Monitoring, preventing, and treating rejection of transplanted organs

• US 6,970,741 B1
• Filed: 09/17/2002
• Issued: 11/29/2005
• Est. Priority Date: 09/18/2001
• Status: Expired due to Fees

• Current Assignee: Boston Scientific Neuromodulation Corporation (Boston Scientific Corporation)
• Original Assignee: Advanced Bionics Corporation (Sonova Holding AG)
• Inventors: Whitehurst, Todd K., Thacker, James R., McGivern, James P., McClure, Kelly H., Marnfeldt, Goran N.
• Primary Examiner(s): LAYNO, CARL HERNANDZ
• Application Number:
  US10/246,554
• Time in Patent Office: 1,169 Days
• Field of Search: 607 1- 3, 607/40, 607/50, 607/61, 607/63, 607/116, 128897-899, 600/547
• US Class Current: 607/3
• CPC Class Codes: A61B 2560/0219 of externally powered implanted units
• CPC Class Codes: A61B 5/053 Measuring electrical impedance or conductance of a portion of the body
• CPC Class Codes: A61B 5/0538 invasively, e.g. using a catheter
• CPC Class Codes: A61B 5/41 Detecting, measuring or recording for evaluating the immune or lymphatic systems
• CPC Class Codes: A61B 5/413 Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant
• CPC Class Codes: A61B 5/415 the glands, e.g. tonsils, adenoids or thymus
• CPC Class Codes: A61B 5/416 the spleen
• CPC Class Codes: A61B 5/418 lymph vessels, ducts or nodes
• CPC Class Codes: A61B 5/4244 liver
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: A61N 1/30 Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
• CPC Class Codes: A61N 1/32 alternating or intermittent currents applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02

Abstract

An implantable system control unit (SCU) includes means for measuring tissue impedance or other condition to determine allograft health, in order to predict or detect allograft rejection. The SCU also includes at least two electrodes coupled to means for delivering electrical stimulation to a patient within whom the device is implanted, and may also include a reservoir for holding one or more drugs and a driver means for delivering the drug(s) to the patient. In certain embodiments, the system is capable of open- and closed-loop operation. In closed-loop operation, at least one SCU includes a sensor, and the sensed condition is used to adjust stimulation parameters. Alternatively, this sensory “SCU” sounds an alarm, communicates an alarm to an external device, and/or is responsive to queries regarding sensed information, such as tissue impedance.

Claims

1. A method for treating a patient with an allograft, comprising:

providing at least one microstimulator having at least two electrodes, the at least one microstimulator capable of implantation via a cannula;

implanting the at least one microstimulator in or near an allograft;

providing operating power to the at least one microstimulator;

providing stimulation parameters to the at least one microstimulator; and

delivering electrical stimulation via the at least two electrodes to allograft tissue adjacent to the at least two electrodes in accordance with the stimulation parameters.

2. The method of claim 1 wherein providing operating power comprises utilizing at least one of an external power source electromagnetically coupled to the microstimulator, a self-contained power source utilizing a primary battery, and a self-contained power source utilizing a replenishable battery.

3. The method of claim 1 wherein providing stimulation parameters comprises utilizing at least one of parameters preprogrammed into the microstimulator, parameters transmitted to the microstimulator after implantation, and parameters controlled by a sensing device.

4. The method of claim 1 further comprising:

providing in the at least one microstimulator a pump coupled to an infusion outlet;

containing at least one drug in the at least one pump; and

delivering the at least one drug via the at least one outlet to allograft tissue adjacent to the at least one infusion outlet in accordance with the stimulation parameters.

5. The method of claim 1 further comprising providing and implanting more than one microstimulator.

6. The method of claim 5 further comprising communicating and coordinating the stimulation provided by the more than one microstimulator.

7. The method of claim 1 further comprising:

providing at least one sensor;

using the at least one sensor to sense a physical condition; and

adjusting the stimulation parameters based at least in part upon the sensed condition.

8. The method of claim 7 wherein the at least one sensor is a part of the microstimulator.

9. The method of claim 7 further comprising sensing impedance.

10. A method for treating a patient with an allograft, comprising:

providing at least one system control unit (SCU) having a pump coupled to an infusion outlet;

implanting the at least one SCU in or near an allograft;

containing as a substance in the at least one pump at least one of a drug used to promote angiogenesis, a gene that encodes a protein that leads to angiogenesis, and a gene product that leads to angiogenesis;

providing operating power to the at least one SCU;

providing stimulation parameters to the at least one SCU; and

delivering the substance via the at least one outlet to allograft tissue adjacent to the at least one SCU in accordance with the stimulation parameters;

wherein the at least one SCU has a size and shape suitable for placement entirely within the neoplasm and implantation via a cannula.

11. The method of claim 10 wherein the at least one drug includes at least one of VEGF, FGF, and phVEGF.

12. A method for treating a patient with an allograft, comprising:

providing at least one system control unit (SCU) having a pump coupled to an infusion outlet;

implanting the at least one SCU in or near an allograft;

containing as a substance in the at least one pump at least one of a drug used to promote angiogenesis, a gene that encodes a protein that leads to angiogenesis, and a gene product that leads to angiogenesis;

providing operating power to the at least one SCU;

providing stimulation parameters to the at least one SCU; and

delivering the substance via the at least one outlet to allograft tissue adjacent to the at least one SCU in accordance with the stimulation parameters;

wherein the substance further comprises at least one of a corticosteroid, cyclosporine, FK506, azathioprine, mycophenolate mofetil, daclizumab, basiliximab, nicotine receptor agonist, a gene that leads to suppression of allograft rejection, and a gene product that leads to suppression of allograft rejection.

