Abstract:
An implant device comprising an electrode for electrical stimulation of the pancreas, the device being adapted to be inserted into the pancreas, and to change at least one of its properties after being inserted into the pancreas, so that it will cause less irritation to the pancreas than before changing said property.

Description:
RELATED APPLICATIONS 
       [0001]    The present application is a continuation-in part of PCT/IL2005/000316 filed on Mar. 18, 2005 to Tami Harel et al. and claims the benefit under 119(e) of U.S. provisional application No. 60/719,517 filed on Sep. 22, 2005, entitled “Non-Immediate Effects of Therapy” and U.S. provisional application No. 60/719,421, filed on Sep. 22, 2005, entitled “Pancreas Lead”, the disclosures of which are incorporated herein by reference. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The field of the invention relates to electrodes implanted in the body, for example in the pancreas. 
       BACKGROUND OF THE INVENTION 
       [0003]    Electrical stimulation therapy of the pancreas to increase or suppress the production of insulin has been described in published PCT application WO 2004/021858, which describes a variety of configurations of electrodes that might be used for this purpose, including point, line, mesh, plate, ball, and hollow coil-shaped electrodes. 
         [0004]    Published PCT application WO 2000/27468 describes an electrode for cardiac stimulation, in the shape of a flexible helical coil. The electrode is coated with a layer of titanium nitride or iridium oxide, which provides a low impedance and high capacitance coupling between the electrode and the heart tissue. The coating, with a microscopic structure that gives it a very high effective surface area, prevents irreversible loss of ions from the tissue and from the electrode. A stiffening stylet may be inserted into the central lumen of the helix. Multi-wire leads are used to independently supply power to several electrodes positioned at different locations in the heart. 
         [0005]    The disclosures of these applications are incorporated herein by reference. 
       SUMMARY OF THE INVENTION 
       [0006]    An aspect of some embodiments of the invention relates to implanting an electrical stimulation device, comprising an electrode, in the pancreas or another organ, which device changes its properties after implantation in such a way that it will cause less irritation which could lead to fibrosis and/or other damage to the pancreas. This is done, for example, by one or more of: 1) mechanically decoupling or removing from the device an element which assists in inserting the device into the pancreas, for example an internal stiffening element, but which may not be needed, and may cause damage, after the device is implanted; 2) using an electrode surrounded by a sleeve, and increasing the mechanical coupling of the sleeve to the pancreatic tissue, and/or decreasing the mechanical coupling of the sleeve to the electrode, while maintaining good electrical coupling, after implantation, so that the electrode can move relative to the pancreas without irritating it; and 3) having the device become more flexible, and/or softer, after implanting it, for example by dissolving a stiffening element. One or more of these measures may tend to decrease the stresses that the electrode exerts on the pancreatic tissue, and/or damage that the electrode may do to the pancreatic tissue, as a result of relative motion between the pancreas and the electrode lead. 
         [0007]    Optionally, the electrode is used in an organ other than the pancreas, for example in another organ comprising spongy tissue, such as the liver, or in an organ comprising muscular tissue, such as the stomach or elsewhere in the digestive track. Using a very flexible electrode in the wall of the stomach, for example, has the potential advantage over using a stiff electrode, that the flexible electrode may be less likely to penetrate through the wall. 
         [0008]    In some embodiments of the invention, the electrode is mechanically decoupled from the lead by using a lead shaped like a helical coil, which provides strain relief to the lead. Alternatively or additionally, strain relief is provided to the lead by having the lead form a loop between a point where the lead is anchored, for example on the duodenum, and a point where the electrode is anchored on the pancreas. Alternatively or additionally, the electrode is mechanically decoupled from the lead by attaching the electrode directly or indirectly to the outer membrane of the pancreas, at a point close to the point where the electrode is implanted in the pancreas, so that any forces exerted on the lead produce stresses at the point of attachment on the outer membrane of the pancreas, rather than on the interior. Stresses on the outer membrane are likely to be less damaging than stresses on the softer interior tissue of the pancreas. 
         [0009]    In some embodiments of the invention, there are barb-like tines which keep the electrode imbedded in the pancreas once it is implanted. In some embodiments of the invention, the electrode has a thin coating with high dielectric constant, such as titanium nitride or iridium oxide, which provides a low impedance AC coupling between the electrode and the pancreatic tissue. 
         [0010]    An aspect of some embodiments of the invention relates to an electrical stimulation device for implanting in the pancreas, comprising an electrode surrounded by a soft sleeve, which causes less irritation and/or damage to the pancreas than the electrode would cause if it were implanted directly in the pancreas without a sleeve. Optionally, there is relative motion between the electrode and the sleeve. 
         [0011]    There is thus provided, according to an exemplary embodiment of the invention, an implant device comprising an electrode for electrical stimulation of the pancreas, the device being adapted to be inserted into the pancreas, and to change at least one of its properties after being inserted into the pancreas, so that it will cause less irritation to the pancreas than before changing said property. 
         [0012]    Optionally, the device comprises an inserting element adapted to assist the device in being inserted into the pancreas, and the device is adapted to become mechanically decoupled from the inserting element after the device is inserted into the pancreas. 
