Method and apparatus for non-invasively evaluating endothelial activity in a patient

• US 6,939,304 B2
• Filed: 10/22/2001
• Issued: 09/06/2005
• Est. Priority Date: 10/23/2000
• Status: Expired due to Term

• Current Assignee: Itamar Medical Ltd. (Asahi Kasei Corporation)
• Original Assignee: Itamar Medical Ltd. (Asahi Kasei Corporation)
• Inventors: Lavie, Peretz, Schnall, Robert P., Sheffy, Jacob
• Primary Examiner(s): Nasser, Robert L.
• Assistant Examiner(s): MALLARI, PATRICIA C
• Application Number:
  US10/398,515
• Publication Number:
  US 20040092832A1
• Time in Patent Office: 1,415 Days
• Field of Search: 600/300, 600/301, 600/323, 600/326, 600/481, 600/490, 600/499, 600500-507, 600/549
• US Class Current: 600/481
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/02241 of small dimensions, e.g. adapted to fingers
• CPC Class Codes: A61B 5/026 Measuring blood flow A61B3/1233, A61B3/1241 take precedence
• CPC Class Codes: A61B 5/6824 Arm or wrist
• CPC Class Codes: A61B 5/6826 Finger
• CPC Class Codes: A61B 5/6828 Leg
• CPC Class Codes: A61B 5/6838 Clamps or clips

Abstract

A method and apparatus for non-invasively evaluating endothelial activity in a patient, particularly for indicating the presence of an endothelial dysfunction condition, by applying an occluding pressure to a predetermined part of an arm or leg of the patient to occlude arterial blood flow therein; maintaining the occluding pressure for a predetermined time period; removing the occluding pressure after the elapse of the predetermined time period to restore arterial blood flow; monitoring a digit of the arm or leg by a digit-probe for changes in the peripheral arterial tone therein before and after the application of the occluding pressure to the arm or leg of the patient; and utilizing any detected changes in the peripheral arterial tone for evaluating endothelial activity in the patient. Particularly important advantages are provided when the occluding cuff is applied to the digit of the patient receiving the monitoring digit-probe, on the proximal side thereof with respect to the patient'"'"'s heart, and also when a reference digit-probe is applied to another digit, not influenced by the occluding pressure, to compensate for shifts inherent to vascular beds.

Claims

1. Apparatus for non-invasively evaluating endothelial activity in a patient, comprising:

an occluding cuff for applying an occluding pressure to a predetermined part of an arm or leg of the patient to occlude blood flow therein for a predetermined time period;

a monitoring digit-probe for monitoring a digit of said arm or leg for changes in the peripheral arterial tone therein before and after the application of said occluding pressure to the arm or leg of the patient;

and a processor for utilizing any detected changes in said peripheral arterial tone for evaluating endothelial activity in the patient;

wherein said processor is controlled by said monitoring digit-probe to indicate when an occluding pressure has been applied to said predetermined part of the patient'"'"'s arm or leg, which is indicated when said monitoring digit-probe measures no pulsatile volume flow in said digit.

2. The apparatus according to claim 1, wherein said processor utilizes the output of said monitoring digit-probe for providing a feedback signal to control the application of said occluding pressure.

3. A method for non-invasively evaluating endothelial activity in a patient, comprising:

applying an occluding pressure to a predetermined part of an arm or leg of the patient to occlude arterial blood flow therein;

maintaining said occluding pressure for a predetermined time period;

removing said occluding pressure after the elapse of said predetermined time period to restore arterial blood flow;

monitoring a digit of said arm or leg for changes in the peripheral arterial tone therein before, during, and after the application of said occluding pressure to the arm or leg of the patient;

and utilizing any detected changes in said peripheral arterial tone, including changes in the dynamic signal time-course following removal of the occluding pressure, for evaluating endothelial activity in the patient;

wherein said digit of the arm or leg of the patient is monitored for changes in the peripheral arterial tone by a monitoring digit-probe which is received on said digit and which measures peripheral arterial pulsatile flow therethrough while applying a non-occluding pressure to the outer extremity of the digit sufficiently high to prevent blood pooling in the veins and to unload the tension in the arterial walls, but not so high as to occlude the arteries; and

wherein a reference digit-probe is applied to a digit of an arm or leg of the patient not to receive the occluding pressure for measuring changes in the peripheral arterial pulsatile flow therein, said latter changes being used for correcting the measured changes by the monitoring digit-probe to compensate for spontaneous short-term shifts in the peripheral arterial tone of local or systemic origin inherent to vascular beds and/or related to sympathetic nervous system activity due to painful stress resulting from the occlusion.

