IP Library › Granted Patent US 12,285,615
Granted Patent B2
US 12,285,615 · App. 18/541,938 · Granted Apr 29, 2025

Neurostimulation titration process via adaptive parametric modification

Inventors: Imad Libbus (St. Paul, MN); Bruce H. KenKnight (Maple Grove, MN); Badri Amurthur (Los Gatos, CA); Scott R. Stubbs (Maple Grove, MN)
Assignee: LivaNova USA, Inc.
A61N1/36139A61B5/349A61B5/355A61N1/0551A61N1/36114A61N1/36132A61N1/3615A61N1/36167A61N1/3702A61N1/37223A61N1/37235G16H20/30G16H20/40G16H40/20G16H40/63G16Z99/00
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,285,615
App. No.
18/541,938
Granted
Apr 29, 2025
Kind
B2
Abstract

Systems and methods are provided for delivering neurostimulation therapies to patients. A titration process is used to gradually increase the stimulation intensity to a desired therapeutic level. Between titration sessions one or more parameters, such as, for example, an acclimation interval, may be adjusted based on the patient's response to the stimulation. This personalized titration process can minimize the amount of time required to complete titration so as to begin delivery of the stimulation at therapeutically desirable levels.

Claims (42)

1. A method of operating an implantable medical device (IMD) comprising:

delivering neurostimulation to a patient by the IMD, the neurostimulation comprising a plurality of stimulation parameters;

titrating the neurostimulation from an initial intensity toward a target intensity by modifying at least one of the stimulation parameters;

receiving an indication of intolerance to the neurostimulation;

in response to receiving the indication, modifying a first stimulation parameter to decrease an intensity of the neurostimulation;

determining that the first stimulation parameter has reached a maximum modification; and

in response to determining that the first stimulation parameter has reached the maximum modification, modifying a second stimulation parameter to decrease the intensity of the neurostimulation, the second stimulation parameter being different than the first stimulation parameter.

2. The method of claim 1 , wherein the stimulation parameters comprise current amplitude, pulse width, frequency, and duty cycle.

3. The method of claim 2 , wherein modifying the first stimulation parameter or the second stimulation parameter comprises decreasing at least one of the current amplitude or the pulse width.

4. The method of claim 1 , further comprising:

in response to receiving a plurality of additional indications of intolerance, modifying a third stimulation parameter to decrease the intensity of the neurostimulation, the third stimulation parameter being different from at least one of the first stimulation parameter or the second stimulation parameter.

5. The method of claim 1 , further comprising receiving, from an external programmer, a prescribed time window during which the intensity of the neurostimulation is increased, the prescribed time window excluding a period during which the patient is likely sleeping.

6. The method of claim 1 , wherein the indication of intolerance is received from the patient via a patient magnet.

7. The method of claim 1 , further comprising modifying an increment at which the neurostimulation is titrated based on a response of the patient to the neurostimulation.

8. A medical device for delivering neurostimulation comprising:

an implantable neurostimulator configured to:

deliver neurostimulation to a patient, the neurostimulation comprising a plurality of stimulation parameters;

titrate the neurostimulation from an initial intensity toward a target intensity by modifying at least one of the stimulation parameters;

receive an indication of intolerance to the neurostimulation;

in response to receiving the indication, modifying a first stimulation parameter to decrease an intensity of the neurostimulation;

determine that the first stimulation parameter has reached a maximum modification; and

in response to determining that the first stimulation parameter has reached the maximum modification, modify a second stimulation parameter to decrease the intensity of the neurostimulation, the second stimulation parameter being different than the first stimulation parameter.

9. The medical device of claim 8 , wherein the stimulation parameters comprise current amplitude, pulse width, frequency, and duty cycle.

10. The medical device of claim 9 , wherein the implantable neurostimulator is further configured to modify the first stimulation parameter or the second stimulation parameter by decreasing at least one of the current amplitude or the pulse width.

11. The medical device of claim 8 , wherein the implantable neurostimulator is further configured to, in response to receiving a plurality of additional indications of intolerance, modify a third stimulation parameter to decrease the intensity of the neurostimulation, the third stimulation parameter being different from at least one of the first stimulation parameter or the second stimulation parameter.

12. The medical device of claim 8 , wherein the implantable neurostimulator is further configured to receive, from an external programmer, a prescribed time window during which the intensity of the neurostimulation is increased, the prescribed time window excluding a period during which the patient is likely sleeping.

13. The medical device of claim 8 , wherein the indication of intolerance is received from the patient via a patient magnet.

14. The medical device of claim 8 , wherein the implantable neurostimulator is further configured to modify an increment at which the neurostimulation is titrated based on a response of the patient to the neurostimulation.

15. A system comprising:

a processor; and

a memory storing instructions that are executable by the processor to:

deliver neurostimulation to a patient, the neurostimulation comprising a plurality of stimulation parameters;

titrate the neurostimulation from an initial intensity toward a target intensity by modifying at least one of the stimulation parameters;

receive an indication of intolerance to the neurostimulation;

in response to receiving the indication, modify a first stimulation parameter to decrease an intensity of the neurostimulation;

determine that the first stimulation parameter has reached a maximum modification; and

in response to determining that the first stimulation parameter has reached the maximum modification, modify a second stimulation parameter to decrease the intensity of the neurostimulation, the second stimulation parameter being different than the first stimulation parameter.

16. The system of claim 15 , wherein the stimulation parameters comprise current amplitude, pulse width, frequency, and duty cycle.

17. The system of claim 16 , wherein the instructions are further executable by the processor to modify the first stimulation parameter or the second stimulation parameter by decreasing at least one of the current amplitude or the pulse width.

18. The system of claim 15 , wherein the instructions are further executable by the processor to, in response to receiving a plurality of additional indications of intolerance, modify a third stimulation parameter to decrease the intensity of the neurostimulation, the third stimulation parameter being different from at least one of the first stimulation parameter or the second stimulation parameter.

19. The system of claim 15 , wherein the instructions are further executable by the processor to receive, from an external programmer, a prescribed time window during which the intensity of the neurostimulation is increased, the prescribed time window excluding a period during which the patient is likely sleeping.

