Source: http://www.patentsencyclopedia.com/app/20140163600
Timestamp: 2020-02-28 15:26:15
Document Index: 775884817

Matched Legal Cases: ['art.\n7', 'art.\n11', 'art.\n20', 'art.\n25', 'art.\n28', 'Application No. 60', 'Application No. 60', 'art 500']

Methods and Apparatus to Increase Secretion of Endogenous Naturetic Hormones - Patent application
Patent application title: Methods and Apparatus to Increase Secretion of Endogenous Naturetic Hormones
Patent application number: 20140163600
1. A method for treating a patient comprising: determining that the patient is suffering from a condition comprising at least one of hypertension, excessive fluid retention, and excessive sodium retention; treating the condition by stressing a wall of at least one atrium of the heart beyond a natural stress condition of the wall, such that the stressed wall secretes a hormone at an elevated level above a natural secretion level occurring naturally when the wall of the at least one atrium is not stressed by the stressing; and achieving a beneficial therapeutic effect in the patient by the hormone secreted at the elevated level, wherein the beneficial therapeutic effect includes a reduction in blood pressure.
2. The method of claim 1, wherein stressing the wall of the at least one atrium comprises expanding and contracting an expandable device implanted in an atrial appendage of the heart to temporarily stretch the wall of the at least one atrium.
4. The method of claim 2, wherein expanding and contracting the expandable device comprises using an implanted pump connected to the expandable device to bidirectionally shuttle fluid in a closed system between the expandable device and the implanted pump.
5. The method of claim 2, further comprising anchoring the expandable device in an apex of a right atrial appendage of the heart.
7. The method of claim 1, wherein stressing the wall of the at least one atrium comprises pacing the at least one atrium.
8. The method of claim 7, wherein pacing the at least one atrium is performed at an accelerated rate.
9. The method of claim 1, wherein stressing the wall of the at least one atrium comprises asynchronously pacing the at least one atrium and at least one ventricle of the heart such that a pacing rate of the at least one atrium exceeds a pacing rate of the at least one ventricle.
10. The method of claim 1, wherein stressing the wall of the at least one atrium comprises mechanical distension of a right atrial appendage of the heart.
11. The method of claim 1, wherein stressing the wall of the at least one atrium comprises pacing of the at least one atrium that results in increased contractions of the at least one atrium.
12. The method of claim 1, wherein stressing the wall of the at least one atrium of the heart comprises pacing of the at least on atrium that stresses the wall of the at least one atrium beyond the natural stress condition.
13. The method of claim 1, wherein the beneficial therapeutic effect includes at least one of: limiting a degree of vasoconstriction, limiting a degree of sodium retention, increasing urine output, inhibiting a renin-angiotensin system, inhibiting endothelin secretion, inhibiting systemic and renal sympathetic activity, and counteracting effects of at least one of norepinephrine, endothelin, and angiotensin II.
14. A programmable implantable pacemaker connectable to at least one electrically conductive lead for connecting to a heart of a patient, the pacemaker being programmed to pace the heart of the patient to stress a wall of at least one atrium of the heart, such that, with the patient suffering from a condition comprising at least one of hypertension, excessive fluid retention, and excessive sodium retention: the stressed wall secretes a hormone at an elevated level above a natural secretion level occurring naturally when the heart is not stressed by the pacing, and a beneficial therapeutic effect is achieved in the patient by the hormone secreted at the elevated level, wherein the beneficial therapeutic effect includes a reduction in blood pressure.
15. The pacemaker of claim 14, wherein the pacemaker is programmed to stress the wall of the at least one atrium of the heart beyond a natural stress condition of the wall.
16. The pacemaker of claim 14, wherein the pacemaker is programmed to asynchronously pace the at least one atrium and at least one ventricle of the heart such that a pacing rate of the at least one atrium exceeds a pacing rate of the at least one ventricle.
17. The pacemaker of claim 14, wherein the pacemaker is programmed to pace the at least one atrium so as to cause increased contractions of the at least one atrium.
18. The pacemaker of claim 14, wherein the pacemaker is programmed to alternate pacing of the heart between a first pacing period that asynchronously paces the at least one atrium and a second pacing period that paces the at least one atrium normally.
