Delivery of a sympatholytic cardiovascular agent to the central nervous system to counter heart failure and pathologies associated with heart failure

• US 7,232,435 B2
• Filed: 02/06/2004
• Issued: 06/19/2007
• Est. Priority Date: 02/06/2004
• Status: Expired due to Fees

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Ujhelyi, Michael R., Zhou, Xiaohong, Sigg, Daniel C., Page, Linda M., Hildebrand, Keith R.
• Primary Examiner(s): Sirmons; Kevin C.
• Assistant Examiner(s): WITCZAK, CATHERINE
• Application Number:
  US10/773,965
• Publication Number:
  US 20050177135A1
• Time in Patent Office: 1,229 Days
• Field of Search: 604/82, 604/508, 604/890.1, 604/891.1, 604/892.1, 604/500, 604/503, 604/66, 424/426, 128/898
• US Class Current: 604/891.1
• CPC Class Codes: A61M 2005/14208 with a programmable infusion control system, characterised by the infusion program
• CPC Class Codes: A61M 2205/3523 using telemetric means
• CPC Class Codes: A61M 2230/00 Measuring parameters of the user
• CPC Class Codes: A61M 2230/04 Heartbeat characteristics, e.g. ECG, blood pressure modulation
• CPC Class Codes: A61M 2230/63 Motion, e.g. physical activity
• CPC Class Codes: A61M 5/142 Pressure infusion, e.g. using pumps
• 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 1/3962 in combination with another heart therapy
• CPC Class Codes: A61N 1/39622 Pacing therapy

Abstract

A sympatholytic cardiovascular agent delivered by a drug delivery pump to a central nervous system site to alleviate symptoms and otherwise treat heart failure (HF) and pathologies associated with HF. The drug delivery pump can be external or implantable infusion pump (IIP) coupled with a drug infusion catheter extending to the site. A patient activator can command delivery of a dosage and/or an implantable heart monitor (IHM) coupled with a sensor can detect physiologic parameters associated with HF (or pathologies associated with HF) and trigger dosage delivery. The IIP and IHM can be combined into a single implantable medical device (IMD) or can constitute separate IMDs that communicate by any of known communication mechanisms. The sympatholytic cardiovascular agent is one of the group consisting of an alpha-adrenergic agonist and an alpha2-adrenergic agonist, e.g., clonidine, p-aminoclonidine, guanabenz, lidamidine, tizanidine, moxonidine, methyldopa, xylazine, guanfacine, detomidine, medetomidine, and dexmedetomidine.

Claims

1. A method of delivering a drug dosage from a drug dispenser to receptors of the central nervous system of a patient'"'"'s body to therapeutically treat one of pre-existing symptoms of heart failure (“

HF”

) and pre-existing pathologies associated with HF, the method comprising the steps of;

surgically implanting a drug infusion catheter with a distal drug delivery portion disposed at a predetermined central nervous system site;

coupling a proximal end of the drug infusion catheter to a drug delivery pump;

monitoring the patient for at least one pre-existing of symptoms of HF and pre-existing pathologies associated with HF; and

in response to a positive detection of one pre-existing of HF and pre-existing pathologies associated with HF, operating the drug delivery pump to discharge a predetermined dosage of a sympatholytic cardiovascular agent to a central nervous system site effective to alleviate at least one of the pre-existing symptoms of HF and the pre-existing pathologies associated with HF.

2. A method according to claim 1, further comprising:

surgically implanting a physiologic sensor in the patient'"'"'s body;

operating the physiologic sensor to derive a physiologic parameter associated with HF or a pathology associated with HF; and

adjusting the dosage as a function of the monitored physiologic parameter associated with HF or a pathology associated with HF.

3. A method according to claim 2, wherein the physiologic sensors comprise one or more of an EGM sensor, a patient activity sensor, a cardiac mechanical function metric determining sensor, a blood chemistry sensor, an arterial, venous or heart chamber blood pressure sensor, a blood temperature sensor, a neural activity sensor, and a molecular probe.

4. A method according to claim 3, wherein the operating step further comprises determining one or more of heart rate, heart rate variability, and aberrations in the PQRST segment include changes in morphology, ST segment elevation, electrical alternans, and interval changes associated with HF or a pathology associated with HF.

5. A method according to claim 4, wherein the sympatholytic agent comprises one of the group consisting of an alpha-adrenergic agonist and an alpha2-adrenergic agonist.

6. A method according to claim 4, wherein the sympatholytic agent consists of clonidine.

7. A method according to claim 3, wherein the sympatholytic agent comprises one of the group consisting of an alpha-adrenergic agonist and an alpha2-adrenergic agonist.

8. A method according to claim 3, wherein the sympatholytic agent consits of clonidine.

9. A method according to claim 2, wherein the sympatholytic agent comprises one of the group consisting of an alpha-adrenergic agonist and an alpha2-adrenergic agonist.

10. A method according to claim 2, wherein the sympatholytic agent consists of clonidine.

11. A method according to claim 1, wherein the sympatholytic agent comprises one of the group consisting of an alpha-adrenergic agonist and an alpha2-adrenergic agonist.

12. A method according to claim 11, wherein the physiologic sensors comprise one or more of an EGM sensor, and the operating step further comprises determining one or more of heart rate, heart rate variability, and aberrations in the PQRST segment include changes in morphology, ST segment elevation, electrical alternans, and interval changes associated with HF or a pathology associated with HF.

