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WO1998005307A1 - Procede et appareil d'administration transmurale de medicaments - Google Patents

Procede et appareil d'administration transmurale de medicaments Download PDF

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Publication number
WO1998005307A1
WO1998005307A1 PCT/US1997/013904 US9713904W WO9805307A1 WO 1998005307 A1 WO1998005307 A1 WO 1998005307A1 US 9713904 W US9713904 W US 9713904W WO 9805307 A1 WO9805307 A1 WO 9805307A1
Authority
WO
WIPO (PCT)
Prior art keywords
tissue
channels
energy
myocardium
advancing
Prior art date
Application number
PCT/US1997/013904
Other languages
English (en)
Inventor
Aaron V. Kaplan
Robert M. Abrams
Enrique J. Klein
Original Assignee
Localmed, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Localmed, Inc. filed Critical Localmed, Inc.
Priority to EP97936444A priority Critical patent/EP0949910A4/fr
Priority to AU39110/97A priority patent/AU3911097A/en
Publication of WO1998005307A1 publication Critical patent/WO1998005307A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B18/22—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
    • A61B18/24—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor with a catheter
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1825—Fibroblast growth factor [FGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1858—Platelet-derived growth factor [PDGF]
    • A61K38/1866—Vascular endothelial growth factor [VEGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/00234—Surgical instruments, devices or methods for minimally invasive surgery
    • A61B2017/00238—Type of minimally invasive operation
    • A61B2017/00243—Type of minimally invasive operation cardiac
    • A61B2017/00247—Making holes in the wall of the heart, e.g. laser Myocardial revascularization
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00315—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
    • A61B2018/00345—Vascular system
    • A61B2018/00351—Heart
    • A61B2018/00392—Transmyocardial revascularisation

