A TANDEMFOREARMPLETHYSMOGRAPHFOR STUDYOF ACUTERESPONSESOF THE PERIPHERALVEINS OF MAN: THE EFFECT OF EN-

VIRONMENTALAND LOCAL TEMPERATURECHANGE,ANDTHE EFFECT OF POOLINGBLOODIN THE

EXTREMITIES 1

By J. EDWINWOOD2AND JOHN W. ECKSTEIN3

(From the Department of Medicine, Boston University School of Medicine, and the EvansMemorial, Massachusetts Memorial Hospitals, Boston, Mass.)

(Submitted for publication November 13, 1956; accepted September 19, 1957)

The primary mechanism of action of the smoothmuscle of the veins upon their contained blood isone of imparting pressure to the blood by a sur-rounding force. This mode of action is to bedistinguished from that of the smooth muscle ofthe arterioles, which is one of maintenance ofarterial pressure through resistance to the outflowof blood. The function of the arterioles as re-sistive elements in the circulation is evaluated bythe relationship between the volume of the flow ofblood through the arterioles per unit period oftime and the change in pressure across the ar-terioles. The function of the veins as containersof the blood volume is best evaluated by the re-lationship between a change of the volume of theveins and the associated change of the pressure ofthe veins.

It is the purpose of this paper to describe anew method for the simultaneous study of thefunctions of the arterioles and the veins of the ex-tremities of man. In addition, the effects ofseveral stimuli upon veins and arterioles of theforearm are also described. The stimuli employedwere the reduction of the temperature of the room,the reduction of the temperature surrounding theforearm under study, and the congestion of theveins of the three extremities not being studied.

METHODS

A water plethysmograph made of lucite which hadtwo chambers was used in all of the experiments (Fig-ure 1). Each chamber was 8.5 cm. long and had sepa-rate sleeves which were thin, loose fitting rubber. The

1 This study was supported by a grant from the LifeInsurance Medical Research Fund.

2Massachusetts Heart Association Research Fellow.3 Special Research Fellow of the National Heart In-

stitute. Present address: Department of Internal Medi-cine, University Hospitals, Iowa City, Iowa.

outer end of each sleeve was everted and attached to aflange at its respective end of the plethysmograph. Theinner ends of the two sleeves were attached to the perma-nent plate that separated the two chambers. Thin (3mm.), rigid plates, held firmly in place, separated thetwo sleeves in the center of the plethysmograph andcame into close apposition with the skin of the forearm.A change of volume in one chamber did not alter thevolume of the other chamber. Similar plates also pre-vented the sleeve from bulging out at the ends of theplethysmograph (1). In effect, the instrument con-sisted of two short plethysmographs placed in tandemon the forearm.

A pneumatic cuff which was 8 cm. wide was placedon the wrist just beyond the distal end of the plethysmo-graph. This cuff was inflated to suprasystolic pressureprior to each determination. A pneumatic cuff 12.5 cm.wide was placed on the upper arm several centimetersdistant from the proximal end of the plethysmograph.Pressure in this cuff was monitored with a water manom-eter. Unless stated otherwise, the temperature of thewater in the plethysmograph was maintained at 320 C.The total volume of the forearm segment was deter-mined by the displacement of water from the plethysmo-graph. Change in volume of the forearm resulted inchange in the water level of the plethysmograph. Thischange of water level was detected with two partiallyimmersed electrodes, constructed as described by Cooperand Kerslake (2), used in conjunction with a Sanbornstrain gauge amplifier and a Sanborn direct writing in-strument.4 The recording system was calibrated by in-troducing known quantities of water into the plethysmo-graph. Venous pressure was measured with a StathamP23D strain gauge from a small polyethylene catheterinserted into a forearm vein (Figure 1). Venous pres-sure was also recorded with the Sanborn direct writinginstrument.

The exact relationships between changes of pressurewithin the forearm veins and the associated changes ofvolume of these veins were studied as follows: The sub-ject was seated with his forearm in the plethysmographat heart level. Change of the volume in the proximal

4 Construction of electrodes and adaptation to San-born strain gauge amplifier by Sanborn Company,Waltham, Massachusetts.