19. The pacemaker of claim 14, wherein the pacemaker is programmed to alternate pacing of the heart between a first asynchronous pacing period and a second normal pacing period that synchronously paces the at least one atrium and at least one ventricle of the heart.
20. The pacemaker of claim 14, further comprising one or more electrically conductive leads connected to the pacemaker.
21. The pacemaker of claim 14, wherein the beneficial therapeutic effect includes at least one of: limiting a degree of vasoconstriction, limiting a degree of sodium retention, increasing urine output, inhibiting a renin-angiotensin system, inhibiting endothelin secretion, inhibiting systemic and renal sympathetic activity, and counteracting effects of at least one of norepinephrine, endothelin, and angiotensin II.
22. A method for treating a patient comprising: determining that the patient is suffering from a condition comprising at least one of hypertension, excessive fluid retention, and excessive sodium retention; treating the condition by pacing a heart of the patient to stress a wall of at least one atrium of the heart, such that the stressed wall secretes a hormone at an elevated level above a natural secretion level occurring naturally when the heart is not stressed by the pacing; and achieving a beneficial therapeutic effect in the patient by the hormone secreted at the elevated level, wherein the beneficial therapeutic effect includes a reduction in blood pressure.
23. The method of claim 22, wherein pacing the heart to stress the wall of the at least one atrium comprises alternating between a first pacing period that asynchronously paces the at least one atrium and a second pacing period that paces the at least one atrium normally.
24. The method of claim 22, wherein pacing the heart to stress the wall of the at least one atrium comprises a first asynchronous pacing period, and wherein the method further comprises alternating between the first asynchronous pacing period and a second normal pacing period that synchronously paces the at least one atrium and at least one ventricle of the heart.
25. The method of claim 24, wherein the first asynchronous pacing period comprises accelerated atrial pacing.
26. The method of claim 24, wherein pacing the heart comprises applying the first asynchronous pacing period three times per day.
27. The method of claim 22, wherein pacing the heart comprises pacing at least one ventricle of the heart.
28. The method of claim 22, wherein pacing the heart comprises pacing a ventricle of the heart at a first rate and pacing the at least one atrium at a second rate that is faster than the first rate.
29. The method of claim 28, wherein the first rate is within a range of about 50 to about 110 bpm and the second rate is within a range of about 120 to about 240 bpm.
30. The method of claim 22, wherein pacing the heart comprises pacing the heart to cyclically contract the at least one atrium, stress the wall of the at least one atrium, and restore the wall of the at least one atrium to a substantially pre-stressed condition.
31. The method of claim 22, wherein pacing the heart produces extra contractions of the at least one atrium.
32. The method of claim 22, wherein the beneficial therapeutic effect includes at least one of: limiting a degree of vasoconstriction, limiting a degree of sodium retention, increasing urine output, inhibiting a renin-angiotensin system, inhibiting endothelin secretion, inhibiting systemic and renal sympathetic activity, and counteracting effects of at least one of norepinephrine, endothelin, and angiotensin II.
[0001] This application is a continuation of U.S. application Ser. No. 13/426,068, filed Mar. 21, 2012 (U.S. Patent Publication No. US 2012/0215272, published Aug. 23, 2012), which is a continuation of U.S. application Ser. No. 11/276,461, filed Mar. 1, 2006, now U.S. Pat. No. 8,165,674, issued Apr. 24, 2012, which claims the benefit of U.S. Provisional Application No. 60/657,389, filed Mar. 2, 2005 and U.S. Provisional Application No. 60/678,220, filed May 6, 2005, all of which are herein incorporated by reference in their entirety.
[0018] One of the most versatile programmable pacemakers available today is the DDDR pacemaker. This pacemaker represents a fully automatic pacemaker which is capable of sensing and pacing in both the atrium and the ventricle, and is also capable of adjusting the pacing rate based on one or more physiological factors, such as the patient's activity level. It is commonly accepted that the DDDR pacemaker is superior in that it can maintain AV synchrony while providing bradycardia (slow heart beat) support. It is also generally more expensive than other, simpler types of pacemakers. A description of DDDR pacing is included in this discloser as a state of the art.
