Abstract: Light generating devices for illuminating portions of vascular tissue, to render photodynamic therapy. In one embodiment, a light source array preferably including a plurality of light emitting diodes, a focusing lens, and a light diffusing element are included in a distal end of a catheter. A balloon is optionally provided to interrupt blood flow that can block the transmission of light, and to center the apparatus in a blood vessel. Optical fibers optionally direct light from the light source to the diffusing element. The light source array can have a radial or linear configuration and can produce more than one wavelength of light for activating different photoreactive agents. Linear light source elements are particularly useful to treat elongate portions of tissue in a vessel. One embodiment intended for use with a conventional balloon catheter integrates light sources into a guidewire.

Abstract: The present invention relates to novel substituted indole compounds that are antagonists of alpha V (?v) integrins, for example ?v?3 and ?v?5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by ?v?3 and ?v?5 integrins, including such conditions as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, and rheumatoid arthritis. The compounds have the general formula: where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, D, X, W, a, m, n, i, j, k and v are defined herein.

Abstract: A light generating device for illuminating tissue adjacent to a body lumen while a distal end of the device is centered in the lumen, to render photodynamic therapy. The device can either occlude or displace bodily fluid, both without the use of a balloon. In one embodiment, a flushing lumen has a port adjacent to an array of light sources, to displace bodily fluid that might otherwise absorb light. Another embodiment employs a centering member that moves between a first position and a second position. The centering member centers the device in the lumen and preferably is formed of a shape memory material. In yet another embodiment, the device includes an outer sheath and an inner member that are independently positionable, enabling the centering member to be selectively positionable. The centering member can be non porous, such that the centering member also occludes fluid flow.

Abstract: Light generating devices for illuminating portions of vascular tissue to administer photodynamic therapy, and usable with, or including a distal protection device. A first device includes a hollow tip, a flushing lumen, a guidewire lumen, and at least one of a light source, and a hollow light transmissive shaft that is adapted to accommodate a light source. If desired, the device can include a balloon, so that a portion of a body lumen between the balloon and the distal protection device is isolated when the balloon is inflated. A second device includes inner and outer catheters, the outer catheter including a balloon, and the inner catheter including a light source and distal protection device comprising a shape memory polymer. Yet another device is a catheter having two balloons and a sleeve extending therebetween. Within the sleeve, the catheter includes a light source and an expanding member.

Abstract: The present invention relates to novel substituted indole compounds that are antagonists of alpha V (?v) integrins, for example ?v?3 and ?v?5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by ?v?3 and ?v?5 integrins, including such conditions as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, and rheumatoid arthritis. The compounds have the general formula: where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, D, X, W, a, m, n, i, j, k and v are defined herein.

Abstract: A rotational ablation atherectomy device including a flexible drive shaft and a compressible burr that may be inserted and extracted from a patient using a catheter having a diameter that is smaller than the operational diameter of the burr. In one embodiment, the burr includes a nose portion coupled to the drive shaft and one or more flexible abrasive disks disposed rearwardly from the nose portion. The flexible disks are foldable to be slidably received within a catheter. In another embodiment, the burr includes a support member coupled to the drive shaft, the support member having a resilient panel that spirals outwardly, forming a generally cylindrical ablation surface. The flexible panel can be elastically urged toward the support member and slidably inserted into the catheter. In a third embodiment, the burr includes a plurality of struts that are coupled to the drive shaft. An elastically compressible body disposed between the struts permits the struts to flex inwardly to reduce the burr diameter.