20. The system of claim 15 , wherein the instructions are further executable by the processor to modify an increment at which the neurostimulation is titrated based on a response of the patient to the neurostimulation.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 31, 2025
From: LIBBUS, IMAD; KENKNIGHT, BRUCE H.; AMURTHUR, BADRI; STUBBS, SCOTT R.
To: CYBERONICS, INC.
Reel/Frame 070683/0317 →
CHANGE OF NAME Recorded Mar 31, 2025
From: CYBERONICS, INC.
To: LIVANOVA USA, INC.
Reel/Frame 070689/0775 →
Continuity (5)
Continuation 16705043 · Dec 5, 2019
Continuation 15360188 · Nov 23, 2016
Continuation 14563181 · Dec 8, 2014
Provisional Application 62078600 · Nov 12, 2014
Related Publication 20240108901A1 · Apr 4, 2024
References Cited (400)
US 5330507A · Schwartz · 1994 [cited by applicant]
US 5522854A · Ideker et al. · 1996 [cited by applicant]
US 5707400A · Terry, Jr. et al. · 1998 [cited by applicant]
US 5928272A · Adkins et al. · 1999 [cited by applicant]
US 5978709A · Begemann et al. · 1999 [cited by applicant]
US 6006134A · Hill et al. · 1999 [cited by applicant]
US 6266564B1 · Hill et al. · 2001 [cited by applicant]
US 6354991B1 · Gross et al. · 2002 [cited by applicant]
US 6449507B1 · Hill et al. · 2002 [cited by applicant]
US 6473644B1 · Terry et al. · 2002 [cited by applicant]
US 6508771B1 · Padmanabhan et al. · 2003 [cited by applicant]
US 6522926B1 · Kieval et al. · 2003 [cited by applicant]
US 6600954B2 · Cohen et al. · 2003 [cited by applicant]
US 6610713B2 · Tracey · 2003 [cited by applicant]
US 6616624B1 · Kieval · 2003 [cited by applicant]
US 6622041B2 · Terry, Jr. et al. · 2003 [cited by applicant]
US 6652449B1 · Gross et al. · 2003 [cited by applicant]
US 6684105B2 · Cohen et al. · 2004 [cited by applicant]
US 6690971B2 · Schauerte et al. · 2004 [cited by applicant]
US 6712772B2 · Cohen et al. · 2004 [cited by applicant]
US 6718208B2 · Hill et al. · 2004 [cited by applicant]
US 6838471B2 · Tracey · 2005 [cited by applicant]
US 6839594B2 · Cohen et al. · 2005 [cited by applicant]
US 6850801B2 · Kieval et al. · 2005 [cited by applicant]
US 6862480B2 · Cohen et al. · 2005 [cited by applicant]
US 6892098B2 · Ayal et al. · 2005 [cited by applicant]
US 6896651B2 · Gross et al. · 2005 [cited by applicant]
US 6904318B2 · Hill et al. · 2005 [cited by applicant]
US 6907295B2 · Gross et al. · 2005 [cited by applicant]
US 6963773B2 · Waltman et al. · 2005 [cited by applicant]
US 6963779B1 · Shankar · 2005 [cited by applicant]
US 6985774B2 · Kieval et al. · 2006 [cited by applicant]
US 7010345B2 · Hill et al. · 2006 [cited by applicant]
US 7072720B2 · Puskas · 2006 [cited by applicant]
US 7123961B1 · Kroll et al. · 2006 [cited by applicant]
US 7136705B1 · Park · 2006 [cited by applicant]
US 7139607B1 · Shelchuk · 2006 [cited by applicant]
US 7158832B2 · Kieval et al. · 2007 [cited by applicant]
US 7184828B2 · Hill et al. · 2007 [cited by applicant]
US 7184829B2 · Hill et al. · 2007 [cited by applicant]
US 7189204B2 · Ni et al. · 2007 [cited by applicant]
US 7218964B2 · Hill et al. · 2007 [cited by applicant]
US 7221979B2 · Zhou et al. · 2007 [cited by applicant]
US 7225017B1 · Shelchuk · 2007 [cited by applicant]
US 7225019B2 · Jahns et al. · 2007 [cited by applicant]
US 7237320B2 · Lam · 2007 [cited by applicant]
US 7245967B1 · Shelchuk · 2007 [cited by applicant]
US 7260431B2 · Libbus et al. · 2007 [cited by applicant]
US 7269457B2 · Shafer et al. · 2007 [cited by applicant]
US 7277761B2 · Shelchuk · 2007 [cited by applicant]
US 7295881B2 · Cohen et al. · 2007 [cited by applicant]
US 7305265B2 · Fukui · 2007 [cited by applicant]
US 7321793B2 · Ezra et al. · 2008 [cited by applicant]
US 7324853B2 · Ayal et al. · 2008 [cited by applicant]
US 7336997B2 · Fukui · 2008 [cited by applicant]
US 7346398B2 · Gross et al. · 2008 [cited by applicant]
US 7387603B2 · Gross et al. · 2008 [cited by applicant]
US 7389149B2 · Rossing et al. · 2008 [cited by applicant]
US 7395119B2 · Hagen et al. · 2008 [cited by applicant]
US 7403819B1 · Shelchuk et al. · 2008 [cited by applicant]
US 7418292B2 · Shafer · 2008 [cited by applicant]
US 7452800B2 · Sosnowchik et al. · 2008 [cited by applicant]
US 7480532B2 · Kieval et al. · 2009 [cited by applicant]
US 7481759B2 · Whitehurst et al. · 2009 [cited by applicant]
US 7485104B2 · Kieval · 2009 [cited by applicant]
US 7493167B2 · Hussein et al. · 2009 [cited by applicant]
US 7499742B2 · Bolea et al. · 2009 [cited by applicant]
US 7499747B2 · Kieval et al. · 2009 [cited by applicant]
US 7499748B2 · Moffitt et al. · 2009 [cited by applicant]
US 7502650B2 · Kieval · 2009 [cited by applicant]
US 7542800B2 · Libbus et al. · 2009 [cited by applicant]
US 7548780B2 · Libbus et al. · 2009 [cited by applicant]
US 7551958B2 · Libbus et al. · 2009 [cited by applicant]
US 7561922B2 · Cohen et al. · 2009 [cited by applicant]
US 7561923B2 · Libbus et al. · 2009 [cited by applicant]
US 7570999B2 · Libbus et al. · 2009 [cited by applicant]
US 7582053B2 · Gross et al. · 2009 [cited by applicant]
US 7584004B2 · Caparso et al. · 2009 [cited by applicant]
US 7587238B2 · Moffitt et al. · 2009 [cited by applicant]
US 7606622B2 · Reeve · 2009 [cited by applicant]
US 7613511B2 · Wu et al. · 2009 [cited by applicant]
US 7613516B2 · Cohen et al. · 2009 [cited by applicant]
US 7616990B2 · Chavan et al. · 2009 [cited by applicant]
US 7617003B2 · Caparso et al. · 2009 [cited by applicant]
US 7623926B2 · Rossing et al. · 2009 [cited by applicant]
US 7627384B2 · Ayal et al. · 2009 [cited by applicant]
US 7628750B2 · Cohen et al. · 2009 [cited by applicant]
US 7630760B2 · Libbus et al. · 2009 [cited by applicant]
US 7634315B2 · Cholette · 2009 [cited by applicant]
US 7634317B2 · Ben-David et al. · 2009 [cited by applicant]
US 7640057B2 · Libbus et al. · 2009 [cited by applicant]
US 7647101B2 · Libbus et al. · 2010 [cited by applicant]
US 7647114B2 · Libbus · 2010 [cited by applicant]
US 7650190B2 · Zhou et al. · 2010 [cited by applicant]
US 7657312B2 · Pastore et al. · 2010 [cited by applicant]
US 7660628B2 · Libbus et al. · 2010 [cited by applicant]
US 7664548B2 · Amurthur et al. · 2010 [cited by applicant]