Definitions

  • the present invention relates generally to methods and apparatus for drug delivery.
  • One aspect of the present invention relates to methods and apparatus for promoting myocardial angiogenesis to treat ischemia.
  • Coronary artery disease usually results from the deposition of atheromatous plaque in the large and maxim - sized arteries supplying the heart. Such blockages of the coronary arteries can in turn cause myocardial ischemia which is a condition characterized by inadequate blood flow from the coronary arteries to heart tissue. In severe cases, coronary artery disease can lead to myocardial infarction (heart attack) and sudden cardiac death.
  • Angina pectoris is a chronic condition associated with myocardial ischemia and characterized by chest discomfort as a result of vigorous and in some cases even mild exertion.
  • Angina pectoris can be treated by the administration of drugs, such as /3-adrenergic blocking agents and vasodilators, including nitroglycerin, a yl nitrite, nitrates, and calcium antagonists. While effective for short-term treatment, such drugs are ineffective at treating the arterial blockages responsible for the underlying coronary artery disease.
  • drugs such as /3-adrenergic blocking agents and vasodilators, including nitroglycerin, a yl nitrite, nitrates, and calcium antagonists.
  • drugs include /3-adrenergic blocking agents and vasodilators, including nitroglycerin, a yl nitrite, nitrates, and calcium antagonists.
  • drugs include nitroglycerin, a yl nitrite, nitrates, and calcium antagonists.
  • nitroglycerin nitroglycerin, a yl nitrite,
  • TMR transmyocardial revascularization
  • PMR percutaneous myocardial revascularization
  • This method accesses the myocardium percutaneously by means of a catheter to the aorta, retrograde access across the aortic valve and into the left ventricle.
  • endocardium channels are formed through the endocardium but not completely through the myocardium.
  • Intramural delivery of angiogenic factors to promote revascularization of cardiac tissue is described in copending application serial no. 08/753,224, assigned to the assignee of the present invention, filed on November 22, 1996, the full disclosure of which is incorporated herein by reference.
  • a transmural drug delivery method for the delivery of angiogenic and other bioactive agents and factors to cardiac tissue broadly includes the steps of forming a plurality of channels at least partly into myocardial, and introducing the angiogenic or other factor into the open channels.
  • the angiogenic factors induced blood vessel growth factors which, together with the open channels, enhance blood flow and/or angiogenesis directly from the ventricular chamber into the cardiac tissue, thus at least partially relieving ischemia in ischemic patients.
  • Collateral vessels are expected to form between the channels and between the channels and the coronary arteries. The formation of collateral vessels provides a substantial network of blood flow paths to enhance blood perfusion directly to the myocardium.
  • Exemplary angiogenic factors include naturally occurring peptides, e.g., vascular endothelial growth factor (VEGF) , acidic fibroblast growth factor (aFGF) , basic fibroblast growth factor (bFGF) and their derivatives or a combination thereof, and the like.
  • VEGF vascular endothelial growth factor
  • aFGF acidic fibroblast growth factor
  • bFGF basic fibroblast growth factor
  • active agents include polypeptides, carbohydrates, nucleic acids, gene vectors, genetically modified cells, and the like.
  • angiogenesis refers to the growth of blood vessels in tissue in response to stimuli, particularly in response to administration of an angiogenic factor in the manner described below.
  • one or more other agents having different activities can be delivered together with an angiogenic factor(s).
  • anti-arrhythmia agents, beta blockers, nitrates such as nitroglycerine, myocardial growth factors, anti-viral agents and anti-rejection agents can be used.
  • FIG. 1 is a simplified overall view of a catheter assembly made according to the inven ion;
  • Fig. 2 shows the catheter of Fig. 1 introduced into the left ventricle of a heart, a portion of the heart broken away to illustrate a series of endocardial channels formed within the myocardium of the heart;
  • Fig. 3A is a simplified enlarged view illustrating growth of new arterioles into the myocardium and between the channels;
  • Fig. 3B is a view similar to Fig. 3A but shows the growth of new arterioles between the channels and various coronary artery branches, the arterioles of Figs. 3A and 3B being illustrated in two different figures for clarity;
  • Fig. 4 illustrates the distal end of an alternative embodiment of the catheter of Fig . 1 ;
  • Fig. 5 illustrates a further alternative embodiment of the invention including an agent delivery needle, shown extended
  • Fig. 6 illustrates a further embodiment of the invention in which the central lumen is somewhat enlarged to permit the delivery of bioeluting or biodegradable/bioerodible particles into the endocardial channels;