41

J. EDWIN WOODAND JOHN W. ECKSTEIN

F-i-

FIG. 1. THE Two CHAMBERPLETHYSMOGRAPHStrain gauge, venous catheter and water level elec-

trodes also shown.

chamber of the plethysmograph, change of the volumein the distal chamber of the plethysmograph and pres-sure in a vein in the distal chamber of the plethysmographwere measured simultaneously. Tracings were obtainedwith and without water in the proximal chamber of theplethysmograph. The water level in the plethysmographwas such that the external hydrostatic pressure exceededthe original venous pressure at the tip of the catheter(without water in the plethysmograph). The originalvenous pressure at the tip of the catheter, relative toatmospheric pressure, will be referred to hereafter asnatural local venous pressure. By placing the membraneof the strain gauge at the level of the water in the distalchamber (Figure 1), the recording obtained was internalvenous pressure minus the external hydrostatic pressureat the level of the tip of the catheter (referred to here-after as the effective venous pressure). The water levelin the proximal chamber was kept 3 mm. lower than thatin the distal chamber so that it could not of itself con-gest the veins of the distal segment. Pressure in thecuff on the upper arm was raised by 1 mm. Hg incre-ments until initial pressure and volume changes had oc-curred. Following this, pressure in the cuff was raisedby 5 mm. Hg increments for a total of 30 mm. Hg.

All additional venous pressure-volume experimentswere performed as follows: Water was added to bothchambers of the plethysmograph to a level such that theexternal hydrostatic pressure was certain to exceed thenatural local venous pressure of the subject. This waterlevel (3 mm. lower in the proximal chamber of theplethysmograph) was maintained throughout each ex-periment. Change in volume of the distal segment onlywas then measured. Pressure within the veins of theforearm in the plethysmograph was not measured.Pressure in the proximal cuff was raised above atmos-

pheric pressure by 1 mm. Hg increments until the firstsmall positive deflection in forearm volume (distal seg-ment) occurred. Sudden release of pressure in the cuffresulted in immediate return of the volume of the fore-arm to its original level unless the rise in volume wasartifactual. The cuff pressure relative to atmosphericpressure which was required to produce this change offorearm volume ranged from 15 to 25 mm. Hg and wasreferred to as "cuff zero." Cuff pressure was raisedfurther from "cuff zero" by six successive 5 mm. Hg in-crements. Forearm volume was allowed to reach a newequilibrium prior to initiation of each increment. Thesmall volume increase produced by "cuff zero" itself wasincluded in the first increment. The volume incrementswere plotted additively against effective venous pressure(Figure 2). The volume increase in ml. per 100 ml. fore-arm tissue with a rise in effective venous pressure of 30mm. Hg was called venous volume [30] (Figure 2).

The effect of sudden venoconstriction upon the volumeof the veins when water was in the plethysmograph asabove but without pressure in the proximal cuff was in-vestigated, utilizing the method just described. The sub-ject was studied in the recumbent position with theplethysmograph on one forearm and an intravenous sa-line infusion in the opposite arm. A venous pressure-volume curve was obtained; then pressure in the proxi-mal cuff was released. The volume of the forearm wasallowed to stabilize; then the saline infusion was switchedto an infusion of 15 to 30 micrograms per minute of nor-epinephrine base. The record of the volume of the fore-arm was observed for three minutes after which themeasurement of the pressure-volume curve of the veinswas repeated and the volume of the forearm reestablishedonce again. Arterial occlusion at the wrist was main-tained through this sequence.

The effects of environmental and local cooling. Nor-mal young male subjects wearing shorts only were stud-

I EFFEVEVEN-OUSPRESSUREGuff;w" (m-.H)

FIG. 2. THE RELATIONSHIP BETWEEN CONGESTINGCUFF PRESSURE, EFFECTIVE VENOUSPRESSUREAND VOL-UME CHANGEOF THE DISTAL FOREARMSEGMENTWITHWATERIN THE PROXIMAL CHAMBER(Two CHAMBERS)AND WITHOUTWATERIN THE PROXIMALCHAMBER(ONECHAMBER)

"Cuff zero" and venous volume [301 are also indicated.

42

STUDIES OF THE VENOUSPRESSURE-VOLUMECURVEOF MAN

5

4 rCONTROL

\ I ,. ~~CO2VGEST/O}

N.L.VY.'41

0 10 20 30EFFECTIVE VENOUSPRESSURE

(mm. HO

FIG. 3. VENOUSPRESSURE-VOLUMECURVESOBTAINEDIN A SINGLE EXPERIMENT DURING CONTROLAND CON-GESTION PERIODS

Concomitantly measured venous pressure is used to de-duce natural local venous volume (N.L.V.V.) in eachcase.

ied in the sitting position in a constant temperatureroom. They were urged to relax but were not allowedto sleep. The wrarm environment ranged from 29° C. to32° C. and was continued until digital skin temperatureshowed no further tendency to rise (usually requiring 30to 60 minutes). An additional 20 to 30 minutes wereutilized to obtain two or three successive venous pres-sure-volume curves. The cool environment consisted of

room temperature of 18 C. to 21 C., associated with. gentle breeze produced by a fan near the subject. Theenvironment was continued until the venous volume [30]values became stable (60 to 90 minutes). Then two orthree more pressure-volume curves were obtained.Eleven of the experiments were started in the warm en-vironment and seven were started in the cool environ-ment. Temperature of the water in the plethysmographwas kept at 32e C. throughout all of these experiments.