Abstract: 3-substituted-6-aryl pyridines of Formula I are provided: 1

Abstract: An intravascular device and methods for forming multiple percutaneous myocardial revascularization (PMR) holes in a heart chamber wall simultaneously. One device includes a basket formed of flexible arms carrying cutting probes over their length. The basket arms are outwardly arcuately biased so as to assume an outwardly bowed, arcuate shape when unconstrained. The device includes an inner shaft distally secured to a proximal portion of the basket and slidably disposed within an outer shaft. The inner shaft and collapsed basket can be retracted within the outer shaft, delivered intravascularly to the left ventricle, and distally advanced, forcing the basket to assume the bowed shape. Radio frequency current supplied to the electrical cutting probes burn holes into the ventricle wall and myocardium. One embodiment has high pressure fluid jet cutting means. Another embodiment uses a basket as an anchor to position a steerable cutting probe.

Abstract: A combination catheter includes an ultrasound transducer and RF ablation electrode. The ultrasound transducer transmits ultrasound signals into and receives echo signals from a vessel. The echo signals are processed and used to produce an image of the tissue surrounding the catheter. A driveshaft rotates the ultrasound transducer to obtain a 360° view of the vessel wall. At the distal end of the driveshaft is an electrode. An RF generator is electrically coupled to the driveshaft to deliver RF energy to the electrode at the distal end of the driveshaft to ablate occluding material in the vessel. The electrode may have a variety of tip shapes including concave, roughened, or expandable configurations, depending on the size of the vessel and composition of the occluding material to be ablated.

Abstract: A system for ablating material in vein grafts includes an ablation burr that is rotated by a driveshaft. The ablation burr preferably includes one or more channels, blades or other mechanisms that direct ablated material and liquid proximally and/or outwardly against a vessel wall. Aspiration is used to remove ablated material and liquid from the treatment area. Finally, methods for treating vein grafts and original native arteries are disclosed.

Abstract: A system for recanalizing an occluded blood vessel including a centering catheter employed to center an ablative guide wire within the blood vessel as the guide wire traverses the occlusion. The centering catheter includes a catheter body with an operative lumen through which the ablative guide wire is slidingly disposed. The centering catheter further includes a distally disposed centering mechanism that, when activated, centers the ablative guide wire within the blood vessel as it traverses the occlusion. The centering mechanism can comprise various embodiments including a single inflatable balloon or segmented inflatable balloon, which is in fluid communication with an inflation lumen. An airless preparation lumen may be disposed within the inflation lumen for ease of centering catheter preparation. The ablative guide wire includes insulation that is preferably formed of heat shrink tubing, which is stretched prior or concurrently with the heating process.

Abstract: An RF ablation system includes a catheter and an RF electrode that delivers RF electrical energy to the site of an occlusion. The system includes a mechanism for minimizing the likelihood that RF electrical energy will be applied directly to the vessel wall. In one embodiment of the invention, the catheter includes a number of tissue expanding jaws to engage a vessel wall and push the vessel wall away from the electrode to shield vessel walls from the electrode. In yet another embodiment of the invention, the electrode has a spiraled distal end with a radius that is larger than the radius of the catheter, such that the electrode engages the vessel wall and pushes the wall away from a conducting portion of the electrode. The portion of the electrode that engages the vessel wall is preferably coated with an insulating material to prevent delivery of RF electrical energy directly to the vessel wall.

Abstract: A system for performing fluid jet myocardial revascularization includes a catheter having a proximal region, a distal region, a lumen extending therethrough and a valve disposed in the lumen for allowing the passage of fluids in the lumen to create holes in the myocardium. A valve control means extends through the proximal region of the catheter to open and close the valve. In one embodiment, the valve also includes a biasing mechanism for biasing the valve in a closed position. The valve may be controlled using an electrically actuated device that is heated with an electrical current to open and close the valve. In one embodiment of the invention, the catheter has a wall that can be expanded within a guide catheter to anchor the catheter during revascularization.

Abstract: An improved guide wire brake that is particularly suited to ablative rotational atherectomy devices is disclosed. The guide wire brake ensures that a guide wire is prevented from rotating or moving axially prior to activation of a primary mover such as a turbine. In one embodiment a pressure relief valve delays the activation of the prime mover on start up, and a check valve delays the release of the guide wire brake on shut down. In a second embodiment the guide wire brake is serially connected to the prime mover such that the prime mover is not connected to the pressurized gas source until after the guide wire brake is engaged. In a third embodiment a guide wire is disposed through a flexible tube within a rigid cylinder that is serially connected to the prime mover, such that when pressurized gas is provided to the prime mover the flexible tube will collapse on the guide wire, to prevent guide wire movement.