  • Fig. 6A illustrates rod-shaped particles which can be used instead of the spherical particles of Fig. 6 ;
  • Fig. 6B illustrates a train of bioeluting tubules for placement into the endocardial channels
  • Fig. 7 illustrates a further embodiment of the invention in which a porous matrix is mounted to the distal end of the catheter shaft.
  • Fig. 8 illustrates a further alternative using TMR so that the channels are formed completely through the myocardium from the epicardium, and illustrating the administration of a drug into the channels by various means.
  • Fig. 1 illustrates a catheter assembly 2 made according the invention.
  • Catheter assembly 2 comprises a catheter 4 having a handle 6, the handle coupled to a laser energy source 8 and a source 10 of an angiogenic factor.
  • the catheter is useful for delivering a variety of active agents to cardiac tissue, particularly angiogenic factors and formulations as described in copending application no. 08/753,224, the full disclosure of which was previously incorporated herein by reference.
  • Catheter 4 also includes a hollow catheter shaft 12 having a proximal end 14 connected to handle 6 and an open distal end 16.
  • the interior catheter shaft 12 houses a set of optical fibers 18 which transmit laser energy from source 8.
  • a central lumen 20 passes along the center of catheter shaft 12 and is used to deliver the angiogenic factor from agent source 10.
  • Fig. 2 illustrates a heart 22 with a portion of the myocardium 24 broken away to show the interior of the left ventricle 26.
  • the left ventricle is supplied oxygenated blood from the lungs.
  • This figure shows a PMR (percutaneous myocardial revascularization) approach to deliver the angiogenic factor in which distal end 16 of catheter shaft 12 is passed through the aorta 28, across the aortic valve in a retrograde fashion and into the left ventricle 26.
  • Catheter shaft 12 is steerable to permit distal end 16 to be positioned against the endocardium 30 at a plurality of target sites.
  • angiogenic factors is delivered to the endocardial channel 32 through central lumen 20 from agent source 10.
  • agent source 10 can be delivered in other forms as well.
  • at least 5 channels will be formed, preferably at least 15, and more preferably at least 30, with from 10 to 40 channels being typical .
  • the catheter 4 may remain outside the myocardium as the channel is formed, as is usually the case with high energy C0 2 lasers. More usually, however, the catheter 4 will penetrate into the myocardium as the channel is being formed, as is the case with moderate energy laser sources, such as holmium: YAG lasers of the type available from Cardiogenesis Corporation, Sunnyvale, California. In a preferred approach, the catheter will penetrate into the myocardium as the laser or other energy is applied to the tissue to create the channel, and the angiogenic factor will be delivered to the tissue immediately following the termination of the energy delivery. Delivery of the angiogenic factor while energy is being delivered is not preferred since the energy would likely degrade the factors and reduce or destroy their activity.
  • the angiogenic factor promotes the growth of new arterioles 34 illustrated in Fig. 3A and 3B.
  • Arterioles 34 are shown in Fig. 3A as they pass into myocardium 24 and connect with other endocardial channels 32 and extend into the myocardium itself.
  • Fig. 3B illustrates a coronary artery 36 along the epicardium 38 and branches 40 which extend from coronary artery 36 into myocardium 24.
  • Fig. 3B illustrates arterioles 34 extending from channels 32 to coronary arteries 36 and branches 40.
  • Arterioles 34 are shown separately in Figs. 3A and 3B for clarity of illustration. However, it is understood that both type of arteriole growth is expected to occur due to the use of angiogenic factors.
  • arterioles 34 The growth of arterioles 34 is very important to ensure that myocardium 24 is provided with sufficient oxygenated blood to reduce or eliminate the occurrence of myocardial ischemia.
  • Heart 22 in Fig. 2 has already undergone a coronary bypass using bypass grafts 42 as a consequence of blockages, such as blockage 44, in the coronary arteries.
  • Additional partial blockages 46, see Fig. 2 have formed along bypass grafts 42 and along coronary artery 36 at blockage 47 (Fig. 3B) .
  • These additional blockages 46, 47 create myocardial ischemia necessitating additional measures to provide oxygenated blood to myocardium 24.
  • arterioles 34 not only provides oxygenated blood into myocardium 24 through endocardial channels 32 but also permits blood along coronary artery 36 to bypass blockage 48 due to the interconnection of arterioles 34 with one another and with coronary artery 36.
  • Fig. 4 illustrates an alternative embodiment of the invention in which the locations of optical fibers 18 and lumen 20 are reversed compared to Fig. 1.
  • Optical fibers 18 of catheter 4a are located in the center of catheter shaft 12a while a number of axially-extending lumens 20a are situated around fibers 18 adjacent to the periphery of shaft 12a.
  • Catheter 4b of Fig. 5 is similar to catheter 4 of