The effect of change of local temperature was in-vestigated by maintaining environmental temperatureunchanged (29m C.) and reducing the temperature of thewater in the plethysmograph. Three venous pressure-volume curves were obtained at a water temperature of32l C., then three more were obtained after water tem-perature had been reduced to 18a C.

The effect of congestion of the legs. The same methodwas used except that the pressure required for the firstincrement was introduced suddenly so that the initial rateof inscription of the pressure-volume curve of the veinswas volume flow of blood. Normal young male subjectswere studied on a tilt table in a 30 degree (from hori-

zontal) head-up position. Room temperature was main-tained at 25° C. The forearm in the plethysmographwas at the level of the heart. The left antecubital spacewas at the level of the heart and at the level of theshoulder as well. The membrane of a Statham straingauge used to measure venous pressure was placed atthe level of the right atrium (3). An arterial occludingcuff was inflated on the left wrist during each venouspressure determination. Arterial pressure was deter-mined at five minute intervals by the auscultatory methodin the left arm. Mean arterial pressure was consideredto be diastolic pressure plus one-third pulse pressure.The rate of the heart was also determined by auscultationat the apex at five minute intervals. Pneumatic congest-ing cuffs encircled both upper thighs and the left elbowbelow the needle in the vein. Pneumatic leggings cov-ered the rest of the legs. The cuffs on the upper partof the legs, the cuff on the left forearm and the leggingswere inflated from three separate sources. The cuffs onthe wrists were inflated from a fourth source. A widecanvas band was used to strap the subject's knees to thetable to allow him to relax comfortably. During theinitial control period which lasted for 30 to 45 minutes,the leggings and upper leg cuffs were inflated to a pres-sure which was equivalent to the vertical hydrostaticdistance between the knee and the level of the rightatrium. Three or more venous pressure-volume curvesfrom the right arm with simultaneous venous pressurefrom the left arm were recorded during this period.Following this, pressure in the pneumatic leggings wasreleased and simultaneously the three congesting cuffswere inflated to 70 mm. Hg. Then, the pressure-volumecurves and venous pressure measurements were repeatedat 5 to 10 minute intervals until venous volume [30] be-came constant. Three more pressure-volume curveswere then obtained. Subjects were not allowed to movetheir legs during the congestion period.

The recovery period was initiated by release of thecuffs on the upper legs and left elbow, followed in 60seconds by inflation of the leggings and cuffs on theupper legs to the pressure originally used in the con-trol period. Venous pressure-volume curves and simul-taneous venous pressures were measured at 5 to 10 minuteintervals until the value for venous volume [30] be-came constant. The last three curves, and their associ-ated venous pressures, mean arterial pressures and pulserates were averaged to obtain a single value for eachfunction during the control period, the congestion period.and the recovery period.

In separate experiments subjects were studied in thehorizontal position utilizing exactly the same procedureas described above.

The venous pressure as measured in the left arm wasthe natural local venous pressure. This pressure andthe concomitantly measured peripheral venous pressure-volume curve were used to deduce the volume of bloodpresent in the venous bed of the limb segment at thatpressure. This volume will be referred to hereafter asthe natural local venous volume. Thus it was possibleto calculate the per cent change in natural local venous

43

J. EDWIN WOODAND JOHN W. ECKSTEIN

volume produced by congestion of both legs and the op-

posite forearm (Figure 3).All the experiments were analyzed statistically on the

basis of paired data. The variability within the controlperiods or the experimental periods (congesting or cool-ing) was investigated by determining the differences be-tween each of the values of venous volume [30] and theirmean (means only are tabulated in Tables I, II, and III)for that period. Standard error of the mean, standarderror of the difference, and probability were then deter-mined for the group of experiments.

RESULTS

Changes in effective venous pressure and fore-arm volume resulting from inflation of the proxi-mal cuff by 1 mm. Hg increments while only thedistal chamber of the plethysmograph was filledwith water were measured on 5 subjects 11 times.A volume change of the distal forearm seg-

ment under these circumstances invariablypreceded a change in measured effective venous

pressure. This discrepancy was such that it was

necessary to inflate the cuff by three to five addi-tional 1 mm. Hg increments, before a rise inmeasured effective venous pressure could be in-duced. Following this and in the same experi-ment, water was added to the proximal chamber ofthe plethysmograph. Volume change of that seg-

ment was also recorded. The procedure of inflat-ing the proximal cuff by 1 mm.Hg increments was

repeated and it was found that the first change ofmeasured effective venous pressure and the firstchange of volume of the distal forearm segmentthen occurred simultaneously. However, a changein volume of the proximal segment invariably pre-ceded a change in its measured effective venous

pressure.Effective venous pressure without pressure in

the proximal cuff but with water in the plethysmo-graph was measured repeatedly in the five sub-jects. It ranged from 0.5 to 1 mm. Hg and re-

mained constant throughout each experiment.This effective venous pressure value was not in-fluenced by the water level of the plethysmographprovided the pressure of the water exceeded thenatural local venous pressure. Volume change inthe proximal chamber always preceded effectivevenous pressure change by three to five 1 mm. Hgincrements in cuff pressure. Figure 2 illustratesthe results of one of these experiments.

