Effects of Electrical Stimulation on Lymphatic Flow

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					Research Report

Effects of Electrical Stimulation on Lymphatic Flow
and Limb Volume in the Rat



Background and Purpose. The mechanism by which electrical stimulation                                          Heather A Cook
affects edemu has not been elucidated The purpose of this study was to determine                               Monlca Morales
whether subcontraction high-voltage stimulation (SC-FNS) (ie,electrical stimula-                               Ellsabeth M La Rosa
tion that did not elicit a visible contraction) applied to the right hind limbs of rats                        Jalmi Dean
would (1) alter the rate of lymphatic uptake of injected albumin labeled with                                  M Kelly Donnelly
Evans blue dye (AL-EBD)and (2)affect experimentally induced edema. Subjects                                    Patti McHugh
and Metbods. The paws of 28 anesthetized Sprague-Dawlq rats (mean                                              Abby Otradovec
weight-263 g,SD =48 @ were injected with AL-EBD. The experimentalgroup                                         Kimberly S Wrlght
(n=13) received I hour of SC-HVS, and the control group (n=15) received sham                                   Theodore Kula
treatment conskting of the same treatment administered to the experimental                                     Steven H Tepper
group but without the SC-HVS. Blood samples and volume measurements were
obtained at intervals over a 7-hourperiod. Results. Analysis of variance and post
hoc testing indicated that higher amounts of AL-EBD were taken up by the lymph
of the e.xperimenta1group animals as compared with the control group animals
at each time period following the treatment. The experimental group's AL-EBD
reached signzjicance immediately after treatment, whereas the control group re-
quired an additional 4 hours. There was no signzjicant reduction in limb volume
in either group. Conclusion and Discusdon. The SC-HVS signzjicantly in-
creased the uptake of AL-EBD by lymphatic vessels, but it did not cause a signiji-
cant decrease in the induced edemu. The results of this study indicate that SC-HVS
has the potential to reduce edemu by increasing lymphatic uptake of proteins.
[Cook  ta   Morales M, La Rosa EM, et al. E$cts of electrical stimulation on lym-
phaticjlow and limb volume in the rat. Phys Ther. 1994;74:1040-1046.1

Key Words: E d m , Electrical stimulation, Evans blue dye, Lymphatics, Rats.



                                                                                                      Subcontraction high-voltage stimula-
                                                                                                      tion (SC-HVS) (ie, electrical stimula-
-      -
                                                                                                      tion below the level needed to elicit a
HA Cook, FT, M Morales, FT,EM L Rosa, FT,J Dean, PT, M Donnelly, PT, P McHugh, FT, A Otra-
                                a                        K
dovec, PT, and KS Wright, FT,were senior physical therapy students at the University of Maryland      visible contraction) has been widely
at Baltimore when this research was conducted in partial fulfillment of their degree requirements.    used in clinical settings for the pur-
                                                                                                      pose of reducing edema. Edema re-
T Kula, PhD, is Visiting Research Assistant Professor, Department of Diagnostic Sciences, School of
Dentistry, The University of North Carolina, Chapel Hill, NC 27514. He was Assistant Professor,       duction is important because edema
Department of Medical and Research Technology, University of Maryland at Baltimore, Baltimore,        results in poor oxygenation of the
MD 21201, when this research was conducted.                                                           affected tissue,l an impaired ability to
SH Tepper, PhD, FT, is Associate Professor, Program in Physical Therapy, Shenandoah University-       function, and a decreased healing
Winches~.erMedical Center, 333 West Cork St, Winchester, V 22601 (USA). He was Assistant Pro-
                                                           A                                          rate.2 Acute edema results from tissue
fessor, Department of Physical Therapy, University of Maryland at Baltimore, when this research
was conducted. Address all correspondence to Dr Tepper.                                               trauma or infection as a result of the
                                                                                                      inflammatory process.
The study protocol was approved by the Institutional Animal Care and Use Committee of the Uni-
versity of Maryland.
                                                                                                      Acute edema occurs as pan of the
This work was supported by CONMED Corp; Chattanooga Corp; and the Department of Physical              inflammatory response as chemical
Therapy, University of Maryland.                                                                      mediators lead to endothelial leakage
This article was submitred July 6 1993, and was accepted June 23, 1994.                               of plasma proteins, primarily albumin,

