Applications of vagal stimulation

Abstract

A method is provided for treating a subject, including applying a current to a site of the subject selected from the list consisting of: a vagus nerve of the subject, an epicardial fat pad of the subject, a pulmonary vein of the subject, a carotid artery of the subject, a carotid sinus of the subject, a vena cava vein of the subject, and an internal jugular vein of the subject. The method also includes configuring the current so as to treat a condition of the subject selected from the list consisting of: an autoimmune disease, an autoimmune inflammatory disease, multiple sclerosis, encephalitis, myelitis, immune-mediated neuropathy, myositis, dermatomyositis, polymyositis, inclusion body myositis, inflammatory demyelinating polyradiculoneuropathy, Guillain Barre syndrome, myasthenia gravis, inflammation of the nervous system, inflammatory bowel disease, Crohn's disease, ulcerative colitis, SLE (systemic lupus erythematosus), rheumatoid arthritis, vasculitis, polyarteritis nodosa, Sjogren syndrome, mixed connective tissue disease, glomerulonephritis, thyroid autoimmune disease, sepsis, meningitis, a bacterial infection, a viral infection, a fungal infection, sarcoidosis, hepatitis, and portal vein hypertension.

1 . A method for treating a subject, comprising: 
 applying a current to a site of the subject selected from the list consisting of: a vagus nerve of the subject, an epicardial fat pad of the subject, a pulmonary vein of the subject, a carotid artery of the subject, a carotid sinus of the subject, a vena cava vein of the subject, and an internal jugular vein of the subject; and    configuring the current so as to treat a condition of the subject selected from the list consisting of: an autoimmune disease, an autoimmune inflammatory disease, multiple sclerosis, encephalitis, myelitis, immune-mediated neuropathy, myositis, dermatomyositis, polymyositis, inclusion body myositis, inflammatory demyelinating polyradiculoneuropathy, Guillain Barre syndrome, myasthenia gravis, inflammation of the nervous system, inflammatory bowel disease, Crohn's disease, ulcerative colitis, SLE (systemic lupus erythematosus), rheumatoid arthritis, vasculitis, polyarteritis nodosa, Sjogren syndrome, mixed connective tissue disease, glomerulonephritis, thyroid autoimmune disease, sepsis, meningitis, a bacterial infection, a viral infection, a fungal infection, sarcoidosis, hepatitis, and portal vein hypertension.    
     
     
         2 . The method according to  claim 1 , wherein the condition includes the rheumatoid arthritis, and wherein configuring the current comprises configuring the current so as to treat the rheumatoid arthritis.  
     
     
         3 . The method according to  claim 1 , wherein the condition includes the autoimmune disease, and wherein configuring the current comprises configuring the current so as to treat the autoimmune disease.  
     
     
         4 . The method according to  claim 1 , wherein the condition includes the autoimmune inflammatory disease, and wherein configuring the current comprises configuring the current so as to treat the autoimmune inflammatory disease.  
     
     
         5 . The method according to  claim 1 , wherein the condition includes the multiple sclerosis, and wherein configuring the current comprises configuring the current so as to treat the multiple sclerosis.  
     
     
         6 . The method according to  claim 1 , wherein the condition includes the SLE, and wherein configuring the current comprises configuring the current so as to treat the SLE.  
     
     
         7 . The method according to  claim 1 , wherein the site includes the epicardial fat pad, and wherein applying the current comprises applying the current to the epicardial fat pad.  
     
     
         8 . The method according to  claim 1 , wherein the site includes the pulmonary vein, and wherein applying the current comprises applying the current to the pulmonary vein.  
     
     
         9 . The method according to  claim 1 , wherein the site includes the carotid artery, and wherein applying the current comprises applying the current to the carotid artery.  
     
     
         10 . The method according to  claim 1 , wherein the site includes the carotid sinus, and wherein applying the current comprises applying the current to the carotid sinus.  
     
     
         11 . The method according to  claim 1 , wherein the site includes the vena cava vein, and wherein applying the current comprises applying the current to the vena cava vein.  
     
