Devices and methods to stimulate therapeutic angiogenesis for ischemia and heart failure

• US 20040186546A1
• Filed: 09/18/2002
• Published: 09/23/2004
• Est. Priority Date: 09/18/2002
• Status: Active Grant

• Current Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Original Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Inventors: Mandrusov, Evgenia, Salo, Rodney W., Consigny, Paul M.
• Granted Patent: US 7,400,931 B2
• Time in Patent Office: Days
• US Class Current: 607/122
• CPC Class Codes: A61N 1/056 Transvascular endocardial electrode systems
• CPC Class Codes: A61N 1/0568 with drug delivery
• CPC Class Codes: A61N 1/306 Arrangements where at least part of the apparatus is introduced into the body
• CPC Class Codes: A61N 1/326 for promoting growth of cells, e.g. bone cells
• CPC Class Codes: A61N 2001/0585 Coronary sinus electrodes

Abstract

A device that includes an electrical output channel adapted to deliver a sub-threshold voltage, a lead that includes a proximal end adapted to be electrically connected to the electrical output channel and a distal end adapted to be placed in the blood conduit where the distal end of the lead is adapted to deliver a treatment agent that stimulates therapeutic angiogenesis, and at least one electrode on the distal end of the first lead.

Claims

1. A device comprising:

an electrical output configured to deliver a sub-threshold voltage;

a lead comprising a proximal end configured to be electrically connected to the electrical output channel, and a distal end adapted to be placed in a blood conduit, wherein the distal end of the lead has dimensions suitable to deliver a treatment agent;

at least one electrode disposed near the distal end of the first lead.

2. The device of claim 1, wherein the electrical output is a first electrical output channel, further comprising:

a second electrical output channel adapted to deliver an above- threshold voltage.

3. The device of claim 1, wherein the electrical output is a first electrical output, further comprising:

a second electrical output channel adapted to deliver a sub-threshold voltage.

4. The device of claim 1, wherein the sub-threshold voltage is less than about 1.0 volts.

5. The device of claim 1, wherein the sub-threshold voltage is less than about 0.75 volts.

6. The device of claim 1, wherein the sub-threshold voltage is less than about 0.5 volts.

7. The device of claim 1, wherein the sub-threshold voltage is less than about 0.1 volts.

8. The device of claim 1, wherein the distal end of the first lead is located in a blood conduit selected from the group consisting of the coronary sinus, the great cardiac vein, the posterior vein of the left ventricle, the anterior interventricular vein, and the middle cardiac vein, and any other vein of sufficient size to place the first lead.

9. The device of claim 1, wherein the treatment agent is selected from the group consisting of poly (L-lactide), poly (D, L-lactide), poly (glycolide), poly (lactide-co-glycolide), polycaprolactone, polyanhydride, polydiaxanone, polyorthoester, polyamino acids, poly (trimethylene carbonare), bioresorbable inorganic compound, fibrin, gelatin, chitin, a bacterial polysaccharide, a metal, polyhydroxybutyratevalerate, a poly(oxy)ethylene, a polyurethane, a silicone, and combinations thereof.

10. The device of claim 1, wherein the treatment agent is selected from the group consisting of vascular endothelial growth factor, fibroblast growth factor, monocyte chemoattractant protein 1, transforming growth factor beta, transforming growth factor alpha, lipid factor, hypoxia-inducible factor 1-alpha, PR39, DEL 1, nicotine, insulin-like growth factor, placental growth factor, hepatocyte growth factor, estrogen, follistatin, proliferin, prostaglandin E1, prostaglandin E2, cytokine, tumor necrosis factor, erythropoietin, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, angiogenin, and mixtures and isoforms thereof.

11. The device of claim 1, wherein the treatment agent is selected form the group consisting of sol gel particles, calcium phosphate glass, iron, fibrin, gelatin, low molecular weight hyaluronic acid, chitin, bacterial polysaccharides, metals, and mixtures thereof.

12. The device of claim 1, wherein the distal end of the lead further comprises a lumen therethrough.

13. The device of claim 12, wherein the lumen comprises a treatment agent that stimulates therapeutic angiogenesis.

14. The device of claim 13, wherein the treatment agent is selected from the group consisting of poly (L-lactide), poly (D, L-lactide), poly (glycolide), poly (lactide-co-glycolide), polycaprolactone, polyanhydride, polydiaxanone, polyorthoester, polyamino acids, poly (trimethylene carbonare), bioresorbable inorganic compound, fibrin, gelatin, chitin, a bacterial polysaccharide, a metal, polyhydroxybutyratevalerate, a poly(oxy)ethylene, a polyurethane, a silicone, and combinations thereof.

15. The device of claim 1, further comprising a reservoir coupled to the lead and adapted to contain a treatment agent that stimulates therapeutic angiogenesis.

16. The device of claim 15, further comprising a means for delivering a treatment agent that stimulates therapeutic angiogenesis to the distal end of the lead.