US 7668602B2 · Ben-David et al. · 2010 [cited by applicant]
US 7672733B2 · Zhou et al. · 2010 [cited by applicant]
US 7676275B1 · Farazi et al. · 2010 [cited by applicant]
US 7684866B2 · Fowler et al. · 2010 [cited by applicant]
US 7689286B2 · Pastore et al. · 2010 [cited by applicant]
US 7711415B1 · Farazi et al. · 2010 [cited by applicant]
US 7711421B2 · Shafer et al. · 2010 [cited by applicant]
US 7734355B2 · Cohen et al. · 2010 [cited by applicant]
US 7738956B1 · Farazi et al. · 2010 [cited by applicant]
US 7751884B2 · Ternes et al. · 2010 [cited by applicant]
US 7769442B2 · Shafer · 2010 [cited by applicant]
US 7769446B2 · Moffitt et al. · 2010 [cited by applicant]
US 7778702B2 · Ben-David et al. · 2010 [cited by applicant]
US 7778703B2 · Gross et al. · 2010 [cited by applicant]
US 7778711B2 · Ben-David et al. · 2010 [cited by applicant]
US 7783353B2 · Libbus et al. · 2010 [cited by applicant]
US 7797041B2 · Libbus et al. · 2010 [cited by applicant]
US 7801603B2 · Westlund et al. · 2010 [cited by applicant]
US 7801604B2 · Brockway et al. · 2010 [cited by applicant]
US 7801614B2 · Rossing et al. · 2010 [cited by applicant]
US 7805193B2 · Libbus et al. · 2010 [cited by applicant]
US 7805203B2 · Ben-David et al. · 2010 [cited by applicant]
US 7813805B1 · Farazi · 2010 [cited by applicant]
US 7813812B2 · Kieval et al. · 2010 [cited by applicant]
US 7835797B2 · Rossing et al. · 2010 [cited by applicant]
US 7840266B2 · Libbus et al. · 2010 [cited by applicant]
US 7840271B2 · Kieval et al. · 2010 [cited by applicant]
US 7844346B2 · Cohen et al. · 2010 [cited by applicant]
US 7848812B2 · Crowley et al. · 2010 [cited by applicant]
US 7848816B1 · Wenzel et al. · 2010 [cited by applicant]
US 7869869B1 · Farazi · 2011 [cited by applicant]
US 7885709B2 · Ben-David · 2011 [cited by applicant]
US 7885711B2 · Ben-Ezra et al. · 2011 [cited by applicant]
US 7890185B2 · Cohen et al. · 2011 [cited by applicant]
US 7894907B2 · Cowan et al. · 2011 [cited by applicant]
US 7904151B2 · Ben-David et al. · 2011 [cited by applicant]
US 7904175B2 · Scott et al. · 2011 [cited by applicant]
US 7904176B2 · Ben-Ezra et al. · 2011 [cited by applicant]
US 7908008B2 · Ben-David et al. · 2011 [cited by applicant]
US 7916013B2 · Stevenson · 2011 [cited by applicant]
US 7925342B2 · Amurthur et al. · 2011 [cited by applicant]
US 7925352B2 · Stack et al. · 2011 [cited by applicant]
US 7974693B2 · Ben-David et al. · 2011 [cited by applicant]
US 7991456B2 · Chow · 2011 [cited by applicant]
US 8005542B2 · Ben-Ezra et al. · 2011 [cited by applicant]
US 8005545B2 · Ben-David et al. · 2011 [cited by applicant]
US 8036745B2 · Ben-David et al. · 2011 [cited by applicant]
US 8060197B2 · Ben-David et al. · 2011 [cited by applicant]
US 8065021B2 · Gross et al. · 2011 [cited by applicant]
US 8083663B2 · Gross et al. · 2011 [cited by applicant]
US 8116881B2 · Cohen et al. · 2012 [cited by applicant]
US 8131362B2 · Moffitt et al. · 2012 [cited by applicant]
US 8160701B2 · Zhao et al. · 2012 [cited by applicant]
US 8160705B2 · Stevenson et al. · 2012 [cited by applicant]
US 8195290B2 · Brockway et al. · 2012 [cited by applicant]
US 8224436B2 · Libbus et al. · 2012 [cited by applicant]
US 8249711B2 · Libbus et al. · 2012 [cited by applicant]
US 8369943B2 · Shuros et al. · 2013 [cited by applicant]
US 8386038B2 · Bianchi et al. · 2013 [cited by applicant]
US 8401640B2 · Zhao et al. · 2013 [cited by applicant]
US 8417354B2 · Zhang et al. · 2013 [cited by applicant]
US 8437837B2 · Zhou · 2013 [cited by applicant]
US 8571654B2 · Libbus et al. · 2013 [cited by applicant]
US 8577458B1 · Libbus et al. · 2013 [cited by applicant]
US 8600505B2 · Libbus et al. · 2013 [cited by applicant]
US 8634921B2 · Chavan et al. · 2014 [cited by applicant]
US 8688212B2 · Libbus et al. · 2014 [cited by applicant]
US 8918190B2 · Libbus et al. · 2014 [cited by applicant]
US 20020107553A1 · Hill et al. · 2002 [cited by applicant]
US 20030040774A1 · Terry et al. · 2003 [cited by applicant]
US 20030153954A1 · Park et al. · 2003 [cited by applicant]
US 20030171781A1 · Florio et al. · 2003 [cited by applicant]
US 20040199210A1 · Shelchuk · 2004 [cited by applicant]
US 20040210261A1 · King et al. · 2004 [cited by applicant]
US 20040215265A1 · Keizer · 2004 [cited by applicant]
US 20050049655A1 · Boveja et al. · 2005 [cited by applicant]
US 20050065553A1 · Ezra et al. · 2005 [cited by applicant]
US 20050125044A1 · Tracey · 2005 [cited by applicant]
US 20050131467A1 · Boveja · 2005 [cited by applicant]
US 20050165465A1 · Pianca et al. · 2005 [cited by applicant]
US 20050267542A1 · David et al. · 2005 [cited by applicant]
US 20060015153A1 · Gliner et al. · 2006 [cited by applicant]
US 20060100668A1 · Ben-David et al. · 2006 [cited by applicant]
US 20060116592A1 · Zhou et al. · 2006 [cited by applicant]
US 20060190053A1 · Dobak · 2006 [cited by applicant]
US 20060206155A1 · Ben-David et al. · 2006 [cited by applicant]
US 20060253161A1 · Libbus et al. · 2006 [cited by applicant]
US 20070067004A1 · Boveja et al. · 2007 [cited by applicant]
US 20070093870A1 · Maschino · 2007 [cited by applicant]
US 20070213773A1 · Hill et al. · 2007 [cited by applicant]
US 20070233194A1 · Craig · 2007 [cited by applicant]
US 20070239210A1 · Libbus et al. · 2007 [cited by applicant]
US 20070255320A1 · Inman et al. · 2007 [cited by applicant]
US 20070276453A1 · Hill et al. · 2007 [cited by applicant]
US 20080015659A1 · Zhang et al. · 2008 [cited by applicant]
US 20080021503A1 · Whitehurst et al. · 2008 [cited by applicant]
US 20080033511A1 · Dobak · 2008 [cited by applicant]
US 20080051839A1 · Libbus et al. · 2008 [cited by applicant]
US 20080058874A1 · Westlund et al. · 2008 [cited by applicant]
US 20080061240A1 · Heuft · 2008 [cited by applicant]
US 20080082133A1 · Zhou · 2008 [cited by applicant]
US 20080091240A1 · Ben-David et al. · 2008 [cited by applicant]
US 20080132983A1 · Cohen et al. · 2008 [cited by applicant]
US 20080135864A1 · David et al. · 2008 [cited by applicant]
US 20080147140A1 · Ternes et al. · 2008 [cited by applicant]
US 20080183258A1 · Inman · 2008 [cited by applicant]