     
         12 . The method according to  claim 1 , wherein the site includes the internal jugular vein, and wherein applying the current comprises applying the current to the internal jugular vein.  
     
     
         13 . The method according to  claim 1 , wherein the site includes the vagus nerve, and wherein applying the current comprises applying the current to the vagus nerve.  
     
     
         14 . The method according to  claim 13 , wherein applying the current comprises applying a stimulating current, which is capable of inducing action potentials in a first set and a second set of nerve fibers of the vagus nerve, and an inhibiting current, which is capable of inhibiting the induced action potentials traveling in the second set of nerve fibers, the nerve fibers in the second set having generally larger diameters than the nerve fibers in the first set.  
     
     
         15 . The method according to  claim 13 , wherein applying the current comprises applying a stimulating current, which is capable of inducing action potentials in the vagus nerve, and an inhibiting current, which is capable of inhibiting action potentials induced by the stimulating current and traveling in the vagus nerve in an afferent direction toward a brain of the subject.  
     
     
         16 . The method according to  claim 1 , wherein applying the current comprises applying the current in respective bursts of pulses in each of a plurality of cardiac cycles of the subject.  
     
     
         17 . The method according to  claim 16 , wherein applying the current comprises applying a first pulse of each of the bursts after a delay from a sensed feature of an electrocardiogram (ECG) of the subject.  
     
     
         18 . The method according to  claim 1 , comprising sensing a physiological parameter of the subject, wherein configuring the current comprises configuring the current at least in part responsively to the sensed physiological parameter.  
     
     
         19 . The method according to  claim 18 , wherein sensing the physiological parameter comprises sensing a heart rate of the subject.  
     
     
         20 . The method according to  claim 1 , wherein configuring the current comprises configuring the current so as to minimize an effect of the applying of the current on a heart rate of the subject.  
     
     
         21 . The method according to  claim 20 , wherein applying the current comprises applying the current in respective bursts of pulses in each of a plurality of cardiac cycles of the subject.  
     
     
         22 . The method according to  claim 21 , wherein applying the current comprises applying the current to a left vagus nerve of the subject.  
     
     
         23 . The method according to  claim 21 , wherein applying the current comprises configuring each of the pulses to have a duration of between about 200 microseconds and about 2.5 milliseconds.  
     
     
         24 . The method according to  claim 21 , wherein applying the current comprises configuring each of the pulses to have a duration of between about 2.5 and about 5 milliseconds.  
     
     
         25 . The method according to  claim 21 , wherein applying the current comprises configuring each of the bursts to have a duration of between about 0.2 and about 40 milliseconds.  
     
     
         26 . The method according to  claim 21 , wherein applying the current comprises configuring each of the bursts to contain between about 1 and about 10 pulses.  
     
     
         27 . The method according to  claim 21 , wherein applying the current comprises configuring the pulses within each of the bursts to have a pulse repetition interval of between about 2 and about 10 milliseconds.  
     
     
         28 . The method according to  claim 21 , wherein applying the current comprises configuring the pulses to have an amplitude of between about 0.5 and about 5 milliamps.  
     
     
         29 . The method according to  claim 21 , wherein applying the current comprises applying the bursts less than every heartbeat of the subject.  
     
     
         30 . The method according to  claim 21 , wherein applying the current comprises applying the bursts once per heartbeat of the subject.  
     
     
         31 . The method according to  claim 21 , wherein applying the current comprises applying the current to the site intermittently during alternating “on” and “off” periods, each of the “on” periods having a duration of at least about 1 second.  
     
     
         32 . The method according to  claim 21 , wherein applying the current comprises applying each of the bursts after a variable delay following a P-wave of the subject, the delay having a duration equal to between about two-thirds and about 90% of a duration of a cardiac cycle of the subject.  
     
     
         33 . The method according to  claim 32 , wherein applying the current comprises substantially continuously measuring the duration of the cardiac cycle.  
     
     
         34 . The method according to  claim 1 , wherein applying the current comprises applying the current in respective bursts of pulses in each of a plurality of cardiac cycles of the subject.  
     