         [0013]    Optionally, the device is adapted to have the inserting element removed from the pancreas after the device is inserted into the pancreas. 
         [0014]    Optionally, the inserting element comprises a needle which is adapted to go through the pancreas and to pull the electrode into the pancreas. 
         [0015]    Additionally or alternatively, the inserting element comprises a stiffening element. 
         [0016]    Optionally, the electrode is hollow with the stiffening element inside. 
         [0017]    Optionally, the stiffening element is a thread coupled to the device, and the device includes a trigger element which releases the thread from being coupled to the device. 
         [0018]    Optionally, the thread is coupled to the device by forming a loop which is pulled tight around the trigger element, and the trigger element releases the thread by being pulled out from the loop. 
         [0019]    In an embodiment of the invention, the device includes a plate, attached to the device, with a hole in it that an end of the thread is threaded through, and the thread is coupled to the device by having said end of the thread knotted, and the trigger element comprises a cutting implement which releases the thread by cutting off the knotted portion of the thread. 
         [0020]    Alternatively, the electrode comprises a crimp in its hollow interior which couples the thread to the device, and an opening which makes a portion of the thread accessible from outside the electrode, and the trigger element comprises a cutting implement which releases the thread by cutting the thread through the opening. 
         [0021]    In an embodiment of the invention, the device includes a sleeve surrounding the electrode, adapted to be sufficiently well electrically coupled to the electrode and to the pancreas for electrical stimulation therapy of the pancreas by the electrode, when the device is inserted into the pancreas. 
         [0022]    Optionally, the sleeve is adapted to become better coupled mechanically to the pancreas after the device is inserted into the pancreas. 
         [0023]    Optionally, the sleeve comprises one or more tines adapted to become set in the pancreas. 
         [0024]    Alternatively or additionally, the sleeve is adapted to expand inside pancreas, thereby increasing its mechanical coupling to the pancreas. 
         [0025]    Alternatively or additionally, the sleeve is adapted to become glued to the pancreas after the device is inserted into the pancreas. 
         [0026]    Optionally, the sleeve is adapted to become mechanically less coupled from the electrode after the device is inserted into the pancreas. 
         [0027]    Optionally, the sleeve is sufficiently soft so that it causes less irritation to the pancreas than the electrode would cause if the electrode were directly in contact with the interior of the pancreas without a sleeve. 
         [0028]    In an embodiment of the invention, the device is adapted to become one or both of softer and more flexible after the device is inserted into the pancreas. 
         [0029]    Optionally, the device comprises a coating of a hard material adapted to dissolve inside the pancreas. 
         [0030]    Optionally, the hard material comprises a sugar. 
         [0031]    Optionally, the coating is on the outside of the electrode. 
         [0032]    Alternatively or additionally, the electrode is hollow, and the coating is inside the electrode, thereby making the electrode stiffer. 
         [0033]    In an embodiment of the invention, the device also includes a lead for supplying current to the electrode, the lead being adapted to being anchored at an anchoring point inside the body, and being sufficiently long and flexible so that a one centimeter increase in distance between the anchoring point and the implanted electrode causes the lead to exert a force no greater than 0.01 newtons on the pancreas. 
         [0034]    Optionally, the device also includes tines coupled to the electrode, oriented so as to prevent the electrode from moving back out of the pancreas after the electrode is implanted in the pancreas. 
         [0035]    Optionally, the electrode is coated with a layer of material capable of reversibly holding at least 100 microcoulombs of ions. 
         [0036]    There is further provided, according to an exemplary embodiment of the invention, an implant device comprising:
       a) an electrode for electrical stimulation of the pancreas; and   b) a sleeve, through which the electrode is electrically coupled to the pancreas with a resistance less than 20 ohms.       
 
         [0039]    Optionally, the sleeve is one or both of sufficiently soft and sufficiently well-coupled mechanically to the pancreas so that the sleeve causes less irritation to the pancreas than the electrode would if the electrode were directly in contact with the interior of the pancreas without a sleeve. 
         [0040]    There is further provided, according to an exemplary embodiment of the invention, a method of implanting an electrical stimulation device in the pancreas, comprising:
       a) inserting the device into the pancreas; and   b) changing at least one property of the device after inserting it into the pancreas, so that it causes less irritation to the pancreas.       
 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0043]    Exemplary embodiments of the invention are described in the following sections with reference to the drawings. The drawings are generally not to scale and the same reference numbers are used for the same or related features on different drawings. 
           [0044]      FIG. 1  shows a schematic perspective view of an electrical stimulation device, according to an exemplary embodiment of the invention; 
           [0045]      FIGS. 2A-2D  show schematic perspective views illustrating a method of implanting the device of  FIG. 1  in the pancreas, according to an exemplary embodiment of the invention; 
           [0046]      FIGS. 3 ,  4 , and  5  show schematic perspective views of electrical stimulation devices according to other exemplary embodiments of the invention; 
           [0047]      FIGS. 6 and 7  show schematic cross-sectional views of the pancreas, with implanted electrodes according to two different exemplary embodiments of the invention; 
           [0048]      FIG. 8  shows a schematic perspective view of an electrical stimulation device implanted in the pancreas, according to another exemplary embodiment of the invention; 
           [0049]      FIG. 9  shows a schematic perspective view of an electrode, according to an exemplary embodiment of the invention; 
           [0050]      FIGS. 10A and 10B  show schematic perspective views illustrating a method of providing strain relief for a lead supplying power to an electrode implanted in the pancreas, according to an exemplary embodiment of the invention; 
           [0051]      FIG. 11  shows a schematic perspective view illustrating a method of providing strain relief for a lead supplying power to an electrode implanted in the pancreas, according to another exemplary embodiment of the invention; 
           [0052]      FIG. 12  shows a schematic side cut-away view of part of an electrode, according to an exemplary embodiment of the invention; and 
           [0053]      FIG. 13  shows a schematic perspective view of an electrical stimulation device with two electrodes implanted in the pancreas, according to an exemplary embodiment of the invention. 