Despite the discrepancies in the time of onset ofthe response in volume and in pressure in thesingle chamber plethysmograph, change of venous

volume in response to a rise of 30 mm. Hg ef-

TABLE I

Venous volume [30] and blood flow in ml. per 100 ml. forearm tissue in the warm and cool environments, with per centreduction of each and notation as to which environment the subject was first exposed

Warm (W) Venous volume [30] Blood flowor Cool (C) % %

Subject first Warm Cool reduction Warm Cool reduction

1 W 1.6 1.4 13 2.9 1.0 661 C 2.2 1.4 36 1.4 1.0 291 C 3.9 3.2 181 W 4.1 2.7 341 W 3.3 2.5 242 W 2.7 2.2 19 4.6 1.0 782 C 2.7 2.0 26 2.5 1.6 363 C 3.7 2.5 32 1.2 1.0 174 W 3.0 1.8 40 4.6 1.1 765 C 3.3 2.7 185 W 2.8 2.0 295 C 2.5 1.1 566 W 3.1 2.6 166 W 4.3 3.7 147 W 2.9 1.4 528 W 4.8 2.8 429 W 3.4 2.2 35

10 C 0.9 1.3

Standard error of the means* 0.052 0.071Standard error of the difference 0.088Mean difference 0.87Probability 0.01

* See text.

AA

STUDIES OF THE VENOUSPRESSURE-VOLUMECURVEOF MAN

TABLE II

Average venous volume [30] and blood flow in ml. per 100 ml. forearm tissue during control (Cl), congestion (Cn), andrecovery (Ry) periods with per cent decrease of control value during congestion of venous volume [30], and

natural local venous volume (N.L. V. V.) per cent decrease of control value during congestion *

Venous volume [30] Blood flow %% decrease

Subject Cl Cn Ry decrease Cl Cn Ry N.L.V.V.

1 2.3 2.0 131 2.8 2.3 2.8 18 2.6 1.1 1.2 441 2.7 2.3 2.8 15 1.2 1.0 1.1 331 2.5 1.7 3.1 32 401 2.5 2.0 2.6 20 0.9 0.7 0.9 221 3.2 2.2 3.1 31 1.1 0.7 0.9 552 4.7 3.3 4.0 30 2.1 1.2 1.62 4.3 3.7 4.3 14 2.0 1.4 1.5 332 4.2 3.4 19 2.0 1.5 323 1.7 1.4 1.7 18 1.2 0.7 1.13 3.5 2.2 2.9 37 584 3.2 2.5 2.8 22 1.9 1.1 1.2 414 3.8 3.3 3.9 13 2.8 1.8 1.84 4.7 3.8 4.1 195 2.2 1.8 1.9 18 2.0 1.5 1.75 2.7 2.0 2.7 26 1.5 1.0 0.96 2.4 2.1 2.4 137 2.8 2.5 2.9 11 2.4 1.1 1.38 3.5 2.3 3.3 34 1.5 1.0 1.09 2.5 2.1 16 1.9 1.3

10 1.7 1.6 1.5 6 3.9 3.4 3.2

Standard error ofthe meanst 0.029 0.035

Standard error ofthe difference 0.045

Mean difference 0.63Probability 0.01

* Thirty degree head-up position.t See text.

fective venous pressure was essentially the same

with or without water in the proximal chamber(Figure 2).

The intravenous infusion of norepinephrine in3 subjects on 12 occasions resulted in no changein the volume of the forearm when there was no

pressure in the proximal cuff. Venous volume[30] decreased in every instance with infusion ofnorepinephrine. Average control venous volume[30] was 3.2 ml. per 100 ml. of forearm while ve-

nous volume [30] with norepinephrine infusionwas 2.4 ml. per 100 ml. of forearm. In two othersubjects and one of the above subjects on fiveoccasions, venous volume [30] was also decreasedby norepinephrine infusion but the volume of theforearm without pressure in the proximal cuff was

also reduced by 0.3 to 0.7 ml. per 100 ml. of fore-arm. Average control venous volume [30] inthese experiments was 1.6 ml. per 100 ml. andaverage venous volume [30] with infusion ofnorepinephrine was 1.0 ml. per 100 ml. of forearm.

