KR20170129767A - Method and apparatus for remote ischemia treatment through partial limb occlusion - Google Patents

Abstract

A single or dual bladder device 100 for automatic delivery of remote ischemic conditioning therapy via partial limb occlusion may be used to deliver a cuff 110 that causes partial or total limb occlusion during a cuff inflation period It includes various methods of manipulating. Achieving the clinical benefit of remote ischemic procedures without extended cessation of limb blood flow is advantageous because less cuff pressure is required and it reduces the risk of clot formation in the vasculature.

Description

Method and apparatus for remote ischemia treatment through partial limb occlusion

<CROSS-REFERENCE DATA>

This patent application is a continuation-in-part of U.S. Patent Application No. 14 / 305,032, entitled "Automatic Device for Remote Ischemic Treatment" This is a continuation of U.S. Patent Application No. 13 / 362,039, filed January 31, 2012, with the same title, now U.S. Patent No. 8,753,283; This is a continuation of U.S. Patent Application No. 12 / 820,273 entitled " Method and Apparatus for Remote Ischemic Preconditioning and Near-Continuous Blood Pressure Monitoring, " filed June 22, 2010, now U.S. Patent No. 8,114,026; U.S. Provisional Application No. 61 / 219,536, entitled "Blood Pressure Lowering Cuff Including Pre-Treatment Device, " filed June 23, 2007 and U.S. Provisional Application No. 61 / 256,038, filed October 29, 2009 , The entire contents of which are incorporated herein by reference in their entirety, all of which are incorporated herein by reference in their entirety.

The present invention generally relates to methods and apparatus for delivering remote ischemic treatment therapies. These treatments may be used to reduce or even reduce the severity of neurological damage after stroke, such as acute myocardial infarction, for example, ischemia and reperfusion injury of the organs. Can be used to achieve a variety of clinical benefits, including a reduction in adverse effects. Other clinical advantages of remote ischemic procedures can be attempted using the apparatus and methods of the present invention, for example, in related literature as well as in methods such as reducing inflammation and improving tissue survival as described in previous patents. In particular, the present invention describes a method and apparatus configured to deliver a remote ischemic procedure to a partial limb vessel occlusion.

The term "remote ischemic conditioning" is used to refer generally to the limb of a patient (e. G., The upper limb) to induce ischemic tolerance, to reduce the adverse effects of ischemia-reperfusion injury or to achieve other clinical benefits. arm, or thigh), and a series of simple sub-lethal episodes of alternating ischemia. Other terms used in the literature to describe this therapy include "remote ischemic postconditioning "," remote ischemic preconditioning ", and "remote ischemic preconditioning " For purposes of this description, all such therapies are contemplated in the present invention and whether treatment is performed before, during, or after ischemia, whether before, during, or after recovery of blood flow to an ischemic organ or tissue layer Is described using the term "remote ischemic procedure &quot;.

An inflatable cuff placed on a patient's limb can be conveniently used to deliver a remote ischemic procedure. These cuffs are familiar to healthcare professionals as well as the general public because they are widely used for blood pressure measurement or as an alternative to airborne hemostasis.

U.S. Patent No. 7,717,855 to Caldarone is incorporated by reference in its entirety and discloses an example of an automated device configured to deliver a remote ischemic procedure due to periodic expansion and contraction of an inflatable cuff disposed in a patient's limb. The blood flow through the limb is completely stopped for at least about 1 minute (typically about 5 minutes) by inflating the cuff to a predetermined set pressure higher than the patient's systolic blood pressure. One example of such a set pressure is 200 mmHg. Upon contraction of the cuff, blood flow is restored to an unrestricted level during the entire duration of the cuff contraction.

The approach described in U.S. Patent No. 7,717,855 is limited in that inflating the cuff at high pressure for extended periods of time can cause pain and discomfort to the patient. Prolonged interruption of blood flow in some patients can lead to platelet formation and increased risk of platelet pigmentation. Especially when the limbs are legs and not the upper arm.

Therefore, a milder approach is needed in providing remote ischemic treatment to obtain effective results at lower cuff expansion pressures and to minimize the risk of thrombosis due to such treatment.

It is an object of the present invention to provide a novel method and apparatus for delivering remote ischemic treatment therapies while minimizing patient pain and discomfort. It is a further object of the present invention to provide a novel method and apparatus for delivering remote ischemic treatment therapies while minimizing the risk of clot formation and subsequent thromboembolism.

According to one aspect of the present invention, complete obstruction of the limb and interruption of blood flow are not required to achieve an effective remote treatment effect. Partial occlusion can be used to induce ischemic stress strong enough to trigger the onset of remote ischemic treatment protection. The terms "partial occlusion" and "partial reduction of blood flow" are used interchangeably herein.

In another aspect of the invention, complete recovery of complete blood flow in the limbs during the cuff contraction period may also be unnecessary. Although not a complete recovery to unlimited levels, a sufficient increase in blood flow can be used to achieve clinically useful remote ischemic treatment benefits.

Generally, the effect of a remote ischemic treatment is induced by repeating periods or ischemia and reperfusion. The prior art describes remote ischemic treatment with multiple treatment cycles, each cycle involving a period of limb ischemia caused by complete occlusion of the limb bloodstream for at least about one minute (typically 5 minutes) Is completely restored to its unlimited state, the cycle of reperfusion follows. This is accomplished by initially inflating the cuff placed on the limb to a pressure that exceeds the patient's systolic blood pressure during the occlusion period and then fully deflating the cuff to restore normal circulation during the perfusion cycle .

The present invention is based on the finding that intermittent complete occlusion of the limb causes a temporary level of transient oxygen deficiency for limb tissue and, in turn, results in a corresponding degree of ischemic stress, which leads to a favorable neural and humoral internal signal and ultimately, And the activation of other protective mechanisms that gradually define the concept of systemic release and the effect of remote ischemic treatment.

Significantly, achieving a minimum effective threshold of ischemic stress sufficient to cause a remote ischemic effect may not require a complete cessation of blood flow according to the present invention. Sufficient ischemia can be caused by a partial but sufficiently deep reduction of the blood flow in the extremities. The incomplete occlusion of the blood stream during at least a portion of the cuff inflation period can provide a number of significant advantages over the complete occlusion of the bloodstream described in the prior art. One of these advantages is the reduction in cuff pressure required to elicit the benefits of remote ischemic procedures. Another advantage is that some blood flow can be allowed to pass through the limb tissue, reducing the risk of thrombus formation, and thus the blood stasis range and duration can be reduced or completely avoided.

The term "ischemic stress" is used herein to describe the minimum state of underperfusion of limb tissue, which triggers the initiation of a remote ischemic treatment mechanism. The present invention then defines the least effective reduction of blood flow in the limb to achieve a threshold of ischemic stress. The present invention also teaches that relieving ischemic stress can be achieved by increasing blood flow from the cuff pressure required to achieve ischemic stress, for example, using at least some shrinkage of the cuff. Importantly, the cuff does not need to be fully retracted. A minimal partial recovery of blood flow and at least some increase in oxygenation may be sufficient to alleviate the ischemic stress needed for the purpose of remote ischemic treatment.

The term "inflating" is used to indicate that the cuff pressure increases from the current level to a certain target level. The term "deflating" is used to describe reducing the cuff pressure to a certain target level at the current level. The term "cuff inflation period" defines a time period that begins after the initial cuff expansion and after the cuff pressure reaches a target level required to induce ischemic stress and lasts for a predetermined period of time, Thereby relieving ischemic stress. The term "cuff deflation period" defines the time at which the cuff begins to contract at a pressure sufficiently low to relieve ischemic stress and lasts until the next cuff inflation period or a predetermined duration.