4. The method according to claim 3, wherein the measurements derived from said monitoring digit-probe in the arm or leg receiving the occluding pressure, are corrected by determining for each measurement, the ratio of the respective measurement after the occluding pressure was applied, to that before the occluding pressure was applied, and dividing said calculated ratio of the monitoring digit-probe measurements by the above-determined ratio of the reference digit-probe measurements;

and by multiplying the resultant ratio by a correction factor based on the magnitude of the measured baseline amplitude of the measured peripheral arterial pulsatile flow.

5. The method according to claim 4, wherein the said correction factor is based on the magnitude of the measured baseline signal amplitude of the measured peripheral arterial pulsatile flow which is used in evaluating endothelial activity in the patient or wherein the magnitude of the measured baseline amplitude of the measured peripheral arterial pulsatile flow is used with respect to a reference baseline amplitude;

and wherein said reference baseline amplitude is produced by measuring the minimal baseline amplitude of the peripheral arterial pulsatile flow after locally cooling the digit receiving the monitoring digit-probe, or by measuring the maximal baseline amplitude of the peripheral arterial pulsatile flow after locally heating the digit receiving the monitoring digit-probe;

or by measuring the baseline amplitude of the peripheral arterial pulsatile flow after locally heating or cooling the digit receiving the monitoring digit-probe to a predetermined temperature;

or wherein said reference baseline amplitude is produced by measuring the peripheral arterial pulsatile flow after administrating to the patient a pharmacological agent known to elicit a peripheral vasodilation or vasoconstriction;

and wherein any of said reference baseline amplitude values may be derived prior to the occlusion of blood flow or at a point in time after the release of blood flow occlusion.

6. The method according to claim 3, wherein said reference digit-probe is applied to a digit of an arm or leg contra-lateral to that to receive the occluding cuff and said monitoring digit-probe.

7. The method according to claim 3, wherein said reference digit-probe is applied to the same arm or leg as, but to a different digit from, that receiving the monitoring digit-probe.

8. The method according to claim 3, wherein the magnitude of the measured baseline amplitude of the measured peripheral arterial pulsatile flow is used with respect to a reference baseline amplitude in evaluating endothelial activity in the patient.

9. The method according to claim 8, wherein said reference baseline amplitude is produced by measuring the maximal baseline amplitude of the peripheral arterial pulsatile flow after locally heating the digit receiving the monitoring digit-probe.

10. The method according to claim 8, wherein said reference baseline amplitude is produced by measuring the minimal baseline amplitude of the peripheral arterial pulsatile flow after locally cooling the digit receiving the monitoring digit-probe.

11. The method according to claim 8, wherein said reference baseline amplitude is produced by measuring the peripheral arterial pulsatile flow after administrating to the patient a pharmacological agent known to elicit a peripheral vasodilation or vasoconstriction.

12. The method according to claim 3, wherein the patient'"'"'s height is used as a correction factor in evaluating endothelial activity in the patient.

13. The method according to claim 3, wherein the pulse propagation velocity of the peripheral arterial pulsatile flow following an occlusion is also measured by said monitoring digit-probe and compared with that measured by said reference digit-probe, which comparison is also utilized in evaluating the endothelial activity of the patient.

14. The method according to claim 13, wherein said pulse propagation velocity is measured by measuring the time difference between pulses in the peripheral arterial pulsatile flow in the digit receiving the monitoring digit-probe following the application of an occluding pressure, and pulses in the peripheral arterial pulsatile flow in a corresponding digit receiving the reference digit-probe and not subjected to an occluding pressure.

15. The method according to claim 13, wherein the pulse propagation velocity is measured by measuring the time difference between pulses in the peripheral arterial pulsatile flow in the digit receiving the monitoring digit-probe following the application of an occluding pressure, and pulses in the ECG wave of the patient.

16. The method according to claim 13, wherein the onset time of blood flow recommencement after occlusion has been released is measured, a prolonged period of the order of several seconds or more being indicative of an endothelial dysfunction condition.