     
         35 . The method according to  claim 34 , wherein applying the current comprises configuring each of the pulses to have a duration of between about 100 microseconds and about 2.5 milliseconds.  
     
     
         36 . The method according to  claim 34 , wherein applying the current comprises configuring each of the bursts to have a duration of between about 1 and about 180 milliseconds.  
     
     
         37 . The method according to  claim 34 , wherein applying the current comprises configuring each of the bursts to contain between about 1 and about 10 pulses.  
     
     
         38 . The method according to  claim 34 , wherein applying the current comprises configuring the pulses within each of the bursts to have a pulse repetition interval of between about 1 and about 20 milliseconds.  
     
     
         39 . The method according to  claim 34 , wherein applying the current comprises configuring the pulses to have an amplitude of between about 0.1 and about 9 milliamps.  
     
     
         40 . The method according to  claim 34 , wherein applying the current comprises applying the bursts once every second heartbeat.  
     
     
         41 . The method according to  claim 34 , wherein applying the current comprises applying the bursts once every third heartbeat.  
     
     
         42 . The method according to  claim 34 , wherein applying the current comprises applying the current to the site intermittently during alternating “on” and “of f” periods, each of the “on” periods having a duration of at least about 1 second.  
     
     
         43 . The method according to  claim 34 , wherein applying the current comprises applying each of the bursts after a delay following an R-wave of the subject, the delay having a duration of about 100 milliseconds.  
     
     
         44 . Apparatus for treating a subject, comprising: 
 an electrode device, adapted to be coupled to a site of the subject selected from the list consisting of: a vagus nerve of the subject, an epicardial fat pad of the subject, a pulmonary vein of the subject, a carotid artery of the subject, a carotid sinus of the subject, a vena cava vein of the subject, and an internal jugular vein of the subject; and    a control unit, adapted to:    drive the electrode device to apply an electrical current to the site, and    configure the current so as to treat a condition of the subject selected from the list consisting of: an autoimmune disease, an autoimmune inflammatory disease, multiple sclerosis, encephalitis, myelitis, immune-mediated neuropathy, myositis, dermatomyositis, polymyositis, inclusion body myositis, inflammatory demyelinating polyradiculoneuropathy, Guillain Barre syndrome, myasthenia gravis, inflammation of the nervous system, inflammatory bowel disease, Crohn's disease, ulcerative colitis, SLE (systemic lupus erythematosus), rheumatoid arthritis, vasculitis, polyarteritis nodosa, Sjogren syndrome, mixed connective tissue disease, glomerulonephritis, thyroid autoimmune disease, sepsis, meningitis, a bacterial infection, a viral infection, a fungal infection, sarcoidosis, hepatitis, and portal vein hypertension.    
     
     
         45 . The apparatus according to  claim 44 , wherein the condition includes the rheumatoid arthritis, and wherein the control unit is adapted to configure the current so as to treat the rheumatoid arthritis.  
     
     
         46 . The apparatus according to  claim 44 , wherein the condition includes the autoimmune disease, and wherein the control unit is adapted to configure the current so as to treat the autoimmune disease.  
     
     
         47 . The apparatus according to  claim 44 , wherein the condition includes the autoimmune inflammatory disease, and wherein the control unit is adapted to configure the current so as to treat the autoimmune inflammatory disease.  
     
     
         48 . The apparatus according to  claim 44 , wherein the condition includes the multiple sclerosis, and wherein the control unit is adapted to configure the current so as to treat the multiple sclerosis.  
     
     
         49 . The apparatus according to  claim 44 , wherein the condition includes the SLE, and wherein the control unit is adapted to configure the current so as to treat the SLE.  
     
     
         50 . The apparatus according to  claim 44 , wherein the site includes the epicardial fat pad, and wherein the electrode device is adapted to be coupled to the epicardial fat pad.  
     
     
         51 . The apparatus according to  claim 44 , wherein the site includes the pulmonary vein, and wherein the electrode device is adapted to be coupled to the pulmonary vein.  
     
