Apparatus and method for controlling systemic blood pressure in patients

Abstract

Some embodiments of the present invention disclose a method to reduce the intracranial cerebral blood pressure in a newborn, comprising: mounting an inflating cuff in at least one extremity of said newborn; monitoring the blood pressure in said newborn; if blood pressure rises above a predetermined value, then: inflating said inflating cuff to a predetermined level; wherein said inflating cuff further comprises blocking venous blood flow in said extremity by means of said inflating cuff and lowering cardiac output and systemic blood pressure.

Claims

1. A device for controlling the blood pressure in a subject, comprising: a. at least one inflating cuff interconnected to at least one pump, said at least one inflating cuff adapted to be mounted on at least one extremity of said subject; b. at least one input entry adapted to receive blood pressure information from said subject; c. a central processing unit with a memory, said memory stores computer-executable instructions for controlling said central processing unit to cause said device to: block venous blood flow by inflating said at least one inflating cuff when at least one of said received blood pressure information exceeds a determined parameter; and unblock said venous blood flow by deflating said at least one inflating cuff when at least one of said received blood pressure information returns below said determined parameter; wherein said executable instructions comprise instructions to block said blood flow by inflating said at least one inflating cuff to block venous blood flow and avoid blocking arterial blood flow.

2. The device according to claim 1, wherein said blood pressure information comprises systemic blood pressure.

3. The device according to claim 1, wherein said blood pressure information comprises cranial blood pressure.

4. The device according to claim 1, wherein said inflating comprises inflating said at least one inflating cuff to an internal cuff pressure from about 50% to about 90% of the diastolic arterial blood pressure value of the subject.

5. The device according to claim 1, wherein said inflating comprises inflating said at least one inflating cuff to an internal cuff pressure from about 50% to about 90% of the systolic arterial blood pressure value of the subject.

6. The device according to claim 1, wherein said device further receives information regarding vital signs information, comprising at least one of PP, HR and O2 SAT.

7. The device according to claim 1, wherein said device further comprises at least one emergency pressure relief valve.

8. The device according to claim 1, further comprising a Doppler ultrasound device configured to monitor venous blood flow in said extremity.

9. The device according to claim 1, further comprising a Doppler ultrasound device configured to show at which internal cuff pressure of said at least one inflating cuff all venous flow through the extremity is blocked.

10. The device according to claim 1, wherein said at least one inflating cuff is configured to be mounted on a newborn subject.

11. The device according to claim 1, wherein said at least one inflating cuff is configured to be mounted on a premature newborn subject.

12. The device according to claim 1, wherein said device further comprises at least one backup pump.

13. The device according to claim 1, wherein said at least one inflating cuff comprises at least one valve at the connection with said at least one pump configured to be closed to prevent gas from leaving said at least one inflating cuff.

14. The device according to claim 1, wherein said at least one pump is a dual direction pump configured to provide gas to said at least one inflating cuff and to remove gas from said at least one inflating cuff.

15. The device according to claim 14, wherein said central processing unit is configured to cause said at least one pump to either deflate or inflate said at least one inflating cuff.

16. The device according to claim 1, wherein said device further comprises at least one outlet port configured to connect external devices to said device.

17. The device according to claim 1, wherein said at least one inflating cuff is sized to be mounted on a non-newborn subject.

18. The device according to claim 1, wherein said computer-executable instructions for controlling said central processing unit are configured to follow a linear model of blood pressure dynamics.

19. The device according to claim 1, wherein said computer-executable instructions for controlling said central processing unit are configured to follow a non-linear model of blood pressure dynamics.

Description

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

(1) Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced.

(2) In the drawings:

(3) FIG. 1 is a schematic concept illustration of the device, according to some embodiments of the present invention;

(4) FIG. 2 is a schematic representation of the parts of the device, according to some embodiments of the present invention;

(5) FIG. 3 is a schematic flowchart of an exemplary method, according to some embodiments of the present invention;

(6) FIG. 4 is a schematic flowchart of an exemplary method of the activation of the inflatable cuffs, according to some embodiments of the present invention;

(7) FIG. 5 is a schematic flowchart of an exemplary scenario of the use of the device, according to some embodiments of the present invention;

(8) FIG. 6 is a graph showing the results of the experiment shown in example 2, according to some embodiments of the present invention; and

(9) FIG. 7 are graphs showing the results of the experiment shown in example 3, according to some embodiments of the present invention.

DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

(10) The present invention, in some embodiments thereof, relates to an apparatus for controlling systemic blood pressure in patients and, more particularly, but not exclusively, to an apparatus for controlling systemic blood pressure fluctuations and preventing intra-ventricular hemorrhage in patients.

(11) Overview

(12) An aspect of some embodiments relates to reduction of arterial blood pressure fluctuations in subjects. In some embodiments, selectively blocking or partially blocking the flow of the venous blood in one or more extremities, leads from about 20% to about 25% reduction of the total venous blood return to the heart. Optionally, leads from about 25% to about 35% reduction of the total venous blood return to the heart. Optionally, leads from about 35% to about 45% reduction of the total venous blood return to the heart. This change leads to reduction of the cardiac output and systemic arterial blood pressure as well and thus blunting any further fluctuation of arterial systolic blood pressure and prevents fluctuations of intra-cranial systolic blood pressure and allows prevention of IVH.

(13) It is to be emphasized that mentioning blocking of blood flow through an extremity means blocking the flow of blood in the venous vasculature but not in the arterial vasculature of the extremity. This allows avoiding ischemia of the cuffed-inflated extremity. In this regard, the above-mentioned Patents no. US20150094755A1, W2017023619A1, WO02076306A1, US200902287069A1, US20150265286A1, US20140024986A1 (underlined words), do intentionally block blood flow through arteries in the cuffed-inflated extremities, and non-intentionally, they do block the veins as well. In some embodiments, inflatable cuffs can be placed and/or inflated in at least one extremity to achieve the desired effect, which is to reduce and/or prevent increasing intracranial blood pressure.

(14) In some embodiments, reduction of intracranial blood pressure is from about 10% to about 20%, optionally from about 20% to about 30%, optionally from about 30% to about 50%. In some embodiments, increasing blood pressure is performed by releasing the inflatable cuffs. In some embodiments, the subjects are neonatal subjects and/or newborn subjects and/or premature neonatal subjects. In some embodiments, selectively blocking or partially blocking blood flow is performed on at least one extremity of the subject. In some embodiments, blocking blood flow is performed by using inflatable cuffs attached to at least one extremity of the subject. In some embodiments, detection of abnormal blood pressure in the subject activates the cuffs. In some embodiments, detection of normal blood pressure in the subject deactivates the cuffs.

(15) In some embodiments, the detection is performed in real-time. In some embodiments, the pressure inside the cuff is from about 5% to about 90% of the diastolic arterial blood pressure value of the subject. Optionally, the pressure inside the cuff is from about 30% to about 80% of the diastolic arterial blood pressure value of the subject. Optionally, the pressure inside the cuff is from about 40% to about 60% of the diastolic arterial blood pressure value of the subject. In some embodiments, the subjects are neonatal subjects. In some embodiments, the goal (and target settings) are selected to prevent brain damage while ensuring sufficient perfusion.

(16) An aspect of some embodiments relates to affecting venous blood flow flowing from the extremities to the body in subjects. In some embodiments, selectively blocking or partially blocking venous blood flow flowing from the extremities to the body affects venous blood flow. In some embodiments, blocking blood flow is performed by using inflatable cuffs attached to at least one extremity of the subject. In some embodiments, detection of abnormal blood pressure in the subject activates the cuffs.

(17) In some embodiments, detection of normal blood pressure in the subject deactivates the cuffs. In some embodiments, the detection is performed in real-time. In some embodiments, the pressure inside the cuff is from about 5% to about 90% of the diastolic arterial blood pressure value of the subject. Optionally, the pressure inside the cuff is from about 30% to about 80% of the diastolic arterial blood pressure value of the subject. Optionally, the pressure inside the cuff is from about 40% to about 60% of the diastolic arterial blood pressure value of the subject. In some embodiments, the subjects are neonatal subjects.