       
    
    
     DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS 
       [0054]      FIG. 1  shows a schematic perspective view of an electrical stimulation device  100  suitable for implantation in the pancreas, according to an embodiment of the invention. Device  100  may also be suitable for implanting in other organs, such as the liver, stomach, heart, and large intestine. Device  100  has features which provide good electrical contact with the pancreas and allow the use of relatively high currents for electrical stimulation therapy over relatively long periods of time, while largely avoiding fibrosis or other damage caused by stresses exerted on the pancreas due to motion of the device relative to the pancreas. 
         [0055]    These features provide device  100 , in some embodiments thereof, with one or more potential advantages over prior art devices. For example, a lead that is too stiff may not be suitable for use in the pancreas, since it may irritate the pancreas, causing necrosis, or causing fibrosis around the electrode which increases the electrical impedance of the tissue in the vicinity of the electrode. Temporary cardiac pacing wire from A&amp;E Medical Corp., catalog number 025-200, is flexible enough for use as an electrode in the pancreas, and uses tines to anchor it in place. The use of tines for holding an electrode in place is described by U.S. Pat. No. 3,902,501, the disclosure of which is incorporated herein by reference. However, the inventors have found that this wire is too thin to use as an electrode for electrical stimulation therapy in the pancreas, which requires up to 10 mA of current. The wire deteriorates over time when it is used for this purpose, because the electrode surfaces (the exposed surfaces at the ends of the wire) do not reversibly hold enough tissue ions after the ions have interacted with the electrode, leading to irreversible loss of tissue ions (bubble formation) and electrode atoms (etching). To prevent irreversible loss of tissue ions and atoms from an electrode used for electrical stimulation of the pancreas, for example, the electrode optionally can reversibly hold at least 100 microcoulombs of tissue ions which have interacted with the electrode. This allows a 10 mA current to persist for 10 milliseconds before reversing polarity, typical of the currents and durations used in electrical stimulation therapy of the pancreas. 
         [0056]    Device  100  comprises an electrode  106 , which is optionally in the form of a helical coil. With this form, electrode  106  has great enough surface area so that it can provide sufficient current, for example at least 10 mA over periods of 10 milliseconds, without deteriorating. For example, there is voltage drop of less than 1 volt across the electrode tissue interface, when electrode  106  is providing a current of 10 mA. As noted by Mund et al, U.S. Pat. No. 4,603,704, the disclosure of which is incorporated herein by reference, no corrosion was observed on an electrode with a titanium nitride coating when the voltage drop across the electrode-tissue interface was 1.1 volts, so keeping the voltage drop less than 1 volt for electrode  106  is expected to keep the electrode from deteriorating, with some safety margin. 
         [0057]    The helical form of electrode  106  also makes it sufficiently flexible and stretchable that it will tend not to irritate the pancreas, since it can move, bend, and stretch, conforming to changes in the position, orientation and shape of the pancreas, without exerting much force on the surrounding pancreatic tissue. For example, electrode  106  can stretch in length by at least 20% without the material exceeding its infinite-cycle strain limit. As an example of a design for electrode  106  which satisfies these criteria, the electrode is made of grade 2, cold-worked titanium wire, 0.03 mm in diameter, wrapped into a helix with 4 wires in parallel, 0.50 mm in outer diameter, 0.44 mm in inner diameter, and 10 mm in length, with a pitch of 0.15 mm, so there are 66.7 turns. The longitudinal spring constant for this design is 0.0026 N/mm, and the bending stiffness is 3.6×10 −5  N-mm/radian. The resistance of each wire is 18 ohms, so the resistance of the 4 wires in parallel is 4.5 ohms. Alternatively, any of the dimensions is greater or less than these numbers, for example by up to 25%, or by up to 50%, or more, and any other bio-compatible metal is used. 
         [0058]    Optionally, an electrical lead  102 , which supplies electric power to electrode  106 , is also in the form of a helical coil, giving it enough flexibility so that it can move relative to a connector or a power supply, accommodating motion of the pancreas for example, without exerting much force on electrode  106  and hence on the pancreas. Optionally, lead  102  is connected to electrode  106  by a tube  104 , whose purpose will be explained below. 