The effect of environmental and local cooling

Ten subjects were studied 18 times in the warmand cool environments. In the cool environmentvenous volume [30] was decreased in every in-stance except one. With the exception of thatsubject, the average decrease in venous volume[30] was 34 per cent and ranged from 13 to 56per cent (Table I).

TABLE III

Average venous volume [30] and blood flow in ml. per 100 ml.forearm tissue during control (Cl), congestion (Cn),

and recovery (Ry) periods-Horizontal position

Venous volume E30] Blood flow

Subject C1 Cn Ry C1 Cn Ry

1 2.2 2.1 2.2 1.0 0.8 0.82 3.8 3.5 1.7 1.24 3.1 3.29 2.1 2.4 1.7 2.09 4.0 4.1 2.6 1.99 4.0 4.2 4.1 4.0 2.8 2.9

45

J. EDWIN WOODAND JOHN W. ECKSTEIN

Six of these experiments on four subjects werecarried out with measurements of blood flow(Table I) on the opposite forearm by the venousocclusion plethysmographic method (4). In thethree experiments with the room warm first, bloodflow fell as room temperature was being lowered(5 to 10 minutes), while venous volume [30] didnot decrease for 30 to 60 minutes. In the threeexperiments done with the room cool first, venousvolume [30] rose during exposure to the warmenvironment, and in two this occurred 5 to 10 min-utes before blood flow rose. In the third therewas no difference in the onset of the responses.

Two subjects were studied four times in thewarm environment with the temperature of thewater in the plethysmograph first at 320 C., thenat 18° C. Venous volume [30] was less withcool water in all four experiments by an averageof 31 per cent, ranging from 18 to 44 per cent.

The effect of congestion of the legs

Ten subjects were studied in 21 experiments inthe 30 degree head-up position (Table II).Venoconstriction in the forearm in response topooling of blood in the veins of the limbs oc-curred in 20 of the 21 experiments. Blood flowdeterminations during the congestion period weresatisfactory in 16 of these experiments. Con-striction of the arterioles, indicated by decreasedblood flow in the presence of a slight rise in meanarterial pressure, occurred in all 16 experiments.Venous pressure decreased in all of the nine ex-periments in which it was measured. The de-creases at their maximum ranged from 4 to 18mm. water.

In the 16 experiments in which both constrictionof the veins and the arterioles was observed, theonset of constriction of the arterioles occurredwithin the first 10 minutes of congestion of thelimbs and clearly preceded the onset of constric-tion of the veins in 11. This difference in timeof onset ranged from 5 to 35 minutes. The timeof onset of these two phenomena could not bedistinguished in four experiments, and constric-tion of the veins clearly preceded constriction ofthe arterioles in one. The congestion period was45 to 90 minutes in duration.

During the recovery period venous volume[30] measurements were satisfactory in 17 ex-

periments and blood flow measurements weresatisfactory in 14 experiments. Dilatation of theveins relative to the state of constriction observedduring the congestion period occurred in all 17 ofthese experiments. Dilatation of the arteriolesoccurred in 11 before termination of the experi-ment, while the constriction of the arterioles in-duced during the congestion period persistedthroughout the recovery period in the remainingthree experiments. In 10 of these 11 experimentsdilatation of the veins started before dilatation ofthe arterioles began. In one case there was noapparent difference in the time of onset of dilata-tion of the veins and the arterioles.

Venous pressure measurements were satisfac-tory in eight recovery periods of these experi-ments. In seven of these, sudden reapplication ofcompression in the leggings resulted in overshootof venous pressure relative to the subsequent rest-ing level. This overshoot ranged from 7 to 24mm. of water and lasted from 1 to 3 minutes.

The average pulse rate during the control pe-riod was 72 per minute. Pulse rate rose in everyexperiment during the congestion period to anaverage maximum level of 80 (the subject withvasovagal syncope is excluded). The averagebasal level in the recovery period was 70. Aver-age mean arterial pressure was 102, 104, and 104mm. Hg, respectively, during these three periods.

The percentile reduction in natural local ve-nous volume during the period of congestion wascomputed in the nine experiments in which venouspressure was measured. It ranged from 22 to 58per cent and averaged 39.8 per cent. The valueexceeded 32 per cent in all cases except one, whichwas 22 per cent. It was of interest to note thatfainting occurred only in this subject. His pulserate was less than 40 during this episode, sug-gesting a vasovagal response. The remainingsubjects had no serious symptoms during con-gestion but did complain variously of warmness,sweating, listlessness and annoyance, in that orderof frequency.