(18) An aspect of some embodiments relates to reducing blood pressure in the brain of subjects by selectively blocking or partially blocking venous blood flow to the heart. In some embodiments, selectively blocking or partially blocking blood flow is performed on blood flow flowing from the extremities to the body in the subjects. In some embodiments, blocking blood flow is performed by using inflatable cuffs attached to at least one extremity of the subject. In some embodiments, detection of abnormal blood pressure in the subject activates the cuffs.

(19) In some embodiments, detection of normal or low blood pressure in the subject deactivates the cuffs. In some embodiments, the detection is performed in real-time. In some embodiments, the pressure inside the cuff is from about 5% to about 90% of the diastolic arterial blood pressure value of the subject. Optionally, the pressure inside the cuff is from about 30% to about 80% of the diastolic arterial blood pressure value of the subject. Optionally, the pressure inside the cuff is from about 40% to about 60% of the diastolic arterial blood pressure value of the subject. In some embodiments, the subjects are neonatal subjects.

(20) Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details of construction and the arrangement of the components and/or methods set forth in the following description and/or illustrated in the drawings and/or the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

(21) In China and USA, a total of 21,810,000 newborns are born annually. Of these infants, about 1.0% (218,100 infants) are born with a birth weight less than 1000 g, which place them in the group at risk for intraventricular hemorrhage (IVH).

(22) IVH is a bleeding into the brain's ventricular system, where the cerebrospinal fluid is produced and circulates through the subarachnoid space. It can result from weakness of blood vessels' walls which cannot hold against significant changes in systemic and cerebral blood pressure, physical trauma or from hemorrhagic stroke.

(23) During pregnancy, the placenta helps regulate the systemic blood pressure in the fetus. Once the fetus is born and the placenta is no longer there to assist regulate the blood pressure, the underweight newborn is at high risk to develop IVH, especially, but not only, during the first 7 days after birth.

(24) It is a scope of some embodiments to provide devices and methods that help regulate the systemic blood pressure, cerebral arterial pressure and possibly avoid the development of IVH in subjects, and in some embodiments, also in newborn subjects.

(25) Exemplary Device

(26) Referring now to FIG. 1, showing a schematic concept illustration of a device of the present invention to be used specifically in newborns and/or premature newborns. Usually, premature newborns with difficulties are placed in dedicated incubators (not shown), which comprise a variety of instruments which role is to ensure the health of the new born. These incubators usually comprise an overhead warmer 100, to keep the newborn at the optimal temperature, a ventilator 102 (when needed), a feeding tube 104, one or more intravenous (IV) pumps 106-108, and a variety of instruments responsible for monitoring the vital signs of the newborn like, for example, an electrocardiogram (ECG) and blood pressure monitor 110, a temperature monitor 112 and an oxygen saturation monitor 114, just to mention a few.

(27) In some embodiments, a device 116 for regulating the blood pressure of the newborn is added to the rest of instruments in the incubator, as shown, for example in FIG. 1. In some embodiments, the boold pressure is systemic blood pressure. In some embodiments, the blood pressure is cranial blood pressure. In some embodiments, the blood pressure is the arterial systemic and/or arterial cranial blood pressure.

(28) Referring now to FIG. 2, showing a schematic representation of the parts of the device 116, according to some embodiments of the present invention. In some embodiments, the device receives vital sign information from the instruments already located in the incubator or infant warmer, and especially blood pressure measurements. In some embodiments, the device includes secondary instruments which provide the vital signs of the new born. In some embodiments, vital sign instruments can be, for example, ECG, EKG, thermometer, blood pressure monitor, heartrate monitor, oxygen saturation monitor, end-tidal carbon dioxide monitor, transcutaneous Carbone dioxide monitor, and NIRS (Near-Infra-RED Spectroscopy. In some embodiments, the vital signs that are monitored are, for example, temperature, heartrate, blood pressure, oxygen saturation, end-tidal carbon dioxide monitor, transcutaneous Carbone dioxide.

