Abstract:
An electrostimulation device including an electrode shaft that includes a plurality of electrodes, a delivery device that includes a cannula, through which the electrode shaft is insertable, a fixation member fixable on the cannula, and a locking mechanism for selectively permitting and preventing relative movement between the electrode shaft and the delivery device.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a continuation of U.S. patent application Ser. No. 13/755,116, filed Jan. 31, 2013, which is incorporated herein by reference. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates generally to electro stimulation of receptors, such as chemoreceptors, baroreceptors and aortic arch receptors, such as for inducing changes in the diameter of blood vessels of the brain, including dilation and constriction. 
       BACKGROUND OF THE INVENTION 
       [0003]    The cardiovascular center of the brain includes groups of neurons scattered within the medulla of the brain stem, which regulate heart rate, contractility of the ventricles, and blood vessel diameter. The cardiovascular center receives input both from higher brain regions and from sensory receptors. The two main types of sensory receptors that provide input to the cardiovascular center are baroreceptors and chemoreceptors. Baroreceptors are pressure-sensitive sensory neurons that monitor stretching of the walls of blood vessels and the atria. Chemoreceptors monitor blood acidity, carbon dioxide level and oxygen level. 
         [0004]    Outputs from the cardiovascular center flow along sympathetic and parasympathetic fibers of the autonomic nervous system. Sympathetic stimulation of the heart increases heart rate and contractility, whereas parasympathetic stimulation decreases heart rate. Thus autonomic control of the heart is the result of opposing sympathetic (stimulatory) and parasympathetic (inhibitory) influences. Autonomic control of blood vessels, on the other hand, is mediated exclusively by the sympathetic division of the autonomic nervous system. 
         [0005]    The primarily function of chemoreceptors is to regulate respiratory activity. This is an important mechanism for maintaining arterial blood gases pO 2 , pCO 2 , and pH within appropriate physiological ranges. For example, a decrease in arterial pO 2  (hypoxemia) or an increase in arterial pCO 2  (hypercapnia) leads to an increase in the rate and depth of respiration through activation of the chemoreceptor reflex. Respiratory arrest and circulatory shock (which decrease arterial pO 2  and pH, and increase arterial pCO 2 ) dramatically increase chemoreceptor activity leading to enhanced sympathetic outflow to the heart and vasculature via activation of the vasomotor center in the medulla. Cerebral ischemia activates central chemoreceptors, which produces simultaneous activation of sympathetic and vagal nerves to the cardiovascular system. 
         [0006]    The carotid bodies are located on the external carotid arteries near their bifurcation with the internal carotids. Each carotid body is a few millimeters in size and has the distinction of having the highest blood flow per tissue weight of any organ in the body. Afferent nerve fibers join with the sinus nerve before entering the glossopharyngeal nerve. A decrease in carotid body blood flow results in cellular hypoxia, hypercapnia, and decreased pH that lead to an increase in receptor firing. The threshold pO2 for activation is about 80 mmHg (normal arterial pO 2  is about 95 mmHg). Any elevation of pCO 2  above a normal value of 40 mmHg, or a decrease in pH below 7.4 causes receptor firing. 
         [0007]    PCT Patent Application PCT/IL2012/000290, filed 2 Aug. 2012, describes stimulation of chemoreceptors and baroreceptors in a carotid artery. In one embodiment, a device is inserted intravascularly via the femoral artery. In another embodiment, a device is introduced in an extravascular approach. 