Thus, the method of the present invention describes a step of delivering alternate ischemic treatment therapies alternately:

a. A limb compression step to reduce the blood flow without having to completely obliterate to achieve or exceed a predefined ischemic stress threshold value

b. When the blood flow is at least increased to a minimum level sufficient to alleviate ischemic stress, a limb reperfusion step.

According to another embodiment of the invention, a method of performing a remote ischemic procedure comprises:

a. Causing ischemic stress in the limbs of the patient by at least partially reducing blood flow for a period of at least about 1 minute while avoiding complete occlusion of the limb lasting more than about one minute;

b. Increasing blood flow in the limb to alleviate ischemic stress; and

c. repeating steps a and b.

Another method of performing a remote ischemic procedure

a. Avoiding the expansion of the cuff causing complete obturator closure of the limb for a period of about one minute or more, resulting in ischemic stresses reaching or exceeding predefined ischemic stress threshold values for at least about one minute and at least partially reducing blood flow Inflating a cuff disposed on a limb of a patient for removal of the cuff;

b. Shrinking the cuff to relieve ischemic stress and increase blood flow in the limb; And

c. repeating steps a and b.

However, in a further embodiment, a method of performing a remote ischemic procedure may include a change in the complete occlusion period during the cuff inflation period and partial occlusion of the limb. For example, to detect a current level of systolic blood pressure in a patient, for example, to change the complete and incomplete occlusion.

Remote ischemic procedures can be performed using manually inflated cuffs, but it is desirable to use automated devices for practical purposes. Such an apparatus 100 is shown generally at 1 and may include a controller 150 attached to or otherwise operably connected to the cuff 110. [ Various examples of such controllers and cuffs suitable for delivering remote ischemic therapy therapies are described in detail in previous patent applications. The present invention describes a number of methods and algorithms for operating such a controller to achieve a mild application of remote treatment therapy.

A single or dual bladder device 100 for automatic delivery of remote ischemic conditioning therapy via partial limb occlusion may be used to deliver a cuff 110 that causes partial or total limb occlusion during a cuff inflation period It includes various methods of manipulating. Achieving the clinical benefit of remote ischemic procedures without extended cessation of limb blood flow is advantageous because less cuff pressure is required and it reduces the risk of clot formation in the vasculature.

A more complete understanding of the nature of the invention and its various advantages may be realized by reference to the following detailed description when taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic view of an apparatus of the present invention.
Figure 2 is a general chart of blood flow versus time showing one method of operating the cuff during the cuff inflation period.
Figure 3 is a general chart of blood flow vs time showing another method of operating the cuff during the cuff inflation period.
Figure 4 is a general chart of blood flow versus time illustrating another method of operating the cuff during a cuff inflation period.
5 is a general chart of blood flow versus time illustrating another method of operating the cuff during a cuff inflation period.
Figure 6 is a general chart of blood flow versus time illustrating another method of operating the cuff during the cuff inflation period.
Figure 7 is a general chart of blood flow versus time illustrating another method of operating the cuff during a cuff inflation period.
8 is a general chart of blood flow versus time illustrating one method of operating the cuff during the period of contraction of the cuff.
Figure 9 is a general chart of blood flow versus time illustrating another method of operating the cuff during the period of cuff contraction.
Figure 10 shows a chart of venous pressure and various bladder pressures while temporarily obliterating the venous return from the limb to measure limb flow.

Figure 1 is a schematic diagram of an apparatus 100 that includes a cuff 110 and a controller 150 that may be removably or permanently attached (or permanently) to the cuff 110 and operably connected thereto. The controller may include an internal microprocessor that may be programmed or otherwise configured to inflate the cuff in accordance with any protocol of delivery of the remote ischemic care therapy.

During operation of the controller, the cuff may expand or contract to a certain level of cuff pressure corresponding to a particular level of limb occlusion. The specification of the present invention encompasses the following distinct states corresponding to cuff expansion and cuff pressures, listed in general order, at least from low pressure to high pressure:

a. Full cuff deflation - there is no limit to the limb blood flow under the cuff, and the cuff pressure is below the atmospheric level;

b. Retain-on-limb cuff state - A cuff inflation is applied at a level low enough to keep the cuff above the limb, and the cuff pressure is generally between about 5 mmHg and about 20 mmHg, much higher than the diastolic pressure and higher than the atmospheric pressure;

c. Venous compression state - The cuff expands approximately from venous pressure to approximately the patient's diastolic blood pressure, which is about 5 mmHg to about 80 mmHg. This causes limited arterial blood inflow leading to early venous compression, temporary occlusion, and swelling of the limb. When the venous pressure at the distal end of the cuff is equal to the arterial pressure, blood continues to flow in and out of the limb beneath the cuff;

d. Initial limb occlusion state - The cuff is inflated to a pressure sufficient to cause at least some arterial compression and ischemic stress. In this state, the cuff may be inflated to a cuff pressure that exceeds at least the diastolic blood pressure of the patient to initiate compression of the limb artery;

e. Partial limb occlusion state - The cuff is usually inflated above the pressure corresponding to the patient's diastolic and systolic blood pressure, which is about half the mean arterial pressure, and the artery of the limb is about half The blood flow is reduced at the blood flow level when the artery is compressed and the artery is not compressed;

f. Ischemic stress state - The main limb artery is compressed to a point of blood flow not completely stopped by the cuff, but is already reduced to a level that causes a minimal effective ischemic stress for the purpose of treatment of a remote ischemic treatment ;

g. Complete limb occlusion state - The cuff is inflated to a minimum cuff pressure at which limb blood flow is completely interrupted, known as the limb occlusion pressure;

h. Systolic pressure or above - The cuff is inflated to the patient's systolic blood pressure or more. In many cases, depending on the width of the cuff, the pressure is higher than the limb occlusion pressure and the extremity is excessively compressed without further inducing ischemic stress for remote ischemic procedures.

The cuffs of the device are configured to provide a level (d), (e), (f), (g) and / or (h) during the cuff- ). &Lt; / RTI &gt;

Ischemic Stress (ISCHEMIC STRESS)

Normal tissue perfusion and tissue oxygenation can be explained as a result of unrestricted blood flow that supplies oxygen over a certain amount of limb tissue over time. Reduced blood flow at least partially deprives the limb tissues of oxygen and other nutrients. In accordance with the present invention, limb tissue may at least partially deprive oxygen over each cycle of cuff expansion, in order to effect a remote ischemic treatment effect strong enough to be useful for therapeutic purposes.

Total ischemic stress in the limb tissue is the result of the degree of blood flow reduction and the duration of the cuff inflation period, when considering each treatment cycle and inflation duration separately. In an embodiment, the value of the ischemic stress threshold may be defined by a simply minimally effectively predetermined threshold value of blood flow reduction sufficient to produce the effect of a remote ischemic procedure. Figure 2 shows an exemplary plot of blood flow expressed as a percentage of normal unrestricted blood flow over time versus limb. As can be seen in FIG. 2, a decrease in blood flow to unrestricted blood flow of less than about 10% throughout the cuff expansion period in each cycle of treatment may be sufficient to produce a benefit of a remote ischemic procedure.

Importantly, the predetermined threshold value of the least effective blood flow reduction can be reached or exceeded in each cycle of treatment-that is, Figure 2 shows the upper level of blood flow allowed in the limb. In an embodiment, the blood flow volume may be less than or equal to a predetermined threshold value of the allowed blood flow volume. Lowering the blood flow below a pre-determined threshold can complete the occlusion by any useful method. One useful objective to further reduce blood flow may be to detect the oscillometric amplitude of oscillations in various limb occlusion states to more accurately detect the patient's current blood pressure.

In an embodiment, blood flow in the limb may be maintained at a predetermined blood flow reduction threshold value for the entire duration of the cuff expansion. In other embodiments, blood flow may be further reduced to achieve complete occlusion. In other embodiments, blood flow may be intermittently or continuously fluctuating at or below a predetermined blood flow reduction threshold value to change the range of ischemic stress, e.g., to achieve complete occlusion. This can be achieved by varying the cuff pressure to vary the degree of compression of the limb.

