FIG. 7, two coils 10 and 11 are seen
`encircling the heart at its base (the lower portion), as well as
`at its apex (the upper portion). These coils may be seen from
`the front, (FIG. 7A), left (FIG. 7B) and back (FIG. 7C) to
`encircle the cardiac Volume.
`Temporal Characteristics
`The temporal characteristics of a PEMF dosage plan
`includes Several aspects: (1) individual frequency compo
`nents of the employed fields, (2) the presence or absence of
`a “carrier' frequency which may be modulated with a
`frequency of lower value; for example, a carrier frequency
`of 100 KHZ-10 GHz might be modulated or pulsed with a
`frequency of 20-10,000 Hz, (3) the particular shape of the
`pulses, expressed as electromagnetic energy varying with
`time, (4) the “duty cycle” of the pulsing field, i.e., whether
`the variable fields are applied continuously or in “burst'
`patterns with intermittent periods of no electrical fields, (5)
`the total time of bodily exposure to the field-generating
`device on a daily basis, and (6) the number of days over
`which the device is to be utilized in a treatment plan. Several
`of these variables have preferred ranges which have been
`defined by observation of biological responses both in vitro
`and in vivo.
`Alternatively, dual or multiple Sinusoidal frequencies in a
`Serial or parallel combination may be provided as non
`Sinusoidal pulse wave forms which may be Square,
`triangular, or intermediate in shape. Such non-sinusoidal
`wave forms contain within them a variety of frequencies
`which comprise the overall shape, as defined by a Fourier
`transform, revealing contained frequency components of
`Simple sinusoidal frequencies. Accordingly, a Single repeti
`tion rate of a non-sinusoidal wave-form can contain numer
`ouS inherent Sinusoidal frequency components, and a range
`of frequencies within this domain of frequencies thus pro
`vides an efficacious biological response. Such pulsed wave
`forms are typically employed at repetition rates within the
`range of 20-4,000 hertz but may incorporate frequency
`components up to 10 GHz. To conserve energy from por
`table batteries or power pack Systems, limited duty cycles of
`the pulsed field are employed for periods of time from
`10-100% of total time. Time or exposure to the device
`ranges from 1-24 hours per day, preferably from about 1-6
`hours per day.
`PREFERRED EMBODIMENT
`A device for treatment of the coronary vasculature com
`prises a thinly configured Set of coils and power Supply
`sufficiently compact to be worn underneath either while the
`patient is ambulatory and active or at rest. Each of a pair of
`coils is positioned anterior and posterior to the region
`requiring angiogenic facilitation of cardiac vessels or tis
`Sues. Optimal positioning of the coils is slightly left of
`midline on the anterior chest wall and on the back, at the
`level of the heart. Diameters of these coils range approxi
`mately from 10-15 centimeters. However, they may be
`Smaller, or, in fact, encompass Virtually the entire chest.
`Homogeneity of the electric field intensity is obtained for
`pairs of coils when Spaced at a coil Separation approximating
`the diameter of the coils. Accordingly, one optimal coil
`diameter is configured to the anterior-posterior thickness of
`the Subject's chest. A reasonably homogeneous field would
`thereby be provided to the entire cardiac tissue Volume.
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`The coils are comprised of wire wrappings providing peak
`magnetic fields of 10 uT-5T, as measured in the treatment
`region between the coils when energized. These wire wrap
`pings are placed within a thin, flexible containing material
`Such as of plastic, cloth, or rubber which may be worn on the
`body underneath clothing, with a minimum of discomfort.
`The coils are connected by power Supply wires to a pulse
`generator which is also worn beneath the clothes, and may
`be placed in apposition to one of the coils. The pulse
`generator is energized during the time periods of treatment,
`typically 1-16 hrs/day, especially 1–4 hrs/day, and provides
`energy to the coils with a temporal configuration which
`results in positive vascular growth modulation. Such signals
`may be pulsed with repetition rates of 20-4000 Hz, with
`emissions of bursts of pulses occurring 1-50 times each
`second. The pulse bursts may include from 10-100 discrete
`pulses, or alternatively the pulses may be provided through
`out the time period, without a burst timing. The pulse
`generator may be programmed for the desired treatment
`modality to be automatically provided for the selected time
`period, once activated by the patient, with a mechanism to
`ensure power-down at the correct time.
`In like manner, the methods of this invention may be
`adapted by those skilled in the arts involved to treat block
`ages of vessels in the peripheral vasculature by noninvasive
`or minimally-invasive procedures.
`What is claimed is:
`1. A method for modulating blood vessel growth in
`targeted coronary vasculature comprising:
`applying an electromagnetic field (EMF) to the desired
`treatment Zone to modify blood flow thereto.
`2. A method for modulating blood vessel growth in
`targeted coronary vasculature comprising:
`
`15
`
`25
`
`US 6,200,259 B1
`
`8
`applying an electromagnetic field (EMF) to the desired
`treatment Zone to modify blood flow thereto in which
`the EMF is induced by pulsed DC or AC current.
`3. The method of claim 2 in which EMF is applied in
`conjunction with mechanical revascularization.
`4. The method of claim 3 in which EMF is applied in
`conjunction with angioplasty.
`5. The method of claim 2 in which FMF is applied in
`conjunction with administration or direct application of
`genetic or growth factor agents to facilitate vascular growth
`or angiogenesis.
`6. The method of claim 2 in which EMF is applied in
`conjunction with transmyocardial mechanical or laser revas
`cularization.
`7. A method for modulating blood vessel growth in
`targeted peripheral vasculature comprising:
`applying an electromagnetic field (EMF) to the desired
`treatment Zone to modify blood flow thereto in which
`the EMF is induced by pulsed DC or AC current, and
`in which EMF is applied in conjunction with mechani
`cal revascularization.
`8. The method of claim 7 in which EMF is applied in
`conjunction with angioplasty.
`9. A method for modulating blood vessel growth in
`targeted peripheral vasculature comprising:
`applying an electromagnetic field (EMF) to the desired
`treatment Zone to modify blood flow thereto in which
`the EMF is induced by pulsed DC or AC current, and
`in which EMF is applied in conjunction with admin
`istration or direct application of genetic or growth
`factor agents to facilitate vascular growth or angiogen
`CSS.
`
`LUMENIS EX1065
`Page 12
`
`

`

`UNITED STATES PATENT AND TRADEMARK OFFICE
`CERTIFICATE OF CORRECTION
`
`PATENT NO. : 6,200,259 B1
`DATED
`: March 13, 2001
`INVENTOR(S) : Keith L. March
`
`Page 1 of 1
`
`It is certified that error appears in the above-identified patent and that said Letters Patent is
`hereby corrected as shown below:
`
`Column 2
`Line 53, replace"(FMF)” with -- (EMF) --
`
`Column 6
`Line 53, replace “underneath” with -- underneath clothing, --
`
`Attest:
`
`Signed and Sealed this
`Sixteenth Day of October, 2001
`7c44, f2 abée
`
`Artesting Officer
`
`NICHOLASP. GODCI
`Acting Director of the United States Patent and Trademark Office
`
`LUMENIS EX1065
`Page 13
`
`