US 20080243196A1 · Libbus et al. · 2008 [cited by applicant]
US 20080319513A1 · Pu et al. · 2008 [cited by applicant]
US 20090024186A1 · Brockway et al. · 2009 [cited by applicant]
US 20090030493A1 · Colborn et al. · 2009 [cited by applicant]
US 20090118777A1 · Iki et al. · 2009 [cited by applicant]
US 20090124848A1 · Miazga · 2009 [cited by applicant]
US 20090149900A1 · Moffitt et al. · 2009 [cited by applicant]
US 20090248097A1 · Tracey et al. · 2009 [cited by applicant]
US 20090270953A1 · Ecker et al. · 2009 [cited by applicant]
US 20090275956A1 · Burnes et al. · 2009 [cited by applicant]
US 20090326595A1 · Brockway et al. · 2009 [cited by applicant]
US 20100010556A1 · Zhao et al. · 2010 [cited by applicant]
US 20100010603A1 · Ben-David et al. · 2010 [cited by applicant]
US 20100016919A1 · Hill et al. · 2010 [cited by applicant]
US 20100042173A1 · Farazi et al. · 2010 [cited by applicant]
US 20100113954A1 · Zhou · 2010 [cited by applicant]
US 20100114197A1 · Burnes et al. · 2010 [cited by applicant]
US 20100114203A1 · Burnes et al. · 2010 [cited by applicant]
US 20100114227A1 · Cholette · 2010 [cited by applicant]
US 20100174341A1 · Bolea et al. · 2010 [cited by applicant]
US 20100286740A1 · Libbus et al. · 2010 [cited by applicant]
US 20100331908A1 · Farazi · 2010 [cited by applicant]
US 20110015692A1 · Libbus et al. · 2011 [cited by applicant]
US 20110082514A1 · Libbus et al. · 2011 [cited by applicant]
US 20110098796A1 · Ben-David et al. · 2011 [cited by applicant]
US 20110224749A1 · Ben-David et al. · 2011 [cited by applicant]
US 20110257708A1 · Kramer et al. · 2011 [cited by applicant]
US 20110270332A1 · Buschman et al. · 2011 [cited by applicant]
US 20110301479A1 · Ghanem et al. · 2011 [cited by applicant]
US 20110313488A1 · Hincapie Ordonez et al. · 2011 [cited by applicant]
US 20120143286A1 · Hahn · 2012 [cited by examiner]
US 20120172742A1 · Arcot-Krishnamurthy et al. · 2012 [cited by applicant]
US 20120185007A1 · Ziegler et al. · 2012 [cited by applicant]
US 20120185010A1 · Zhou et al. · 2012 [cited by applicant]
US 20120192874A1 · Bolea et al. · 2012 [cited by applicant]
US 20120271374A1 · Nelson et al. · 2012 [cited by applicant]
US 20120303080A1 · Ben-David et al. · 2012 [cited by applicant]
US 20130158616A1 · Libbus et al. · 2013 [cited by applicant]
US 20130158617A1 · Libbus et al. · 2013 [cited by applicant]
US 20130158618A1 · Libbus et al. · 2013 [cited by applicant]
US 20130238047A1 · Libbus et al. · 2013 [cited by applicant]
US 20130289646A1 · Libbus · 2013 [cited by examiner]
US 20140025132A1 · Libbus et al. · 2014 [cited by applicant]
US 20140135862A1 · Libbus et al. · 2014 [cited by applicant]
US 20140135863A1 · Libbus et al. · 2014 [cited by applicant]
US 20140135864A1 · Libbus et al. · 2014 [cited by applicant]
US 20140228905A1 · Bolea · 2014 [cited by applicant]
US 20140277232A1 · Libbus et al. · 2014 [cited by applicant]
US 20150073511A1 · Libbus et al. · 2015 [cited by applicant]
US 20150073512A1 · Libbus et al. · 2015 [cited by applicant]
US 20150094962A1 · Hoegh et al. · 2015 [cited by applicant]
US 20150119956A1 · Libbus et al. · 2015 [cited by applicant]
US 20150119959A1 · Libbus et al. · 2015 [cited by applicant]
US 20150196762A1 · Amurthur et al. · 2015 [cited by applicant]
WO WO2010005482A1 · 2010 [cited by applicant]
US 8,315,702 B2, 11/2012, Chavan et al. (withdrawn) [cited by applicant]
Abraham et al., “Devices in the management of advanced, chronic heart failure,” Nature Reviews, Feb. 2013, vol. 10, Published online Dec. 11, 2012 (pp. 98-110). [cited by applicant]
Adamson et al., “Continuous Autonomic Assessment in Patients with Symptomatic Heart Failure: Prognostic Value of Heart Rate Variability Measured by an Implanted Cardiac Resynchronization Device,” Circulation, Journal of… [cited by applicant]
Agostoni et al., “Functional and Histological Studies of the Vagus Nerve and its Branches to the Heart, Lungs and Abdominal Viscera in the Cat,” The Journal of Physiology, 1957, vol. 135 (pp. 182-205). [cited by applicant]
Ajani et al., “Prevalence of High C-Reactive Protein in Persons with Serum Lipid Concentrations within Recommended Values,” Chemical Chemistry, 2004, vol. 50, No. 9 (pp. 1618-1622). [cited by applicant]
Akiyama et al., “Effects of right and left vagal stimulation on left ventricular acetylcholine levels in the cat,” Acta Physiological, The Scandinavian Physiological Society, 2001, vol. 172 (pp. 11-16). [cited by applicant]
Anand et al., “C-Reactive Protein in Heart Failure: Prognostic Value and the Effect of Valsartan,” Circulation, Journal of the American Heart Association, 2005, vol. 112, (pp. 1428-1434). [cited by applicant]
Anholt et al., “Recruitment and blocking properties of the CardioFit stimulation lead,” Journal of Neural Engineering, 2011 8 (pp. 1-6). [cited by applicant]
Ardell et al., “Selective vagal innervation of sinoatrial and atrioventricular nodes in canine heart,” American Physiological Society Journal, 1986, vol. 251 (Heart Circ. Physiol. 20) (pp. H764-H773). [cited by applicant]
Armour et al., “Functional anatomy of canine cardiac nerves,” Acta Scientiae Anatomica, 1975, vol. 91, (pp. 510-528). [cited by applicant]
Armour et al., “Localized myocardial responses to stimulation of small cardiac branches of the vagus,” American Journal of Physiology, Jan. 1975, vol. 228, No. 1 (pp. 141-148). [cited by applicant]
Armour, “Cardiac neuronal hierarchy in health and disease,” American Journal of Physiology, vol. 287 (pp. R262-R271). [cited by applicant]
Armour, “Myocardial ischaemia and the cardiac nervous system,” Cardiovascular Research, 1999, vol. 41 (pp. 41-54). [cited by applicant]
Armour, “Potential clinical relevance of the ‘little brain’ on the mammalian heart,” Experimental Physiology, Feb. 2008, vol. 93, No. 2 (pp. 165-176) Online Publication Date: Nov. 2, 2007. Available at: http://ep.physoc… [cited by applicant]
Armour, “The little brain on the heart,” Cleveland Clinic Journal of Medicine, Feb. 2007, vol. 74, supp. 1 (pp. S48-S51). [cited by applicant]