Six experiments were done in the horizontalposition (Table III) without venous pressuremeasurements. Constriction of the veins oc-curred in two of these subjects to a mild degree,while no response was evident in the remainingfour experiments. Pulse rate, blood flow andarterial pressure were little affected by congestion

46

STUDIES OF THE VENOUSPRESSURE-VOLUMECURVEOF MAN

of the limbs of subjects in the horizontal position.The congestion period was maintained for 60 to 90minutes in these experiments.

DISCUSSION

The method utilized for these studies is a fur-ther modification (5) of a previously describedmethod (6). The further modification was donein order to approximate more closely in vivo theideal in vitro circumstances necessary for measur-ing the pressure-volume characteristics of a dis-tensible system (7), in this case the veins of theforearm. This ideal situation would have as itsstarting point a completely empty system at zeroor even negative pressure and permit one to raisethe pressure in convenient steps while measuringthe simultaneously induced volume change witheach step. However, it is impractical to use abloodless venous bed at zero effective pressurein vivo because of its attendant physiologic (cir-culatory arrest) and technical (pressure plethys-mography) disadvantages. Therefore, it becomesnecessary to demonstrate that changes of volumeof the undistended veins induced by a strong veno-constrictor stimulus are small or at least predicta-ble. The points along the venous pressure-volumecurve are valid only if it can be demonstrated thatassociated changes of pressure and volume occursimultaneously.

The phenomenon of volume increase precedingpressure increase when a single chamber plethys-mograph was used was probably due to early con-gestion of the poorly pressurized cone of tissueat the proximal end of the plethysmograph (8).A pressure cone occurs between two segments offorearm subjected to different pressures, with thebase at the level of the change in pressure and theapex toward the higher of the two pressures.Thus, there would be no cone within the distalend of the plethysmograph, although there wouldbe a cone beneath the proximal end of the arterialocclusion cuff distal to the plethysmograph.

The total measured increase in volume of thevenous system of the forearm (ml. per 100 ml. oftissue per 30 mm. Hg increase in effective venouspressure) was not altered significantly by thepresence or absence of the proximal chamber ofthe plethysmograph. Thus studies of venous vol-ume [30] utilizing a single chamber plethysmo-

graph (5) would not be invalidated by the find-ings described herein. On the contrary, the largersingle chamber plethysmograph has the advantageof smaller variability of results when one subjectis to be compared with another (due presumablyto the smaller variability from one subject to an-other of the bone to soft tissue ratio of a longersegment) and is preferable for this type of study.Since the additional refinement of a proximalchamber allows inscription of an accurate pres-sure-volume curve, local venous volume at lowvenous pressures may be accurately predicted.The two-chamber plethysmograph, therefore, ap-pears to be superior to the single-chamber plethys-mograph for study of acute responses of veinswhen a subject is used as his own control duringa single continuous experiment.

The forearm venous pressure-volume curve is agraphic presentation of the volume of blood that avenous system of 100 ml. of forearm tissue willaccept with a given change of effective venouspressure. Constriction of the smooth muscle ofthe veins results in a less distensible system. Inaddition, venous pressure-volume curves indicatethe magnitude of the decrease in local venous vol-ume, at a given effective venous pressure, whichhas been caused by venoconstriction if the volumeof the veins at their lowest effective venous pres-sure (0.5 to 1.0 mm. Hg) is unaltered by thevenoconstriction. When venoconstriction is in-tense or occurs in an already constricted venousbed, the initial volume of the veins at this loweffective venous pressure may decrease. In thiscase, decrease in venous volume at a given effec-tive venous pressure would be greater than thatindicated by the venous pressure-volume curvewhich has been observed. Moderate venocon-striction of a previously dilated venous bed, in-duced by infusion of norepinephrine, did not alterthe volume of the veins at low effective venouspressure. Leonard and Sarnoff have observedthat an unstretched helical section of vein shortenswhen exposed to a constrictor agent (9). Theexplanation for the apparently contradictory ob-servations may be that dilated veins at low effec-tive venous pressures may be elliptical in cross-section and may tend to become circular withconstriction. This geometric change would al-low the cross-sectional area (thus volume of thetube) to remain unchanged despite a decrease in

47

J. EDWIN WOODAND JOHN W. ECKSTEIN

circumference of the tube. Once the circular con-figuration was reached, further constriction wouldresult in a decrease in volume even at low effectivevenous pressure. The observation that venousbeds with a low control venous volume [30]tended to diminish in volume at low effective ve-nous pressure after infusion of norepinephrine isconsistent with this hypothesis. The length, widthand thickness of the unstretched venous systemcannot be determined in vivo by presently avail-able methods; thus, its length-tension relationshipsrelative to resting length cannot be calculated.This fact does not alter the contribution of thevenous pressure-volume curve to a more com-plete understanding of the physiology of theperipheral veins.