17. The method according to claim, 3, wherein the measurements by said monitoring digit-probe in the arm or leg to receive the occluding pressure are corrected by determining, for each measurement, the ratio of the respective measurement after the occluding pressure was removed, to that before the occluding pressure was applied, and dividing the ratio of the monitoring digit-probe measurements by the above-determined ratio of the reference digit-probe measurements.

18. A method for non-invasively evaluating endothelial activity in a patient, comprising:

applying an occluding pressure to a predetermined part of an arm or leg of the patient to occlude arterial blood flow therein;

maintaining said occluding pressure for a predetermined time period;

removing said occluding pressure after the elapse of said predetermined time period to restore arterial blood flow;

monitoring a digit of said arm or leg for changes in the peripheral arterial tone therein before and after the application of said occluding pressure to the arm or leg of the patient;

and utilizing any detected changes in said peripheral arterial tone, including changes in the dynamic signal time-course following removal of the occluding pressure, for evaluating endotheial activity in the patient.

19. The method according to claim 18, wherein said changes in the peripheral arterial tone are recorded by a thermal washout technique.

20. The method according to claim 18, wherein the endothelial activity evaluated is an indication of the presence of an endothelial dysfunction condition in the patient.

21. The method according to claim 18, wherein said digit of the arm or leg of the patient is monitored by a digit-probe, comprising:

a tubular socket for receiving a predetermined length of a distal end of the digit, including the extreme distal tip of the digit;

an end thimble having a membrane configured to exert pressure on the extreme distal tip of the digit and a portion of the digit preceding it for receiving the distal portion of the digit including its extreme distal tip to prevent venous blood from pooling in the distal portion of the digit and its extreme distal tip;

at least one pressure cuff having a membrane configured to exert pressure on part of the digit preceding the extreme distal tip of the digit, to function as a venous tourniquet to prevent venous pooling and venous shock wave propagation in the digit;

a pressure source for applying a static pressure field around the distal end of the digit when received in said tubular socket, which static pressure is sufficient to substantially prevent venous pooling and propagation of venous shock waves in the distal end of the digit, and to partially unload, but not to occlude, arteries therein;

means for preventing expulsion of said digit from said digit probe when it is pressurized to above atmospheric pressure; and

a measuring device for measuring changes in the distal end of the digit accompanying blood pressure waves.

22. The method according to claim 18, wherein said changes in the peripheral arterial tone are recorded by an optical density measurement technique.

23. The method according to claim 18, wherein the oxygen saturation of the blood in said digit is measured by pulse oximetry.

24. The method according to claim 18, wherein said digit of the arm or leg of the patient is monitored for changes in the peripheral arterial tone by a monitoring digit-probe which is received on said digit and which measures peripheral arterial pulsatile flow therethrough while applying a non-occluding pressure to the outer extremity of the digit sufficiently high to prevent blood pooling in the veins and to unload the tension in the arterial walls, but not so high as to occlude the arteries.

25. The method according to claim 24, wherein said occluding pressure is applied proximally with respect to the heart of the patient relative to the site of said monitoring digit probe.

26. The method according to claim 24, wherein said occluding pressure is applied to the digit of the patient receiving said monitoring digit-probe from within said monitoring digit-probe.

27. The method according to claim 24, wherein said monitoring digit-probe is also used for indicating when an occluding pressure has been applied to said predetermined part of the patient'"'"'s arm or leg, which is indicated when said monitoring digit-probe measures no pulsatile volume flow in said digit.

28. The method according to claim 24, wherein said monitoring digit-probe is used for providing a feedback signal to control the application of said occluding pressure.

29. Apparatus for non-invasively evaluating endothelial activity in a patient, comprising:

an occluding cuff for applying an occluding pressure to a predetermined part of an arm or leg of the patient to occlude blood flow therein for a predetermined time period;

a monitoring digit-probe for monitoring a digit of said arm or leg for changes in the peripheral arterial tone therein before and after the application of said occluding pressure to the arm or leg of the patient;

and a processor for utilizing any detected changes in said peripheral arterial tone for evaluating endothelial activity in the patient;

wherein said occluding cuff is designed to be applied to the digit of the patient receiving said monitoring digit-probe on the proximal side thereof with respect to the patient'"'"'s heart; and

wherein part or all of said monitoring digit-probe is itself used to apply occluding pressure to occlude the flow of blood to the tissue contained within.