Asala et al., “An electron microscope study of vagus nerve composition in the ferret,” Anatomia Histologia Embryologia, 1986, vol. 175 (pp. 247-253). [cited by applicant]
Aukrust et al., “Inflammatory and anti-inflammatory cytokines in chronic heart failure: Potential therapeutic implications,” Annals of Medicine, 2005, vol. 37 (pp. 74-85). [cited by applicant]
Author Unknown, “Nerve fiber—Types and Function,” www.boddunan.com Available at ww.boddunan/education/20-medicine-a-surgery/12730-nerver-fiber-types-and-function.html (Apr. 19, 2010) (4 pages). [cited by applicant]
Author Unknown, American Diabetes Association, “Standards of Medical Care in Diabetes—2012,” Diabetes Care, Jan. 2012, vol. 35, supplement 1 (pp. S11-S63. [cited by applicant]
Author Unknown, Staff of Adinstruments, “Principles of Nerve Stimulation,” Application Note, ADInstruments, Apr. 2002, (6 pages). [cited by applicant]
Bae et al., “Gliosis in the Amygdala Following Myocardial Infarction in the Rat,” Journal of Veterinary Medical Science, 2010, vol. 72, No. 8 (pp. 1041-1045). [cited by applicant]
Bernik et al., “Pharmacological Stimulation of the Cholinergic Antiinflammatory Pathway,” Journal of Experimental Medicine, Mar. 18, 2002, vol. 195, No. 6 (pp. 781-788). [cited by applicant]
Berthoud et al., “Functional and chemical anatomy of the afferent vagal system,” Autonomic Neuroscience: Basic and Clinical, 2000, vol. 85 (pp. 1-17). [cited by applicant]
Bhagat et al., “Differential Effect of Right and Left Vagal Stimulation on Right and Left Circumflex Coronary Arteries,” S A Medical Journal, 1976, vol. 50 (pp. 1591-1594). [cited by applicant]
Biasucci et al., “Elevated Levels of C-Reactive Protein at Discharge in Patients with Unstable Angina Predict Recurrent Instability,” Circulation, Journal of the American Heart Association, 1999, vol. 99, (pp. 855-860). [cited by applicant]
Bibevski et al., “Evidence for impaired vagus nerve activity in heart failure,” Heart Fail Review, 2011, vol. 16 (pp. 129-135). [cited by applicant]
Bibevski et al., “Ganglionic Mechanisms Contribute to Diminished Vagal Control in Heart Failure,” Circulation, Journal of the American Heart Association, 1999, vol. 99 (pp. 2958-2963). [cited by applicant]
Bilgutay et al., “Vagal Tuning a new concept in the treatment of supraventricular arrhythmias, angina pectoris, and heart failure,” Journal of Thoracic and Cardiovascular Surgery, Jul. 1968, vol. 56, No. 1 (pp. 71-82). [cited by applicant]
Binkley et al., “Parasympathetic Withdrawal is an Integral Component of Autonomic Imbalance in Congestive Heart Failure: Demonstration in Human Subjects and Verification in a Paced Canine Model Of Ventricular Failure,” … [cited by applicant]
Bois et al., “Mode of action of bradycardic agent, S 16257, on ionic currents of rabbit sinoatrial node cells,” Abstract, British Journal of Pharmacology, 1996, vol. 118, No. 4 (pp. 1051-1057). [cited by applicant]
Bonaz et al., “Vagus nerve stimulation: From epilepsy to the cholinergic anti-inflammatory pathway,” Neurogastroenterology & Motility, 2013 (pp. 1-14). [cited by applicant]
Borggrefe et al., “Vagal Stimulation Devices,” ESC Congress, 2010 (38 pages). [cited by applicant]
Borovilkova et al., “Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin,” Nature, May 25, 2000, vol. 405, (pp. (458-462). [cited by applicant]
Brack et al., “Mechanisms underlying the autonomic modulation of ventricular fibrillation initiation—tentative prophylactic properties in vagus nerve stimulation on malignant arrhythmias in heart failure,” Heart Fail Re… [cited by applicant]
Bronzino, “Biomedical Engineering Fundamentals,” CRC Press, Chapter 30, Apr. 2006 (pp. 30-10-30-15). [cited by applicant]
Buschman et al., “Heart Rate Control Via Vagus Nerve Stimulation,” Neuromodulation, 2006, vol. 9, No. 3 (pp. 214-220). [cited by applicant]
Butterwick et al., “Tissue Damage by Pulsed Electrical Stimulation,” IEEE Transactions on Biomedical Engineering, Dec. 2007, vol. 54, No. 12 (pp. 2261-2267). [cited by applicant]
Calkins et al., “Comparison of Responses to Isoproterenol and Epinephrine During Head-Up Tilt in Suspected Vasodepressor Syncope,” The American Journal of Cardiology, Jan. 15, 1991, vol. 67 (pp. 207-209). [cited by applicant]
Castoro et al., “Excitation properties of the right cervical vagus nerve in adult dogs,” Experimental Neurology, Jan. 2011, vol. 227, No. 1 (pp. 62-68)—Online Publication Date: Sep. 17, 2010. Available at: http://www.sc… [cited by applicant]
Chapleau, et al., “Methods of assessing vagus nerve activity and reflexes,” Heart Fail Review, 2011, vol. 16 (pp. 109-127). [cited by applicant]
Chen et al., “National and Regional Trends in Heart Failure Hospitalization and Mortality Rates for Medicare Beneficiaries, 1998-2008,” JAMA, vol. 306, No. 15 (Oct. 19, 2011). [cited by applicant]
Chen et al., “Role of Atrial Electrophysiology and Autonomic Nervous System in Patients with Supraventricular Tachycardia and Paroxysmal Atrial Fibrillation,” Journal of the American College of Cardiology, Sep. 1998, vo… [cited by applicant]
Cheng et al., “Long-term Outcomes in Individuals with Prolonged PR Interval or First-Degree Atrioventricular Block,” JAMA, Jun. 24, 2009, vol. 301, No. 24 (pp. 2571-2577). [cited by applicant]
Chiou et al., “Effects of Continuous Enhanced Vagal Tone and Dual Atrioventricular Node and Accessory Pathways,” Circulation, Journal of the American Heart Association, 2003, vol. 107, (pp. 2583-2588). [cited by applicant]
Cohen et al., “Histopathology of the stimulated Vagus nerve: Primum non nocere,” Heart Fail Review, 2011, No. 16 (pp. 163-169). [cited by applicant]
Colombo et al., “Comparison between spectral analysis and the phenylephrine methods for the assessment of baroreflex sensitivity in chronic heart failure,” Clinical Science, 1999, vol. 97 (pp. 503-513). [cited by applicant]
Cryan et al., “Animal models and mood disorders: recent developments,” Current Opinion in Psychiatry, 2007, No. 20 (pp. 1-7). [cited by applicant]
Das, “Vagal nerve stimulation in prevention and management of coronary heart disease,” World Journal of Cardiology, Apr. 26, 2011, vol. 3, No. 4 (pp. 105-110). [cited by applicant]