13. A method according to claim 1, wherein the sympatholytic agent consists of clonidine.

14. A method according to claim 13, wherein the physiologic sensors comprise one or more of an EGM sensor, and the operating step further comprises determining one or more of heart rate, heart rate variability, and aberrations in the PQRST segment include changes in morphology, ST segment elevation, electrical alternans, and interval changes associated with HF or a pathology associated with HF.

15. A method according to claim 1, wherein the sympatholytic cardiovascular agent is preferably delivered into the central nervous system accessed at one of:

the sub-arachnoid space;

the sub-arachnoid space of the spinal cord;

the sub-arachnoid space of the thoracic spinal cord;

the sub-arachnoid space between the first and fifth thoracic vertebrae;

the sympathetic preganglionic cell bodies located in the intermediolateral cell column of the spinal cord;

the preganglionic sympathetic neurons which provide innervation to the heart; and

the preganglionic sympathetic neurons which provide innervation to the kidneys.

16. A method according to claim 15, wherein the sympatholytic agent comprises one of the group consisting of an alpha-adrenergic agonist and an alpha2-adrenergic agonist.

17. A method according to claim 15, wherein the sympatholytic agent comprises one of the group consisting of clonidine, p-aminoclonidine, guanabenz, lidamidine, tizanidine, moxonidine, methyldopa, xylazine, guanfacine, detomidine, medetomidine, dexmedetomidine, lidocaine, bupivacaine, and ropivacaine.

18. A method according to claim 1, wherein the drug delivery pump comprises an externally worn drug pump coupled to the proximal end of the drug infusion catheter.

19. A method according to claim 18, further comprising:

surgically implanting a physiologic sensor in the patient'"'"'s body;

operating the physiologic sensor to derive a physiologic parameter associated with HF or a pathology associated with HF; and

adjusting the dosage as a function of the monitored physiologic parameter associated with HF or a pathology associated with HF.

20. A method according to claim 18, wherein the sympatholytic agent comprises one of the group consisting of an alpha-adrenergic agonist and an alpha2-adrenergic agonist.

21. A method according to claim 18, wherein the sympatholytic agent comprises one of the group consisting of clonidine, p-aminoclonidine, guanabenz, lidamidine, tizanidine, moxonidine, methyldopa, xylazine, guanfacine, detomidine, medetomidine, dexmedetomidine lidocaine, bupivacaine, and ropivacaine.

22. A method according to claim 1, wherein the drug delivery pump comprises an implantable infusion pump coupled to the proximal end of the drug infusion catheter.

23. A method according to claim 22, further comprising:

surgically implanting a physiologic sensor in the patient'"'"'s body;

operating the physiologic sensor to derive a physiologic parameter associated with HF or a pathology associated with HF; and

adjusting the dosage as a function of the monitored physiologic parameter associated with HF or a pathology associated with HF.

24. A method according to claim 23, further comprising providing the patient with a patient activator whereby the operating step comprises operating the patient activator to command the delivery of a dosage of the sympatholytic cardiovascular agent to a the central nervous system site.

25. A method according to claim 22, further comprising providing the patient with a patient activator whereby the operating step comprises operating the patient activator to command the delivery of a dosage of the sympatholytic cardiovascular agent to a the central nervous system site.

26. A method according to claim 22, wherein the sympatholytic agent comprises one of the group consisting of an alpha-adrenergic agonist and an alpha2-adrenergic agonist.

27. A method according to claim 22, wherein the sympatholytic agent consists of clonidine.

28. A method according to claim 1 wherein the central nervous system site comprises one of:

the sub-arachnoid space;

the sub-arachnoid space of the spinal cord;

the sub-arachnoid space of the thoracic spinal cord;

the sub-arachnoid space between the first and fifth thoracic vertebrae;

the sympathetic preganglionic cell bodies located in the intermediolateral cell column of the spinal cord;

the preganglionic sympathetic neurons that provide innervation to the heart; and

the preganglionic sympathetic neurons that provide innervation to the kidneys.

29. A method according to claim 28, wherein the sympatholytic agent comprises one of the group consisting of an alpha-adrenergic agonist and an alpha2-adrenergic agonist.

30. A method according to claim 28, wherein the sympatholytic agent consists of clonidine.

31. A method according to claim 28, wherein the sympatholytic agent comprises clonidine delivered from into the central nervous system by continuous intrathecal infusion at a dosage of 0.01 to 1.0 mg/day.

32. A method according to claim 28, wherein the sympatholytic agent comprises clonidine delivered from into the central nervous system by continuous intrathecal infusion at a dosage of 0.01 to 1.0 mg/day.

33. A method according to claim 28, wherein the sympatholytic agent comprises clonidine delivered from into the central nervous system by continuous intrathecal infusion at a dosage of 50 to 500 mcg/day.

34. A method according to claim 28, wherein the sympatholytic agent comprises clonidine delivered from into the central nervous system by continuous intrathecal infusion at a dosage of 100 to 400 mcg/day.

35. A method according to claim 1, wherein the sympatholytic agent comprises clonidine delivered from into the central nervous system by continuous intrathecal infusion at a dosage of 0.01 to 1.0 mg/day.

36. A method according to claim 1, wherein the sympatholytic agent comprises clonidine delivered from into the central nervous system by continuous intrathecal infusion at a dosage of 50 to 500 mcg/day.

37. A method according to claim 1, wherein the sympatholytic agent comprises clonidine delivered from into the central nervous system by continuous intrathecal infusion at a dosage of 100 to 400 mcg/day.