[0036] Current cardiac pacemakers with the capability of pacing both the atrium and the ventricle stimulate the heart chambers in a "1:1" ratio, that is no more than one ventricular stimulus per atrial stimulus and vice versa. Few normal people, and certainly no patient with CHF, can tolerate high ventricular rates without hemodynamic compromise from decreased filling. This is one of the reasons many previous therapies have chosen to try to slow heart rate in CHF and why beta-blockers or other negative chrontropic agents (drugs that slow down the heart rate) are preferred in the clinical treatment of CHF. For the purpose of this invention it would be desirable to have a device where the atrium could be stimulated at a high rate to cause release of ANP/BNP but without causing clinically unacceptably high ventricular rates. For example, atrial rates could range from 120 to 240 bpm with ventricular rates in the range of 50 to 110 per minute during pacing intended to release endogenous ANP/BNP. These rates would return to the normal ranges and atrial:ventricular stimulation ratio (i.e., 1:1) pacing as is in currently clinically available pacemakers when the therapy is interrupted or stopped.
[0059] FIG. 1 shows a normal heart. Electrical pulses in the heart are controlled by special groups of cells called nodes. The rhythm of the heart is normally determined by a pacemaker site called the sinoatrial (SA) node 107 located in the posterior wall of the right atrium 102 near the superior vena cava (SVC) 101. The SA node consists of specialized cells that undergo spontaneous generation of action potentials at a rate of 100-110 action potentials ("beats") per minute. This intrinsic rhythm is strongly influenced by autonomic nerves, with the vagus nerve being dominant over sympathetic influences at rest. This "vagal tone" brings the resting heart rate down to 60-80 beats/minute in a healthy person. Sinus rates below this range are termed sinus bradycardia and sinus rates above this range are termed sinus tachycardia.
[0060] The sinus rhythm normally controls both atrial and ventricular rhythm. Action potentials generated by the SA 107 node spread throughout the atria, depolarizing this tissue and causing right atrial 102 and left atrial 106 contraction. The impulse then travels into the ventricles via the atrioventricular node (AV node) 108. Specialized conduction pathways that follow the ventricular septum 104 within the ventricles rapidly conduct the wave of depolarization throughout the right 103 and left 105 ventricles to elicit the ventricular contraction. Therefore, normal cardiac rhythm is controlled by the pacemaker activity of the SA node and the delay in the AV node. Abnormal cardiac rhythms may occur when the SA node fails to function normally, when other pacemaker sites (e.g., ectopic pacemakers) trigger depolarization, or when normal conduction pathways are not followed.
[0061] FIG. 2 shows a heart treated with one embodiment of the invention. Pulse generator (pacemaker) 201 is implanted in a tissue pocket in the patient's chest under the skin. In this embodiment the generator 201 is connected to the heart muscle by two electrode leads. The ventricular lead 202 is in contact with the excitable heart tissue of the right ventricle 103. The atrial lead 203 is in contact with the excitable heart tissue of the right atrium 102. It is understood that the pacemaker can have more leads such as a third lead to pace the left ventricle 105. It is expected that in future cardiac pacemakers will have even more leads connecting them to various parts of the anatomy.
[0062] Leads 203 and 202 can combine sensing and pacing electrodes as known and common in the field. The atrial lead 203 can therefore sense the natural intrinsic contractions of the atria before they occur and communicate them to the generator 201. The generator is equipped with the programmable logic that enables it to sense signals, process the information, execute algorithms and send out electric signals to the leads.
[0063] In this embodiment the natural conduction path between the SA node 107 and the AV node 108 is blocked. The patient may already have a natural complete AV block. In this case no intervention is needed. If the patient has functional electric pathways from atria to ventricles, the patient's AV node can be disabled (blocked) by tissue ablation. It is understood that many irreversible and reversible methods of selectively blocking conduction in the heart are known. These include treatment with chemical agents and blocking with subthreshold electric stimulation (non-excitatory stimulation that does not cause muscle fibers to contract). Ablation of the AV node is used as an example since it is widely accepted and easily performed using RF energy catheters. Other devices that use cold, laser and ultrasound energy to perform ablation are also known.
[0064] FIG. 3 illustrates one possible embodiment of the invention with a sequence of stimulation pulses. Pulses are simplified and presented as rectangular blocks spaced in time as represented by the X-axis.
[0065] Trace 301 illustrates the natural or intrinsic rate generated by the SA node of the heart. The SA node generates pulses 304, 305, 306 and 307. These pulses can be sensed by the atrial lead 203.