         [0059]    In order to provide electrode  106  with enough stiffness to penetrate into the pancreas, a thread  108  passes through electrode  106 , at least initially when electrode  106  is implanted, and optionally thread  108  is anchored to device  100 , so that thread  108  can be used to pull device  100  into position when it is implanted. Thread  108  extends some distance beyond the end of electrode  106 , and the distal end of thread  108  is attached to a surgical needle  110  which is used to implant electrode  106  in the pancreas. Optionally, needle  110  is simply a continuation of thread  108 , made of the same material and sharpened at the end. Such a configuration has the potential advantage that there need not be any increase in the diameter of the needle and thread where they are attached, due to an eye of the needle or a knot in the thread, for example. With the needle and thread having a uniform diameter over their length, they are more likely to go smoothly through a hole in the pancreas made by the needle when the electrode is implanted, without exerting undue stress on pancreatic tissue surrounding the opening. 
         [0060]    Optionally, thread  108  is anchored to device  100  in such a way that a release mechanism can be used to easily free thread  108  from being anchored. For example, in  FIG. 1 , thread  108  extends through the entire length of electrode  106  and tube  104 , and optionally part way into electrode  102 . A loop  112  of thread  108  extends out from an opening  114  in the side of tube  104 , and a trigger suture  116 , passing through loop  112 , prevents loop  112  from going back into tube  104  when someone pulls on thread  108 , for example by pulling on needle  110 , and prevents thread  108  from being pulled out of device  100  by pulling on thread  108  or needle  110 . Trigger suture  116  prevents thread  108  from being pulled out because, for example, a force pulling on thread  108  causes the surface of thread  108  to press against trigger suture  116 , and/or against the edge of opening  114 , with a force that increases with the force pulling on thread  108 , and the resulting friction force on thread  108  is enough to prevent thread  108  from moving. This mechanism is similar to the mechanism by which a thread can be anchored to another body by winding it or knotting it around the body. 
         [0061]    Optionally, tube  104 , the parts of lead  102  and electrode  106  adjacent to tube  104 , loop  112 , and part of trigger suture  116 , are embedded in a silicone plate  118 , which may be sutured to the outer surface of the pancreas to hold device  100  in place after it has been implanted. An end  120  of trigger suture  116  optionally extends outside silicone plate  118 , however, so that trigger suture  116  may be removed, after device  100  has been implanted, allowing thread  108  to be removed. Silicone plate  118  optionally has two holes  122  and  124 , or a different number of holes, which may be used to suture plate  118  to the outer surface of the pancreas. 
         [0062]    Lead  102  is optionally covered by a sheath  126 , which optionally has a proximal end outside of the body, and a distal end near the point where lead  102  joins tube  104 . Optionally, the distal end of sheath  126  is embedded in silicon plate  118 . Sheath  126  is shown as transparent in  FIG. 1 , so that lead  102  will be visible, but sheath  126  need not be transparent. Sheath  126  also optionally covers lead  102  in any of the embodiments of the invention shown in the drawings, but for clarity sheath  126  is not shown in the other drawings. 
         [0063]      FIGS. 2A-2D  schematically illustrate how device  100  is implanted in the pancreas, in an embodiment of the invention. Optionally, the procedure is performed with endoscopic or laparoscopic surgery. In  FIG. 2A , surgical needle  110 , attached to the end of thread  108 , is inserted into pancreas  200 . Needle  110  is optionally curved, so that it can be inserted into a location  202  in the pancreas, and can emerge from another location  204 , without distorting the shape of the pancreas, as shown in  FIG. 2B . Alternatively, needle  110  is straight, and the pancreas is manipulated by the surgeon to make a curved hole. Needle  110  is then pulled through the pancreas and out from location  204 , so that thread  108  goes through the pancreas along the curved path followed by the needle, as shown in  FIG. 2C . Needle  110  is then pulled, pulling thread  108  with it, until a portion of electrode  106 , which surrounds thread  108 , passes into the hole made by the needle at location  202 , as shown in  FIG. 2D . Thread  108  pulls electrode  106  with it when thread  108  is pulled through the hole, because trigger suture  116  locks loop  112  in place, and prevents from thread  108  from sliding relative to tube  104  and electrode  106 . Once electrode  106  is inside the hole at location  202 , electrode  106  will generally remain in place and continue to make good electrical contact with the pancreas for electrical stimulation therapy. 
         [0064]    Optionally, needle  110  is a blunt tapered needle, which has the potential advantage, in the pancreas or other spongy tissue, that it only pushes aside tissue in order to make a hole, and does not produce a cut which may propagate. Alternatively, needle  110  is a cutting tapered needle that cuts tissue in order to make a hole, which may be advantageous to use in muscular tissue, such as the digestive track. 
         [0065]    If, as described previously, there is not a separate needle, but needle  110  comprises a distal portion of thread  108  with a sharpened end, then thread  108  is sufficiently stiff, or at least the distal portion of thread  108  is sufficiently stiff, so that the distal portion of thread  108  can act like a needle, making a curved hole through the pancreas. Optionally, the distal portion of thread  108  is curved, and stiff enough to hold its curved shape. Alternatively, the distal portion of thread  108  is not curved, and need not be stiff enough to hold a curved shape, but the pancreas is manipulated by the surgeon so that a straight needle can make a curved hole. 