(29) In some embodiments, the device receives the vital sign information and other information via an input socket 118, which is connected to the central processing unit (CPU) 120. In some embodiments, the device comprises a memory unit 122 interconnected to the CPU 120, and capable of storing software, data, etc. In some embodiments, the CPU 120 is further connected to a series of pumps 124a-d (for example digital pumps or any other pump known in the art). In this embodiment, there are shown 4 pumps 124a-d, as a matter of example only. In some embodiments, the number of pumps is between 1 and 24. In some embodiments, each pump comprise at least one other pump for backup purposes.

(30) In some embodiments, the device 116 comprises a gas inlet 125, which is connected to each of the pumps 124a-d so as to provide the pumps with the necessary gas when necessary. In some embodiments, the gas is air. In some embodiments, the gas is a gas other than air. In some embodiments, to each of the pumps 124a-d is connected to a proximal end of a flexible tube (126a-d), and on the distal end of each flexible tube (126a-d) there is an inflatable cuff (128a-d). In some embodiments, there are as many flexible tubes and inflatable cuffs as there are pumps. In some embodiments, the CPU 120 is programmed to control each inflatable cuff (128a-d), via said pumps (124a-d), independently to each other.

(31) In some embodiments, each pump comprises an opening (not shown) from which air can be collected from the environment to inflate the cuffs. In some embodiments, each pump comprise a valve (not shown) at the connection with the gas inlet 125 which can be opened and closed according to the necessities of the system. In some embodiments, each pump comprise a second valve (not shown) at the connection with each flexible tube (126a-d). In some embodiments, once the inflatable cuffs are inflated to the required pressure, either of the valves can be closed so as to avoid gas from leaving the inflatable cuffs.

(32) In some embodiments, the pumps are dual direction pumps, adapted to provide gas to the cuffs and also to remove gas from the cuffs. In some embodiments, the flexible tubes (126a-d) are used to conduct gas to the cuffs and also from the cuffs (see dualhead arrow 136). In some embodiments, the CPU 120 controls the direction of the gasflow according to the needs of the system (inflate the cuffs, deflate the cuffs).

(33) In some embodiments, the cuffs are configured to be used on newborn subjects. In some embodiments, the cuffs are configured to be used on premature newborn subjects. Examples of cuffs for premature newborns are Neonatal One Piece Disposable Blood Pressure Cuffs by Welch Allyn or any other similar cuffs.

(34) In some embodiments, the device 116 comprises an outlet port 130, which can be used to connect a variety of devices like, for example, a user interface unit and/or a wireless communication unit and/or a printer and/or any peripheral device.

(35) In some embodiments, at least one of the inflatable cuffs is mounted on at least one extremity of the newborn. In some embodiments, the extremities are the arms and/or the legs. In some embodiments, more than one inflatable cuff is mounted on the most proximal part of the extremities of the newborn.

(36) In some embodiments, the inflatable cuff is adapted to block or partially block the venous blood flow to and/or from the extremity. In some embodiments, the inflatable cuff is adapted to block or partially block the blood flow from the extremity alone without affecting the blood flow coming from the body to the extremity. In some embodiments, the inflatable cuff is adapted to block the venous blood flow alone without affecting the arterial blood flow. In some embodiments, the arterial blood flow is not blocked and/or affected at all.

(37) In some embodiments, real-time blood pressure measurements are used to regulate the activation of the inflatable cuff in order to block or partially block the venous blood flow.