The effect of environmental and local cooling

The responses of the veins to cooling of the en-vironment and to cooling of the extremity locallyindicate that it is necessary to control these tem-peratures during experiments designed for studyof the veins. The difference in rate of response(though the direction was the same) of the ar-terioles and veins is further evidence that themethod measures the characteristics of the veins,independently of arteriolar changes.

Greenfield and Patterson (10) found that highenvironmental temperatures produced no furthervenodilatation when the experiment was startedin a comfortable environment. Although theirmethod was more analogous to the pressureplethysmographic approach (11) rather than tothe method presently described, the resulting datacan probably be compared at least qualitativelywith those obtained by methods reported here.Results obtained with these methods with bodywarming are essentially the same (12). Furtherdilatation of veins does not occur despite themarked arteriolar dilatation that occurs with bodyheating. (This is another example of a differencein the response of the arterioles and veins.) Un-like the arterioles, the peripheral veins appear tobe maximally dilated when the subject is com-fortably warm.

The effect of congestion of the legsThere is little doubt that the peripheral venous

system participates actively in the complex vascu-

lar responses to a diminution of effectively circu-lating blood volume (13-16). Further questionsare: 1) What is the time-course relationship ofthe venoconstriction and the arteriolar constric-tion? 2) What is the degree of venoconstrictionin terms of the venous pressure-volume curve andthe resultant change in natural local venousvolume.?

The intensity of the stimulus employed in theseexperiments depends upon the volume of bloodremoved from the parts of the vascular bed notsubjected to congestion and the position of thesubject. It may be categorized further by theseverity of symptoms and signs induced by thecongestion of the limbs.

Ebert and Stead (17) measured the volume ofblood pooled in both legs and one arm of supinenormal subjects by cuffs on these extremities in-flated to diastolic pressure. The volume changesobtained were probably similar to those producedin the experiments reported here despite the dif-ference in position of the subjects, since pneumaticleggings were used to prevent dependent poolingof blood during the control periods in the experi-ments here reported. They found that the bloodvolume normally present in the head, trunk andone arm was reduced by an average of 720 ml. or15 per cent, with a range of 13 to 18 per cent.

The signs and symptoms of the subjects and theobservations of Ebert and Stead (17) indicatethat the intensity of the stimulus to the cardio-vascular system was of the order of that producedby an acute reduction of effectively circulatingblood volume of 500 to 1,000 ml. when the sub-ject is in the head-up position.

It has been suggested (18) that under most cir-cumstances venous and arteriolar responses oc-cur simultaneously. This implies that the responseof veins and arterioles is one of a parallel increasein tone, the degree and rapidity of which dependsupon the stimulus. However, under the circum-stances of the experiments described here, rigidparallelism of these responses in the forearm wasusually absent. With the onset of limb congestionarteriolar constriction began almost at once whilevenoconstriction not only began later, but re-quired more time to reach maximum intensity.Relief from congestion resulted in just the op-posite response inasmuch as arteriolar constric-tion persisted after remission of venoconstriction.

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STUDIES OF THE VENOUSPRESSURE-VOLUMECURVE OF MAN

These differences in rate of response suggestthat initial moderate reduction of effectively cir-culating blood volume of an uptilted subject repre-sents only a mild stimulus to the forearm veins.On the contrary, the same stimulus appeared ade-quate to induce an immediate response of the fore-arm arterioles and thus might be considered tobe a relatively more intense stimulus to the periph-eral arterioles.

Limb congestion in the horizontal position failedto induce significant peripheral vascular responsesin these experiments and has failed to alter cardiacoutput in other experiments (19). Limb conges-tion in the 30 degree upright position resulted ina dissociation of the venous and arteriolar re-sponses. It is reported that sudden tilting to theupright position causes an immediate (within 50seconds) constrictor response of a single super-ficial vein (15). These observations suggest thatin man the peripheral arterioles respond to in-creasing reductions of effectively circulating bloodvolume at a lower level than do the peripheralveins.

The per cent reduction of natural local venousvolume of the right arm induced by pooling ofblood was much greater (40 per cent) than thepresumed reduction of the vascular volume of thehead, trunk, and right arm (15 per cent). Thisfinding implies that the veins of uncongestedskeletal muscles did not merely reduce their vol-ume by the amount of blood that was removed butactually tended to move the remaining blood vol-ume centrally. That is, the amount of venocon-striction in the periphery exceeded that of morecentrally placed veins.

Sudden restoration of blood volume followingcongestion of the legs caused a sharp rise in ve-nous pressure to a point above the level that itwas to assume later in the recovery period. Thefinding of venous pressure "overshoots" suggestedthat the venoconstriction induced by congestionof the limbs persisted for a few moments after re-lief from congestion.