Physical Therapy/Volume 74, Number 11/November 1994
and increased capillary hydrostatic       in edema for 4.5 hours following            right hind limbs of rats would (1)
pressure. The resulting increased         treatment. No difference between the        modify the rate of lymphatic uptake of
capillary hydrostatic and interstitial    control and the experimental limbs          albumin labeled with Evans blue dye
oncotic forces draw fluid from the        was measured during subsequent              (AL-EBD) and (2) influence limb
blood vessels into the interstitium.3     time periods.                               volume.
Because albumin is too large to be
reabsorbed by blood vessels, it is        The second hypothesis addresses the         Method
returned to the bloodstream from the      reduction of edema. Alon and De
interstitium almost exclusively by the    Domenicoll hypothesized that SC-HVS         Subjects
lymphatic system.G7 Consequently,         enhances the movement of charged
when albumin is taken up by the           proteins into the lymphatic channels.       A total of 30 male Sprague-Dawley
lymph channels, fluid follows and         When an electric field is introduced        rats (mean weight=263 g, SD=48 g)
edema decreases. The importance of        into an area, charged proteins are put      were housed in a lighudark (12 hours
the oncotic mechanism is readily          into motion and migration into the          each) and temperature-controlled
apparent in cases of lymphatic ob-        lymphatic channels is accelerated. The      (72°F) environment. They were pro-
struction, in which protein uptake is     lymphatic channels' osmotic pressure        vided food and water ad libitum.
inhibited and edema occurs."              is thereby increased, hastening the
                                          absorption of fluid from the intersti-      Procedure
The use of SC-HVS could theoretically     tial space.
affect edema either by preventing                                                     The animals were divided into two
edema formationS1O or by reducing         A study on reduction of edema               groups: a control group (n= 15) and
edema that has already been pro-          yielded results that are seemingly          an experimental group (n= 15). All
duced." The first hypothesis is that      contradictory to Alon and De Domini-        animals were initially anesthetized
SC-HVS restricts leakage from the         co's theory." Mohr et all2 applied one      with an intraperitoneal injection of
microvasculature by decreasing per-       daily 20-minute treatment of SC-HVS         sodium pentobarbital (50 mg per
meability to proteins.8 This mecha-       (continuous mode, pulse rate=80             kilogram of body weight) and were
nism addresses the prevention of          pulses per second, average current          given subsequent doses as needed.
edema and is supported by the re-         flow=35 PA, with the positive elec-         Sodium pentobarbital has been
search of Reeds and Bettany et al.9       trode placed over the right hip and         shown not to influence the contrac-
ReedHfound reduced leakage of             the negative electrode over the right       tion rate of lymph vessels.l3 Initial
flourescein-labeled dextran from the      edematous hind paws of 20 rats) on 3        paw volume measurements and blood
microvasculature of the golden ham-       consecutive days after traumatization       samples were taken from each rat. All
ster cheek pouch receiving high-          by weight drop (50 g, 0.5 cm in diam-       of the animals' right hind paws were
voltage stimulation as compared with      eter, from a height of 50 cm). Vol-         then injected with AI-EBD, utilizing
control animals. Bettany et a19 found     umes of the traumatized limbs were          sterile techniques, between the sec-
that following trauma, formation of       assessed by a plethysmograph. Both          ond and third metatarsals, which
edema was significantly less in frogs'    the control and experimental groups         created the experimentally induced
limbs immersed in water and treated       revealed a volume reduction over the        edema. Over the course of the experi-
with SC-HVS (four 30-minute treat-        testing days. The reduction of edema        ment, the AI-EBD was absorbed from
ments at 1.5-hour intervals of continu-   in the experimental group, however,         the interstitium into the lymphatics,
ous twin pulses at 75 microseconds,       did not reach statistically significant     entered the bloodstream via the tho-
120 Hz, with negative polarity) as        levels as compared with the control         racic duct, and was monitored
compared with the control limbs.          group animals. A possible flaw in the       through blood samples. Postinjection
Experimental limb volume also con-        study by Mohr et a1 was their failure       blood samples and paw volumes were
tinued to be less than that of the        to establish reliability for their volume   taken. The experimental group re-
control limb throughout 17 hours of       measurements.                               ceived 1 hour of SC-HVS. The control
subsequent treatment and measure-                                                     group received a 1-hour sham treat-
ment intervals. Because there was no      No studies have been found that ex-         ment. Sham treatment consisted of
further reduction of edema with the       amined the effects of SC-HVS on pro-        the same procedure used for the
subsequent SC-HVS treatments, this        tein uptake and lymphatic flow. In          experimental group but without the
result cannot be differentiated from      view of the scarcity of research on         SC-HVS. Volume measurements and
prevention of edema versus reduction      this subject, the goal of our experi-       blood samples were then taken from
of edema.                                 ment was to determine whether SC-           both groups as follows: 1 hour postin-
                                          HVS alters the flow of interstitial sub-    jection (corresponding to the termina-
In a follow-up study, Taylor et a1,lO     stances into the lymphatic system,          tion of the sham or SC-HVS treat-
using variables similar to those de-      thereby decting edema. The twofold          ment), 3 hours postinjection, 5 hours
scribed (except with a single 30-         purpose was to determine whether            postinjection, and 7 hours postinjec-
minute treatment), found a reduction      SC-HVS applied to the edematous             tion (Tab. 1).