30. The apparatus according to claim 29, wherein said monitoring digit-probe measures peripheral arterial pulsatile volume as a function of time through said digit while applying a non-occluding pressure to the outer extremity of the digit sufficiently high to prevent blood pooling in the veins and to unload the tension in the arterial walls, but not so high as to occlude the arteries.

31. The apparatus according to claim 30, wherein said monitoring digit-probe, comprises:

a tubular socket for receiving a predetermined length of a distal end of the digit, including the extreme distal tip of the digit;

an end thimble having a membrane configured to exert pressure on the extreme distal tip of the digit and a portion of the digit preceding it for receiving the distal portion of the digit including its extreme distal tip to prevent venous blood from pooling in the distal portion of the digit and its extreme distal tip;

at least one pressure cuff having a membrane configured to exert pressure on part of the digit preceding the extreme distal tip of the digit, to function as a venous tourniquet to prevent venous pooling and venous shock wave propagation in the digit;

a pressure source for applying a static pressure field around the distal end of the digit when received in said tubular socket, which static pressure is sufficient to substantially prevent venous pooling and propagation of venous shock waves in the distal end of the digit, and to partially unload, but not to occlude, arteries therein;

means for preventing expulsion of said digit from said digit probe when it is pressurized to above atmospheric pressure; and

a measuring device for measuring changes in the distal end of the digit accompanying blood pressure waves.

32. Apparatus for non-invasively evaluating endothelial activity in a patient, comprising:

an occluding cuff for applying an occluding pressure to a predetermined part of an arm or leg of the patient to occlude blood flow therein for a predetermined time period;

a monitoring digit-probe for monitoring a digit of said arm or leg for changes in the peripheral arterial tone therein before and after the application of said occluding pressure to the arm or leg of the patient;

and a processor for utilizing any detected changes in said peripheral arterial tone for evaluating endothelial activity in the patient;

wherein the apparatus further includes a reference digit-probe designed to be applied to a digit of an arm or leg of the patient not to receive the occluding pressure for measuring changes in the peripheral arterial pulsatile flow therein; and

wherein said processor utilizes said latter changes for correcting the measured changes by the monitoring digit-probe to compensate for spontaneous short-term shifts in the peripheral arterial tone of local or systemic origin inherent to vascular beds and/or for sympathetic nervous system vasomotor activity due to painful stress resulting from the occlusion.

33. The apparatus according to claim 32, wherein said reference digit-probe is designed to be applied to a digit of an arm or leg contra-lateral to that to receive the occluding cuff and said monitoring digit-probe.

34. The apparatus according to claim 32, wherein said reference digit-probe is designed to be applied to the same arm or leg as, but to a different digit from, that receiving the monitoring digit-probe.

35. The apparatus according to claim 32, wherein said processor utilizes the magnitude of the measured baseline amplitude of the measured peripheral arterial pulsatile flow in evaluating endothelial activity in the patient.

36. The apparatus according to claim 32, wherein said processor utilizes the patient'"'"'s physical structure as a correction factor in evaluating endothelial activity in the patient.

37. The apparatus according to claim 32, wherein said processor measures the pulse propagation velocity of the peripheral arterial pulsatile flow prior to and following blood flow occlusion as detected by said monitoring digit-probe and as detected by said reference digit-probe, compares said measurements and utilizes said comparison in evaluating the endothelial activity of the patient.

38. The apparatus according to claim 37, wherein processor measures said pulse propagation velocity changes by measuring the time difference between pulses in the peripheral arterial pulsatile flow in the digit receiving the monitoring digit-probe following the application of an occluding pressure, and pulses in the peripheral arterial pulsatile flow in a corresponding digit receiving the reference digit-probe and not subjected to an occluding pressure.

39. The apparatus according to claim 37, wherein said processor measures pulse propagation velocity changes by measuring the time difference between pulses in the peripheral arterial pulsatile flow in the digit receiving the monitoring digit-probe following the application of an occluding pressure, and pulses in the ECG wave of the patient and compares the respective differences before and after blood flow occlusion.

40. The apparatus according to claim 32, wherein said processor corrects the measurements derived from said monitoring digit-probe in the arm or leg receiving the occluding pressure, by determining for each measurement, the ratio of the respective measurement after the occluding pressure was applied, to that before the occluding pressure was applied, and dividing said calculated ratio of the monitoring digit-probe measurements by the above-determined ratio of the reference digit-probe measurements.