  • Fig. 1 with the exception of the use of an extendable hollow needle 49 housed within lumen 20. Needle 49, shown in its extended position in Fig. 5, is extended after laser energy is used to form an endocardial channel 32 but before distal end 16 has been moved to ensure proper positioning of the needle into the channel. This embodiment is particularly useful when the catheter 4b is not penetrated into the tissue while energy is delivered.
  • Fig. 6A illustrates a catheter 4c similar to catheter 4 but having a somewhat enlarged central lumen 20c. This permits catheter 4c to deliver spherical particles 48 through central lumen 20c for delivery into the recently formed endocardial channels 32. Note that in procedures such as PMR it is obligatory to maintain distal end 16 of catheter shaft 12 in position after endocardial channels 32 have been formed to ensure that the agent is properly delivered into the endocardial channels. Where visualization of the channel entrances is not a problem, as in the case of TMR, this restriction may not be necessary.
  • Spherical particles 48 may be biodegradable/bioerodible or bioeluting to provide the angiogenic factors to myocardium 24 over a period of time. Fig.
  • FIG. 6A illustrates rod-shaped particles 50 which may be used instead of spherical particles 48.
  • Fig. 6B illustrates tubules 52 which can be delivered in series through central lumen 20c.
  • Tubules 52 are preferably bioeluting polymeric materials to deliver an angiogenic agent to myocardium 24 over a period of time.
  • Tubules 52 also help to keep endocardial channels 32 from closing and allow blood to traverse their central lumens.
  • Other shapes of particles and elements for delivery of the agent can also be used.
  • a coil construction could be inserted into endocardial channels 32 to both help keep endocardial channels 32 open and minimize the obstruction of the walls of the channels, preferably within 24 hours of the channel formation, more preferably simultaneously with the channel formation. All such particles and elements are referred to collectively as controlled release element herein.
  • Fig. 7 shows an alternative embodiment in which a catheter 4d is shown to include a solid bundle of optical fibers 18 at its center and a compressible porous matrix 54 extending beyond the distal end 16 of catheter 4d. Porous matrix 54 contains the angiogenic agent so that after endocardial channels 32 are formed, pressing porous matrix 54 against endocardium 30 surrounding channel 32 causes the agent to flow into the channel .
  • Fig. 8 illustrates a further aspect of the invention practiced using a TMR technique.
  • Fig. 8 shows a section of myocardium 24 having myocardial channels 58 formed completely through myocardium 24.
  • Fig. 8 illustrates two different methods for delivering angiogenic agent into channels 58.
  • One way is to use a syringe 60 following the formation of channels 58. This is possible with this type of technique because epicardium 38 is exposed and visible to the physician so that the openings into channels 58 at the epicardium 38 are visible to permit proper placement of syringe needle 62.
  • Syringe needle 62 could also be totally or partially blocked at its distal end and have a set of side openings to allow the agent to be dispensed into the channels.
  • a slow-release gel for example a pluronic gel 64, can be painted over the openings channels 58 formed in epicardium 38. This permits the slow release of an angiogenic agent into channels 58 as is desired.
  • a time-released patch not shown, could be used over the openings to channels 58 formed in epicardium 38.
  • an agent can be introduced into the pericardial space surrounding the heart after channels have been formed into the epicardium.
  • the angiogenic or other factor can then reach the target myocardial channels through the left ventricle and initiate the desired angiogenesis.
  • this use of system angiogenic factor delivery may be less preferred, because of both reduced delivery to the myocardium and an increased risk of side effects because of the higher amounts of agent that would likely be employed.
  • catheter assembly 2 for a PMR procedure proceeds generally as follows.
  • Distal end 16 is passed percutaneously into the vascular system of the patient, through aorta 28, retrograde across the aortic valve, into the left ventricle 26 and to a target site against endocardium 30.
  • Laser energy source 8 is then activated to cause laser energy to exit optical fibers 18 to ablate or burn endocardial channels 32 into myocardium 24.
  • agent source 10 supplies an agent, typically an agent containing an angiogenic factor, into newly formed endocardial channel 32.
  • Distal end 16 is then repositioned to a new target site along endocardium 30 and the process is repeated.
  • arterioles 34 is promoted as suggested in Figs. 3A and 3B to provide oxygenated blood to myocardium 24 both from left ventricle 26 and typically from coronary artery 36 bypassing blockage 47.
  • channels 32 may be formed, for example, using ultrasound, radio frequency energy, microwave energy, drills or puncturing elements such as needles, in place of or in addition to laser energy.