De Castro, et al., “Parasympathetic-mediated atrial fibrillation during tilt test associated with increased baroreflex sensitivity,” The European Society of Cardiology, Europace, 8, pp. 349-351 (2006). [cited by applicant]
De Ferarri et al., Chronic Vagus Nerve Stimulation: a New and Promising Therapeutic Approach for Chronic Heart Failure, European Heart Journal, vol. 32, Oct. 28, 2010, pp. 847-855. [cited by applicant]
De Ferrari et al., “Baroreflex Sensitivity Predicts Long-Term Cardiovascular Mortality After Myocardial Infarction Even in Patients with Preserved Left Ventricular Function,” Journal of the American College of Cardiolog… [cited by applicant]
De Ferrari, et al., “Chronic Vagal Stimulation in Patients with Congestive Heart Failure,” 31st Annual International Conference of the IEE EMBS (2009). [cited by applicant]
De Ferrari, et al., “Vagus nerve stimulation: from pre-clinical to clinical application: challenges and future directions,” Heart Failure Review, 2011, No. 16 (Published Online Dec. 17, 2010) (pp. 195-203). [cited by applicant]
De Jonge et al., “Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway,” Nature Immunology, Aug. 2005, vol. 6, No. 8 (pp. 844-852). [cited by applicant]
Desai et al., “Pharmacologic modulation of parasympathetic activity in heart failure,” Heart Failure Review, 2011, No. 16 (Published online: Oct. 6, 2010) (pp. 179-193). [cited by applicant]
Dickerson et al., “Parasympathetic neurons in the cranial medial ventricular fat pad on the dog heart selectively decrease ventricular contractility,” Journal of the Autonomic Nervous System, 1998, vol. 70 pp. (pp. 129-… [cited by applicant]
Dunlap et al., “Mechanisms of altered vagal control in heart failure: influence of muscarinic receptors and acetylcholinesterase activity,” American Journal of Physiology-Heart and Circulatory, Jun. 26, 2003, vol. 285 (… [cited by applicant]
Elsenbruch et al., “Heart Rate Variability During Waking and Sleep in Healthy Males and Females,” Sleep, 1999, vol. 22, No. 8, (pp. 1067-1071). [cited by applicant]
Euler et al., “Acetylcholine release by a stimulus train lowers atrial fibrillation threshold,” American Journal of Physiology, 1987, vol. 253 (pp. H863-H868). [cited by applicant]
Evans et al., “Histological and functional studies on the fibre composition of the vagus nerve of the rabbit,” Journal of Anatomy, 130, pp. 139-151 (1954). [cited by applicant]
Fallen, “Vagal Afferent Stimulation as a Cardioprotective Strategy? Introducing the Concept,” A.N.E., vol. 10, No. 4 (Oct. 2005). [cited by applicant]
Fan et al., “Transvenous vagus nerve stimulation: a potential heart failure therapy is feasible in humans,” JACC, 2010, vol. 55, issue 10A (pp. E152-E153). [cited by applicant]
Fazan et al., “Diabetic Peripheral Neuropathies: a Morphometric Overview,” International Journal of Morphology, 2010, vol. 28, No. 1 (pp. 51-64). [cited by applicant]
Feinauer et al., “Ouabain enhances release of acetylcholine in the heart evoked by unilateral vagal stimulation,” Archives Pharmacology, 1986, vol. 333 (pp. 7-12). [cited by applicant]
Fonarow et al., “Incremental Reduction in Risk of Death Associated with Use of Guideline-Recommended Therapies in Patients with Heart Failure: a Nested Case-Control Analysis of Improve HF,” Journal of the American Heart… [cited by applicant]
Ford et al., “The effects of electrical stimulation of myelinated and non-myelinated vagal fibres on heart rate in the rabbit,” The Journal of Physiology, 1986, vol. 380 (pp. 341-347). [cited by applicant]
Furukawa et al., “Effects of Verapamil, Zatebradine, and E-4031 on the Pacemaker Location and Rate in Response to Sympathetic Stimulation in Dog Hearts,” The Journal of Pharmacology and Experimental Therapeutics, 1999, … [cited by applicant]
Furukawa et al., “Selective inhibition by zatebradine and discrete parasympathetic stimulation of the positive chronotropic response to sympathetic stimulation in anesthetized dogs,” Abstract, Journal of Pharmacology & … [cited by applicant]
Gatti et al., “Can neurons in the nucleus ambiguous selectively regulate cardiac rate and atrio- ventricular conduction?” Journal of the Autonomic Nervous System, 1996, vol. 57 (pp. 123-127). [cited by applicant]
Gatti et al., “Vagal control of left ventricular contractility is selectively mediated by a cranioventricular intracardiac ganglion in the cat,” Journal of the Autonomic Nervous System, 1997, vol. 66 (pp. 138-144). [cited by applicant]
Gibbons et al., “Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias,” American Journal of Physiology, 2012, vol. 302 ((First published Nov. 16, 2011) (pp. R357-R364). [cited by applicant]
Gottdiener et al., “Predictors of Congestive Heart Failure in the Elderly: The Cardiovascular Health Study,” Journal of the American College of Cardiology, 2000, vol. 35, No. 6 (pp. 1628-1637). [cited by applicant]
Gray et al., “Parasympathetic control of the Heart. II. A novel interganglionic intrinsic cardiac circuit mediates neural control of heart rate,” Journal of Applied Physiology, 2004, vol. 96 (pp. 2273-2278). [cited by applicant]
Gray, et al., “Parasympathetic control of the Heart. III. Neuropeptide Y-immunoreactive nerve terminals synapse on three populations of negative chronotropic vagal preganglionic neurons,” Journal of Applied Physiology, … [cited by applicant]
Grill, “Chapter 14—Principles of Electric Field Generation for Stimulation of the Central Nervous System,” Neuromodulation, Academic Press, 2009 (11 pages). [cited by applicant]
Guilleminault, et al., “Cyclical Variation of the Heart Rate in Sleep Apnea Syndrome,” The Lancet, Jan. 21, 1984 (pp. 126-131). [cited by applicant]
Hardwick et al., “Remodeling of the guinea pig intrinsic cardiac plexus with chronic pressure overload,” American Journal of Physiology Regulatory Integrative and Comparative Physiology, 2009, vol. 297 (pp. 859-866). [cited by applicant]
Hardwick et al., “Chronic myocardial infarction induces phenotypic and functional remodeling in the guinea pig cardiac plexus,” American Journal of Physiology, 2008, vol. 295 (pp. 1926-1933). [cited by applicant]