The predetermined threshold value of the minimum effective blood flow reduction can be defined either absolutely or relatively. In an embodiment, the predetermined threshold value of blood flow reduction may be defined as a specific portion or percentage of the unrestricted flow of the limb. Figure 2 shows that the level is about 10% of the unrestricted flow, but the invention is not limited in this regard. In an embodiment, the minimum effective threshold value of the blood flow reduction is 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 2%, 1%, 0.1% About 40% or less of the unrestricted blood flow, such as blood flow rate, partial blood flow rate, or any arbitrary position.

Another way to define a given blood flow reduction threshold value is to use normalized (differentiated) blood flow units with absolute units of blood flow or limb tissue weights. Depending on the choice of a particular limb that can be an upper arm or a leg, the absolute blood flow threshold value selection may be different. On average, about 20% of the total cardiac output or about 1,000 ml / min is consumed mainly by the muscles in the arms and legs for the resting person. For the average arm, an unrestricted (unrestricted) blood flow at rest may be about 150 ml / min. In this case, the threshold value of the blood flow reduction may be set to a value of 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, 10, 5, 1, 0.1 ml / min, About 40% or 60 ml / min or less. In the case of an average leg, in a resting state, the total blood flow may be about 300 ml / min and the threshold value of blood flow reduction may be defined as about 40% of the value or about 120 ml / min or less. The threshold value for blood flow reduction may be defined as 120, 110, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10, 5, It is not limited. The adjustment of the number can be made considering the size and weight of the patient.

Using the tissue oxygenation parameter as the threshold value for blood flow reduction, the average unrestricted tissue perfusion for an average 70 kg adult with a cardiac output of 5 l / min is about 70 ml / min. The blood flow reduction threshold value is defined as 40% or less of the perfusion level, such as blood flow at 28, 25, 20, 15, 10, 5, 4, 3, 2, .

In a further embodiment, the method of remotely treating ischemic injuries may include avoiding complete occlusion of the limb bloodstream for at least about 30 seconds or more than 1 minute during the cuff inflation period to reduce the risk of thrombus formation in the limb blood vessel . Since the entire cuff inflation period can be longer than one minute, the method of the present invention allows the blood flow to be below a predetermined blood flow reduction threshold value, and at the same time avoids a complete occlusion lasting for about one minute or more And operating the cuff.

In a further embodiment, the ischemic stress threshold value required for the purpose of a remote ischemic procedure is such that the cumulative limb oxygenation reduction threshold value, defined as the product of variable blood flow over the cuff inflation time, To reduce blood flow. More specifically, the degree of ischemic stress can be defined as the area under the curve of the chart plotting the integral of blood flow or tissue oxygenation over time, or more specifically, the limb blood flow (or limb tissue oxygenation) vs time . For example, for a constant blood flow at the minimum effective blood flow reduction level shown in FIG. 2, the plot is a straight horizontal line and the area under the curve is a simple multiple of the blood flow rate to the cuff expansion time.

Blood flow through the limb can be expressed in absolute terms such as cubic centimeters per minute or milliliter blood flow. The flow can also be normalized to tissue weight or volume, in which case the chart can be plotted to represent the degree of tissue oxygenation expressed in cubic centimeters or ml of blood per minute per gram of limb tissue weight . The flow may also be expressed in relative terms, such as the percent of normal unrestricted flow as described above.

Blood flow reduction time can be expressed in absolute terms such as minutes of cuff expansion time. It may also be expressed in relative terms, such as the percent complete of a given cuff expansion period.

The method of performing the remote treatment treatment of the present invention is defined as reducing the blood flow in the limb at least to be sufficient to achieve minimal effective ischemic stress, which in turn is defined as a flow vs time plot to be below the predefined cumulative limb oxygenation threshold value As shown in FIG. The cumulative limb oxygenation reduction threshold value may be expressed as a percentage of the full oxygen supply with unrestricted blood flow, in which case anywhere less than about 40% of the full unrestricted perfusion can be selected. In a further embodiment, the predetermined cumulative limb oxygenation reduction threshold value is at least 40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 0.1% But it can be any other ratio. When dealing with a variable but variable blood flow during cuff inflation, it may be advantageous to use the threshold value of limb oxygenation reduction rather than the threshold value of blood flow reduction.

Figure 3 shows an example of variable blood flow wherein the total area under the curve of flow vs time is less than 10% of the complete oxygen supply. In this example, the blood flow is expressed as a percentage of the unrestricted blood flow (total flow is 100%) and the total duration of blood flow reduction is expressed as a percentage of the full cuff expansion period (total cuff expansion time is 100%). In this example, during most of the cuff expansion period, the blood flow is reduced to about 7% of the normal unrestricted value and the degree of cuff expansion is reduced, but the blood flow can be increased for a short period of time. The total area under the blood flow curve during the entire cuff inflation period is still less than about 10% of the total tissue perfusion (dotted line in Figure 3), despite the rapid increase in blood flow during the cuff inflation period, Satisfies the requirement to reach ischemic stress sufficiently strong to cause the benefit.

An increase in one or more short-term blood flow to 20%, 30%, 50% or more, or even a full unrestricted flow may not impair the purpose of causing sufficient cumulative ischemic stress, Sometimes increases the blood pressure of the patient more accurately, reducing the risk of clot formation, or useful for other useful purposes can be used. In one embodiment, the transient increase in blood flow above a predetermined threshold value may last for a few seconds, so as not to reduce the overall cumulative degree of ischemic stress. The increased blood flow duration may be 1, 2, 3, 5, 10, 15, 20 seconds or any duration therebetween, and the present invention is not limited thereto. This increase in blood flow can also be expressed as 1, 2, 3, 5, 10, 15, 20, 25, 30 heartbeats or any heart rate between them during the increase of blood flow in the limb tissue.

Figure 4 shows another example of variable blood flow reduction during a cuff expansion period to induce ischemic stress. In this case, blood flow reduction progressively expands to an even more restrictive level at the initial, less restrictive level. The area under the curve in Figure 4, which defines total limb tissue oxygenation, is almost the same as in Figures 2 and 3. A gradual increase in limb compression may be developed to improve patient comfort at the beginning of the ischemic duration interval.

Figure 5 shows yet another example of operating the cuff, which is designed to gradually reduce the compression of the limb during the cuff expansion period. This strategy can be used to reduce patient discomfort at the end of the cuff expansion period when the limbs feel coldest and paralyzed. It should be noted that the general degree of oxygen deficiency in the limb tissue is still the same as the previous figures, as evidenced by the area under the curve during the cuff inflation period.

Figure 6 shows another example of operating the cuff to cause the same degree of ischemic stress as in the previous figure, where the cuff pressure causes periodic increases and decreases in limb compression and then decreases blood flow and variable Lt; RTI ID = 0.0 &gt; a &lt; / RTI &gt; varying level of tissue oxygenation. Periodic partial relief of ischemia may be used to reduce the inconvenience of the patient during treatment. This can be accomplished by cyclically changing the cuff pressure to change the degree of limb compression.

Although all previous examples show deep reduction rather than complete occlusion of the limb blood flow, the present invention also contemplates that at least one cycle of remote ischemic treatment treatment, at least at least one of complete occlusion and total blood flow interruption in limb during cuff expansion period Consider having one or more limited periods. Figure 7 shows an example of a technique in which a cuff is initially inflated to induce complete occlusion and then the complete occlusion is partially relieved twice during the cuff inflation period so that at least a small amount of blood passes through the cuff. In an embodiment, each period of complete occlusion can not exceed about one minute to reduce the risk of thrombus formation in the limbs. Fluctuations in one or more cuff pressures may be used throughout the cuff expansion period, depending on the total duration.

Operating the cuff in various modes, as shown in Figures 2-7, may require adjustment if the patient's blood pressure changes - for example, by monitoring the amplitude of the vibration of the cuff pressure, or by monitoring other blood pressure Or by using blood flow monitoring techniques.

Monitoring the initial and progression of blood flow reduction as well as detecting the onset of complete limb occlusion can be accomplished using a variety of manual or automated techniques. In an embodiment, some examples of techniques available for assessing the blood flow level of the limb include manual or machine-implemented detection of the Korotkoff sound, oscillometric amplitude evaluation, direct or indirect blood flow through the cuff Monitoring tissue temperature or heat release capability, measuring limb tissue oxygenation levels, measuring SP02 and Plethysmograph signals.

Measuring the extent of blood flow occlusion can be accomplished using cuff pressure alone or in conjunction with other techniques discussed above. In an embodiment, full or partial oscillometric envelope information may be collected at the beginning or end of at least one processing cycle. This information may be collected at least once or at a scheduled time during the cuff inflation period. The term "oscillometric envelope" is used to describe the curve for the peak of the oscillometric oscillation amplitude obtained at various cuff pressures, for example from the diastolic blood pressure of the patient to the range of systolic blood pressure. In a typical oscillometric envelope, the maximum peak amplitude can be used and determined to detect the corresponding mean arterial pressure (MAP). The patient's systolic and diastolic pressures can be calculated using known ratios and equations . Alternatively, the systolic and / or diastolic blood pressures may be determined using a linear derivative of the oscillometric envelope curve or other signal processing techniques.

Significant reductions in limb blood flow can occur due to abnormal arterial pressure, which corresponds to the maximum amplitude of oscillometric oscillation at the arterial occlusion point when arterial pressure is compressed by approximately 50%. This degree of compression leads to maximum transmission of arterial pressure fluctuations to the cuff compressing the limb from the artery, thus allowing the cuff pressure oscillation to exhibit the maximum amplitude. Here, a reduction of approximately 50% of the arterial cross-section may not necessarily be consistent with a 50% reduction in blood flow, but this reduction may be minimally effective in inducing ischemic stress to produce a remote ischemic effect. The advantage of using the MAP as a marker of minimum effective stress is that it can be easily determined using only the cuff pressure signal without using any additional sensors.

In an embodiment, the ischemic stress threshold value for the target to inflate the cuff may be determined by MAP plus an absolute unit such as mmHg or a predetermined MAP offset that may be expressed as a percentage of the detected MAP value . In accordance with the present invention, the minimum effective cuff pressure that causes sufficient ischemic stress is the detected MAP pressure plus 60 mmHg (e.g., 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 55 or 60 mmHg, or any mmHg therebetween). In another embodiment, the predetermined MAP offset is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45% And may be any other predetermined value between, but not limited to.

In another embodiment, the current level of systolic blood pressure detected may be used to define a minimum effective cuff expansion target pressure. Depending on the width of the cuff, blood flow may be completely blocked or not when the cuff is inflated to the patient's systolic blood pressure. In an embodiment, the minimum effective cuff pressure may be selected to be within the pressure range determined using the patient &apos; s systolic blood pressure. This range can be extended to a high value calculated by adding the detected systolic blood pressure and a predetermined second systolic blood pressure offset from a low value calculated by subtracting a predetermined first systolic pressure offset from the detected systolic blood pressure. In an embodiment, the first systolic blood pressure offset and the second systolic blood pressure offset may be defined as an absolute unit such as mmHg or a percentage of the systolic blood pressure detected. The first systolic blood pressure offset may be 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 mmHg or any mmHg therebetween. The first systolic blood pressure offset may be up to 50%, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40 and 50% But the present invention is not limited to this. The second systolic blood pressure offset may be 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 mmHg or any mmHg therebetween. The second systolic blood pressure offset may also be determined by comparing the systolic blood pressure of the detected patient to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20% , But the present invention is not limited thereto.

If the cuff is inflated to the target pressure to cause a predetermined limb compression level and blood flow reduction, the limb compression level may be maintained at the limb compression level for a portion or all of the entire duration of the cuff expansion. Because the patient's blood pressure may change over time, the cuff pressure may need to be adjusted continuously or intermittently to maintain the required level of limb pressure. One way of achieving this is to determine the amplitude of the oscillometric oscillation when the desired initial limb compression is achieved and then adjust the cuff pressure to maintain the level of oscillometric amplitude for the desired portion of the cuff expansion period. When the patient's blood pressure increases during the duration interval, the amplitude of the cuff pressure oscillation also increases. In this case, the cuff pressure may increase until the amplitude of the vibration decreases to the desired initial level. On the other hand, if the patient's blood pressure falls while the cuff is inflated, the vibration amplitude of the cuff also decreases. In this case, the cuff may gradually contract until the amplitude reaches the same initial level. Periodic or continuous dithering of the cuff pressure may be necessary to ensure that the desired level of limb compression is maintained regardless of the patient's varying blood pressure.

REPERFUSION

Similar to the teachings of the above-described concept that a complete occlusion may not be required during the entire period of cuff expansion, the present invention may be applied to a cuff contraction period, which may or may not reach the complete recovery of the cuff and the blood flow of the limb Lt; RTI ID = 0.0 &gt; flow. &Lt; / RTI &gt;

According to the present invention, after the cuff inflation period, it is necessary to sufficiently increase the blood flow of the limb for the purpose of treatment of the remote ischemia treatment. The increase in blood flow should be sufficient to at least alleviate the ischemic stress generated during the previous period of cuff expansion. Complete contraction of the cuff to remove all compression of the limb is effective in restoring complete perfusion, but is not the only way to achieve a remote ischemic effect while achieving other useful goals.

As described above, tissue oxygenation is a result of blood flow as a function of time. Using such a concept, tissue oxygenation, as mentioned above, can be expressed as the area under the curve plotting blood flow or tissue oxygenation as a function of time. Limitations over the entire reperfusion duration of the cuff contraction period Restoring tissue perfusion to an unreliable level can be seen as 100% reperfusion and complete tissue oxygenation. According to the present invention, partial reperfusion caused by increased but not fully restored blood flow may be sufficient to deliver clinically effective remote ischemic treatment therapies.

In an embodiment, during the cuff contraction period, the blood flow may be increased to a level or above a predetermined perfusion threshold value. The reperfusion threshold value may be defined in terms of absolute or relative terms, for example, using a measurement of blood flow at a percentage point or ml / minute. Depending on the choice of limb and the body weight of the patient, the value of the reperfusion threshold may be selected to be at least 40% of the unrestricted blood flow to alleviate ischemic stress. In an embodiment, the reperfusion threshold value may be selected to be 40, 50, 60, 70, 80, 90, 99, 100, 105, 110% or any other level of unrestricted blood flow. In particular, unrestricted blood flow after the ischemic duration of the cuff-inflation period may temporarily exceed the previous blood flow level by 10% due to the flow-mediated dilatation effect.

When the absolute value of blood flow is used as a measure of the reperfusion threshold value, the value of the reperfusion threshold of the arm is 60 ml / min or more, for example, 60, 65, 70, 75, 80, 85, 90, 100, 110, 120, 130 ml / min or 60 ml / min or more, but the present invention is not limited thereto. In the case of a leg, the reperfusion threshold value may be greater than or equal to 120 ml / min of the blood flow, for example, 120, 130, 140, 150, 160, 170, 180, 190, 200, 220, 240, 260, 280, 300, 320, 340, 360 ml / min, or any other value in between.

In addition, a predetermined reperfusion threshold value can be selected by normalizing blood flow to tissue weight. Assuming a normal mean blood flow of 5 l / min for an adult of 70 kg, the mean unrestricted blood flow per unit weight of tissue is about 70 ml / min per 1,000 g tissue weight. In an embodiment, the cuff may contract to reach or exceed about 40% of the value or about 28 ml / min per 1,000 g of limb tissue weight. In another embodiment, the threshold value may be set at 30, 35, 40, 45, 50, 55, 60, 65, 70 or more ml / min per 1,000 g limb weight.

Figure 8 shows a simple example of manipulating the cuff during the cuff contraction period, in which ischemic stress is alleviated by increasing blood flow to a predefined reperfusion threshold value of about 70% of the previously unrestricted blood flow level.

In addition to increasing blood flow to a predetermined constant perfusion threshold value as shown in FIG. 8, the present invention contemplates providing variable flow during the cuff contraction period. The blood flow of these limbs should meet the requirement that the parameters provide a minimal effective tissue oxygenation to help cumulatively relax the ischemic stress and to demonstrate to the patient the remote treatment treatment. Figure 9 shows an example of a variable blood flow during a cuff contraction period, in which the cuff is inflated to reduce blood flow in the limb for a short period of time, halfway through the duration of the cuff contraction. One or several flow decays with sustained heartbeats of a few seconds or several times will record the current oscillometric envelope and help to detect the patient's blood pressure, minimum diastolic blood pressure and possibly the current level of the mean arterial blood pressure . In another embodiment, full occlusion of the blood pressure may be performed during the cuff contraction period to characterize the patient's total blood pressure, including systolic blood pressure, mean arterial blood pressure, and diastolic blood pressure.

In an embodiment, the reperfusion threshold value can be defined as about 70% of the unrestricted perfusion of the limb. In another embodiment, the reperfusion threshold value is at least 50% or more of resting tissue oxygenation, for example, restoration of any value of 50, 60, 70, 80, 90, 99% ). &Lt; / RTI &gt;

The reperfusion threshold value may be defined by the absolute term or the cuff pressure in relation to the patient's blood pressure. In an embodiment, the reperfusion threshold value is about 120 mmHg or less, such as 110, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10, 5, Can be defined as contracting the cuff to a pressure level.

Associating the patient's blood pressure with the target cuff pressure during the cuff contraction period may also be used. In some embodiments, the target cuff pressure during the cuff contraction period may be selected to be below the limb occlusion pressure. In another embodiment, the target cuff pressure may be selected to be equal to or less than the systolic blood pressure. Further, in a further embodiment, the target cuff pressure may be selected to be below the mean arterial pressure of the patient. In a further embodiment, the target cuff pressure may be selected to be below the patient's diastolic blood pressure.

The respective threshold values for ischemic stress and reperfusion discussed above were generally discussed with reference to the average patient with normal blood circulation and tissue oxygenation. Adjustments to these baseline values may be determined by various factors and circumstances of the individual patient. Examples of factors that need adjustment to manipulate the cuff include:

a. Abnormally high or low baseline tissue oxygenation, which includes breathing at a recent exercise or other physical activity, breathing at high altitudes, oxygen-enriched or oxygen-deficient gas mixture (eg through a ventilator) It can be caused by respiration near the fire where oxygen is consumed by flame, and breathing by smoking.

b. The inability of the lung to supply oxygen to the blood (inability)

c. For example, if oxygen is not used in tissue, such as occurs in cyanide poisoning

d. Anemia Chronic hypoxemia reduces the oxygen content in the blood

e. Recent blood transfusions

f. Recent serious blood loss due to trauma, accidents or other causes

g. Cold or hot ambient conditions

h. An abnormally high or low body temperature that causes an increase or decrease in oxygen demand

i. Abnormal hemoglobin content of blood

j. Abnormal oxygen saturation

k. Reduced cardiac output

l. Hypertension or hypotension

m. Limb vasoconstriction or cramps due to certain drugs or shocks

n. Acid base imbalance such as acidosis or alkalosis

o. Arterial gas imbalance

In such a case, the method of the present invention may be adapted to achieve a remote treatment effect by periodically expanding the cuff to reduce blood flow and to reduce tissue oxygenation below the adjusted ischemic stress threshold value for a predetermined time of at least 1 minute And alternate with the cuff contraction cycle when blood flow is increased above the regulated reperfusion threshold to relieve ischemic stress.

In another embodiment of the method of the present invention, identifying a patient with abnormally low or abnormally high levels of tissue oxygenation prior to initiating a remote ischemic treatment treatment is aimed at moderately restoring limb tissue oxygenation to near normal You may need to take additional steps. This additional step may be taken before, during, or immediately after the administration of the remote ischemic treatment treatment. An example of such additional treatment may be infusion or transfusion which may be performed on the victim of severe blood loss to mitigate as low a cardiac output and / or hypotension as possible. Another example is to move the patient away with a fire or smoke and to start breathing with oxygen-rich as possible to restore normal tissue oxygenation of a burn victim suffering from smoke inhalation.

AUTOMATIC SINGLE-BLADDER DEVICES FOR REMOTE ISCHEMIC CONDITIONING VIA PARTIAL LIMB OCCLUSION FOR TREATMENT OF REMOTE ISCHEMIC TREATMENTS WITH PARTIAL REMOTE OBJECTION

Some or all of the above-mentioned methods for inflating and deflating a cuff for the purpose of providing a remote ischemic therapy treatment may be implemented in an automatic controller operably connected to the cuff. The controller may comprise a microprocessor which, when activated, may be programmed or otherwise configured to execute the method of the present invention. A microprocessor may include an embedded computer memory including software designed to implement the method of the present invention. Alternatively, the software may reside on a removable hardware portion, such as a memory stick, and the memory stick may be plugged into the controller before being activated. In another embodiment, the software may reside on a central server, and the controller may be operatively connected to the server before treatment or at least some time during therapy. Such server connection may be performed using known wired or wireless connection means and protocols. One advantage of using a central server to control the expansion and contraction of the cuff through the local controller is the ability to integrate into the hospital data recording system, which not only records the patient's blood pressure, but also maintains a record of care. Another advantage is that you can provide the latest algorithms from a single central server to all local controllers without having to update each controller individually. The patient-side controller has wired or wireless transmission capability and can record all relevant data and transmit this data to the central data recording facility.

In some embodiments, the cuff may be configured for placement of the subject's limb and for the purpose of a remote ischemic procedure with a single inflatable bladder that can reduce or stop the blood flow of the limb upon inflation. In this case, the controller may have pneumatic components (air pumps, valves, reservoirs, etc.) configured to inflate and deflate the single bladder according to the remote treatment treatment method described above. The controller may also be equipped with one or more sensors, such as a bladder pressure sensor, to monitor the inflation or deflation state of the cuff bladder. The apparatus may further comprise one or more sensors for monitoring the patient or other parameters specifying the treatment delivery process. Examples of such sensors include tissue oxygenation sensors, blood flow sensors, temperature sensors, microphones or other sensors that sense Korotkoff sounds, and SPO2 sensors.

The controller can be operatively connected to the cuff in a state in which it is attached directly to or coupled to the cuff. The controller can be configured to deliver a remote ischemic treatment treatment by performing a plurality of remote ischemic treatment treatment cycles upon activation, wherein each treatment cycle generally includes a cuff inflation period and a period of cuff contraction. During at least one cuff expansion period, the controller may be operated to expand and maintain the cuff at least over a pressure sufficient to at least partially reduce blood flow in the limb to produce ischemic stress and last for at least about one minute. The controller may be further operative during at least one cuff contraction period such that the cuff contracts to an extent sufficient to at least increase blood flow in the limb and relieve ischemic stress. In a further embodiment, the controller may be configured to avoid complete obstruction of the limb by at least one more minute of the cuff during at least one remote ischemic treatment treatment cycle. In yet another embodiment of the present invention, the controller is further configured to provide at least a partial pressure of the patient's limb occlusion pressure or the systolic blood pressure of the patient to ensure partial flow of blood at least below the cuff during at least a portion of the cuff expansion, in

The cuff may be configured to expand. In yet another embodiment, the controller can be programmed to maintain the cuff pressure above the minimum effective cuff pressure selected to reduce blood flow at 90% or more limb from the original, unrestricted level. Each period of cuff expansion The desired cuff pressure and blood flow reduction level can be maintained or varied using the method detailed above, depending on the desired ischemic stress level and the fluctuating blood pressure of the patient. In an embodiment, at least one or all of the cuff inflation periods may comprise at least one complete blood flow occlusion period and at least one partial blood flow occlusion period. In a further embodiment, the one or more treatment cycles may comprise an alternating period of complete and partial blood flow occlusion.

[0069] In some embodiments, the controller is configured to inflate the cuff to a greater pressure in both, above the systolic pressure of the patient or above the patient's limb occlusion pressure, to completely stop the blood flow of the limb from the beginning or at any time during the cuff inflation period Lt; / RTI &gt; In order to allow a small amount of blood to pass into the artery of the limb under the cuff, the controller is operated either once or twice, depending on the systolic blood pressure or the limb occlusion pressure of the patient, the width of the cuff and other factors, And may be further programmed to periodically constrict the cuff (e.g., according to predetermined criteria). The procedure can be used to determine the oscillometric oscillation of the cuff, which can be used at least in addition to determining the patient's updated systolic blood pressure. Signal processing operations and / or further contractions of the cuff may be used to detect mean arterial pressure, diastolic blood pressure, heart rate and other parameters of interest of the treated patient. The entire process of collecting data for detecting updated values for one or more parameters that specify the patient &apos; s blood pressure may be performed within a few seconds or several heartbeats of the patient. Once the data is collected, the cuff may be inflated to a pressure above the updated limb occlusion pressure and the blood flow of the limb may be completely interrupted until the next scheduled cuff contraction process. In an alternative embodiment, the cuff pressure can be continuously varied or dithered to go above and below the limb occlusion pressure to continuously or at least frequently detect the patient's systolic blood pressure or other desired level of interest. The occasional contraction of the cuff pressure to contact the patient's systolic blood pressure may not cause more than a few percentage points of the blood flow through the cuff during the entire duration of the cuff expansion, Frequent determination of the patient's updated blood pressure can be advantageously made without jeopardizing it.

In another embodiment, the controller can be programmed to maintain a generally higher cuff pressure than a point at which blood flow is reduced from unrestricted level to about 90%. To reduce the risk of thrombus formation in the vasculature, care should be taken to ensure that the limb's blood flow is not completely blocked for an extended period of time, such as the cuff does not swell and lasts longer than one minute.

Upon expiration of a predetermined period of cuff expansion or other signal for which sufficient ischemic stress has been achieved, the controller may be configured to initiate a cuff contraction period. The present invention discloses a system that can be configured so as not to shrink the cuff completely during the entire duration of the cuff contraction, as compared to the full contraction of the cuff that is typically performed. As described in more detail above, the cuff can be contracted enough to increase blood flow and alleviate ischemic stress, but at the same time, the cuff has some residual that can be changed for useful purposes during the cuff contraction period ) Pressure.

In some embodiments, the cuff pressure can be maintained at a low pressure level to keep the cuff in the limb and avoid its slippage or change in position. The level of "keep on limb" cuff pressure may be about 5 mmHg or other suitably low pressure level, for example 1, 2, 3, 4, 5, 10, 15 or about 20 mmHg.

In a further embodiment, the cuff pressure may be increased for a short time to detect oscillometric vibrations once or periodically during the cuff contraction period. The period may be as short as a few seconds and may be scheduled at 20, 30, 45, 60, 90, 120 seconds or any other interval during the cuff contraction period. The cuff pressure may be increased to a predetermined fixed level or until sufficient oscillometric data is obtained as described above. Once the cuff contraction is complete, the controller can be programmed to begin a subsequent period of cuff expansion. After all predetermined cuff expansion and cuff contraction periods have been completed, the controller can be fully programmed to shrink the cuff and optionally inform the user that the procedure is complete.

AUTOMATIC DUAL-BLADDER DEVICES FOR REMOTE ISCHEMIC CONDITIONING VIA PARTIAL LIMB OCCLUSION

Additional beneficial functions and / or biological monitoring can be performed when the cuff comprises two or more inflatable bladders. The use of multiple bladders can increase the overall width of the cuff, which can be delivered when the cuff pressure is low, while performing an accurate measurement of the patient's blood pressure during treatment. In an embodiment, the cuff may include two or more inflatable bladders, such as a proximal bladder and a distal bladder. The proximal bladder is closer to the heart and is generally located on the distal bladder in the limbs. The two bladders can be placed next to each other on the limbs, overlapping each other, or positioned with some space in between. In at least one of the inflatable bladders, the distal bladder, for example, may be configured to have a width corresponding to the width of the standard blood pressure monitoring cuff and may be used to detect the patient's blood pressure. In another embodiment, if the width of the cuff is not consistent with a typical cuff width recommendation, a computational correction correction of the computer may be implemented to compensate for this mismatch. For example, the measured blood pressure may be computationally increased to compensate for the narrow width of the bladder, or it may be computationally reduced to compensate for the wider bladder width. The overall width of the cuff having a plurality of inflatable bladders may be as long as the entire upper arm and even extend over a portion of the elbow or below the elbow.

The controller can be configured to independently actuate each inflatable bladder by individually inflating and deflating each bladder. In another embodiment, the controller may be configured to connect both or all of the bladders together to equalize the pressure therein sometimes, if necessary. This configuration is described in more detail in the previous patent cited above.

One advantageous method of operating the two bladders is described below. Upon activation of the controller, the distal bladder, which typically has a width of the blood pressure cuff, is moved from an initial pressure of 0 to a first target pressure, e.g., 140, 150, 160, 170, 180, 190, 200, Hg or any other suitable pressure above the patient &apos; s systolic blood pressure. Another way to determine the first target pressure is to measure the patient's current systolic blood pressure and inflate the distal bladder above the measured pressure as described below. The oscillometric data can be collected to rise during the initial expansion of the distal bladder and the patient's blood pressure can be determined therefrom. The distal bladder may be inflated either continuously or with a predetermined increment of cuff pressure. Once the oscillometric data is recorded, the systolic blood pressure can be determined using known oscillometric techniques.

The proximal bladder may be inflated to the same first target pressure as the distal bladder, for example. Amplitude data of the oscillometric oscillation during the expansion of the proximal bladder can be recorded. Preferably, the MAP and systolic blood pressure of a previously known patient may be correlated with the oscillation amplitude of the proximal cuff, so that the amplitude of the oscillation of the proximal bladder at the previously measured patient's MAP and systolic blood pressure Data correlating with the pressure of the further is recorded. The inflatable bladder may be inflated to a first target pressure, for example, to completely block the blood flow of the limb.

At any point in the cuff inflation period, both the proximal inflatable bladder or the inflatable bladder may be slowly contracted to record the oscillometric vibration together. In an embodiment, the proximal bladder may be retracted to detect systolic blood pressure, for example by measuring the amplitude of the oscillometric oscillation and matching it to a pre-detected amplitude corresponding to a pre-measured systolic blood pressure. Reaching the same amplitude of oscillation, such as the previous systolic blood pressure, in the proximal bladder can be used to detect the current updated value of the systolic blood pressure.

Other criteria for reaching a sufficiently low pressure in a proximal or distal bladder, such as curve to the peak of the oscillometric oscillation and to detect systolic blood pressure from the first derivative of the curve, may also result in additional shrinkage of the bladder . &Lt; / RTI &gt; Once the patient's updated blood pressure is determined, the two bladders can be inflated beyond the newly detected systolic blood pressure or calculated updated limb occlusion pressure based on the current systolic blood pressure, so that ischemic stress The blood flow may be completely blocked or partially reduced. The cuff pressure in one or both bladders can sometimes be re-dithered or varied to keep up with the patient's varying blood pressure.