17. The device of claim 15, further comprising a pump adapted to deliver a treatment agent that stimulates therapeutic angiogenesis to the distal end of the lead.

18. The device of claim 17, wherein the pump is osmotically operated.

19. The device of claim 17, wherein the pump is electrically operated.

20. The device of claim 1, wherein the lead comprises a first lead, the device further comprising a second lead adapted to be used for cardiac defibrillation.

21. The device of claim 20, wherein the second lead further comprises a treatment agent that stimulates angiogenesis, wherein the second lead is adapted to administer the treatment agent by electroporation.

22. The device of claim 1, wherein the lead comprises a first lead, further comprising a second lead comprising a proximal end adapted to be electrically connected to the device and a distal end adapted to be placed in a blood conduit;

at least one electrode on the distal end of the second lead;

wherein the first and second leads are adapted to create an electrical field to administer the treatment agent by iontophoresis.

23. The device of claim 22, wherein the first and second leads comprise different portions of one lead.

24. The device of claim 1, wherein the sub-threshold voltage of the first electrical output channel comprises a waveform, wherein the waveform is selected from the group consisting of sinusoidal, block, exponential decay, polynomial, power function, linear function, alternating current, direct current, step, and combinations thereof.

25. The device of claim 1, wherein the electrical output channel is configured to deliver a sub-threshold voltage and an above-threshold voltage in a modified waveform.

26. The device of claim 2, further comprising:

a second lead comprising a proximal end configured to be electrically connected to the second electrical output channel, and a distal end adapted to be placed in a blood conduit, and at least one electrode disposed at the distal end of the second lead;

wherein the at least one electrode disposed at the distal end of the first lead is placed in a vein in proximity to an infarcted region of a heart, and the at least one electrode disposed at the distal end of the second lead is placed in a second vein in proximity to the infarcted region of the heart, and a voltage is applied between the at least one electrode disposed at the distal end of the first lead, and the at least one electrode disposed at the distal end of the second lead so that a current flows in a direction across the infarcted region of the heart to stimulate therapeutic angiogenesis.

27. The device of claim 1, wherein the sub-threshold voltage is high enough to normally stimulate tissue, wherein the voltage is delivered to an infarcted region of a heart.

28. The device of claim 1, wherein the sub-threshold voltage is applied to a heart near an infarcted region to pre-excite the infarcted region, and the voltage comprises a waveform to produce therapeutic angiogenesis.

29. The device of claim 1, wherein the sub-threshold voltage comprises a waveform comprising an above-threshold voltage, that occurs during a time when a tissue of a heart is refractory to stimulation.

30. The device of claim 1, wherein the lead is adapted to be used for cardiac defibrillation.

31. A method for stimulating angiogenesis comprising:

positioning an electrode on a lead at a location in a blood vessel;

connecting the lead to an electrical output channel adapted to deliver a sub-threshold voltage;

activating the electrical output channel to deliver the sub-threshold voltage through the lead to the electrode; and

delivering a treatment agent adapted to stimulate therapeutic angiogenesis at the location.

32. The method of claim 31, further comprising positioning a second electrode on a second lead at a location in a blood vessel;

connecting the second lead to a second electrical output channel adapted to deliver an above-threshold voltage; and

activating the second electrical output channel to deliver the above- threshold voltage through the second lead and to the second electrode to stimulate heart beats.

33. The method of claim 31, further comprising activating the electrical output channel to deliver a voltage sufficient to achieve electroporation to facilitate delivery of the treatment agent, wherein the voltage is delivered through the lead to the electrode at the location.

34. The method of claim 31, further comprising activating the electrical output channel to deliver at least one of an above-threshold stimulation for pacing and an above-threshold stimulation for pre-excitation.

35. The method of claim 31, wherein the location comprises the first location and wherein the electrical output channel comprises the first electrical output channel, further comprising positioning a second electrode on a second lead at a second location in a blood vessel;

connecting the second lead to a second electrical output channel; and

activating the first and second electrical output channels to create an electrical field to facilitate delivery of the treatment agent by iontophoresis.

36. The method of claim 31, wherein the location comprises the first location and wherein the electrical output channel comprises the first electrical output channel, further comprising positioning a second electrode on a second lead at a second location in a blood vessel;

connecting the second lead to a second electrical output channel; and

activating the first and second electrical output channels to create an electrical field to facilitate delivery of the treatment agent by iontophoresis and cellular uptake by electroporation.

37. The method of one of claims 31, 33, or 34, further comprising a second electrode positioned on the lead adjacent to the first electrode.

38. The method of claim 35, further comprising activating at least one of the first and second electrical output channels to deliver an above-threshold stimulation for at least one of pacing and pre-excitation.

39. A device comprising:

a voltage source adapted to be implanted within a patient;

a lead comprising a proximal end coupled to the voltage source, and a distal end, wherein the distal end of the lead is adapted to deliver a treatment agent that stimulates therapeutic angiogenesis; and

an electrode on the distal end of the lead;

wherein the voltage source is to deliver a sub-threshold voltage to the electrode.