Hauptman et al., “The vagus nerve and autonomic imbalance in heart failure: past, present, and future,” Heart Failure Review, 2011, vol. 16 (pp. 97-99). [cited by applicant]
Hellyer et al., “Autonomic nerve activity and blood pressure in ambulatory dogs,” Heart Rhythm, Feb. 2014, vol. 11, No. 2) (pp. 307-313). [cited by applicant]
Hirooka et al., “Imbalance of central nitric oxide and reactive oxygen species in the regulation of sympathetic activity and neural mechanisms of hypertension,” American Journal of Physiology, 2011, vol. 300 (pp. 818-82… [cited by applicant]
Hoffman et al., “Vagus Nerve Components,” The Anatomical Record, 1957, vol. 127 (pp. 551-568). [cited by applicant]
Hu et al., “Role of sympathetic nervous system in myocardial ischemia injury: Beneficial or deleterious?” Letters to the Editor, Elsevier Ireland Ltd., Mar. 27, 2012. [cited by applicant]
Hua, et al., “Left vagal stimulation induces dynorphin release and suppresses substance P release from the rat thoracic spinal cord during cardiac ischemia,” American Journal of Physiology, 2004, vol. 287 (pp. 1468-1477… [cited by applicant]
Huston et al., “Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis,” Critical Care Medicine, 2007, vol. 35, No. 12 (pp. 2762-2768). [cited by applicant]
Huston et al., “Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis,” Journal of Experimental Medicine, Jun. 19, 2006, vol. 203, No. 7 (pp. 1623-1628). [cited by applicant]
Ingemansson et al., “Autonomic modulation of the atrial cycle length by the head up tilt test: non-invasive evaluation in patients with chronic atrial fibrillation,” Heart, 1998, vol. 80 (pp. 71-76). [cited by applicant]
International Search Report and Written Opinion for PCT Appl. No. PCT/US2012/068223 dated Apr. 3, 2013 (11 pages). [cited by applicant]
International Search Report and Written Opinion for PCT Appl. Ser. No. PCT/US2012/068205 dated Feb. 8, 2013 (15 pages). [cited by applicant]
International Search Report and Written Opinion for PCT Appl. Ser. No. PCT/US2012/068211 dated Jun. 13, 2013 (9 pages). [cited by applicant]
International Search Report and Written Opinion for PCT Appl. Ser. No. PCT/US2012/068213 dated Mar. 15, 2013 (11 pages). [cited by applicant]
International Search Report and Written Opinion for PCT Appl. Ser. No. PCT/US2013/021964 dated Jul. 25, 2013 (15 pages). [cited by applicant]
International Search Report and Written Opinion for PCT Appl. Ser. No. PCT/US2013/050390 dated Nov. 5, 2013. [cited by applicant]
International Search Report and Written Opinion for PCT Appl. Ser. No. PCT/US2013/068541 dated Jan. 7, 2014 (11 pages). [cited by applicant]
International Search Report and Written Opinion for PCT Appl. Ser. No. PCT/US2014/024827 dated Nov. 11, 2014 (18 pages). [cited by applicant]
International Search Report and Written Opinion for PCT Appl. Ser. No. PCT/US2015/060200 dated Feb. 8, 2016 (14 pages). [cited by applicant]
International Search Report and Written Opinion on PCT Appl. Ser. No. PCT/US2015/020116 dated Jul. 6, 2015 (12 pages). [cited by applicant]
Ito et al., “Efferent sympathetic and vagal innervation of the canine right ventricle,” Circulation, Journal of the American Heart Association, 1994, vol. 90 (pp. 1469-1468). [cited by applicant]
Jacques et al., “Spinal Cord Stimulation Causes Potentiation of Right Vagus Nerve Effects on Atrial Chronotropic Function and Repolarization in Canines,” Journal of Cardiovascular Electrophysiology, Apr. 2011, vol. 22, … [cited by applicant]
Jaenisch, et al., “Respiratory muscle training improves baroreceptor sensitivity, decrease sympathetic tonus and increase vagal effect in rats with heart failure,” European Heart Journal, 2011, vol. 32 (Abstract Supplem… [cited by applicant]
Jammes et al., “Afferent and efferent components of the bronchial vagal branches in cats,” Journal of the Autonomic Nervous System, 5, pp. 165-176 (1982). [cited by applicant]
Janabi et al., “Oxidized LDL-Induced NF-kB Activation and Subsequent Expression of Proinflammatory Genes are Defective in Monocyte-Derived Macrophages from CD36-Deficient Patients,” Arterioscler Thromb Vase Biol., 20:19… [cited by applicant]
Janse et al., “Effects of unilateral stellate ganglion stimulation and ablation on electrophysiologic changes induced by acute myocardial ischemia in dogs,” Circulation, Journal of the American Heart Association, 72, pp… [cited by applicant]
Jessup et al., “2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults,” Circulation, Journal of the American Heart Association, vol. 119, pp. 1977-2016 (2009). [cited by applicant]
Johnson et al., “Parasympathetic control of the heart. I. An interventriculo-septal ganglion is the major source of the vagal intracardiac innervation of the ventricles,” J Appl Physiol, 96, pp. 2265-2272 (2004). [cited by applicant]
Kakinuma et al., “Cholinoceptive and cholinergic properties of cardiomyocytes involving an amplification mechanism for vagal efferent effects in sparsely innervated ventricular myocardium,” FEBS Journal, 276, pp. 5111-5… [cited by applicant]
Kalman, “Specific effects of zatebradine on sinus node function: suppression of automaticity, prolongation of sinoatrial conduction and pacemaker shift in the denervated canine heart,” Abstract, Journal of Pharmacology … [cited by applicant]
Kaneko et al., “C-Reactive Protein in Dilated Cardiomyopathy,” Cardiology, 1999, vol. 91 (pp. 215-219). [cited by applicant]
Katare et al., “Vagal nerve stimulation prevents reperfusion injury through inhibition of opening of mitochondrial permeability transition pore independent of bradycardiac effect,” The Journal of Thoracic and Cardiovasc… [cited by applicant]
Katz et al., “Diseases of the heart in the Works of Hippocrates,” British Heart Journal, 24, pp. 257-264 (1962). [cited by applicant]
Kawada et al., “High-frequency dominant depression of peripheral vagal control of heart rate in rats with chronic heart failure,” Acta Physiol 207, 494-502 (2013). [cited by applicant]