[0066] In response to the sensing of intrinsic atrial pulses, the pulse generator 201 generates a series of pulses represented by the trace 302. Pulses are conducted to the atria by the atrial lead 203. Device generated atrial stimulation pulses 311, 313, 315 and 317 are in synchrony with the SA node pulses 304, 305, 306 and 307. They represent the intrinsic heart rate. The generator 201 (based on an embedded algorithm) also generates extra atrial pulses 312, 314 and 316. Together synchronous pulses 311, 313, 315, 317 and asynchronous pulses 312, 314, 316 determine the atrial rate of the heart.
[0067] Trace 303 represents ventricular stimulation pulses 321, 322, 323 and 324 conducted to the ventricle of the heart by the ventricular lead 202. The AV node of the heart in this embodiment is blocked. Therefore the ventricular stimulation is generated by the generator 201 based on an embedded algorithm. To ensure better performance of the heart ventricular pulses 321, 322, 323 and 324 are synchronized to the synchronous atrial pulses 311, 313, 315 and 317 with a short delay 308 determined by the embedded algorithm that simulates the natural delay of the AV node conduction.
[0068] The algorithm illustrated by the FIG. 3 can be described as a following sequence:
[0069] a. sensing an intrinsic SA node pulse (P-wave),
[0070] b. generating a synchronous atrial pacing pulse,
[0071] c. calculating the intrinsic atrial rate based on previous SA node pulse intervals,
[0072] d. generating synchronous ventricular pacing signal delayed from the synchronous atrial pacing signal at the ventricular rate equal to the intrinsic SA node excitation rate (sinus rhythm),
[0073] e. calculating the desired increased atrial rate, such as for example, a 2:1 (A:V) rate,
[0074] f. generating asynchronous atrial pacing signal based on the calculated increased atrial rate, and
[0075] g. waiting for the next intrinsic SA node pulse (P-wave).
[0076] It is understood that this example of an algorithm is an illustration and many other embodiments of the invention can be proposed. It can be envisioned that more than 2:1 (atrial:ventricular) rate can be tolerated by the patient or that less than 2:1 rate is desired such as accelerating every second atrial beat.
[0077] It may be not essential to preserve the natural sinus rhythm (from the SA node). In some patients it may be desired for the algorithm to take over the heart rate and force all the atrial contraction. Pacing modalities that do not rely on the SA node to generate the heart rate are known and used to treat bradycardia. The SA node of a patient can be ablated similar to the AV node and the embedded pacemaker algorithm will pace the atria. Alternatively, atria may be paced if the natural SA node pulse is not sensed within the expected time from the last ventricular contraction. Various activity sensors such as accelerometers can be used to accelerate the heart rate as needed.
[0078] FIG. 4 illustrates intermittent application of the proposed therapy. It is possible that some patients will not need or will not be able to tolerate continuous asynchronous A-V (atria-ventricular) pacing. In such patient period of normal (synchronous) pacing 401 is followed by the period of asynchronous (accelerated atrial) pacing 402 followed again by the period of synchronous pacing 403. The ventricular pacing rate 405 in this example stays the same. Switching between rates can be based on timing, patient's activity or physiologic feedbacks. For example, the pattern of therapy using electrical stimuli to generate high atrial rates can be intermittent of varying duration of accelerated atrial pacing in intervals of 10-minute durations occurring, for example, 3 times per day.
[0079] Commonly, in comparison to previous devices, this embodiment of the invention purposefully creates ratios of atrial to ventricular contraction higher than 1:1, such as for example in the range of 1:1 to 4:1. In addition, any previous device that allowed more than a 1:1 ratio of contraction based this relationship on sensing native atrial depolarization and deferring generation of a ventricular pacing stimulus (skipping premature ventricular beats). In contrast, in the illustrated embodiment, the higher than 1:1 rate is intentionally and controllably initiated by the implantable generator. As a result the atrial rate is increased to a rate which causes the release of sufficient endogenous naturetic hormone to result in a therapeutically beneficial increase in blood plasma levels of the hormones or increased levels in any other vascular or non-vascular space in which these hormones a found.