                                                                 Physical Therapy / Volume 74, Number 1l/November 1994
-
Table 1. Basic Design of the
Experimental Protocol


                       Blood
                       Sample
                                      Llmb
                                      Volume
                                                  with waterproof ink. The rat was sus-
                                                  pended in a rat restrainer from a rod
                                                  clamped to a camera tripod. Each rat's
                                                  Daw was dampened prior to being
                                                  lowered into the immersion vessel of

                                                  paw's ink mark. The immersion of the
                                                                                      -
                                                  the plethysmograph to the level of the
                                                                                            blood was collected from the nicked
                                                                                            tips of the rats' tails into heparinized
                                                                                            capillary tubes." After 5 minutes of
                                                                                            centrifugation, the plasma was re-
                                                                                            moved and stored in a refrigerator.
                                                                                            For analysis, 100 pL of each plasma
                                                                                            sample was diluted with 3 mL of 0.9%
                                                  limb caused a displacement of fluid,      saline. The concentration of EBD in
Anesthetization                                   which was drawn off by a calibrated       the solution (absorbance value) was
Preinjectis~n          XXXa           XXX
                                                  microsyringe until the circuit was        measured by a DW-2 UV, VIS spectro-
                                                  broken, as indicated on the oscillo-      photometer' using a wavelength of
Injection of
   EBD~                                           scope. The amount of displaced fluid      620 nm, a band pass of 3 nm, and a
Postinjection          XXX            XXX
                                                  was taken to be equivalent to the         cuvette path length of 1 cm.3 Reliabil-
                                                  animal's paw volume (in milliliters).     ity testing of the apparatus was
Treatment-1     h
                                                  The procedure was performed until         performed.
  Sham
                                                  two measurements were within 0.1
  SC-HV!SC
                                                  mL of each other. The average of the      Electrical Stimulation
1 h postinjection      XXX            XXX         two immersions was used for statisti-
3 h postinjection      XXX            XXX         cal analysis. The volumetric measure-     The 1 hour of monophasic pulsed
5 h postinjection      XXX            XXX         ments were performed by the same          SC-HVS was applied to the experi-
7 h postinjection      XXX            XXX         experimenter (HAC) throughout the         mental group animals, with the posi-
                                                  study. The experimenter measured          tive electrode on the plantar surface
"XXX=point at which blood sample and limb         the volume of 10 animals' limbs three     and the negative electrode on the
volume were taken.                                times, and intratester reliability was    shaved dorsal surface of the paw.l5
            v a n s
b ~ ~ ~ = ~blue dye.                              assessed by subjecting the data to an     Self-adhesive electrodesg measuring
'SC-HVS= high-voltage electrical stimulation      intraclass correlation coefficient        2.3X 1.5 cm were used and did not
that did not elicit a visible contraction.        (ICC[2,1])procedure.                      overlap each other. The voltage set-
                                                                                            ting was determined for each rat by
                                                  Blood Sampling and                        eliciting a visible contraction of the
                                                  Measurement of Evans Blue Dye             digital muscles and reducing the in-
Volumetric Measurements                                                                     tensity until the contraction ceased.12
                                                  A mixture was prepared using Evans        The setting was readjusted after 15
Volume measurements of the right
                                                  blue dye (EBD) and rat plasma (2 mg       minutes to account for accommoda-
hind paws were performed using a                  of EBD per milliliter of heparinized      tion. The stimulatorll was set on con-
small-volume plethysmograph as
                                                  rat plasma). At this concentration, all   tinuous mode at a pulse rate of 100
described by Mohr and Akers,14with
                                                  of the EBD binds to albumin.16 The        pulses per second, with an average
modifications as described by Cos-                concentration of the solution was         current of 251.54 p A (SD=96.96) and
grove el. all5 The modifications in-
                                                  doubled by centrifuging the mixture       a voltage of 100.62 V (SD=38.78). The
cluded the addition of a biopolar                 through an Amicon CentrifloTM    mem-     control group animals received 1
needle electrode,* an oscilloscope,               brane cone,+which removed one half        hour of sham treatment using the
and a tripod, which increased the
                                                  of the fluid volume. This concentra-      same electrode placement.
accuracy of the volume measure-                   tion was found to be necessary in
ments. The microsyringe of the ple-               order to monitor the EBD in the           Data Analysis
thysmograph was set at zero, and
                                                  plasma by the spectrophotometer.
water was added until the fluid level             This concentrated solution (0.5 mL        The data collected from this research,
met the tip of the needle electrode.              per kilogram of body weight) was          the amount of AL-EBD in the plasma
The circuit was thereby closed, as
                                                  injected into the rats' paws.             (absorbance value) and the limb
indicated on the oscilloscope. To                                                           volume measurements (in milliliters),
measure the paw volumes, the lateral              To assess the EBD concentration in        were evaluated by a two-way analysis
malleohs of each animal was marked
                                                  the plasma of the rats, 2oo pL            of variance for repeated measures
                                                                                            with an alpha level of .05. A
                                                                                            Student-Neuman-Keuls post hoc test
'Bioelectronics, 5696 Park Rd SW, Ft Myers, F 33908.
                                             L
                                                                                            was used to determine where signifi-
                                                                                            cant results had occurred.
+Amicon,72 Cherry Hill Dr, Beverly, MA 01915.