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Abstract

L'invention porte sur un procédé d'administration transmurale de médicaments consistant, d'une manière générale, à ouvrir un canal pénétrant dans la surface du tissu puis à introduire le médicament dans le canal. La méthode préférée favorisant l'angiogenèse du myocarde consiste d'abord à ouvrir des canaux (32) dans l'endocarde (30) depuis l'intérieur du ventricule gauche (26), puis à introduire dans les canaux le facteur angiogène qui favorise la croissance de nouvelles artérioles (34) dans le myocarde (24). Les nouvelles artérioles qui se forment dans le myocarde relient les canaux entre eux et aux artères coronaires (36). De ce fait, le sang du ventricule gauche passe directement dans le myocarde et des voies d'écoulement peuvent se former autour des obstructions (47) des coronaires qui réduisent ou suppriment l'ischémie du myocarde. L'invention permet également d'introduire d'autres agents dans les tissus du myocarde ou dans les tissus d'autres organes.
PCT/US1997/013904 1996-08-08 1997-08-07 Procede et appareil d'administration transmurale de medicaments WO1998005307A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP97936444A EP0949910A4 (fr) 1996-08-08 1997-08-07 Procede et appareil d'administration transmurale de medicaments
AU39110/97A AU3911097A (en) 1996-08-08 1997-08-07 Transmural drug delivery method and apparatus

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US2374396P 1996-08-08 1996-08-08
US60/023,743 1996-08-08
US90699197A 1997-08-06 1997-08-06
US08/906,991 1997-08-06

Publications (1)

Publication Number Publication Date
WO1998005307A1 true WO1998005307A1 (fr) 1998-02-12

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PCT/US1997/013904 WO1998005307A1 (fr) 1996-08-08 1997-08-07 Procede et appareil d'administration transmurale de medicaments

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EP (1) EP0949910A4 (fr)
AU (1) AU3911097A (fr)
WO (1) WO1998005307A1 (fr)

Cited By (40)