       SUMMARY 
       [0008]    The present invention seeks to provide further features to some of the devices described in PCT Patent Application PCT/IL2012/000290. The invention has many uses in the treatment of physiological disorders such as, but not limited to cerebral brain vasospasm, ischemia and brain injury. Embodiments of the invention can be used to stimulate the carotid sinus nerve, aortic nerve, chemoreceptors adjacent to the bifurcation of the carotid, baroreceptors adjacent to the bifurcation of the carotid, aortic arch chemoreceptors and aortic arch baroreceptors, and others, in order to induce changes in the diameter of blood vessels of the brain, including dilation and constriction. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0009]    The present invention will be understood and appreciated more fully from the following detailed description, taken in conjunction with the drawings in which: 
           [0010]      FIGS. 1-1 and 1-2  are simplified illustrations of an electrostimulation device, constructed and operative in accordance with a non-limiting embodiment of the present invention; 
           [0011]      FIG. 1-3  is a simplified illustration of an expandable member, useful in fixation of the device; 
           [0012]      FIGS. 2-1 to 2-16  are simplified illustrations of a method of using the electrostimulation device, in accordance with a non-limiting embodiment of the present invention; 
           [0013]      FIG. 3  is a simplified illustration of the electrostimulation device inserted in a neck of a patient with electrodes positioned at the carotid bifurcation, in accordance with a non-limiting embodiment of the present invention; 
           [0014]      FIG. 4  is a simplified schematic illustration of dipole stimulation of the receptors or neurons, showing the electrical field around the electrodes; 
           [0015]      FIGS. 5-1 to 5-3  are simplified illustrations of electrodes positioned at both sides of the carotid bifurcation, wherein all electrodes are collinear, in accordance with a non-limiting embodiment of the present invention; 
           [0016]      FIGS. 6-1 to 6-4  are simplified illustrations of electrodes positioned at both sides of the carotid bifurcation in a three-dimensional pattern, in accordance with a non-limiting embodiment of the present invention; and 
           [0017]      FIGS. 7-1 to 7-2  are simplified illustrations of electrodes are positioned lateral to the carotid bifurcation and parallel to the common carotid artery, in accordance with a non-limiting embodiment of the present invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0018]    Reference is now made to  FIGS. 1-1 and 1-2 , which illustrate an electrostimulation device  10 , constructed and operative in accordance with a non-limiting embodiment of the present invention. Electrostimulation device  10  includes an electrode shaft  12 , which has a distal opening  14  and a proximal valve  16  plus one or more proximal branches  18 , to which an electrical connector  20  is connected via a flexible cable  22 . Electrode shaft  12  may include a plurality of axially spaced electrodes  24 , such as near a distal portion thereof, which may be energized by an energy source (not shown). Electrodes  24  extend at least partially around a circumference of shaft  12 . Thus in one embodiment, electrodes  24  are full 360° rings around shaft  12 . In another embodiment, electrodes are partial rings that do not extend completely 360° around shaft  12 . One or more fiducial markers  26 , such as axially spaced stripes (which may be radiopaque), are proximal to the electrodes  24  ( FIG. 1-2 ). 
         [0019]    The electrical connector  20  is connected to a controller  28  (also called miniature autonomic unit  28 ,  FIG. 1-1 ), which controls operating parameters associated with energization of electrodes  24 , such as current and frequency of signals used to energize the electrodes. 
         [0020]    The electric stimulation can be optimized by controller  28  and positioning the electrodes  24  relative to the target anatomy in order to achieve effective nerve stimulation and minimize side effects. These parameters control the shape and strength of the electrical field and its anatomic location. For example, current applied to the electrodes may be in, but is not limited to, the range of 0-10 mA. Voltage applied to the electrodes may be in, but is not limited to, the range of 0-25 V. The signals are preferably biphasic, but may be monophasic or a combination thereof. The distance between the effective electrodes can be in the range of about 1-20 mm, but the distance is not limited to this range. 
         [0021]    The electrodes can be activated in any combination and in any order. The combinations and order can be changed during a stimulation session, either as part of a pre-determined sequence or in response to feedback from the patient. 
         [0022]    The electrodes can range, without limitation, from about a tenth of a millimeter long to about 10 millimeter long. The electrodes can be cylindrical, partly-cylindrical with the base forming a sector of a circle, spherical, hemispheric, forming a section of a sphere, cylindrical with a polygonal base, cylindrical with a base forming a sector of a polygon, in the form of a triangular prism, in the form of a rectangular solid, in the form of an octahedral solid, in the form of a dodecahedral solid, in the form of an icosahedral solid, rectangular prism, ellipsoid, parallelepiped, star-shaped solid, helical and any combination thereof. Electrodes can be mounted longitudinally, transversely, or at an angle to supports. 
         [0023]    The signal profile used to energize the electrodes can be of a wide variety—burst, prolonged, intermittent and any combination thereof. Individual groups of signals, such as but not limited to individual bursts, can have a step profile, a ramped profile that increases monotonically from the beginning to the end of the group of signals, a ramped profile that decreases monotonically from the beginning to the end of the group, a ramped profile which increases from a small value to a predetermined value, then remains constant until the end of the group, a ramped profile that starts at a predetermined value, remains at that value for a predetermined portion of the group, then decreases to a small value at the end of the group, a sinusoidal signal profile, a triangular signal profile, and any combination thereof. 