$American Instruments, Silver Spring, MD 20902.                                             Results
$CONMET)Corp, 310 Broad St, Utica, NY 13501.
                                                                                            Although the study began with 30 rats,
II~hattanoo~a
           Group Inc, 4717 Adams Rd, Hixson, TN 37343.                                      only data from 28 rats (15 control

Physical Therapy /Volume 74, Number 1l/November 1994
                                               Evans Blue Dye Concentration
Table 2. Statistical Analysis of Evans         Main effect differences of the AL-EBD
                                                                                          Table 3 Statistical Analysis #Limb
                                                                                                 .
Blue Dye in Rat Plasma                                                                    Volume Measurements
                                                                  and
                                               between g r o u ~ s over time were
                                                        "   1


                                               significant. For this study, however,
                MSE     df    F       P        the interaction effect between groups                   MSE       df    F        P
                                               and time was considered to be the
Groups          125.6    24    0,7    ,0035a   most important comparison (Tab. 2).        Groups       0.1 168    25       0.23 ,6406
                                               The following interaction effects were
Time periods     25.2   120   40.5    .OOOOa                                              Time periods 5 , 63 25       33,25 ,OOOOa
                                               of greatest importance:
Interaction      25.2   120    4.4    ,0013"                                              Interaction  5.1 163 125         1.54 ,1802

                                               1. No differences were found be-
                                                  tween control and experimental
                                                  groups in the AL-EBD concentra-
group animals and 13 experimental                 tion in the preinjection and postin-       5-, and 7-hour postinjection blood
group animals) were included in the               jection blood samples (ie, before          samplings (Fig. 1).
data analysis. One rat died as a result           treatment began) (Fig. 1).
o an overdose from the anesthesia. A
 f                                                                                        3. The experimental group animals
second rat's data were discarded due           2. Increases in the amount of AL-EBD         exhibited increases of AL-EBD from
to technical error (volume of blood               were found in the plasma of the           the postinjection (ie, pretreatment)
from the tail was inadequate).                    experimental group as compared            values at 1, 3, 5, and 7 hours
                                                  with the control group at the I-, 3-,     postinjection, as opposed to 5 and
                                                                                            7 hours postinjection needed in
                                                                                            the control group animals before
                                                                                            an increase was noted (Fig. 1).The
                                                                                            AL-EBD values remained above the
                                                                                            postinjection values for both
                                                                                            groups in the subsequent time
                                                                                            intervals.
       10
                                                                                          4. Successive increases of the AL-EBD
                                                                                             occurred in the experimental
                                                                                             group between the time periods of
 T                                                                                           postinjection (ie, pretreatment) and
  -
  51
  X
  0
                                                                                             1 hour postinjection ([4.40-+0.62
                                                                                             to 5.77k 1.281X         and between
  Z
  6                                                                                          1 and 3 hours postinjection
  8                                                                                          ([5.77+1.28 to 6.95+ 1.521x
  I
  4     4
                                                                                             (Fig. 1). In contrast, no increase
                                                                                             was seen between successive time
                                                                                             periods in the control group
                                                                                             animals.
        2                                                                                 The reliability (Y) of the spectrophoto-
                                                                                          metric readings, as determined by
                                                                                          ICC (3,1), was found to be .99.
       0
            Preinjury Postinjury          1h        3h           5h          7h           Llmb Volume
                                          Time Period                                     Main effect differences of limb volume
                                                                                          between the control and experimental
                                     Control      Experimental                            groups were not significant through-
                                     Group        Group                                   out the study. A significant main effect
                                                                                          alteration, however, was noted be-
Flgure 1. Comparison of mean amounts of Evans blue dye in the plasma over the             tween time intervals with both groups
course of the experiment between control and experimental groups (a=P<.O5) (error         combined (Tab. 3, Fig. 2). The inter-
bars represent standard deviation). Signifcant increases occurred between successive      action effect revealed no difference
time periods (c=P<.05), and specificallyfrom postinjection values in the experimental     between groups and time periods
group only (b=P<.05). Signifcant increases specfically from postinjection values oc-
curred in the control group only (d=P<.05).                                               (Tab. 3, Fig. 2). The reliability (Y)of