SUMMARYANDCONCLUSIONS

1. A new two-chamber plethysmographicmethod for accurately recording the peripheralvenous pressure-volume curve in man is described.

2. Using this method, peripheral venoconstric-tion is found to occur in a cool environment, or

after locally cooling the part in the plethysmo-graph.

3. Arterial constriction commonly precedesvenoconstriction on going from a warm to acool environment while venodilatation usuallyprecedes arteriolar dilatation on going from a coolto a warm environment.

4. Congestion of the legs in the 30 degree(from horizontal) head-up position usually re-sulted in prompt arteriolar constriction and ve-nous pressure reduction followed by peripheralvenoconstriction (in the forearm).

5. Relief of congestion usually caused in se-quence: 1) venous pressure "overshoot," 2) veno-dilatation, and 3) arteriolar dilatation.

6. Natural local venous volume of the forearmveins was reduced by two and one-half times thepresumed percentile reduction in effectively cir-culating blood volume. This finding suggeststhat after congestion of the lower limbs the remain-ing blood volume was moved centrally by veno-constriction in the periphery which was more in-tense than that in the central veins.

7. The venous pressure overshoot followingrestoration of effectively circulating blood volumeto "normal" suggested that the venoconstrictionthat had taken place in response to a reduction ofblood volume had persisted for a short time afterits restoration.

REFERENCES

1. Wilkins, R. W., and Eichna, L. W., Blood flow to theforearm and calf. I. Vasomotor reactions: roleof the sympathetic nervous system. Bull. JohnsHopkins Hosp., 1941, 68, 425.

2. Cooper, K. E., and Kerslake, D. McK., An electricalvolume recorder for use with plethysmographs(abstract). J. Physiol., 1951, 114, 1 P.

3. Winsor, T., and Burch, G. E., The plebostatic axisand plebostatic level. Proc. Soc. Exper. Biol. &Med., 1945, 58, 165.

4. Wood, J. E., Litter, J., and Wilkins, R. W., Themechanism of limb segment reactive hyperemiain man. Circ. Research, 1955, 3, 581.

5. Wood, J. E., Litter, J., and Wilkins, R. W., Periph-eral venoconstriction in human congestive heartfailure. Circulation, 1956, 13, 524.

6. Litter, J., and Wood, J. E., The venous pressure-volume curve of the human leg measured in vivo(abstract). J. Clin. Invest., 1954, 33, 953.

7. Ryder, H. W., Molle, W. E., and Ferris, E. B., Jr.,The influence of the collapsibility of veins onvenous pressure, including a new procedure for

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measuring tissue pressure. J. Clin. Invest., 1944,23, 333.

8. Landowne, M., and Katz, L. N., A critique of theplethysmographic method of measuring blood flowin the extremities of man. Am. Heart J., 1942, 23,644.

9. Leonard, E., and Sarnoff, S. J., Effect of aramine-induced smooth muscle contraction on length-ten-sion diagrams of venous strips. Circ. Research,1957, 5, 169.

10. Greenfield, A. D. M., and Patterson, G. C., On thecapacity and distensibility of the blood vessels ofthe human forearm. J. Physiol., 1956, 131, 290.

11. Litter, J., and Wood, J. E., The volume and distri-bution of blood in the human leg measured in vivo.

I. The effects of graded external pressure. J.Clin. Invest., 1954, 33, 798.

12. Litter, J., and Wood, J. E. Unpublished observa-tions.

13. Wilkins, R. W., Haynes, F. W., and Weiss, S., Ther6le of the venous system in circulatory collapse

induced by sodium nitrite. J. Clin. Invest., 1937,16, 85.

14. Landis, E. M., and Hortenstine, J. C., Functionalsignificance of venous blood pressure. Physiol.Rev., 1950, 30, 1.

15. Page, E. B., Hickam, J. B., Sieker, H. O., McIntosh,H. D., and Pryor, W. W., Reflex venomotor ac-tivity in normal persons and in patients withpostural hypotension. Circulation, 1955, 11, 262.

16. Alexander, R. S., Venomotor tone in hemorrhageand shock. Circ. Research, 1955, 3, 181.

17. Ebert, R. V., and Stead, E. A., Jr., The effect of theapplication of tourniquets on the hemodynamicsof the circulation. J. Clin. Invest., 1940, 19, 561.

18. Gollwitzer-Mier, K., Venensystem und Kreislauf-regulierung. Ergebn. d. Physiol., 1932, 34, 1145.

19. Warren, J. V., Brannon, E. S., Stead, E. A., Jr., andMerrill, A. J., The effect of venesection and thepooling of blood in the extremities on the atrialpressure and cardiac output in normal subjectswith observations on acute circulatory collapse inthree instances. J. Clin. Invest., 1945, 24, 337.

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