         [0066]    When thread  108  is pulling electrode  106  into the pancreas, the extra stiffness that thread  108  gives to electrode  106  is advantageous, since it helps electrode  106  to go through the hole made by the needle, without collapsing. Once electrode  106  is in place inside the pancreas, however, it may be advantageous for it to be very flexible, so that it moves with the pancreas, and does not exert any stress on the pancreas, when the pancreas moves or bends relative to lead  102 . Such stresses could induce fibrosis or other damage to the pancreas. In order to make electrode  106  more flexible, thread  108  is removed from electrode  106  once electrode  106  is in place inside the pancreas. Removing thread  108  also reduces the amount of foreign material in contact with the pancreas, which may also reduce damage to the pancreas. Preferably, thread  108  is removed carefully, to avoid exerting forces that might damage the pancreas during the removal of the thread. 
         [0067]    To remove thread  108  from electrode  106 , trigger suture  116  is pulled out of loop  112 , by pulling on end  120  of trigger suture  116 , which end is not embedded in silicone plate  118 . This is done, for example, via an endoscope. Once trigger suture  116  is removed, thread  108  is pulled out of electrode  106  and tube  104 , for example by pulling on needle  110 . 
         [0068]    Using trigger suture  116  and loop  112  to lock thread  108  to tube  104  is only one of several possible methods of keeping thread  108  locked to tube  104  until thread  108  is ready to be removed. Other exemplary methods of accomplishing the same goal, according to different embodiments of the invention, are illustrated in  FIGS. 3 ,  4 , and  5 , and described below. 
         [0069]    Silicone plate  118  is optionally sutured to the surface of the pancreas, using holes  122  and  124 . This is optionally done before thread  108  is removed from electrode  106 . Alternatively, it is done after thread  108  is removed from electrode  106 . Although thread  108  is removed because keeping thread  108  inside electrode  106  may irritate the interior of the pancreas, the sutures used to attach silicone plate  118  to the surface of the pancreas may not cause so much irritation, even if the sutures are as stiff as thread  108 , since the surface of the pancreas comprises a membrane that is tougher than the soft interior of the pancreas. 
         [0070]    In  FIG. 3 , instead of thread  108  forming a loop  112  emerging from opening  114 , a proximal end portion  302  of thread  108  emerges from opening  114 , and ends in a knot  304  embedded in silicone plate  118 . Knot  304 , being wider than the path made by thread  108  in the silicone, keeps the proximal end of thread  108  anchored in silicone plate  118 , so thread  108  will not be pulled out of electrode  106  when the distal end of thread  108  is pulled, for example by pulling on needle  110 . Optionally, portion  302  of thread  108  comprises a loop that extends outside silicone plate  118 , as shown in  FIG. 3 . To remove thread  108  from electrode  106 , once electrode  106  is implanted in the pancreas, portion  302  is cut, so thread  108  will no longer be anchored in silicone plate  118 . Pulling on the distal end of thread  108 , for example by pulling on needle  110 , then removes thread  108  from tube  104  and electrode  106 . Optionally, thread  108 , silicone plate  118 , or both, is coated with Teflon or another low friction material, so that thread  108  will slide more easily when it is pulled out. 
         [0071]    In  FIG. 4 , the proximal portion of thread  108  does not emerge from tube  104  at all, but thread  108  passes by opening  114 . Tube  104  is optionally crimped, at a crimp location  402  proximal to opening  114 , and crimp  402  anchors thread  108  to tube  104 , preventing thread  108  from being pulled out of tube  104  and electrode  106  if the distal end of thread  108  is pulled. Alternatively or additionally, thread  108  is anchored to tube  104  in another way, for example the proximal end of thread  108  is knotted, and the knot is too big to pass through tube  104 . Alternatively or additionally, thread  108  is anchored to lead  102  or to sheath  126 , or extends to the outside of the body and is anchored there. When electrode  106  has been implanted in the pancreas and thread  108  is ready to be removed, a sharp instrument  404  is inserted through opening  114  into tube  104 , and cuts thread  108 . Instrument  404  also optionally cuts through silicone plate  118  to reach opening  114 , if there is a silicone plate, although for clarity the silicone plate is not shown in  FIG. 4 . Alternatively, instrument  404  is imbedded in the silicone plate, for example pre-positioned with its sharp tip inserted into opening  114 , or directed toward opening  114 , and with the other end of instrument  404  extending outside the silicone plate, so that instrument  404  can be readily manipulated to cut thread  108 . Once thread  108  has been cut, it is no longer anchored to tube  104 , and may be removed from tube  104  and electrode  106  by pulling on needle  110 , for example. 
         [0072]    In  FIG. 5 , a proximal end portion  502  of thread  108  emerges from opening  114  in tube  104 , and extends outside silicone plate  118 . A clip  504  is clipped to end portion  502  of thread  108 . Clip  504  prevents thread  108  from being pulled out of silicone plate  118 , since clip  504  is too big to pass through the hole in silicone plate  118  made by thread  108 . Hence thread  108  cannot be pulled out of electrode  106  by pulling on the distal end of thread  108 , as long as clip  504  is in place. Once electrode  106  has been implanted in the pancreas, and thread  108  is ready to be removed, clip  504  is removed from end portion  502  of thread  108 . Thread  108  is then removed from tube  104  and electrode  106  by pulling on needle  110 , for example. 
