as noted above , the invention is concerned with devices which release no during insertion or implantation . the present invention is applicable to mammals , such as humans and domestic or research animals or livestock . for convenience , the recipient of the device is described herein as the patient . the natural release of intravascular no occurs when the endothelial cells lining the vessels release a puff of no at each systole . this diffuses into the underlying smooth muscle cells , causing them to relax and permitting a surge of blood to pass . no also inhibits the aggregation of platelets and prevents clotting from interfering with blood flow . further , no inhibits inflammation in blood vessels . as it has many physiological functions , the preparation and use of no - releasing materials has grown widely and at present a number of materials are available for use in the present invention . according to the invention , no can be released directly or indirectly . that is , the device itself can directly release no by , for example , a stream of no which is passed through the device to its distal end . this can be accomplished by providing a device with a lumen through which no can pass from an external source to an opening at the distal end of the device . alternatively , a coating containing no in actively - releasable form can be applied to the device , either during manufacture or immediately prior to use , or both . one example is to provide no in a sugar solution which is rapidly dissolved once in contact with patient fluids , thereby releasing the no . existing devices could be dipped in or otherwise treated with this solution prior to insertion to take advantage of the benefits of the present invention and facilitate insertion of the device . alternatively , the no can be indirectly released , for example , by stimulating nearby endothelial cells to release no . indirect release can rely on the patient &# 39 ; s own cells since no is found in nearly every cell type , where it is enzymatically synthesized through the oxidization of l - arginine to n - omega - hydroxy - l - arginine , which is converted into l - citrulline and an uncharged no free radical . three enzymes , neuronal , endothelial , and inducible no synthase , are involved in the process . using techniques and materials known to the skilled worker , appropriate materials can be present on or in the device which affect this pathway and / or otherwise cause no present in cells to be released . indirect release of no can also occur by releasing compounds which , once in contact with a patient &# 39 ; s blood or bodily fluids , convert to no . the selection of the appropriate precursor compound depends upon which tissues and fluids the device will be expected to contact during insertion , such precursors are known in the art . for example , nitroglycerine can be used in a coating or released from the distal end of a device ; it is readily available in numerous formulations such as ointments and solutions and rapidly degrades in the mammalian body to no . the present device and methods related thereto are effective even in cases where insertion causes a device to move against blood flow or counter current to the movement of patient bodily fluids . for example , when implanting a cardiac pacemaker lead , the distal end of the lead travels into the heart while the blood passing the distal end progresses back along the length of the lead . no released at the distal end nonetheless causes dilation of the vessel located near the tip of the device , as well as in a direction along the length of the lead , thus resulting in the beneficial effect . in some applications , a device which requires substantial dilation or rapid blood flow can be preceded during insertion by a distal end which tapers to a narrow tip . this narrow tip can optionally be dissolvable . rapidly dissipated no from the narrow distal end can thereby facilitate insertion of the larger , wider device . when the distal end of the device is in the vascular system and is releasing no , it will also have the beneficial side effect of increasing blood flow . this helps prevent complications from clotting and thrombosis . systemic administration of anti - thrombotic agents may thus be avoided , potentially reducing the overall cost of materials and also reducing stress on the patient &# 39 ; s system during certain applications . thus , instead of relying on teachings that no loss during implantation should be minimized — so as to prolong the duration of no release during the lifetime of the device — the present invention provides a device configured to release no during implantation in an effort to make the insertion procedure quicker , easier , and safer . a no - generating device is prepared by first providing an implantable device comprising a biocompatible material . l - cysteine or an l - cystiene - containing compound is immobilized to the surface of the device . when the device is inserted and contacts the patient &# 39 ; s blood plasma , transnitrosation occurs in which no , which is abundant in the plasma , is transferred from s - nitrosoalbumin to l - cysteine . because nitrosated l - cysteine is unstable it will then release no , causing adjacent vascular structures to dilate and facilitating the insertion and placement of the device ( see grappa - fahlenkamp and lewis ). such a coated device may be particularly well suited for vascular applications as it relies on components of the patient &# 39 ; s blood to release no . a further benefit of this configuration is the ease with which it can be adapted to existing devices , as the coating may be provided immediately prior to insertion . an implantable device is provided , comprising biocompatible materials such as silicon . a sol - gel coating is provided on the device , solidified to a xerogel and modified to comprise no - donors ( see nablo et al ). the coating can be provided on the device at the time or manufacture or prior to use . the degree of no saturation of the xerogel can be tailored to the chosen application of the device , for example , to release at least 0 . 1 picomol / cm 2 and not more than 1000 picomol / cm 2 , for example 100 picomol / cm 2 of no for between 1 - 5 hours , preferably 1 - 3 hours . if the teaching of nablo is followed without modification , the resultant device could be primed prior to insertion , so that the initial burst of no released from the device coincides with the insertion period . an implantable device is provided which has a polymeric outer layer or barrier . examples include polymeric insulation on electrical leads for pacemakers . the polymer is selected based on the potential application of the device , and n - diazeniumdiolate is incorporated into the polymeric structure ( see frost et al ). one adjustment to be made to known methods , of course , is to select the appropriate amount and localization of the n - diazeniumdiolate to provide rapid no release during implantation , instead of conservation and long - term stable release as taught by previous methods . a device can be provided , which device has a tubular structure such as a hollow guide wire which can be used to insert “ over the wire ” cardiac pacemaker electrodes . the hollow tip of the guide wire can be provided with a plurality of openings , or exclusively with the opening at the end of the wire . at the proximal end of the guide wire , located external to the patient during the insertion , a no source can be connected , such as a fluid or liquid containing no in rapidly - diffusible form . prior to insertion of the guide wire , the flow of no from the source through the guide wire and out the distal end can be primed . during insertion the flow of no can be controlled to maximize the beneficial vessel dilation properties as needed . the flow can be terminated prior to removal of the guide wire or after , as determined by the person managing the insertion . in addition to openings at or near the distal end of the guide wire , additional outlets for the no stream can be provided along the length of the device to help keep vessels in the relaxed state during insertion . implantation of devices encompassed by the present invention can be performed as known to those in the art , e . g ., implantation of pacemaker leads as known to interventional cardiologists . although modifications and changes may be suggested by those skilled in the art , it is the intention of the inventor to embody within the patent warranted heron all changes and modifications as reasonably and properly come within the scope of her contribution to the art .
an implantable medical device can be configured to directly or indirectly release nitric oxide during its insertion in a patient . such a device can reduce the amount of time required for implantation as well as reduce or prevent damage to the region surrounding the implanted device .