(38) Without being limited by a particular explanation or theory, the blood pressure is defined as the pressure of circulating blood on the walls of blood vessels. Used without further specification, blood pressure usually refers to the pressure in large arteries of the systemic circulation. Blood pressure is usually expressed in terms of the systolic pressure (maximum during one heart beat) over diastolic pressure (minimum in between two heart beats) and is measured in millimeters of mercury (mmHg), above the surrounding atmospheric pressure. The pressure that can block arterial blood flow is equal or higher to the systolic blood pressure. For example, in an adult having blood pressure of 120/80, arterial blood flow can be blocked by applying pressure (i.e. with an inflatable cuff) of 120 mmHg on the extremity. Similarly, the pressure that can block venous blood flow is lower or equal to the diastolic blood pressure. Therefore, in the example of the adult having blood pressure of 120/80, venous blood can be blocked by applying pressure (i.e. with an inflatable cuff) of at least 75% of the diastolic blood pressure, which is: 80*(75/100)=60 mmHg.

(39) In some embodiments, each flexible tube (126a-d), which are connected to each inflatable cuff (128a-d), comprises a pressure measuring device (134a-d), optionally in communication with the CPU 120. Since each flexible tube is in direct communication to each respective cuff, the pressure inside the cuff will be the same as the pressure inside the flexible tube.

(40) Each inflatable cuff (128a-d) has an opening immediately at its entrance where each cuff is connected to a pressure measuring device. In some embodiments, the intra-cuff pressure should not exceed 75% of the patient's diastolic blood pressure. In some embodiments, the pressure inside the cuff is from about 60% to about 75% of the diastolic arterial blood pressure value of the subject. In some embodiments, detection of venous blood flow is monitored by performing Doppler ultrasound proximal to the site where the cuff is located.

(41) In some embodiments, each inflatable cuff (128a-d) comprises an emergency pressure relief valve (132a-d), which can be activated in cases of emergency.

(42) In some embodiments, the device is used in newborn subjects. In some embodiments, the device is used in non-newborn subjects, for example adolescents, adults and/or elderly patients.

(43) Exemplary Method

(44) Referring now to FIG. 3, showing a schematic flowchart of an exemplary method of the machine. In some embodiments, the device continuously monitors the vital signs of the newborn 140. In some embodiments, the device's software subroutines monitor if the blood pressure 142 is within the predetermined acceptable parameters. In some embodiments, in case the answer is yes and the blood pressure is within acceptable parameters, the device continues to monitor the vital signs 140. In some embodiments, if the answer is no, then it is assessed if the blood pressure is higher than the acceptable parameters 144, and an alarm is delivered to the user 146. In some embodiments, the alarm is a silent alarm since it is known that noise can affect negatively the newborn. In some embodiments, the alarm is sent to the personnel's digital devices (i.e. cellphone, tablet, beeper, etc.).

(45) In some embodiments, if the answer is yes, and the blood pressure is higher than the acceptable parameters, then the device activates the pumps, which inflate the inflatable cuffs and concomitantly continues to monitor the blood pressure 148. In some embodiments, it is then assessed, by the input received from the vital sign devices, if the blood pressure has returned between the acceptable parameters 150. In some embodiments, if the answer is yes, then the device deactivates the pumps and deflates the inflatable pumps 152, and returns to monitor the vital signs of the newborn 140. In some embodiments, if the answer is no, then the device maintains the activation of the pumps 148 until the answer is yes. Returning to point 144 where it is assessed if the blood pressure is higher than the acceptable parameters, if the answer is no, then, in some embodiments, an alarm of low blood pressure is activated 154.

(46) In some embodiments, the device continues to work in order to keep the blood pressure at a stable level. In some embodiments, this is performed by activating the device intermittently and/or according to the blood pressure measurements received from the external sensors.

(47) In general, acceptable parameters are set according to the specific vital signs parameters of the subject and/or the specific health status of the subject. In some embodiments, dedicated tables comprising historical statistical data on subjects are used to set the parameters of the device. In some embodiments, the parameters of the device are set manually according to the specific necessities of the subject.