         [0073]      FIG. 6  shows a schematic side cross-sectional view of electrode  106  implanted in pancreas  200 , according to an embodiment of the invention. Electrode  106  could have been implanted using any of the methods shown in  FIGS. 2-5 , for example. There are one or more tines  602  on the sides of electrode  106 , which point in a direction opposite to the direction that the electrode travels when it is being implanted. These tines, which act like barbs, do not prevent the forward motion of the electrode when it is being implanted, but prevent the electrode from moving backwards, out of the pancreas. Optionally, once the electrode is in a desired location in the pancreas, it is pulled back slightly, for example by pulling on lead  102 , to set the tines in the pancreatic tissue. The distance that lead  102  has to be pulled back, in order to set the tines, may be considerably longer than the length of the tines, depending on the axial compliance of lead  102  and electrode  106 . Optionally, there are tines along all or much of the length of electrode  106 . Alternatively, there are tines only in a small region of electrode  106 , for example only at or near the distal end of electrode  106 . 
         [0074]    Although the tines shown in  FIG. 6  are relatively short in length, comparable to the diameter of the electrode  106 , optionally the tines are much longer. It is potentially advantageous for the tines to extend to the outside of the pancreas, where the sharp ends of the tines cannot damage the pancreas if the tines move relative to the pancreas. For example, the tines are made of ETFE, and they are 2 to 5 mm long, 0.1 to 0.3 mm thick, and 0.3 to 0.8 mm wide. With this design, the tines are flexible enough to be pulled against electrode  106  when the electrode is pulled into the pancreas, but rigid enough to keep the electrode from pulling out of the pancreas once the tines are set. Other compositions and dimensions for the tines are also possible. 
         [0075]    Optionally, electrode  106  has a longitudinal stiffness that increases toward the distal end. Then, if the tines are located only at the distal end, the additional longitudinal stiffness will tend to hold the entire electrode in place, while the proximal end will still be stretchable enough to allow sufficient relative motion between the pancreas and lead  102 . Optionally, electrode  106  is provided with additional longitudinal stiffness, without increasing its bending stiffness, by one or more thin fibers which run longitudinally through electrode  106 , at least along part of its length, and are bonded to electrode  106  at several locations along its length. 
         [0076]      FIG. 7  schematically illustrates another method of keeping electrode  106  from irritating the pancreas, according to an embodiment of the invention. The method shown in  FIG. 7  may be used instead of, or in addition to, any of the methods shown in  FIGS. 2-5  which involve removing thread  108  from electrode  106  and making electrode  106  more flexible. In  FIG. 7 , part or all of electrode  106  is surrounded by a sleeve  702 . Optionally, particularly if thread  108  is not removed from electrode  106 , sleeve  702  also extends over part or all of the portion of thread  108  that is inside the pancreas after electrode  106  is implanted. In an exemplary embodiment of the invention, sleeve  702  is well coupled to electrode  106  electrically, for example with a resistance of less than 20 ohms, or less than 5 ohms, but largely uncoupled from electrode  106  mechanically. For example, sleeve  702  comprises an electrically conductive material, and there is a gap between electrode  106  and sleeve  702  that is filled with a conducting electrolytic fluid, such as a body fluid or a saline solution. Optionally, sleeve  702  is flexible enough so that it can conform to bending and other changes in shape of the pancreas, without exerting forces that could irritate or damage the pancreas. 
         [0077]    Once electrode  106  and sleeve  702  are implanted in the pancreas, sleeve  702  is well coupled mechanically to the surrounding pancreatic tissue, and may move together with the pancreas, if the pancreas moves relative to the lead  102 . Electrode  106  is largely decoupled mechanically from sleeve  702 , so if lead  102  moves relative to the pancreas, electrode  106  may also move relative to the pancreas, sliding inside sleeve  702 . But because electrode  106  is not directly in contact with the pancreas mechanically, it does not irritate the pancreas when it moves relative to the pancreas. 
         [0078]    Optionally, sleeve  702  becomes well coupled to the pancreas by expanding radially after it is inserted, for example by setting sleeve  702  like a stent, or by absorption of fluid. Alternatively or additionally, sleeve  702  has barbs which couple it to the pancreas once they are set. Alternatively or additionally, sleeve  702  is attached to thread  108 , and pulled into the pancreas by thread  108 . In that case, thread  108  is optionally detached from sleeve  702  after sleeve  702  is in place, so that thread  108  may be removed. Alternatively or additionally, sleeve  702  becomes well coupled to the pancreas by growth of tissue around it after it is inserted. Alternatively or additionally, sleeve  702  becomes well coupled to the pancreas by an adhesive coating, which does not set until after it is inserted. 
         [0079]    In some embodiments of the invention, sleeve  702  does move relative to the pancreas, at least to some extent, when lead  102  moves relative to the pancreas, but sleeve  702  is optionally soft enough so that it does not irritate or damage the pancreas when it moves. 