[0080] It is desirable to cause a therapeutic increase of blood plasma ANP and BNP via an increased endogenous release of ANP and BNP from the atria of the patient's heart. Atrial release is mediated via increase of atrial wall stress. The best embodiment of the invention known to the inventors at the time of the invention is rapid pacing of the atria that is expected to increase the rate of contractions of the atria and release ANP and BNP. The invention has been described in connection with the best mode now known to the applicant inventors. The invention is not to be limited to the disclosed embodiment. Rather, the invention covers all of various modifications and equivalent arrangements included within the spirit and scope of the appended claims.
[0081] FIG. 1 shows a normal heart. Electrical pulses in the heart are controlled by special groups of cells called nodes. The rhythm of the heart is normally determined by a pacemaker site called the sinoatrial (SA) node 107 located in the posterior wall of the right atrium 102 near the superior vena cava (SVC) 101. The SA node consists of specialized cells that undergo spontaneous generation of action potentials at a rate of 100-110 action potentials ("beats") per minute. This intrinsic rhythm is strongly influenced by autonomic nerves, with the vagus nerve being dominant over sympathetic influences at rest. This "vagal tone" brings the resting heart rate down to 60-80 beats/minute in a healthy person. Sinus rates below this range are termed sinus bradycardia and sinus rates above this range are termed sinus tachycardia.
[0082] FIG. 5 shows a human heart 500 treated with one embodiment of the invention. Heart is shown inside the pericardial sac 509 that is cut open. Heart has a right atrium (RA) 501, a superior vena cava (SVC) 503 and an inferior vena cava (IVC) 504. The purpose of the embodiment is to stretch the walls of the right atrial appendage (RAA) 502. The RAA stretching results in the ANP and BNP increase and benefits to patients with heart disease and such as heart failure (CHF) or hypertension. RAA stretching is achieved by periodically expanding the inflatable balloon 505 inside the RAA. The balloon 505 is mounted on the tip of the catheter 507. The catheter 507 is connected with an inflation device (See FIG. 2) that can be implanted elsewhere in the body. Both IVC 504 and SVC 503 can be used to advance the catheter into the RA 501 and further into RAA 502. Methods of placing and securing similar devices in the RA of the heart are well known in the field of electrophysiology and cardiology and routinely used to place pacemaker electrode leads in patients. In the illustrated embodiment the balloon 505 is advanced deep into the apex 508 of the RAA 502 and secured there with an anchor 506. The purpose of advancing the balloon into the apex and securing it there is to reduce the probability of clotting of the blood in the stagnant blood flow zones formed by the balloon and to prevent the balloon from floating out of the RAA. The anchor 506 can be a barb or a screw similar to ones used to anchor pacemaker leads in the heart. The surface of the balloon can be made of a material or is externally coated with a material such as porous ePTFE that encourages in-growth of tissue. It is known that, when a tissue implant is porous with pore entry diameters larger than approximately 20 to 500 microns, tissue grows into these pores. This phenomenon appears desirable in many medical device applications because it makes an implant one with the implanted organ and in theory it allows tissue ingrowth into the implant and reduces capsular contraction. This way in several weeks after the implantation the balloon 505 will be fused with the inner walls of the RAA 502 to further prevent clotting or dislodgement of the balloon.
[0083] FIG. 6 shows a patient 600 treated with one embodiment of the invention. Fluid pump 602 is implanted in a tissue pocket in the patient's body under the skin. In this embodiment the pump 602 is connected to the balloon 505 placed in the RAA 508 by the fluid filled catheter 507. It is understood that the pump 602 can be implanted elsewhere in the body, that the catheter 507 can follow a different vascular route and that the balloon 505 can be placed in different locations in the RA or Left Atrium (LA) of the heart. These modifications to the embodiment will not change the substance of the invention.
[0084] An implantable pump 602 is an implantable device that is inserted under the patient's skin and can be refilled using a transdermal needle 602 access. An implantable pump may be attached to a separate catheter 507 that delivers fluid to and from the expandable balloon 505. Depending on the desired treatment modality, a preferred implantable pump can be programmable, patient controlled or physician controlled. The pump can be mechanical (activated by finger pressure) or electro-mechanical using motors or solenoid pistons to generate flow and pressure.