(48) Referring now to FIG. 4, showing a schematic flowchart of an exemplary method of the activation of the inflatable cuffs. In some embodiments, when the device needs to activate the pumps 148 in order to inflate the inflatable cuffs, the system assesses if there is more than one inflatable cuff connected to the device 156. If the answer is no, then the device continues to work as shown in 150 in FIG. 3 (158). In some embodiments, when more than one inflatable cuff is used, the device alternates the activation of the different cuffs 160. Then, the device continues to work as shown in 150 in FIG. 3 (162). In some embodiments, alternation of the activation of the inflatable cuffs helps prevent physical damage to the extremity due to long term blockage of the blood flow. In some embodiments, alternation of the activation of the inflatable cuffs helps reduce the systemic blood pressure by providing multiple points of blockage of blood pressure.

(49) Referring now to FIG. 5, showing a schematic flowchart of an exemplary scenario of the use of the device, according to some embodiments of the present invention.

(50) As mentioned above, during pregnancy, the placenta helps regulate the internal blood pressure in the fetus via the umbilical cord. Once the fetus is born and the umbilical cord is cut, the placenta can no longer assist in regulating the blood pressure. In some embodiments, the device is mounted on the newborn patient before the umbilical cord is cut 164. In some embodiments, the device is mounted on the newborn patient at the moment when the umbilical cord is cut 166. In some embodiments, the device is mounted on the newborn patient shortly after the umbilical cord is cut 168. In some embodiments, after the device is mounted on the newborn patient, the device monitors the vital signs and the blood pressure in the newborn patient 170. In some embodiments, the device operates according to the methods disclosed above 172. Without being limited by a particular explanation or theory, it is known that there is a critical period, or danger period, after the umbilical cord is cut, when the newborn patient can develop IVH.

(51) As mentioned above this danger period can be of 7 days, but it may be longer or shorter. In some embodiments, the doctor inquires and decides when the patient has exited this danger period 174. If it is decided that the patient has not exited the danger period, then the machine stays mounted on the patient and the monitoring continues 170. If it is decided that the patient has exited the danger period, then the device can be unmounted from the patient 176. In some embodiments, stabilization of blood pressure to normal values for more than 3 days indicates that subject has exited the danger period. In some embodiments, stabilization of blood pressure to normal values from about 3 days to about 7 days indicates that subject has exited the danger period. In some embodiments, when the premature neonatal arrives at the end of what supposed to be the end of the 10 weeks of pregnancy, then it may be an indication that subject has exited the danger period.

(52) Exemplary Combined Treatment

(53) In some embodiments, the patient, either newborn or not, is treated using a combination of the device and methods as disclosed herein together with a pharmacological treatment. In some embodiments, the combination of the treatments provides a positive synergistic effect on the status of the patient. For example, a premature infant who is ventilated and managed by the device and also receives coagulation factor xiii to treat hemophilia, which is an abnormality that can lead to IVH.

(54) Exemplary Use of the Device/Methods in Adults

(55) In some embodiments, the device/methods are used on adults subjects. In some embodiments, the device/methods are used to prevent increasing and/or maintaining the intracranial blood pressure in adults subjects.

(56) Exemplary Non-Linear Blood Pressure Dynamics

(57) In some embodiments, blood pressure dynamics may behave in a non-linear manner in light of the use of the device and/or the methods performed by the device. In some embodiments, this non-linear behaviour is translated into a non-linear model usable in a software. In some embodiments, the software of the device further comprises methods to compress/release cuffs according to this non-linear model.

(58) Exemplary Chronic Use of Device/Methods

(59) In some embodiments, the device/methods are used for a long period of time. In some embodiments, the period of time is from days to weeks. For example, the device/methods can be used when there is a hypertensive crisis.

(60) It is expected that during the life of a patent maturing from this application many relevant sensors, pumps, inflatable cuffs and vital signs monitoring devices will be developed; the scope of the term inflatable cuffs is intended to include all such new technologies a priori.

(61) As used herein with reference to quantity or value, the term about means within 20% of.

(62) The terms comprises, comprising, includes, including, has, having and their conjugates mean including but not limited to.

(63) The term consisting of means including and limited to.

(64) The term consisting essentially of means that the composition, method or structure may include additional ingredients, steps and/or parts, but only if the additional ingredients, steps and/or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure.