     
         52 . The apparatus according to  claim 44 , wherein the site includes the carotid artery, and wherein the electrode device is adapted to be coupled to the carotid artery.  
     
     
         53 . The apparatus according to  claim 44 , wherein the site includes the carotid sinus, and wherein the electrode device is adapted to be coupled to the carotid sinus.  
     
     
         54 . The apparatus according to  claim 44 , wherein the site includes the vena cava vein, and wherein the electrode device is adapted to be coupled to the vena cava vein.  
     
     
         55 . The apparatus according to  claim 44 , wherein the site includes the internal jugular vein, and wherein the electrode device is adapted to be coupled to the internal jugular vein.  
     
     
         56 . The apparatus according to  claim 44 , wherein the site includes the vagus nerve, and wherein the electrode device is adapted to be coupled to the vagus nerve.  
     
     
         57 . The apparatus according to  claim 56 , wherein the control unit is adapted to configure the current to include a stimulating current, which is capable of inducing action potentials in a first set and a second set of nerve fibers of the vagus nerve, and an inhibiting current, which is capable of inhibiting the induced action potentials traveling in the second set of nerve fibers, the nerve fibers in the second set having generally larger diameters than the nerve fibers in the first set.  
     
     
         58 . The apparatus according to  claim 56 , wherein the control unit is adapted to configure the current to include a stimulating current, which is capable of inducing action potentials in the vagus nerve, and an inhibiting current, which is capable of inhibiting action potentials induced by the stimulating current and traveling in the vagus nerve in an afferent direction toward a brain of the subject.  
     
     
         59 . The apparatus according to  claim 44 , wherein the control unit is adapted to drive the electrode device to apply the current in respective bursts of pulses in each of a plurality of cardiac cycles of the subject.  
     
     
         60 . The apparatus according to  claim 59 , wherein the control unit is adapted to drive the electrode device to apply a first pulse of each of the bursts after a delay from a sensed feature of an electrocardiogram (ECG) of the subject.  
     
     
         61 . The apparatus according to  claim 44 , wherein the control unit is adapted to sense a physiological parameter of the subject, and to configure the current at least in part responsively to the sensed physiological parameter.  
     
     
         62 . The apparatus according to  claim 61 , wherein the physiological parameter includes a heart rate of the subject, and wherein the control unit is adapted to sense the heart rate.  
     
     
         63 . The apparatus according to  claim 44 , wherein the control unit is adapted to configure the current so as to minimize an effect of the applying of the current on a heart rate of the subject.  
     
     
         64 . The apparatus according to  claim 63 , wherein the control unit is adapted to drive the electrode device to apply the current in respective bursts of pulses in each of a plurality of cardiac cycles of the subject.  
     
     
         65 . The apparatus according to  claim 64 , wherein the electrode device is adapted to be coupled to a left vagus nerve of the subject.  
     
     
         66 . The apparatus according to  claim 64 , wherein the control unit is adapted to configure each of the pulses to have a duration of between about 200 microseconds and about 2.5 milliseconds.  
     
     
         67 . The apparatus according to  claim 64 , wherein the control unit is adapted to configure each of the pulses to have a duration of between about 2.5 and about 5 milliseconds.  
     
     
         68 . The apparatus according to  claim 64 , wherein the control unit is adapted to configure each of the bursts to have a duration of between about 0.2 and about 40 milliseconds.  
     
     
         69 . The apparatus according to  claim 64 , wherein the control unit is adapted to configure each of the bursts to contain between about 1 and about 10 pulses.  
     
     
         70 . The apparatus according to  claim 64 , wherein the control unit is adapted to configure the pulses within each of the bursts to have a pulse repetition interval of between about 2 and about 10 milliseconds.  
     
     
         71 . The apparatus according to  claim 64 , wherein the control unit is adapted to configure the pulses to have an amplitude of between about 0.5 and about 5 milliamps.  
     
     
         72 . The apparatus according to  claim 64 , wherein the control unit is adapted to drive the electrode device to apply the bursts less than every heartbeat of the subject.  
     