         [0024]    The electrostimulation device  10  also includes a delivery device  30 , which includes a cannula  32 , which has a distal fixation member (which in this embodiment is a balloon)  34 , a lockable proximal insertion port  36  and one or more proximal branch ports  38 . A syringe  39 , or other suitable fluid source, is provided for inflating balloon  34 , such as through branch port  38  (also called inflation port  38 ) which may be in fluid communication with balloon  34 . Delivery device  30  also includes an external fixation member  31  and a locking element or valve  35  ( FIG. 1-2 ), distal to lockable proximal insertion port  36 , also referred to as locking mechanism  36 . As will be explained later, balloon  34  serves as an internal fixation member for fixation of the device in the patient. As seen in  FIG. 1-3 , instead of a balloon, other internal fixation members may be used, such as an expandable member  23  with loops that bend or buckle or otherwise deform outwards. The maximal axial cross-section of the internal fixation member ( 23  or  34 ) is increased in the deployment state of the device and decreased in the delivery state of the device. In one embodiment, the ratio of the maximal cross-sections of the internal fixation member ( 23  or  34 ) between the deployment and delivery states of the device is larger than 2. Fixation of the device is important, because even slight movement of the device may adversely affect treatment or even worse may cause harm to neighboring tissues. The external fixation member  31  may be a plate member with mounting holes for suturing. 
         [0025]    The electrostimulation device  10  also includes a needle  40  with an echogenic distal tip  42  and a plurality of fiducial markers  44  proximal to tip  42 . 
         [0026]    The electrostimulation device  10  also includes a spacer  46 , whose function will be described below. 
         [0027]    Reference is now made to  FIGS. 2-1 to 2-16 , which illustrate a method of using the electrostimulation device  10 , in accordance with a non-limiting embodiment of the present invention. 
         [0028]    Referring to  FIG. 2-1 , electrode shaft  12  is introduced through proximal insertion port  36  of delivery device  30 . Spacer  46  is poised for positioning. In  FIG. 2-2 , spacer  46  is snapped, clamped or otherwise affixed to electrode shaft  12  and delivery device  30 . For example, spacer  46  may be formed with a pair of notched ears  47  at opposite ends thereof ( FIG. 2-1 ), one of which snugly fits into a groove  49  ( FIG. 2-1 ) formed on a proximal head of electrode shaft  12  and the other of which snugly fits behind a collar  43  ( FIG. 2-1 ) on delivery device  30 . The affixed spacer  46  establishes a relative position of electrode shaft  12  with respect to delivery device  30 . The electrode markers  26  on shaft  12  will serve as an indication for the amount of electrode exposure at the distal tip of delivery device  30 , as explained later. 
         [0029]    In  FIG. 2-3 , needle  40  is introduced through proximal valve  16  of electrode shaft  12  and passes all the way through delivery device  30 , so that tip  42  of needle  40  extends out the distal end of delivery device  30 . In  FIG. 2-4 , needle  40  is positioned axially to a desired position along electrode shaft  12  and delivery device  30 , using fiducial markers  44  to indicate the axial position. In  FIG. 2-5 , proximal valve  16  of electrode shaft  12  is closed to lock needle  40  in place. 
         [0030]    In  FIG. 2-6 , tip  42  of needle  40  punctures tissue  33 , such as the tissue in a neck of a patient, for introducing the device to the carotid bifurcation (see  FIG. 3 ). The assembly is passed through tissue  33  so that balloon  34  is on the inner side of the tissue wall. In  FIG. 2-7 , balloon  34  is inflated with fluid (e.g., saline) via inflation port  38 , such as with the syringe  39  of  FIG. 1-2 . In  FIG. 2-8 , spacer  46  is removed. 
         [0031]    In  FIG. 2-9 , the proximal valve  16  is unlocked so as to permit relative movement of shaft  12  with respect to needle  40 . While holding needle  40  in place, electrode shaft  12  is moved distally until the proximal valve  16  moves past and just exposes a distal marker  44  of needle  40 . Electrode shaft  12  now extends distally beyond the distal end of delivery device  30 . As mentioned above, electrode markers  26  on shaft  12  serve as an indication for the amount of electrode exposure at the distal tip of delivery device  30 . In  FIG. 2-10 , needle  40  is retracted slightly (if needed—until the most distal marker  44  is exposed) so that its distal tip does not protrude beyond electrode shaft  12 . Proximal valve  16  is relocked. 