(65) As used herein, the singular forms a, an and the include plural references unless the context clearly dictates otherwise. For example, the term a compound or at least one compound may include a plurality of compounds, including mixtures thereof.

(66) Throughout this application, embodiments of this invention may be presented with reference to a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc.; as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

(67) Whenever a numerical range is indicated herein (for example 10-15, 10 to 15, or any pair of numbers linked by these another such range indication), it is meant to include any number (fractional or integral) within the indicated range limits, including the range limits, unless the context clearly dictates otherwise. The phrases range/ranging/ranges between a first indicate number and a second indicate number and range/ranging/ranges from a first indicate number to, up to, until or through (or another such range-indicating term) a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numbers therebetween.

(68) Unless otherwise indicated, numbers used herein and any number ranges based thereon are approximations within the accuracy of reasonable measurement and rounding errors as understood by persons skilled in the art.

(69) As used herein the term method refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.

(70) As used herein, the term treating includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition or substantially preventing the appearance of clinical or aesthetical symptoms of a condition.

(71) It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

(72) Various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below find experimental support in the following examples.

EXAMPLES

(73) Reference is now made to the following examples, which together with the above descriptions illustrate some embodiments of the invention in a non-limiting fashion.

Example 1

(74) In the following paragraphs, an exemplary experiment in a human subject will be disclosed.

(75) An experiment on a 27 weeks old premature infant with RDS and umbilical artery catheter (aortic BP) was performed. Due to weak pulses and the diagnosis of aortic stenosis (coarctation of aorta) measurement of blood pressure was performed in the four extremities. Inflation of one cuff mounted in the proximal part of the leg led to a 3 mmHg decrease of systolic blood pressure: from 51 mmHg to 48 mmHg (a reduction of 5.9%), and a reduction of mean blood pressure: from 40 mmHg to 37 mmHg (reduction of 6.25%).

(76) See table below showing the results of the experiment.

(77) TABLE-US-00001 Location Systolic Diastolic Mean Pulse Heart of Limb Cuff BP BP BP Pressure rate Measurement obstructed pressure Baseline no 51 31 40 20 132 Descending Close 102 obstruction aorta to inguinal line Both 53 32 42 21 138 Descending Close 130 arterial and aorta to venous inguinal flow line obstruction Venous 48 30 37 21 134 Descending Close 20-30 flow aorta to obstruction inguinal only line

Example 2

(78) An adult volunteer (40 years old).

(79) Inflatable cuffs were mounted on 3 limbs.

(80) Results:

(81) A summary of the results can be seen in the table below:

(82) TABLE-US-00002 TIME MIN 10 20 30 40 50 60 Systolic Blood 127 118 123 133 119 123 Pressure
1. Inflation of the cuffs during rest led to an (11/116) 8.6% reduction in systolic blood pressure. It is hypothesized that mounting inflatable cuffs in all 4 limbs should achieve a reduction of at least 10% in systolic blood pressure.
2. Inflation of the cuffs after physical effort led to a (14/133) 10.5% reduction in systolic blood pressure. It is hypothesized that mounting inflatable cuffs in all 4 limbs should achieve a reduction of at least 12.5% in systolic blood pressure.
See FIG. 6 for the graph showing the results of the experiment.

Example 3

(83) Blood pressure profile in a healthy adult volunteer: Impact of venous return reduction on blood pressure fluctuations.

(84) Volunteer Data

(85) Age: 27 years old, weight: 85 Kilograms, height: 185 centimeters, BMI: 24.5

(86) Experimental Protocol

(87) TABLE-US-00003 Phase I II III Time 0 .fwdarw. 22 minutes 23 .fwdarw. 45 minutes 46 .fwdarw. 70 minutes plan Effect of VR Effect of VR obstruction on obstruction on blood pressure blood pressure after after relax. intense exercise Action Inflation of cuffs Inflation of cuffs at Follow up of blood at 15 minutes 35 minutes pressure, HR, O2sat and pulse pressure. Full Inflation of cuffs within 20 seconds, 3 cuffs rotated around legs and one arm., up to a venous obstructing pressure of 65 mmHg.