         [0080]    In some embodiments of the invention, needle  110  goes into and out of the pancreas twice, or more times, pulling thread  108  behind it. Optionally, as schematically shown in  FIG. 8 , there are two electrodes,  802  and  804 , arranged along thread  108 , and when the electrodes are pulled into place, they are each located at different locations inside the pancreas. Optionally, electrodes  802  and  804  are in fact only a single long electrode, which extends into the pancreas, out of the pancreas, and into the pancreas again, when it is implanted. Optionally, lead  102  comprises a single wire connected to both electrodes  802  and  804 , applying the same voltage to both of them. Alternatively lead  102  comprises two separate wires in parallel, one wire connected to each electrode, and different voltages may be applied to the two electrodes. Optionally, instead of only two electrodes there are three or more electrodes, and the needle optionally goes into and out of the pancreas once for each electrode, or there is one long electrode which goes into the pancreas at three or more different locations. Having multiple electrodes, or one long electrode, which go into and out of the pancreas more than once, has the potential advantage that the electrodes are not implanted very deep in the pancreas, and may be less likely to damage the pancreas. Having a single electrode, which enters the pancreas only at one point, has the potential advantage that it may be less likely to pull out of the pancreas accidentally. 
         [0081]    Optionally, if there are two or more electrodes pulled by thread  108 , thread  108  is attached only to the most distal electrode, which in turn pulls the other electrode or electrodes. However, it may be advantageous for thread  108  to run through all the electrodes, and to be mechanically attached only to the most proximal electrode, or to be mechanically coupled to some extent, for example by friction, to all of the electrodes, in order to avoid exerting a tensile force on one or more of the electrodes when they are pulled by the thread, which could damage or break the electrodes. 
         [0082]    Optionally, in addition to or instead of being stiffened by thread  108  running through it, electrode  106  is also stiffened by a soluble coating or filling.  FIG. 9  schematically shows electrode  106  with a soluble coating  902 , made of sugar, for example, or polyethylene glycol  3350 , according to an embodiment of the invention. The coating is produced, for example, by dipping electrode  106  into a saturated sugar solution, then allowing the coating to dry, and optionally buffing the coating to remove any sharp edges. 
         [0083]    Coating  902  gives electrode  106  extra stiffness, making it easier to pull electrode  106  into the hole in the pancreas made by the needle, or, in some embodiments of the invention, to push electrode  106  into the pancreas. The coating may also provide lubrication to help pull or push electrode  106  into the pancreas, and for this purpose polyethylene glycol may be particularly suitable. Optionally, if electrode  106  has a soluble coating to stiffen it, then thread  108  is attached only to the end of electrode  106 , and is used to pull electrode  106  through the hole made by the needle, rather than thread  108  going through electrode  106  and contributing to the stiffness of electrode  106 . Alternatively, thread  108  does go through electrode  106 , as in the embodiments shown in the other drawings, and optionally contributes to the stiffness of electrode  106 , together with coating  902 . Optionally, whether or not thread  108  goes through electrode  106 , it is attached to electrode  106  by soluble coating  902 , or by a soluble filling, or it is held in place by a soluble crimp, and thread  108  becomes detached from electrode  106  when the soluble material dissolves, for example after a well-defined time. Alternatively, there is no thread  108  at all, and coating  902  makes electrode  106  stiff enough to push it into the pancreas, assisted for example by a sharpened tip, rather than pulling electrode  106  into the pancreas. 
         [0084]    Once electrode  106  is implanted inside the pancreas, coating  902  dissolves, completely or partially, making electrode  106  more flexible, so that it will not cause fibrosis or other damage to the pancreas. Optionally, coating  902  comprises a drug, for example particles of a drug slowly released from a matrix, and the drug is released into the pancreas when the coating dissolves. Optionally, particularly if coating  902  is insulating, coating  902  dissolves relatively quickly, for example within 10 or 15 minutes after electrode  106  is implanted in the pancreas, so that electrode  106  may be tested during the surgical procedure to verify that it is in good electrical contact with the pancreas. 
         [0085]    Optionally, instead of or in addition to coating electrode  106  on the outside, it is filled on the inside, and/or between the turns of electrode  106  with a similar soluble material that stiffens the electrode, and dissolves after the electrode is implanted. 
         [0086]    The optionally helical shape of lead  102  helps to decouple it mechanically from electrode  106 , allowing the pancreas to move relative to lead  102  without electrode  106  exerting stress on the pancreas. This is illustrated schematically in  FIGS. 10A and 10B , according to an embodiment of the invention. In  FIG. 10A , electrode  106 , implanted in a hole in the pancreas, is attached to tube  104  and lead  102 . In  FIG. 10B , the other end of lead  102  (not shown in the drawing) is pulled. This can happen, for example, if lead  102  is anchored in the duodenum, and the duodenum moves relative to the pancreas, and lead  102  does not include a loop for strain relief. The force on lead  102  causes the turns of the helix to unwind somewhat, accommodating the force, and transferring little or no force to electrode  106 , or to tube  104  which is optionally attached to the pancreas (for example via silicone plate  118 , shown in  FIG. 1 ). The helix of lead  102  has a pitch, for example, of between 82 and 85 degrees to the axis, when there is no force pulling on lead  102 . As an example of a design for lead  102 , it is made of 3 strands in parallel of 0.076 mm MP35N shell with silver core wire, with outer diameter 0.54 mm. The spring constant of lead  102  is comparable to, or as much as an order of magnitude smaller than, the spring constant of electrode  106 , for example, depending on the length of lead  102 . 