13. A method for treating a patient with an allograft, comprising:

providing at least one system control unit (SCU) having a pump coupled to an infusion outlet;

implanting the at least one SCU in or near an allograft;

containing as a substance in the at least one pump at least one of a drug used to promote angiogenesis, a gene that encodes a protein that leads to angiogenesis, and a gene product that leads to angiogenesis;

providing operating power to the at least one SCU;

providing stimulation parameters to the at least one SCU;

delivering the substance via the at least one outlet to allograft tissue adjacent to the at least one SCU in accordance with the stimulation parameters;

providing at least one sensor;

using the at least one sensor to sense a physical condition; and

adjusting the stimulation parameters based at least in part upon the sensed condition.

14. The method of claim 13 wherein the at least one sensor is a part of the SCU.

15. A method for treating a patient with an allograft, comprising:

providing at least one system control unit (SCU) having a pump coupled to an infusion outlet;

implanting the at least one SCU in or near an allograft,

containing as a substance in the at least one pump at least one of a drug used to promote angiogenesis, a gene that encodes a protein that leads to angiogenesis, and a gene product that leads to angiogenesis,

providing operating power to the at least one SCU,

providing stimulation parameters to the at least one SCU,

delivering the substance via the at least one outlet to allograft tissue adjacent to the at least one SCU in accordance with the stimulation parameters; and

providing and implanting more than one SCU.

16. A method for treating a patient with an allograft, comprising:

providing at least one means for stimulating tissue;

implanting the at least one stimulating means in or near an allograft;

providing operating power to the at least one stimulating means;

providing stimulation parameters to the at least one stimulating means; and

delivering stimulation to allograft tissue adjacent to the at least one stimulating means according to the stimulation parameters,

wherein the stimulation comprises both electrical stimulation and stimulation via at least one drug; and

wherein the at least one stimulating means has a size and shape suitable for placement entirely within the allograft and for implantation via a cannula.

17. The method of claim 16, further comprising:

providing at least one sensor;

using the sensor to sense a physical condition; and

determining stimulation parameters based at least in part upon the sensed condition.

18. The method of claim 17 wherein the at least one sensor is a part of the stimulator.

19. The method of claim 17 wherein the sensed physical condition includes level or change in level of at least one of impedance, inflammation, necrosis, volume, pressure, oxygen, pH, EMG, ECG, a neurotransmitter, a neurotransmitter breakdown product, a medication, a hormone, an enzyme, an interleukin, a cytokine, a lymphokine, a chemokine, a growth factor, a medication, a blood plasma substance, and a body fluid.

20. The method of claim 16 wherein the stimulation parameters are determined using at least one external appliance.

21. The method of claim 18 wherein the stimulation parameters are determined by the at least one stimulator.

22. The method of claim 18 further comprising providing and implanting more than one stimulator.

23. A method for treating a patient with an allograft comprising:

providing at least one means for stimulating tissue;

implanting the at least one stimulating means in or near an allograft;

providing operating power to the at least one stimulating means;

providing stimulation parameters to the at least one stimulating means; and

delivering stimulation to allograft tissue adjacent to the at least one stimulating means according to the stimulation parameters;

wherein the stimulation comprises both electrical stimulation and stimulation via at least one drug,

wherein the at least one drug delivered to the allograft is at least one of a corticosteroid, cyclosporine. FK506, azathioprine, mycophenolate mofetil, daclizumab, basiliximab, nicotine receptor agonist, a gene that leads to suppression of allograft rejection, and a gene product that leads to suppression of allograft rejection; and

wherein the at least one drug further includes at least one of a medication used to promote angiogenesis or a gene that encodes a protein or other gene product that leads to angiogenesis.

24. The method of claim 23 wherein the at least one drug includes at least one of VEGF, FGF, and phVEGF.

25. A method for monitoring the health of an allograft prior to transplant, comprising:

providing at least one system control unit (SCU) having at least two electrodes;

placing the at least one SCU in or on an allograft prior to transplant;

providing operating power to the at least one SCU;

providing monitoring parameters to the at least one SCU; and

measuring electrical impedance of allograft tissue adjacent to the at least two electrodes in accordance with the monitoring parameters;

wherein the at least one SCU is placed entirely within the allograft.

26. A method for monitoring the health of an allograft, comprising:

providing at least one system control unit (SCU) with sensing capabilities;

implanting the at least one sensor SCU in or on an immune system organ;

measuring the health of the allograft by sensing changes in the immune system organ; and

communicating the sensed changes in the immune system organ.

27. The method of claim 26 further comprising:

providing at least one SCU with stimulation capabilities;

implanting the at least one stimulation SCU in or on an immune system organ;

stimulating the immune system organ as directed by stimulation parameters; and

adjusting the stimulation parameters in closed loop fashion based on the sensed changes in the immune system organ.

28. The method of claim 27 wherein the SCU with sensing capabilities and the SCU with stimulation capabilities are one SCU with both sensing and stimulation capabilities.

29. The method of claim 26 further comprising:

providing at least one SCU with stimulation capabilities;

implanting the at least one stimulation SCU in or on an allograft;

stimulating the allograft as directed by stimulation parameters; and

adjusting the stimulation parameters in closed loop fashion based on the sensed changes in the immune system organ.