Abstract: Infusion liquid is expelled distally of an ablation burr for washing a blood vessel lesion being treated by the burr. The infusion liquid can be aspirated in a proximate direction to carry the infusion liquid and loose ablated particles of the lesion away from the treatment area. The infusion liquid can be supplied through one or more passages in the burr, In addition to distally extending passages, the burr can include transverse passages extending at least partly in a proximate direction, with the distally extending and proximately extending passages sized so that only a minor portion of the infusion liquid is expelled distally.

Abstract: The present invention relates to novel substituted indole compounds that are antagonists of alpha V (&agr;v) integrins, for example &agr;v&bgr;3 and &agr;v&bgr;5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by &agr;v&bgr;3 and &agr;v&bgr;5 integrins, including such conditions as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, and rheumatoid arthritis.

Abstract: A rotational ablation atherectomy device including a flexible drive shaft and a compressible burr that may be inserted and extracted from a patient using a catheter having a diameter that is smaller than the operational diameter of the burr. In one embodiment, the burr includes a nose portion coupled to the drive shaft and one or more flexible abrasive disks disposed rearwardly from the nose portion. The flexible disks are foldable to be slidably received within a catheter. In another embodiment, the burr includes a support member coupled to the drive shaft, the support member having a resilient panel that spirals outwardly, forming a generally cylindrical ablation surface. The flexible panel can be elastically urged toward the support member and slidably inserted into the catheter. In a third embodiment, the burr includes a plurality of struts that are coupled to the drive shaft. An elastically compressible body disposed between the struts permits the struts to flex inwardly to reduce the burr diameter.

Abstract: Devices and methods for performing myocardial revascularization using fluid jets. Devices can include a pressurized fluid source coupled through fluid supply lumens to a distal-most nozzle disposed on the distal end of the catheter. Some devices have separate myocardial revascularization catheters disposed within guide catheters, while other devices have unitary devices including a generally steerable myocardial revascularization catheter shaft. Preferred embodiments include a distally disposed control valve. One valve is controlled using an electrically actuated device, another valve is controlled using a low-pressure control fluid, while yet another device valve is controlled using an axially slidable activation wire. The fluid valve can include a biasing spring to shut the valve and preclude fluid flow, with the bias opposed by a user-applied fluid, mechanical, or electrical force.

Abstract: Infusion liquid is expelled distally of an ablation burr for washing a blood vessel lesion being treated by the burr. The infusion liquid can be aspirated in a proximate direction to carry the infusion liquid and loose ablated particles of the lesion away from the treatment area. The infusion liquid can be supplied through one or more passages in the burr. In addition to distally extending passages, the burr can include transverse passages extending at least partly in a proximate direction, with the distally extending and proximately extending passages sized so that only a minor portion of the infusion liquid is expelled distally.

Abstract: A combination catheter includes an ultrasound transducer and RF ablation electrode. The ultrasound transducer transmits ultrasound signals into and receives echo signals from a vessel. The echo signals are processed and used to produce an image of the tissue surrounding the catheter. A driveshaft rotates the ultrasound transducer to obtain a 360° view of the vessel wall. At the distal end of the driveshaft is an electrode. An RF generator is electrically coupled to the driveshaft to deliver RF energy to the electrode at the distal end of the driveshaft to ablate occluding material in the vessel. The electrode may have a variety of tip shapes including concave, roughened, or expandable configurations, depending on the size of the vessel and composition of the occluding material to be ablated. Alternatively, the RF ablation energy may be delivered to a guidewire that is used to route the ultrasound catheter through a patient's vasculature.