     
         73 . The apparatus according to  claim 64 , wherein the control unit is adapted to drive the electrode device to apply the bursts once per heartbeat of the subject.  
     
     
         74 . The apparatus according to  claim 64 , wherein the control unit is adapted to drive the electrode device to apply the current to the site intermittently during alternating “on” and “off” periods, each of the “on” periods having a duration of at least about 1 second.  
     
     
         75 . The apparatus according to  claim 64 , wherein the control unit is adapted to drive the electrode device to apply each of the bursts after a variable delay following a P-wave of the subject, the delay having a duration equal to between about two-thirds and about 90% of a duration of a cardiac cycle of the subject.  
     
     
         76 . The apparatus according to  claim 75 , wherein the control unit is adapted to substantially continuously measure the duration of the cardiac cycle.  
     
     
         77 . The apparatus according to  claim 44 , wherein the control unit is adapted to drive the electrode device to apply the current in respective bursts of pulses in each of a plurality of cardiac cycles of the subject.  
     
     
         78 . The apparatus according to  claim 77 , wherein the control unit is adapted to configure each of the pulses to have a duration of between about 100 microseconds and about 2.5 milliseconds.  
     
     
         79 . The apparatus according to  claim 77 , wherein the control unit is adapted to configure each of the bursts to have a duration of between about 1 and about 180 milliseconds.  
     
     
         80 . The apparatus according to  claim 77 , wherein the control unit is adapted to configure each of the bursts to contain between about 1 and about 10 pulses.  
     
     
         81 . The apparatus according to  claim 77 , wherein the control unit is adapted to configure the pulses within each of the bursts to have a pulse repetition interval of between about 1 and about 20 milliseconds.  
     
     
         82 . The apparatus according to  claim 77 , wherein the control unit is adapted to configure the pulses to have an amplitude of between about 0.1 and about 9 milliamps.  
     
     
         83 . The apparatus according to  claim 77 , wherein the control unit is adapted to drive the electrode device to apply the bursts once every second heartbeat.  
     
     
         84 . The apparatus according to  claim 77 , wherein the control unit is adapted to drive the electrode device to apply the bursts once every third heartbeat.  
     
     
         85 . The apparatus according to  claim 77 , wherein the control unit is adapted to drive the electrode device to apply the current to the site intermittently during alternating “on” and “off” periods, each of the “on” periods having a duration of at least about 1 second.  
     
     
         86 . The apparatus according to  claim 77 , wherein the control unit is adapted to drive the electrode device to apply each of the bursts after a delay following an R-wave of the subject, the delay having a duration of about 100 milliseconds.  
     
     
         87 . The apparatus according to  claim 44 , wherein the control unit is adapted to monitor a heart rate of the subject, and withhold the applying of the current in response to the heart rate being lower than a threshold heart rate.  
     
     
         88 . The method according to  claim 1 , wherein applying the current comprises monitoring a heart rate of the subject, and withholding the applying of the current in response to the heart rate being lower than a threshold heart rate.  
     
     
         89 . The apparatus according to  claim 44 , wherein the condition includes the inflammatory bowel disease, and wherein the control unit is adapted to configure the current so as to treat the inflammatory bowel disease.  
     
     
         90 . The apparatus according to  claim 44 , wherein the condition includes the Crohn's disease, and wherein the control unit is adapted to configure the current so as to treat the Crohn's disease.  
     
     
         91 . The apparatus according to  claim 44 , wherein the condition includes the ulcerative colitis, and wherein the control unit is adapted to configure the current so as to treat the ulcerative colitis.  
     
     
         92 . The method according to  claim 1 , wherein the condition includes the inflammatory bowel disease, and wherein configuring the current comprises configuring the current so as to treat the inflammatory bowel disease.  
     
     
         93 . The method according to  claim 1 , wherein the condition includes the Crohn's disease, and wherein configuring the current comprises configuring the current so as to treat the Crohn's disease.  
     
     
         94 . The method according to  claim 1 , wherein the condition includes the ulcerative colitis, and wherein configuring the current comprises configuring the current so as to treat the ulcerative colitis.