(88) See FIG. 7 for the graph showing the results of the experiment.

(89) See table below

(90) TABLE-US-00004 When What 0 10 20 30 40 50 60 70 SYSTOLIC ABP 113 106 111 101 113 124 115 122 Mean BP 78 76 80 74 81 84 81 84 DIASTOLIC ABP 62 61 65 59 65 65 64 66 Pulse pressure 48 45 46 47 48 57 51 56 HR 74 65 76 70 66 78 66 68 O2 sat 97 96 96 96 96 98 95 97
1. Inflation of the cuffs during rest led to a 7/113 (6.2%) reduction in systolic blood pressure. It is hypostasized that mounting inflatable cuffs in all 4 limbs should achieve a reduction of at least 8% in systolic blood pressure.
2. Inflation of the cuffs after physical effort led to a (9/124) 7.2% reduction in systolic blood pressure. It is hypostasized that mounting inflatable cuffs in all 4 limbs should achieve a reduction of at least 8% in systolic blood pressure.

(91) Blocking venous blood return to the body and/or the heart by using the inflatable cuffs around the most proximal part of at least one extremity lead to reduction of systolic blood pressure even when the body was at rest (sleeping baby). Furthermore, it is expected that the device will perform better when initiated after stress to the body (infant crying, infant being touched and handled by nurses). Infants treated with the device for 20-60 seconds should present positive results, i.e. avoiding the increasing systolic blood pressure, can show compensatory rise of blood pressure after deflation of the cuffs. In some cases, it might be required to perform repetitive activation of the device.

Example 4

(92) In the following paragraphs, an exemplary experimental protocol for a proof of concept in non-human animals will be explained.

(93) Exemplary General Protocol for the Experiment

(94) Type of animal: piglets that were born up to 36 hours before the experiment.

(95) Pre-Experimental Conditions:

(96) Anesthesia: partially or total anesthetized

(97) Respirator: only if necessary

(98) IV: fluids only.

(99) Parameters Observed Systemic blood pressure (BP) Blood pressure fluctuations (any increase or decrease in mean systemic BP of 10% or more) Pulse pressure Breathing Pulse Saturation CO.sub.2 in exhaled air or subcutaneously measured Urine Inflation pressure of limb via manual BP apparatus and its cuffs Cerebral blood flow via us carotids Venous blood flow above obstruction Which inflation pressure stops venous flow from limb Cardiac output via Doppler US in descending abdominal aorta

(100) Devices Used Monitor showing BP, PP, HR, O2 SAT, transcutaneous CO.sub.2 monitor. Online with alarms Manual pressure monitors Inflatable cuffs Ultrasound to monitor cerebral blood flow (CBF) and the required pressure needed to complete block venous blood flow in the proximity Central arterial catheter Central venous catheter Respirator Urine catheter
Experimental Procedure

(101) Phase 1: Adaptation Period (Between 20 to 30 Minutes)

(102) During this phase the non-human subject is prepared for the experiment. All catheters and devices (Gastric, arterial central, venous central, Peripheral venous, BP via a monitor, Cuffing limbs) are mounted into the subject and connected to the device.

(103) Phase 2: Induced Change in Blood Pressure in the Subject (Between 40 to 90 Minutes)

(104) During this phase the change in the blood pressure is induced in the subject by reducing the dosage of anesthesia medication to a marginal dosage (near wake up state). The effect of the reduction of the anesthesia is to cause discomfort to the subject in order to increase the blood pressure. Several measurements will be performed: BP, PP, HR, O2 SAT, brain ultrasound, venous flow in the extremities.

(105) Phase 3: Experiment

(106) During this phase the cuffs will be inflated in order to block or partially block the venous blood flow until the blood pressure in the subject returns to normal values (similar to those measured during Phase 1).

(107) It is hypothesized that there will be a systolic blood pressure increase of more than 10% (8-12%) that lasts for at least 30 seconds.

(108) Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

(109) All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting.