Venous occlusion plethysmography in cardiovascular research: methodology and clinical applications

The use of venous occlusion plethysmography to measure blood flow in humans was first described over 90 years ago by Hewlett with modern ultrasound scanners the 3dB beam width is typically 1–2 mm, so that this condition is not met in most vessels of interest, leading to an overestimation of mean velocity. Assessment of vessel diameter relies on the ability to image the anterior and posterior vessel walls and depends on the angle of the probe to the artery. As the area is obtained by squaring the diameter, any error in diameter estimation results in doubling of the error for area; in general it is difficult to measure area in vessels less than about 3–4 mm in diameter, though this is dependent on the location of the vessel and the frequency of the transducer used, with greater accuracy being achieved if high frequency transducers are used for scanning superficial vessels. Typically, in vessels of 5–10 mm in diameter, the flow may be measured at best with an accuracy of ∼20–30%. In routine practice, using the above technique, it is easy to generate very large errors of ∼50 or even 100% in flow estimation, but in the experimental setting improved accuracy, below 10%, may be possible 16. Overall, the use of ultrasound does not confer any particular advantage over plethysmography in assessing blood flow, although it does allow conduit vessel diameter to be determined at the same time. Moreover, ultrasonic methods require expensive equipment and highly skilled operators and can be difficult to use with intra-arterial needles. Following limb ischaemia there is a rapid increase in forearm blood flow, which slowly returns to baseline values and is termed reactive hyperaemia. The maximum flow and area under the curve for this increase in blood flow are directly related to the duration of ischaemia 17 until ∼13 min, after which lengthening the period of ischaemia does not increase the maximum recorded FBF further 9. Indeed, the maximal post-ischaemic FBF is not influenced by sympathetic tone 18 or administration of vasodilators 9 and seems to represent the minimum forearm vascular resistance, which is a function of the average wall:lumen ratio of the resistance vessels 19. Therefore, minimum vascular resistance provides indirect information concerning the structure of resistance vessels in the forearm. Moreover, minimum forearm vascular resistance correlates well with more direct measurements of resistance vessel structure, such as the media:lumen ratio 20. Increased minimum vascular resistance has been demonstrated in individuals with established hypertension 19, 21, young men with ‘borderline’ hypertension 18, and those with ‘white-coat’ hypertension 22. Interestingly, such structural changes can be reversed with antihypertensive medication 23–25. Minimum vascular resistance can be assessed reproducibly in the forearm following 13 min of ischaemia, induced by inflating a cuff sited around the upper arm to 300 mmHg for 13 min, and asking subjects to perform 20–30 hand contractions during the last 1 min of ischaemia 9. As is usual, the hands should be excluded from the circulation before starting the study and measurements of FBF, using venous occlusion plethysmography, should be made at 15 s intervals for 3 min following ischaemia. Maximum FBF usually occurs 5 and s after cuff and, vascular resistance is as mean arterial Although this technique may it is well The of the forearm can be assessed using venous occlusion plethysmography Moreover, this can be during intra-arterial drug to information the effect of drugs on resistance vessels and techniques for venous However, one of the simple is to increase the upper arm cuff pressure in a to at intervals of Under these conditions, changes in forearm volume changes in venous and thus can be to venous (Figure of venous Changes in forearm volume arterial pressure and pressure occluding cuff when was increased in a with Following inflation of the upper arm cuff to above venous there is a rapid in forearm which a after 1–2 min, on the inflation pressure used However, during venous occlusion there is a but increase in forearm volume (Figure This to be due to of from the than venous and, venous occlusion plethysmography can be used to assess The pressure in the occluding cuff may be in a or in by in which is by of the volume after the vascular is Changes in have been described in and in to infused as illustrated in of to inflation of the upper arm is a rapid increase in forearm volume followed by a in volume of slope due to of from the into the forearm. with Effect of on Effect of a and on forearm volume during cuff inflation to with of a of pressure to the lower produces venous in the and of the This results in increased sympathetic in the the upper and an in FBF, any change in arterial pressure or heart This technique has been used to the of drugs on sympathetic in does not alter FBF, but the to lower pressure one of the most of venous occlusion plethysmography has been the study of the local effect of vasoactive or drugs in the forearm vascular bed. can be by of a into the brachial artery under local which This is a technique and over of subjects can be at the first Indeed, a from around the that have been conducted over the last 15 years any the technique of is best from an and general concerning and the of drugs for infusion need to be at the of such as and local usually any However, it is practice to the subject the after to ensure that have not any can be but there seems particular advantage of this technique, in most and it is less well and does not allow for Indeed, studies can be safely with the use of a and have 50 The particular advantage of the technique is that drugs can be at doses below those systemic because FBF 50 ml is lower than Therefore, if drugs are used for infusion or drugs for on resistance vessels can be systemic or minimizing the potential for and Moreover, the arm can be used as a the to into any changes in blood flow both such as or changes in temperature is for studies to be and this technique should not be have assessed the of venous occlusion plethysmography. demonstrated for blood flow with a of of for FBF measurement and for blood flow under resting conditions, and for blood flow Although have values of for assessment of FBF over the of forearm venous occlusion plethysmography over 1 and a of of for at but when the ratio of was infusion of the and of the was improved by the results as change in FBF ratio and for However, that the of the to and was less when as values of FBF than when as change in the FBF The same also to be for in FBF When FBF is results may be expressed in ml per 100 ml of forearm volume per or as a change from However, as is practice, blood flow is measured in both to and these FBF may be expressed in values for arm, the arm concerning any systemic the of which such an Changes may be in or as a of baseline values the ratio of FBF in the infused arm to the arm around may be as a change from This approach was first by & and has been used by since has the advantage of minimizing the of changes in FBF both for to alteration in sympathetic or blood pressure the arm as a and to than flow, at least for However, with those that can large in blood flow, changes in blood flow may be since changes in the flow in the arm can have a large on the change in the FBF ratio at high should be that in studies different vasoactive are infused it is to use the flow infusion as the baseline to assess changes in FBF than the baseline at the of the may also be used to forearm vascular resistance, and results expressed in this However, this approach such as assuming flow and that in blood pressure have effect on the of muscle and Indeed, forearm vascular resistance particular advantage over FBF values and on be if baseline blood pressure study The most employed method for of FBF is of with may be used, such as maximal which may be of more use when the is or area under the However, the of method may well on the one to Venous occlusion plethysmography, with brachial artery drug administration, provides an method with which to assess the local effect of drugs and hormones on resistance vessels systemic receptor are usually employed to more information physiology of the under When vasoactive drugs changes in blood pressure and sympathetic tone that will alter FBF Moreover, the of systemic allows to be for agonists, such as (Figure and However, for such as and substance P of a curve is not possible due to from the arm and systemic at high Moreover, large in flow will also the of a drug in the forearm due to and of the although this does not appear to be a in However, limited can be which may be employed to assess the effect of receptor or such as of or Effect of and on forearm blood flow. FBF in the infused and arm, during infusion of the two with The FBF technique potential with systemic administration of and although of the forearm vascular is a with it has not been even with large in FBF with and when doses and measurement periods are Moreover, the of the forearm vascular to infused drugs correlates well with systemic for and In when drugs are the changes in local blood flow not those during local intra-arterial Indeed, being a powerful when administered directly into the forearm vascular systemic infusion blood flow at high doses even though this is by a in blood pressure and systemic vascular resistance Therefore, changes in FBF cannot be used to the of drugs on resistance vessels when such are infused Measurement of FBF with intra-arterial infusion of an is for the of a or of a receptor and the potential for or However, studies with receptor more information concerning the physiology and of when are made and In this the forearm vascular provides an with which to safely potential and effect on resistance vessels. Indeed, and substance P and both and have been infused and information about the that such to vascular tone at or during such as of the sympathetic infusion of drugs that the in of vasoactive such as or can also information the of such The forearm circulation can also be used to studies to assess the of a particular which may be by local intra-arterial infusion or the local of in the forearm resistance well with systemic venous into both it is possible to venous from the infused and This can information local drug and the effect of the infused drug on other vasoactive the and from the arm, as a and also provides information systemic or drug The with which drugs and act is an when such as have a rapid of with a maximal effect and, assessment of FBF after starting an intra-arterial infusion may to an the maximum vascular In has a of maximum being after min This effect was not in the first intra-arterial studies and a to the of infusion of to have to doses being with In a of it difficult to during a as is the most powerful of using the FBF may with to such as and substance P In such it to on different because of the increased of may require a of subjects to be or for and to be Therefore, a of studies may be to assess the of the to intra-arterial before on When and in blood flow or mean arterial pressure are potential of to an infused drug be when resting blood flow is due to the effect of and a local drug although this should become an at the of flow due to the of most However, an increased to and in subjects with but that the change from baseline to be of baseline flow which be a more method for However, which method of is more Indeed, different are to Therefore, a more as discussed is the use of arterial pressure resting muscle tone and thus the a mean arterial by of an increased should the to vasodilators and This may well the increased to a of and in subjects with hypertension resting tone the in to vasodilators of resting tone may the to which can be detected and, can increase the to vasodilators during of two vasoactive when changes in baseline flow by one may alter the to the In such use of FBF as discussed in more may a method with which to the potential of changes in baseline flow, but use of is an that the best to for in flow or arterial pressure is the use of the of a such as in a to in the to which are two and for may any is to that or is a general for by baseline The potential from infusion of a drug which baseline FBF, such as to administration of a vasoactive such as can be in a by using as a Indeed, it may be to use a and a drug However, that measurement of FBF is an is to blood flow to baseline after infusion of the first drug with an one that acts directly on and then to the a has been use to the of of on the to drugs the The vascular a of and which vessel tone and have been the focus of in is that is one of by the vascular and also have a of other of and muscle and In the also and a of other a in the of which can be by a of This that the vascular not a in vessel tone and blood but also in the of and Therefore, assessment of function has been the subject of most as determined by in the forearm, but techniques for from the forearm vascular have been developed more function is assessed by the in the forearm, to brachial artery infusion of an which of is also to assess the to a direct in order to exclude any alteration in vascular muscle to (Figure of have been employed in studies and substance P although such as appear to that is not not of but also other and Moreover, the on the of used and vascular for the same particular when is employed are in forearm length, since this is in Indeed, following brachial artery administration less than of the infused the hand and the to is related to forearm length However, for forearm length is possible and, the difference in the to men and Effect of and on forearm blood flow in and normotensive FBF in the infused arm of and normotensive individuals in to an intra-arterial infusion of and As the to but not is in the with such has been described in with a of and although the results in subjects are Interestingly, can be reversed by in individuals and by in with hypertension and to be a systemic resistance and conduit vessels in the forearm as well as the that and Interestingly, there is a forearm and those in the and, the forearm vascular can be used as a for assessing function in the minimizing the of such However, forearm information concerning resistance most studies the which are conduit vessels. Moreover, in the of may the in the forearm to in the of disease, and thus assessment of function may a for those at increased before vascular does this the of improved but also the of to or at those most in of in the forearm can be assessed by the into the brachial artery. In under resting conditions, produces a in FBF of up to which that there is of that in the forearm. Interestingly, of may be in than men and in with such as but not in in hypertension both and have been of can also be used to assess the of to any induced by a particular thus of However, can also be used to the of of such as in of to and to has been described in with However, when was with were in the but not in the that there was of in the results have been in individuals with hypertension and has a changes in baseline FBF may alter the to agonists, in a a to infused also be a and may also be for other Therefore, the use of of in studies using is This may using a or or the function can also be assessed in the forearm by of ischaemia, which is the subject of a more detailed review in this This method was first by in but as the technique of by in forearm ischaemia as a to increase flow in the brachial in an increase in and, of the brachial which can be assessed using ultrasound. is used as a although the seems to be a of this technique has the advantage of being it and expensive equipment, and over its and Moreover, studies a in the forearm and function are difficult to since different ischaemia and are usually employed in the two However, one may and intra-arterial studies as since are assessing function in different of the arterial provides information about arterial conduit and FBF about function in the resistance vessels. The vascular also an in the of The and a in the which can be by a of the basic technique of FBF with intra-arterial drug have demonstrated that substance P in the infused arm with the arm assessing in venous and that this is not due to increased blood flow per Moreover, the effect of substance P can be by of Interestingly, has been described in which may a by may increase the of due to This has also been in the circulation is in the of on the effect of drugs in However, drugs can also be used to individuals with which may or may not be in the resting the of in the forearm in to an intra-arterial infusion of a is dependent on of the Interestingly, the same also the to in with assessing the FBF to drugs may a for improved of individuals and a of the potential of Venous occlusion plethysmography provides a and method for assessing blood flow in is most applied to the forearm and is a technique that has in assessing human vascular physiology and pharmacology, when with intra-arterial drug has also been employed extensively to assess function in vivo, for which it the the of the technique has its use in the of changes in following drug are a of is to be in this and must a of function to this However, assessment of FBF does an method for assessing the of drugs and on the resistance vessels in vivo, the need to systemic The technique is at its most powerful when used to an during a for of before and after administration of an of receptor has also of the and blood flow in 100 years after its first the of venous occlusion plethysmography in physiology and pharmacology established due to the of the technique and its for the of the time. to for of the and for the information of intra-arterial and for with