ASSESSING ENDOTHELIAL FUNCTION USING A BLOOD PRESSURE CUFF

• US 20150359437A1
• Filed: 04/03/2015
• Published: 12/17/2015
• Est. Priority Date: 04/03/2014
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Maltz, Jonathan S.
• Granted Patent: US 10,945,612 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 17/135 inflatable for measuring blood pressure A61B5/022; inflatable pressure pads A61F5/34
• CPC Class Codes: A61B 17/1355 Automated control means therefor
• CPC Class Codes: A61B 2017/00123 and automatic shutdown
• CPC Class Codes: A61B 2017/00199 with a console, e.g. a control panel with a display
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/02141 Details of apparatus construction, e.g. pump units or housings therefor, cuff pressurising systems, arrangements of fluid conduits or circuits A61B5/02233, A61B5/0235 take precedence
• CPC Class Codes: A61B 5/0225 the pressure being controlled by electric signals, e.g. derived from Korotkoff sounds
• CPC Class Codes: A61B 5/107 Measuring physical dimensions, e.g. size of the entire body or parts thereof
• CPC Class Codes: A61B 5/6824 Arm or wrist
• CPC Class Codes: A61B 5/6828 Leg
• CPC Class Codes: A61B 5/7246 using correlation, e.g. template matching or determination of similarity
• CPC Class Codes: A61B 5/7285 for synchronising or triggering a physiological measurement or image acquisition with a physiological event or waveform, e.g. an ECG signal A61B6/5205, A61B6/541, A61B8/5207, A61B8/543 take precedence

Abstract

Methods and apparatus are provided for assessing endothelial function in a mammal. In certain embodiments the methods involve applying to the artery a substantially constant external pressure that causes the tension in the arterial wall to be reduced, where the pressure is provided via a cuff adjacent to and/or around a region of the mammal'"'"'s body; determining, over the course of one or more cardiac cycles, changes in pressure in the cuff resulting from cardiac activity of the mammal to establish a baseline value for a parameter related to endothelial function in the mammal; applying a stimulus to the mammal; determining, over the course of one or more cardiac cycles, changes in pressure in the cuff resulting from cardiac activity of the mammal to establish a stimulus-effected value for a parameter related to endothelial function in the mammal; wherein the baseline value is determined from measurements made when the mammal is not substantially effected by the stimulus; and wherein differences in the baseline value and the stimulus-effected value provide a measure of endothelial function in the mammal.

Claims

1. A method of assessing endothelial function in a mammal, said method comprising:

a) applying to the artery a substantially constant external pressure that causes the tension in the artery wall to decrease, where said pressure is provided via a cuff adjacent to and/or around a region of the mammal'"'"'s body;

b) determining, over the course of one or more cardiac cycles, changes in pressure in said cuff resulting from cardiac activity of said mammal, or an artificially induced arterial pulse to establish a baseline value for a parameter related to endothelial function in said mammal;

c) applying a stimulus to said mammal; and

d) determining, over the course of one or more cardiac cycles, changes in pressure in said cuff resulting from cardiac activity of said mammal, or an artificially induced arterial pulse, to determine a stimulus-effected value for a parameter related to endothelial function in said mammal;

wherein said determining of steps (b) and (d) comprise

i) during a first time interval stabilizing the pressure in said cuff at or close to the measurement pressure set point during the period where tissue compression under the cuff leads to a natural pressure drop; and

ii) once the natural pressure drop stabilizes, during a second time interval determining over a course of one or more cardiac cycles said changes in pressure in said cuff; and

wherein said baseline value is determined from measurements made when said mammal is not substantially effected by said stimulus and differences in said baseline value and said stimulus-effected value provide a measure of endothelial function in said mammal.

2. The method of claim 1, wherein during said first time interval pressure is applied to said cuff using a control feedback system to adjust a pump or other pressure source and/or a proportional release valve to maintain said desired pressure set point.

4. The method of claim 1, wherein

during said second time interval adjustment of said pressure is stopped;

or

during said second time interval adjustment of said pressure is periodically adjusted using an on-off control system.

5. The method of claim 1, wherein during said second time interval adjustment of said pressure is periodically adjusted using an on-off control system.

6. The method of claim 1, wherein during said second time interval adjustment of said pressure is by a pump and a proportional valve that operate simultaneously to maintain pressure where pump remains on while the valve is adjusted to maintain a constant pressure, this system being characterized by a time constant such that a cardiac pulse signal is not appreciably attenuated by the servo mechanism.

7. The method of claim 1, wherein

during said first time interval pressure is maintained within a first pressure range (Δ

P₁) around said measurement set point; and

/or

during said second time interval pressure is maintained within a second pressure range (Δ

P₂) around said measurement set point.

9. The method of claim 7, wherein said second pressure range is greater than said first pressure range.

10. The method of claim 7, wherein said first pressure range (Δ

P₁) ranges from about 1 mm Hg to about 6 mm Hg and said second pressure range (Δ

P₂) ranges from about 5 mm Hg up to about 15 mm Hg.

14. The method of claim 1, wherein the duration of said first time interval and/or said second time interval ranges from about 1 sec up to about 30 min;

and/or

16. The method of claim 1, wherein said establishing a baseline value comprises establishing a baseline value for an artificially induced arterial pulse.

17. The method of claim 16, wherein said determining a stimulus-effected value comprises determining a stimulus-effected value for an artificially induced arterial pulse.

18. The method of claim 1, wherein said establishing a baseline value comprises establishing a baseline value for changes in pressure resulting from cardiac activity of said mammal.

19. The method of claim 18, wherein said determining a stimulus-effected value comprises establishing a stimulus-effected value for changes in pressure resulting from cardiac activity of said mammal.

20. The method of claim 1, wherein said substantially constant pressure is applied by a pressurized cuff disposed around an arm or leg of said mammal.

23. The method of claim 1, wherein said substantially constant external pressure is maintained by a system that monitors and adjusts the pressure in said cuff and whose response time is sufficiently slow so that the changes in pressure resulting from said cardiac activity are not substantially attenuated by said system.

24. The method of claim 23, wherein said response time is sufficiently slow so that said pressure changes resulting from said cardiac activity are attenuated by less than 10%.

25. The method of claim 1, wherein said substantially constant external pressure is maintained by setting the pressure in said cuff to a value and not altering external pressure applied to said cuff during the measurements of pressure variations due to said cardiac activity.

29. The method of claim 1, wherein said substantially constant external pressure is equivalent to or below the average diastolic pressure measured for said subject or below an expected diastolic pressure for said subject or said substantially constant external pressure is set to a predetermined pressure.

35. The method of claim 1, wherein said determining, over the course of one or more cardiac cycles, changes in pressure in said cuff resulting from cardiac activity of said mammal comprises determining the pressure in said cuff as a function of time.

36. The method of claim 35, wherein

said determining comprises integrating the value of a pressure change over time (calculating the area under a pressure/time curve) for one or for a plurality of cardiac cycles to determine an integrated pressure value;

or

said determining comprises determining the maximum, or a certain percentile rank of the derivative of the pressure versus time wave form on the rising edge of a pressure pulse for one or for a plurality of cardiac cycles to determine a compliance value.

38. The method of claim 36, wherein

said integrated pressure value and/or said compliance value is averaged over a plurality of cardiac cycles;

or

said integrated pressure value and/or said compliance value is determined for a single cardiac cycle.

39. The method of claim 36, wherein said integrated pressure value and/or said compliance value is determined for a single cardiac cycle;

and

said single cardiac cycle is a cardiac cycle selected for the maximum change in said value in a plurality of cardiac cycles;

or

said single cardiac cycle is a cardiac cycle selected for the maximum change in said value between a baseline measurement and a stimulus-effected measurement.

42. The method of claim 1, wherein applying the stimulus comprises

restricting flow of blood to the limb by occlusion of a blood vessel;

or

administering a drug to the patient;

or

applying acoustic/mechanical tissue vibration.

3. (canceled)

8. (canceled)

11-13. -13. (canceled)

15. (canceled)

21-22. -22. (canceled)

26-28. -28. (canceled)

30-34. -34. (canceled)

37. (canceled)

40-41. -41. (canceled)

43-57. -57. (canceled)

58. A method of assessing endothelial function in a mammal, said method comprising:

a) applying to the artery at a first location a substantially constant external pressure that causes the artery to fully or partially collapse, where said pressure is provided via a first cuff adjacent to and/or around a region of the mammal'"'"'s body;

b) applying to the artery at a second location a substantially constant external pressure that causes the artery to fully or partially collapse, where said pressure is provided via a second cuff adjacent to and/or around a region of the mammal'"'"'s body;

c) determining, over the course of one or more cardiac cycles, changes in pressure in said first cuff resulting from cardiac activity of said mammal or an artificially induced arterial pulse, determining, over the course of one or more cardiac cycles, changes in pressure in said second cuff resulting from cardiac activity of said mammal or an artificially induced arterial pulse; and

calculating a baseline transit time of a pressure pulse from said first cuff to said second cuff to establish a baseline value for a parameter related to endothelial function in said mammal;

d) applying a stimulus to said mammal;

e) determining, over the course of one or more cardiac cycles, changes in pressure in said first cuff resulting from cardiac activity of said mammal or an artificially induced arterial pulse, determining, over the course of one or more cardiac cycles, changes in pressure in said second cuff resulting from cardiac activity of said mammal or an artificially induced arterial pulse; and

calculating the stimulus-effected transit time of a pressure pulse from said first cuff to said second cuff to establish a stimulus-effected value for a parameter related to endothelial function in said mammal;

wherein said determining of steps (c) and (e) comprise

i) during a first time interval stabilizing the pressure in said cuff at or close to the measurement pressure set point during the period where tissue compression under the cuff leads to a natural pressure drop; and

ii) once the natural pressure drop stabilizes, during a second time interval determining over a course of one or more cardiac cycles said changes in pressure in said cuff; and

wherein said baseline value is determined from measurements made when said mammal is not substantially effected by said stimulus and differences in said baseline value and said stimulus-effected value for the transit time provide a measure of endothelial function in said mammal.

59-112. -112. (canceled)

113. An apparatus for assessment endothelial function in a mammal comprising:

a measurement cuff adapted to apply a substantially constant pressure to an artery in said mammal;

a measurement unit adapted to detect and quantify over one or more cardiac cycles, pressure pulses in said cuff while said substantially constant pressure is applied;

a controller that is adapted to apply to the cuff a said substantially constant pressure where said controller monitors and adjusts the pressure in said cuff and whose response time is sufficient slow so that the changes in pressure resulting from said cardiac cycles are not substantially attenuated by said system, and/or that is adapted to control a pressure source and a valve to provide on-off control of the pressure in said cuff, wherein said controller is configured to

i) regulate and stabilize the pressure in said cuff at or close to the measurement pressure set point during a first time period where tissue compression under the cuff leads to a natural pressure drop; and

ii) once the natural pressure drop stabilizes, during a second time interval to regulate or stop regulating the pressure in said cuff to produce a different pressure regime than during said first time period; and

a processor adapted to analyze, and/or store, and/or compare values determined from said pressure pulses in at least two measurement rounds.

114-148. -148. (canceled)

149. An apparatus for assessment endothelial function in a mammal comprising:

a first measurement cuff adapted to apply a substantially constant first pressure to an artery in said mammal;

a second measurement cuff adapted to apply a substantially constant second pressure to an artery in said mammal;

a measurement unit adapted to detect and quantify over one or more cardiac cycles, pressure pulses in said first cuff and/or said second cuff while said substantially constant pressure is applied;

a controller adapted to apply to said first cuff said substantially constant first pressure and/or said second cuff said substantially constant second pressure where said controller monitors and adjusts the pressure in said first cuff and/or said second cuff and whose response time is sufficient slow so that the changes in pressure in said first cuff and said second cuff resulting from said cardiac cycles are not substantially attenuated by said system, and/or where said controller is configured to provide simple on-off pressure control, wherein said controller is configured to

i) regulate and stabilize the pressure in said cuff at or close to the measurement pressure set point during a first time period where tissue compression under the cuff leads to a natural pressure drop; and

ii) once the natural pressure drop stabilizes, during a second time interval to regulate or stop regulating the pressure in said cuff to produce a different pressure regime than during said first time period; and

a processor configured to monitor pressure pulses in said first cuff and in said second cuff, identify corresponding pulses in said first and said second cuff and calculate a transit time for the pressure pulse in an artery from the location of said first cuff to said second cuff.

150-186. -186. (canceled)