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US5899915A (en) * 1996-12-02 1999-05-04 Angiotrax, Inc. Apparatus and method for intraoperatively performing surgery
US5910150A (en) * 1996-12-02 1999-06-08 Angiotrax, Inc. Apparatus for performing surgery
US5925012A (en) * 1996-12-27 1999-07-20 Eclipse Surgical Technologies, Inc. Laser assisted drug delivery
US5999678A (en) * 1996-12-27 1999-12-07 Eclipse Surgical Technologies, Inc. Laser delivery means adapted for drug delivery
US6010476A (en) * 1996-12-02 2000-01-04 Angiotrax, Inc. Apparatus for performing transmyocardial revascularization
WO1999049926A3 (fr) * 1998-03-31 2000-02-10 Cardiogenesis Corp Apport d'une substance angiogene
US6045565A (en) * 1997-11-04 2000-04-04 Scimed Life Systems, Inc. Percutaneous myocardial revascularization growth factor mediums and method
WO2000018462A2 (fr) 1998-09-30 2000-04-06 C.R. Bard, Inc. Dispositif d'alimentation en medicament administre par voie transthoracique
US6051008A (en) * 1996-12-02 2000-04-18 Angiotrax, Inc. Apparatus having stabilization members for percutaneously performing surgery and methods of use
US6067988A (en) * 1996-12-26 2000-05-30 Eclipse Surgical Technologies, Inc. Method for creation of drug delivery and/or stimulation pockets in myocardium
US6102926A (en) * 1996-12-02 2000-08-15 Angiotrax, Inc. Apparatus for percutaneously performing myocardial revascularization having means for sensing tissue parameters and methods of use
US6120520A (en) * 1997-05-27 2000-09-19 Angiotrax, Inc. Apparatus and methods for stimulating revascularization and/or tissue growth
WO2000067647A1 (fr) * 1999-05-07 2000-11-16 Boston Scientific Limited Appareil et procede associes a un bloc d'injection
US6152141A (en) * 1994-07-28 2000-11-28 Heartport, Inc. Method for delivery of therapeutic agents to the heart
US6165188A (en) * 1996-12-02 2000-12-26 Angiotrax, Inc. Apparatus for percutaneously performing myocardial revascularization having controlled cutting depth and methods of use
EP1071485A4 (fr) * 1998-03-27 2001-06-20 Brigham & Womens Hospital Methode et appareil permettant de combiner une therapie mise en oeuvre par formation d'une lesion et une administration de medicament
US6254573B1 (en) 1998-02-05 2001-07-03 Biosense, Inc. Intracardiac drug delivery device utilizing spring-loaded mechanism
US6319230B1 (en) 1999-05-07 2001-11-20 Scimed Life Systems, Inc. Lateral needle injection apparatus and method
US6344027B1 (en) 1999-12-08 2002-02-05 Scimed Life Systems, Inc. Needle-less injection apparatus and method
WO2002000278A3 (fr) * 2000-06-26 2002-04-04 Microheart Inc Procedes et dispositifs pour le traitement de tissus ischemiques
US6432119B1 (en) 1999-03-17 2002-08-13 Angiotrax, Inc. Apparatus and methods for performing percutaneous myocardial revascularization and stimulating angiogenesis using autologous materials
US6530914B1 (en) 2000-10-24 2003-03-11 Scimed Life Systems, Inc. Deflectable tip guide in guide system
US6551302B1 (en) 1997-09-24 2003-04-22 Michael J. Rosinko Steerable catheter with tip alignment and surface contact detector
US6554794B1 (en) 1997-09-24 2003-04-29 Richard L. Mueller Non-deforming deflectable multi-lumen catheter
US6582400B1 (en) 2000-10-24 2003-06-24 Scimed Life Systems, Inc. Variable tip catheter
US6591129B1 (en) 1996-02-15 2003-07-08 Biosense, Inc. Method for treating tissue through injection of a therapeutic agent
US6595958B1 (en) 2000-08-08 2003-07-22 Scimed Life Systems, Inc. Tortuous path injection device and method
US6613017B1 (en) 2000-08-08 2003-09-02 Scimed Life Systems, Inc. Controlled depth injection device and method
US6613026B1 (en) 1999-12-08 2003-09-02 Scimed Life Systems, Inc. Lateral needle-less injection apparatus and method
US6616626B2 (en) 2000-12-21 2003-09-09 Scimed Life Systems, Inc. Infusion devices and method
US6749617B1 (en) 1997-11-04 2004-06-15 Scimed Life Systems, Inc. Catheter and implants for the delivery of therapeutic agents to tissues
US6855160B1 (en) 1999-08-04 2005-02-15 C. R. Bard, Inc. Implant and agent delivery device
US6893421B1 (en) 2000-08-08 2005-05-17 Scimed Life Systems, Inc. Catheter shaft assembly
US6949117B2 (en) 1998-09-30 2005-09-27 C. R. Bard, Inc. Vascular inducing implants
US6986784B1 (en) 1999-05-14 2006-01-17 C. R. Bard, Inc. Implant anchor systems
US7051738B2 (en) 1996-07-28 2006-05-30 Uri Oron Apparatus for providing electromagnetic biostimulation of tissue using optics and echo imaging
US7147633B2 (en) 1999-06-02 2006-12-12 Boston Scientific Scimed, Inc. Method and apparatus for treatment of atrial fibrillation
US7204847B1 (en) 2000-07-28 2007-04-17 C. R. Bard, Inc. Implant anchor systems
US7211041B2 (en) 1999-05-07 2007-05-01 Boston Scientific Scimed, Inc. Apparatus and method for delivering therapeutic and diagnostic agents
US7232421B1 (en) 2000-05-12 2007-06-19 C. R. Bard, Inc. Agent delivery systems

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US5330467A (en) * 1992-04-10 1994-07-19 Abela George S Cell treatment apparatus and method

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Cited By (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6152141A (en) * 1994-07-28 2000-11-28 Heartport, Inc. Method for delivery of therapeutic agents to the heart
US6591129B1 (en) 1996-02-15 2003-07-08 Biosense, Inc. Method for treating tissue through injection of a therapeutic agent
US7051738B2 (en) 1996-07-28 2006-05-30 Uri Oron Apparatus for providing electromagnetic biostimulation of tissue using optics and echo imaging
US6051008A (en) * 1996-12-02 2000-04-18 Angiotrax, Inc. Apparatus having stabilization members for percutaneously performing surgery and methods of use
US6102926A (en) * 1996-12-02 2000-08-15 Angiotrax, Inc. Apparatus for percutaneously performing myocardial revascularization having means for sensing tissue parameters and methods of use
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EP0949910A1 (fr) 1999-10-20
AU3911097A (en) 1998-02-25
EP0949910A4 (fr) 2001-01-17

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