Kawada, et al., “Vagal stimulation suppresses isschemia-induced myocardial interstitial norepinephrine release,” Life Sciences, 78, pp. 882-887 (2006). [cited by applicant]
Kawashima, “The autonomic nervous system of the human heart with special reference to its origin, course, and peripheral distribution,” Anat Embryol, 209, pp. 425¬438 (2005). [cited by applicant]
Klein et al., “Vagus nerve stimulation: a new approach to reduce heart failure,” Cardiology Journal, vol. 17, iss. 6, pp. 638-643 (2010). [cited by applicant]
Kliks et al., “Influence of Sympathetic Tone on Ventricular Fibrillation Threshold During Experimental Coronary Occlusion,” The American Journal of Cardiology, vol. 36, pp. 45-49 (Jul. 1975). [cited by applicant]
Kolman et al., “The effect of vagus nerve stimulation upon vulnerability of the canine ventricle: role of sympathetic-parasympathetic interactions,” Journal of the American Heart Association, 52, pp. 578-585 (1975). [cited by applicant]
Kong et al., “Optimizing the Parameters of Vagus Nerve Stimulation by Uniform Design in Rats with Acute Myocardial Infarction,” PLOS One, vol. 7, issue 11 (Nov. 2012). [cited by applicant]
Koopman et al., “Pilot study of stimulation of the cholinergic anti-inflammatory pathway with an implantable vagus nerve stimulation device in patients with rheumatoid arthritis,” Abstract (2012). [cited by applicant]
Kulbertus et al., ed., “Neurocardiology,” Futura Publishing Co., pp. 13 (“Anatomy of the Cardiac Efferent Innvervation”); 61-63 (“Autonomic Neural Control”); 87, 89, 92¬93 (“Sympathetic-Parasympathetic Interactions”); 1… [cited by applicant]
La Rovere et al., “Baroreflex Sensitivity and Heart Rate Variability in the Identification of Patients at Risk for Life-Threatening Arrhythmias: Implications for Clinical Trials,” Circulation, Journal of the American He… [cited by applicant]
La Rovere et al., “Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators,”… [cited by applicant]
Lane et al., “Prediction and Prevention of Sudden Cardiac Death in Heart Failure,” Heart, 91, pp. 674-680 (2005). [cited by applicant]
Lechat et al., “Heart rate and Cardiac Rhythm Relationships with Bisoprolol Benefit in Chronic Heart Failure in CIBIS II Trial,” Circulation, Journal of American Heart Association, 103, pp. 1428-1433 (2001). [cited by applicant]
Lewis et al., “Vagus nerve stimulation decreases left ventricular contractility in vivo in the human and pig heart,” Journal of Physiology, 534, pp. 547-552 (2001). [cited by applicant]
Li et al., “Inflammatory cytokines and nitric oxide in heart failure and potential modulation by vagus nerve stimulation,” Heart Fail Rev, 16, pp. 137-145 (2011). [cited by applicant]
Li et al., “Low-Level Vagosympathetic Stimulation. A Paradox and Potential New Modality for the Treatment of Focal Atrial Fibrillation,” Gire Arrhythm Electrophysiol, Journal of American Heart Association, 2, pp. 645-65… [cited by applicant]
Li et al., “Restoration of vagal tone by donepezil, on top of losartan treatment, markedly suppresses ventricular dysfunction and improves long-term survival in chronic heart failure rats,” European Heart Journal, 32 (A… [cited by applicant]
Li et al., “Vagal Nerve Stimulation Markedly Improves Long-Term Survival After Chronic Heart Failure in Rats,” Circulation: Journal of the American Heart Association, Jan. 2004, vol. 109, iss. 1, (pp. 120-124)—Online pu… [cited by applicant]
Li et al., “Early vagal stimulation markedly prevented cardiac dysfunction in rats after acute myocardial infarction in addition to suppressing arrhythmic death,” European Heart Journal, 32 (Abstract Supplement), pp. 29… [cited by applicant]
Libby et al., “Inflammation and Atherosclerosis,” Circulation, Journal of the American Heart Association, 105, pp. 1135-1143 (2002). [cited by applicant]
Liu et al., “Differing sympathetic and vagal effects on atrial fibrillation in dogs: role of refractoriness heterogeneity,” American Journal of Physiology 273 (Heart Gire. Physiol. 42), pp. H805-H816 (1997). [cited by applicant]
Lo et al., “Paradoxical long-term proarrhythmic effects after ablating the ‘head station’ ganglionated plexi of the vagal innervation to the heart,” Heart Rhythm, vol. 10, No. 5, pp. 751-757 (May 2013). [cited by applicant]
Lohmeier et al., “Prolonged Activation of the Barorelfex Produces Sustained Hypotension,” Hypertension, Journal of the American Heart Association, 43, pp. 306¬311 (2004). [cited by applicant]
Lu et al., “Vagal nerve stimulation produces cardiac injury by attenuating mitochondrial dysfunction in a murine burn injury model,” Journal of Cellular and Molecular Medicine, 2013 Vol. 17, No. 5 (pp. 664-671). [cited by applicant]
Ma et al., “Analysis of afferent, central, and efferent components of the baroreceptor reflex in mice,” American Journal of Physiology, 2002, vol. 283 (pp. 1033-1040). [cited by applicant]
Maj et al., “P5775: Autonomic imbalance and circulating androgens and estrogens in men with systolic heart failure,” European Heart Journal, 32 (Abstract Supplement), pp. 1090 (2011). [cited by applicant]
Malkin, et al., “Life-saving or life-prolonging? Interpreting trial data and survival curves for patients with congestive heart failure,” The European Journal of Heart Failure, 7, pp. 143-148 (2005). [cited by applicant]
Mann, “Chapter 12—Peripheral Nerves,” The Nervous System in Action, michaeldmann.net/mannl2.html, (Jul. 2011). [cited by applicant]
Mann, “Inflammatory Mediators and the Failing Heart. Past, Present, and the Foreseeable Future,” Circ Res., 91, pp. 988-998 (2002). [cited by applicant]
Mann, “Stress-Activated Cytokines and the Heart: From Adaptation to Maladaptation,” Annu. Rev. Physiol., 65, pp. 81-101 (2003). [cited by applicant]
Martin-Portugues et al., “Histopathologic features of the vagus nerve after electrical stimulation in swine,” Histol Histopathol, 20, pp. 851-856 (2005). [cited by applicant]
Martins et al., “Distribution of Local Repolarization Changes Produced by Efferent Vagal Stimulation in the Canine Ventricles,” JACC, Dec. 1983, vol. 2, No. 6 (pp. 1191-1199). [cited by applicant]