         [0087]    If tube  104  is attached to the pancreas, that may further reduce any force on electrode  106  caused by the motion of lead  102 . Although forces on tube  104  may then be transferred to the pancreas, this may cause less damage to the pancreas than forces on electrode  106 , if tube  104  is attached to the outer membrane of the pancreas, which is tougher than the interior of the pancreas that electrode  106  is in contact with. Additionally or alternatively, tube  104  may be attached to fat layers or other tissue that is adjacent to the pancreas, to prevent or reduce damage to the pancreas. 
         [0088]      FIG. 11  schematically illustrates another method of relieving strain in lead  102  according to an embodiment of the invention, instead of or in addition to the strain relief provided by making lead  102  helical, described above. In  FIG. 11 , as in the previous drawings, lead  102  is attached to tube  104 , which is embedded in silicone plate  118  which is sutured to pancreas  200 , and electrode  106 , implanted in the pancreas, is attached to the other end of tube  104 . Lead  102  is also optionally anchored in duodenum  1102 , for example using a plate  1104  which is sutured to the duodenum. To accommodate strain in lead  102  due to motion of the duodenum relative to the pancreas, lead  102  optionally forms a loop  1106  between the duodenum and the pancreas. Optionally, lead  102  is sufficiently long and flexible so that a one centimeter increase in distance between anchoring plate  1104  and electrode  106  causes the lead to exert a force no greater than 0.05 newtons on the pancreas, or no greater than 0.01 newtons, or no greater than 0.002 newtons. 
         [0089]    To prevent formation of bubbles and other irreversible loss of ions from the pancreatic tissue or from electrode  106  (etching) when tissue ions interact with electrode  106 , the electrode is optionally coated with a thin layer of a material with high dielectric constant and high effective surface area. A thin layer  1202  of such a material is shown schematically in  FIG. 12 , which is a cross-sectional view of electrode  106  according to an embodiment of the invention. Layer  1202  may be, for example, iridium oxide, or titanium nitride. The layer is vapor deposited on the electrode, while the electrode is held on a mandrel, in some embodiments of the invention. Such a vapor deposited layer tends to be thicker on the outer surface of the electrode than on the inner surface, which the vapor cannot reach as easily. 
         [0090]    If layer  1202  is thin and has a high dielectric constant and high effective surface area, then it will have a high capacitance, and hence a low impedance to the alternating or pulsed current that the electrode supplies to the pancreas. (In some medical therapies, only alternating or pulsed current is used, in some cases for safety reasons.) The high effective surface area of layer  1202 , due to its porous microscopic structure, allows layer  1202  to capture ions that are neutralized by the electrode, so they can be charged again and return to the tissue when the electrode changes polarity, rather than being irreversibly lost from the tissue, which can cause tissue damage. The currents used in electrical stimulation therapy of the pancreas may be relatively lower in frequency and higher in amplitude than the currents typically applied in cardiac stimulation, for example, so having such a surface layer may be more important for an electrode used in the pancreas than for a cardiac electrode. 
         [0091]    Optionally, layer  1202  has a capacitance of several microfarads per square millimeter, or several tens of microfarads per square millimeter, many orders of magnitude greater than electrode  106  would have without layer  1202 . Optionally, layer  1202  is between 1 and 10 micrometers thick, for example about 5 micrometers thick. Optionally, layer  1202  has a capacity to capture at least 100 microcoulombs of neutralized ions. If layer  1202  extends around the part of the surface of each wire which is on the outer surface of electrode  106 , and if electrode  106  is 10 mm long and 0.5 mm in diameter, for example, then an average storage capacity of 4 microcoulombs per square millimeter would give a total of about 100 microcoulombs, which, as noted above, is a typical integrated current used for electrical stimulation therapy of the pancreas. These are typical parameters for vapor deposited titanium nitride coatings used on electrodes inside the body. Any material and method known in the art for coating electrodes used inside the body is optionally used to produce layer  1202 , and the parameters may differ from those described above, depending on the material and method used to form layer  1202 . 
         [0092]      FIG. 13  schematically shows an embodiment of the invention in which two electrodes  1302  and  1304  are implanted in the pancreas in parallel. Each electrode optionally has the configuration of any of the electrodes described previously, and is implanted using any of the methods described previously. Electrodes  1302  and  1304  optionally have their own leads  1306  and  1308 , respectively, which split off from a single multi-wire lead  1310 . Hence, the voltages applied to electrodes  1302  and  1304  optionally can be controlled independently. Alternatively, leads  1306  and  1308  split off from a single wire in lead  1310 , and always have the same voltage. It may be advantageous to make the split close to the pancreas, to minimize the area of the leads in contact with body tissue. 
         [0093]    The invention has been described in the context of the best mode for carrying it out. It should be understood that not all features shown in the drawings or described in the associated text may be present in an actual device, in accordance with some embodiments of the invention. Furthermore, variations on the method and apparatus shown are included within the scope of the invention, which is limited only by the claims. Also, features of one embodiment may be provided in conjunction with features of a different embodiment of the invention. As used herein, the terms “have”, “include” and “comprise” or their conjugates mean “including but not limited to.”