         [0032]    In  FIG. 2-11 , electrical connector  20  is connected to controller  28  for operating electrodes  24 . In  FIG. 2-12 , controller  28  is used to select and optimize stimulation parameters, such as but not limited to, voltage, frequency, pulse width, duty cycle and type of signals, used to energize the electrodes  24  (as mentioned more in detail above). In addition, the axial and radial orientation of the electrodes  24  may be optimized by unlocking locking mechanism  36  to allow radial and axial movement of shaft  12 . In  FIG. 2-13 , after the optimization and orientation are done, the needle may be removed from electrode shaft  12 . The assembly is now more flexible, because the needle is much more rigid than shaft  12  and cannula  32 . 
         [0033]    The flexibility of the assembly is now described with reference to  FIG. 2-14 . After removing the needle, electrode shaft  12  has a strain relief portion  77 , which may be positioned between proximal branches  18  and electrodes  24 . The strain relief portion  77  is flexible, and as seen in the drawing, can be bent to a curved shape (e.g., S-shape). The strain relief portion  77  significantly reduces any transfer of rotational torque and/or linear forces (push and/or pull forces) between the electrode shaft proximal valve  16  and branches  18  and the electrodes  24 . This helps prevent disturbing the fixation of the device. Accordingly, without the needle, the strain relief portion  77  is considered to assume an active state, in which it is capable of reducing passage of rotational torque and linear forces. With the needle, the strain relief portion  77  is considered to assume a neutralized state, in which passage of rotational torque or linear forces is permitted (e.g., at least two fold higher than in its active state). 
         [0034]    In  FIG. 2-15 , the external fixation member  31  is mounted on delivery device  30 . In  FIG. 2-16 , external fixation member  31  is moved against tissue  33  and locking element  35  is secured against cannula  32 . The external fixation member  31  is sutured to tissue  33 . 
         [0035]    Reference is now made to  FIG. 3 , which illustrates electrostimulation device  10  inserted in an extravascular approach through a neck of a patient, in accordance with a non-limiting embodiment of the present invention. Device  10  is inserted and positioned (as described above with reference to  FIG. 2-12 , so that the electrodes  24  are closely superior to the carotid bodies  50  near the carotid bifurcation  51 , which is superior to the common carotid artery  52  and next to the internal jugular vein  53 . The internal fixation balloon  34  and the external fixation member  31  are on opposite sides of the skin. 
         [0036]    Electrostimulation of receptors, such as chemoreceptors, baroreceptors and aortic arch receptors, such as for inducing vasodilatation in blood vessels of the brain, is performed by energizing the electrodes  24  with the controller (also called electrical stimulation unit (ESU))  28  (not shown in  FIG. 3 ). 
         [0037]    Dipole stimulation of the receptors or neurons is carried out by rapidly changing the electrical field around the electrodes  24 , which is seen schematically in  FIG. 4 . The waveform of the electrical signal significantly affects the threshold of energy applied to the receptors. The longitudinal component of the electric field excites the nerve, so the current lines should be along the nerve&#39;s longitudinal axis; in other words, the electric field should be optimally implemented so that the longitudinal vectors are along the carotid body region. Balance biphasic waveforms are preferred because the equivalent charge is neutral and thus reduces possible tissue damage. The electric field should be localized and balanced as much as possible (longitudinally and radially) and its amplitude should be as low as possible in order to reduce possible side effects, such as other physiological effects, and tissue damage. 
         [0038]    The following are non-limiting examples of position and orientation of electrodes for electrostimulation of the receptors. 
         [0039]    In  FIGS. 5-1 to 5-3 , electrodes  24  are positioned at both sides of the carotid bifurcation  51 , wherein all electrodes  24  are collinear, that is, along a single axis. This is the simple configuration of electrodes  24 , which all lie on shaft  12 . 
         [0040]    In  FIGS. 6-1 to 6-4 , one or more electrodes  24  are positioned on shaft  12  and one or more electrodes  24  are positioned on some inner deployed element, which may be a fixation member, either internal fixation balloon  34  or other expandable element or other structure. In this manner, the electrodes  24  are positioned at both sides of the carotid bifurcation  51  in a three-dimensional pattern.  FIG. 6-3  shows possible 3D electrical fields  63  created by the electrodes  24 , wherein the electrodes are not collinear but instead are positioned in different positions in 3D space. The electrodes can be positioned and energized in various manners to create many possible electrical fields. 
         [0041]    In  FIGS. 7-1 to 7-2 , electrodes  24  are positioned lateral to the carotid bifurcation  51  and parallel to the common carotid artery  52 . The electrodes  24  are collinear, that is, along a single axis.