[0085] The catheter 504 can be introduced into the RAA space under fluoroscopic, MRI or CT guidance without major surgery. The procedure is performed using an access point in a femoral vein 601 in the groin of the patient 600 using tools and techniques commonly used in interventional cardiology and radiology. One end of the catheter can be left outside of the body for the test period that requires only a short duration. Later, if the atrial stretching therapy is clinically successful, an implanted pump or a simple implanted subcutaneous infusion port such as a commercially available Port-A-Cath® device can be connected to the already implanted catheter for repeat infusions and withdrawals of fluid into and from the balloon 505. Alternatively the balloon can be inserted into the RAA surgically by piercing the wall of the RAA 508 from the outside. The actual method of inserting and securing the balloon in the RAA will not change the substance of the invention. General approach in implantable devices is that less invasive methods of implantation are preferred in most cases but tend to be more demanding.
[0086] In the illustrated embodiment the pump 602 in implanted in a pocket under the patient's skin. All the mechanisms of the pump are enclosed in a titanium or polymer case. Fluid is stored in the internal reservoir (not shown). To refill the pump or to add or remove fluid, a needle 602 can be used to puncture the patient's skin and the pump reservoir septum (Not shown). The catheter 504 is in bidirectional fluid communication with the pump 602 and the balloon 505. All the fundamental elements described above are known to the developers of implantable drug pumps. An example of an implantable drug infusion device is the MiniMed 6007® implantable insulin pump system for treatment of diabetes or the SynchroMed® Infusion System used to control chronic pain, both manufactured by Medtronic Inc.
[0087] The proposed embodiment is different from the existing implantable drug infusion pumps in the following significant way. In existing drug infusion pumps fluid is infused in one direction always from the implanted pump reservoir into the body. In this invention the fluid is bidirectionally moved (shuttled) inside a closed system in both directions between the implanted pump and the implanted balloon. Historically implantable infusion devices have been used for intravenous, intraarterial, intrathecal, intraperitoneal, intraspinal and epidural drug delivery but not to control inflation and deflation of implanted balloons.
[0088] For the purpose of an estimate the balloon 105 can have a diameter of 1 cm when the RAA is not stretched and the diameter of 2 to 3 cm when the RAA is stretched. The balloon is 3 cm long. This implies shuttling of approximately 5 to 20 ml of incompressible fluid between the pump reservoir and the balloon. This requirement is within reasonable range for a fully implanted pump of the described type. The Medtronic SynchroMed pump for example has a miniature peristaltic pump mechanism that can be modified to operate bidirectionally and generate necessary pressures. It also has an internal fluid reservoir of 30 ml. The fluid can be a sterile, biocompatible fluid that will not harm the patient if it leaks out such as saline, glycerin or medical grade oil. The balloon 105 can be made of silicone, nylon or other strong medical plastic suited for multiple cycle inflation and deflation. Methods and materials for manufacturing of durable, implantable balloons exist and have been successfully implemented in many medical device applications.
[0089] The therapy may include the following steps:
[0090] Identifying a patient that will benefit from elevated levels of ANP and BNP likely from the group with heart failure, fluid retention or hypertension
[0091] Implanting an expandable device in an atrial appendage of the patients heart
[0092] Periodically expanding and contracting the device to temporarily stretch the walls of the atrium to achieve therapeutically significant increase of blood hormones.
[0093] The exact regiment of stretching and contracting the atrial wall is likely to be individual for each patient. For example a regiment can be proposed where the balloon is inflated for several minutes followed by several minutes of rest. These cycles will be repeated for several hours several times each day. In heart failure patients with fluid retention the objective of therapy will be to achieve minimum additional urine output of 250 ml per day and preferably 500 ml per day. The high end of the therapeutic range may be 1,000 additional ml of urine per day. This additional urine output is likely to improve patient's condition, allow more exercise and prevent hospital admissions from fluid overload. It is likely that the device will require a pump component that is remotely programmable so that the therapy parameters can be adjusted using wireless communication.
[0094] The adjustable programmable parameters may include:
[0095] Volume of Balloon Expansion
[0096] Duty cycle and frequency of inflation cycles in each therapy session
[0097] Number and time of therapy sessions hourly, daily or weekly
[0098] The methodology of programming an implantable pump is not different from programming a common heart pacemaker.
[0099] The invention has been described in connection with the best mode now known to the applicant inventors.
[0100] The invention is not to be limited to the disclosed embodiment. Rather, the invention covers all of various modifications and equivalent arrangements included within the spirit and scope of the appended claims.
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