Once the predetermined cuff expansion period is complete, the proximal bladder may first contract and may no longer restrict arterial blood flow. The distal bladder can then be retracted and the entire range of the oscillometric envelope can be recorded through a slow contraction process. This allows accurate detection of the patient's updated systolic, diastolic and MAP blood pressures and can be displayed to the user or clinician. The controller may be configured to perform a cuff inflation period and to alleviate ischemic stress for a specified period of time.

Measurement of limb blood flow using double bladder cuff (DETECTION OF LIMB BLOOD FLOW USING A DUAL-BLADDER CUFF)

It may be useful to determine the blood flow volume of the cuff during one or more cuff contraction periods. Blood flow information can be a means of regulating cuff pressure to induce a sufficient level of reperfusion and to relieve ischemic stress. Blood flow may also be useful in determining the degree of mediated vasodilation, and the phenomenon of compensatory following an ischemic period increases blood flow in the limb. The degree of transient increase in limb blood flow may indicate endothelial health or dysfunction, which determines whether the minimum number and duration of the treatment cycle is sufficient for therapeutic purposes or whether an extended treatment protocol should be implemented Can be used.

The reason for choosing an extended treatment protocol is explained in more detail in other patents of the present inventor and may include meeting uncompensated diabetes, hyperlipidemia or other conditions of the patient.

In an embodiment, the blood flow of the limb can be measured by inflating the proximal inflatable bladder at a venous occlusion pressure that is generally higher than the central venous pressure but lower than the patient &apos; s diastolic blood pressure. In an embodiment, the target proximal bladder pressure may be about 30, 35, 40, 45, 50, 55, 60, 65, 70, 75 or 80 mmHg. Methods for measuring blood flow include preventing unrestricted arterial flow into the vasculature while preventing venous return from the limb. Incoming blood flow accumulates in the enlarged venous system of the limb blood vessels widened by them. At first, the venous blood pressure of the limb may not rise significantly because the vein expands to easily store blood. As more blood flows into the limbs and accumulates in the veins, their swelling decreases and the venous blood pressure rises above the normal level to the pressure of the proximal bladder. Depending on which limb is used to provide the remote treatment regimen, the entire procedure can be performed anywhere from about 30 seconds to about 120 seconds until the venous pressure reaches the cuff pressure. When that happens, blood flow is resumed while the vein is fully expanded.

The initial volume expansion rate and degree of limb at low venous pressure can be used to assess blood flow. The expanded limb volume can be sensed using the pressure of the distal cuff. As the limb volume expands, compression can occur in the distal bladder, which tightly surrounds the limb. Immediately after the expansion of the proximal pressure to prevent venous reflux, elevation of the distal bladder pressure may indicate the rate of blood flow in the limb. Once the rate of incoming blood flow is detected, the two bladders are placed at the level of normal central venous pressure (5-10 mmHg) to relieve congestion and allow the blood to escape from the limb It can be contracted at low pressure around it.

10 shows a process for detecting limb blood flow using a double bladder cuff during a cuff contraction period. One or both bladders can be contracted to a low initial pressure between 0 and about 10 mmHg. The chart of Figure 10 shows three pressure lines as a function of time: the upper solid line is the pressure chart of the proximal inflatable bladder, the middle solid line is the venous pressure of the limb and the lower solid line is the distal bladder. The upper solid line can consist of three steps; A diastolic blood pressure that is selected so as to block the flow of blood out of the limb's veins but not interfere with the incoming blood flow from the limb artery, for example to a predetermined target level of less than 50 mmHg An initial inflation stage 202 of the proximal bladder; A steady state 204 to maintain proximal bladder pressure at the target venous occlusion pressure and a contraction phase 206 when the proximal bladder is contracted to allow blood outflow from the limb .

Referring to portion 222 of FIG. 10, in response to vein occlusion by the expanded proximal bladder, the limb vein vasculature expands to absorb the incoming blood flow and the venous pressure initially rises steadily. Because the large portion of the limb is below the distal bladder of the cuff, the expanding volume causes an increase in the distal bladder pressure, which is the same as portion 222 of FIG. At some point the vein becomes full and subsequent inflation involves stretching and elastic deformation, which results in constantly increasing pressure within the vein system. If the vein can no longer expand, the distal bladder pressure curve is separated from the intravenous pressure curve. The cuff does not absorb much of the incoming volume from the expanded limb tissue, but the blood pressure of the veins continues to rise by incoming arterial blood. The distal cuff pressure reaches steady state 216 while venous pressure continues to rise along portion 214 until it reaches the blood pressure level of the proximal bladder. When the proximal bladder is deflated, the venous pressure drops to an initial level and the distal bladder pressure also decreases (218).

The slope of the initial curve portion 222 can be measured using a straight line 220 and a fit shown in dashed lines in FIG. The more the blood stream enters the limb, the larger the slope becomes, and the smaller the blood flow into limb, the smaller the slope becomes. Thus, blood flow in the limb can be measured indirectly and noninvasively using the initial slope of the distal bladder pressure curve.

The above method of detecting limb blood flow can be performed once or repeatedly during the cuff contraction period. In one embodiment, blood flow can be performed once every about 20-30 seconds after the end of the cuff expansion period. In another embodiment, this may be repeated every 10-20 seconds by dithering the pressure of the proximal bladder or during the first minute of the cuff contraction period between low venipuncture and venous occlusion pressure according to another suitable schedule . The peak of the limb blood flow can be detected by repeated blood flow measurement. This is an increase in blood flow circulation due to flow-mediated dilatation. These peaks generally occur within the first 15-45 seconds after restoring blood flow. The limb blood flow peak can be compared to non-limiting blood flow at the top of the limb, which can be obtained, for example, before the start of treatment or at the end of the cuff contraction period using the same procedure. The ratio of peak blood flow to normal blood flow can be used to assess a patient &apos; s health condition and determine the need to activate standard or extended remote treatment protocols.

[0088] If the rate of flow referred to above is used to determine the best treatment protocol for a patient, absolute blood flow measurement may not be required and the process may be simplified. In an embodiment, the ratio of the peak to normal slope of the increase in distal bladder pressure is the ratio of the peak to normal blood flow to the normal blood flow, proxy. If the ratio is below a predetermined threshold value, the need for extended therapy can be demonstrated.

[0089] Any embodiment discussed herein may be implemented in connection with any method of the invention, and vice versa. It will also be appreciated that the specific embodiments described herein are illustrated by way of example and not by way of limitation of the invention. The main features of the invention may be used in various embodiments without departing from the scope of the invention. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific procedures described herein. Such equivalents are considered to be within the scope of the present invention and are covered by the claims.

[0090] All publications and patent applications mentioned in this specification are indicative of the proficiency of those of ordinary skill in the art to which this invention belongs. All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

[0091] The use of the term "a" when used in conjunction with the term "comprising" in the claims and / or the specification may mean "one," but also "one or more," " Means one or more than one. This disclosure supports the definitions referring to alternatives and " and / or ", but the use of the term "or" in the claims is used to refer to alternatives only " Or ". Throughout this application, the term " about "is used to indicate that there is a unique error variation in the device to a value, which method is used to determine the value or variation that exists between subjects.

As used in this specification and the claims, the terms "comprising" (and any form including, for example, "comprising"), "having" (and any form including, (And any form of incorporation, for example, "contains"), is intended to be inclusive or illustrative of any form And does not exclude any element or method step not further described. In embodiments of any of the compositions and methods provided herein, "comprising" may be replaced by "consisting essentially of" or "consisting of. &Quot; As used herein, the phrase " consisting essentially of "requires certain integers or steps that do not materially affect the features or functions of the claimed invention. As used herein, the term "configured" is intended to encompass a set of integers (eg, features, elements, characteristics, method / (S), method (s) / process steps or limit (s)).

[0093] As used herein, the term "or a combination thereof" means all permutations and combinations of the listed items listed before the term. For example, "A, B, C or a combination thereof is intended to include at least one of A, B, C, AB, AC, BC or ABC. , CBA, BCA, ACB, BAC, or CAB.

Continuing use of this example explicitly includes combinations that repeatedly include one or more items or terms, such as BB, AAA, AB, BBC, AAABCCCC, CBBAAA, CAB ABB, It will be appreciated by those of ordinary skill in the art that there is no limit to the number of items or terms in any combination, unless the context clearly dictates otherwise.

[0094] As used herein, the terms approximate, such as "about", "substantial" or "substantially" mean a condition that is understood to be not necessarily absolute or complete when so modified, Will be considered to be sufficiently close to those of ordinary skill in the art. The extent to which the description can vary depends on how large the change can occur, and still the ordinary technician can recognize the modified feature while still retaining the desired characteristics and capabilities of the unmodified feature. Generally, however, subject to the foregoing discussion, the numerical values modified by approximate terms such as "about" should be understood to include values that are at least 1, 2, 3, 4, 5, 6, 7, 10, 12 , 15, 20, or 25%.

[0095] All devices and / or methods disclosed and claimed herein may be made and executed without undue experimentation in light of the present disclosure. While the apparatus and method of the present invention has been described in connection with preferred embodiments, it will be understood by those skilled in the art that variations may be applied in the apparatus and / or in the order of steps, steps or steps without departing from the concept, spirit and scope of the present invention. Will be apparent to one of ordinary skill in the art. All such alternatives and modifications apparent to those of ordinary skill in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

100: Delivery device for remote ischemic treatment
110: cuff
150:

Claims (21)

A device (100) for delivering a remote ischemic treatment treatment to a patient,
The device includes a cuff (110) configured to be positioned on a limb of a patient; And
And a controller (150) operatively connected to the cuff (110)
The cuff 110 at least partially reduces blood flow in the limb during inflation;
Characterized in that it comprises a controller (150) for performing a plurality of remote ischemic treatment treatment cycles upon activation, and delivering said remote ischemic treatment treatment,
Each treatment cycle is performed such that the cuff 110 is inflated and maintained at a pressure sufficient or greater than the controller 150 to cause at least a partial reduction of the limb blood flow to generate ischemic stress for at least one minute or more. A cuff expanding period to allow the cuff to expand;
Wherein the controller (150) includes a cuff constriction period to constrict the cuff (110) to alleviate the ischemic stress and increase the limb blood flow,
Wherein said ischemic stress is sufficient to cause said remote ischemic treatment,
The controller 150 is configured to avoid complete occlusion of the limb by the cuff 110 by sustaining at least one or more of the treatment cycles for at least one minute or more. .
The method according to claim 1,
The controller 150 is configured to inflate the cuff 110 to a lower pressure or lower of the patient's limb occlusion pressure or the systolic blood pressure of the patient during at least a portion of the cuff inflation period (100). &lt; / RTI &gt;
3. The method of claim 2,
Wherein the controller (150) is configured to inflate the cuff (110) at or above a pressure sufficient to reduce the unrestrained blood flow of the limb by about 90% during the entire cuff inflation period. (100).
A device (100) for delivering a remote ischemic treatment treatment to a patient,
The device includes a cuff (110) configured to be positioned on a limb of a patient; And
And a controller (150) operatively connected to the cuff (110)
The cuff 110 at least partially reduces blood flow in the limb during inflation;
Characterized in that it comprises a controller (150) for performing a plurality of remote ischemic treatment treatment cycles upon activation, and delivering said remote ischemic treatment treatment,
Each treatment cycle includes a cuff expansion period during which the cuff 110 is inflated to a pressure sufficient to cause the controller 150 to at least partially reduce blood flow in the limb and cause the ischemic stress to cause the remote ischemic procedure;
And a cuff contracting period wherein the controller (150) contracts the cuff (110) and increases blood flow of the limb to relieve the ischemic stress, wherein the cuff inflation period lasts for at least about one minute,
Wherein the controller (150) is configured to vary the pressure of the cuff (110) during at least one of the cuff inflation periods to reduce or increase the ischemic stress in the limbs.
5. The method of claim 4,
The controller 150 may be configured to vary the pressure of the cuff 110 to generate at least one complete occlusion period and at least one partial occlusion period of blood flow in the limb during at least one cuff inflation period of the treatment cycle (100). &Lt; / RTI &gt;
6. The method of claim 5,
Wherein the controller (150) is configured to periodically change the cuff pressure to alternate between partial limb occlusion and complete limb occlusion during at least one cuff inflation period of the treatment cycle. .
A device (100) for delivering a remote ischemic treatment treatment to a patient,
The device includes a cuff (110) configured to be positioned on a limb of a patient; And
And a controller (150) operatively connected to the cuff (110)
The cuff 110 at least partially reduces blood flow in the limb during inflation;
Characterized in that it comprises a controller (150) for performing a plurality of remote ischemic treatment treatment cycles upon activation, and delivering said remote ischemic treatment treatment,
Each treatment cycle includes a cuff inflation period during which the cuff 110 is inflated to a pressure sufficient to reduce the blood flow of the limb to thereby reach or exceed a predetermined ischemic stress threshold and to cause ischemic stress thereon ;
And a cuff constriction period during which the cuff (110) contracts to increase blood flow in the limb and thereby alleviate ischemic stress, wherein the cuff inflation period lasts for at least about one minute,
The controller 150 is configured to avoid complete occlusion of the limb by the cuff 110 by sustaining at least one or more of the treatment cycles for at least one minute or more. .
8. The method of claim 7,
Wherein the predetermined ischemic stress threshold value is achieved by reducing the blood flow of the limb below a predetermined blood flow reduction threshold.
9. The method of claim 8,
Wherein the predetermined blood flow reduction threshold value is about 10% of the unrestricted blood flow of the limb.
9. The method of claim 8,
Wherein the predetermined blood flow reduction threshold value is about 30 ml / min.
9. The method of claim 8,
Wherein the predetermined blood flow reduction threshold value is about 10 ml / min per 1,000 g of limb tissue weight.
8. The method of claim 7,
Wherein the predetermined blood flow reduction is achieved by reducing cumulative limb oxygenation to below a predetermined cumulative tissue oxygenation reduction threshold value during a cuff inflation period.

13. The method of claim 12,
Wherein the cumulative limb oxygenation reduction threshold value is about 40% of the unrestricted limb oxygenation defined in the unrestricted blood flow.
8. The method of claim 7,
During at least a portion of the cuff inflation period, the cuff (110) is inflated to at least the mean arterial pressure of the patient.
15. The method of claim 14,
During at least a portion of the cuff inflation period, the cuff (110) is inflated to a pressure exceeding the patient's mean arterial pressure to a predetermined mean arterial pressure offset.
8. The method of claim 7,
During at least a portion of the cuff inflation period, the cuff (110) is inflated to a pressure of less than or equal to the systolic blood pressure of the patient or the patient's obturator occlusion pressure.
17. The method of claim 16,
During at least a portion of the cuff inflation period, the cuff (110) is inflated to a pressure less than the systolic blood pressure of the patient until a predetermined first systolic pressure offset.
18. The method of claim 17,
Wherein the first systolic pressure offset is about 10 mm Hg.
8. The method of claim 7,
During the cuff constriction period, the cuff (110) is retracted to increase blood flow above a predetermined reperfusion threshold value.
20. The method of claim 19,
The controller (150) is configured to vary the cuff pressure during a cuff contraction period to increase or decrease blood flow of the limb during the at least one treatment cycle.
20. The method of claim 19,
Wherein the reperfusion threshold value is defined as 70% of the unrestricted perfusion of the limb.

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