52 / 1043                                                             Physical Therapy/Volume 74, Number ll/November 1994
                                                                                           experimental group animals, as op-
                                                                                           posed to 5 hours postinjection
                                                                                           needed in the control group animals
                                                                                           (Fig. 1). This finding substantiates the
                                                                                           efficacy of SC-HVS for rapid removal
                                                                                           of the AL-EBD from the interstitial
                                                                                           area. Due to the enhancement of
                                                                                           lymphatic flow inherent during an
                                                                                           edematous situation, the control
                                                                                           group eventually did exhibit an in-
                                                                                                            .~
                                                                                           ~ r e a s e . l 9The~continual rise in the
                                                                                           subsequent AL-EBD values supports
                                                                                           our methodology.

                                                                                           The dramatic increases that were
                                                                                           found between two successive time
                                                                                           intervals in the experimental group
                                                                                           (Fig. I), as compared with the gradual
                                                                                           rise in the control group, are another
                                                                                           illustration of the beneficial effect of
                                                                                           SC-HVS. In addition, SC-HVS contin-
                                                                                           ued to exert its effect for 2 hours
1         Preinjury Postlnjury 1 h
                                     Time Period
                                                  3h          5h          7h           I   poststimulation, for the amount of
                                                                                           AL-EBD at the 3-hour measurement
                                                                                           was also higher in the experimental
                           Control        Experimental                                     group than in the control group (Fig.
                                                                                           1). At the present time, we have no
                           Group          Group
                                                                                           explanation for this phenomenon.

Flgure 2. Comparison of mean limb volumes specifcally from preinjection values             We hypothesize that SC-HVS increases
(b=P<.05) and between successive time intervals with control and experimental groups
combined (a=P< .05)(error bars represent standard deviation).
                                                                                           lymphatic uptake of AL-EBD by the
                                                                                           following mechanisms: (1) The move-
                                            lymphatics and entered the blood-              ment of charged proteins into the
the limb volume measurements, as
                                            stream via the thoracic duct, the              lymphatic channels is accentuated,
determined by ICC (2,1), was 92.
                                            amount of AL-EBD in the blood                  and (2) the contraction of lymphatic
Discussion                                  plasma was directly related to lym-            smooth muscle is enhanced. Alon and
                                            phatic uptake from the area.l6818 In           De Domenico's theory," as previously
Evans Blue Dye                              addition, recent studies using radiola-        discussed, states that the introduction
                                            beled albumin support the concept              of an electrical field into an area ex-
In both .the control and experimental       that tagged albumin returns to the             pedites the movement of charged
groups, preinjection values of AL-EBD       bloodstream via the lymphatics.7J9 If          proteins into the lymphatic channels.
were not significantly dflerent from        the injected AL-EBD had gone directly          Hargens and Zweifach13 studied the
postinjection values. This finding          into the bloodstream, it would have            contractility of bovine mesenteric
revealed that the AL-EBD was not            been detected in the postinjection             lymphatics and showed that when
inadvertently injected into the blood-      blood samples. The AL-EBD in the               lymph vessel volume was increased,
stream. This finding was important for      plasma, however, did not increase              the contractile rate of lymphatic
establishing the credibility of our         until at least 1 hour postinjection,           smooth muscles spontaneously in-
methods.                                    showing further support that the lym-          creased. Therefore, the hypothesized
                                            phatics are responsible for plasma             mechanism is that the SC-HVS facili-
The level of AL-EBD was higher in the       uptake.                                        tated lymph transport by augmenting
experimental group than in the con-                                                        the movement of AL-EBD into the
trol group at 1, 3, 5, and 7 hours          Both the control and experimental              rats' lymphatic vessels. The fluid
postinjection. The SC-HVS apparently        groups showed an increase in AL-EBD            drawn into the vessels by the oncotic
exerted a positive effect on movement       concentration in the plasma over the           force of the AL-EBD distended the
of the AL,-EBD from the interstitium        course of the experiment (Fig. 1). A           lumen of the lymphatic vessel and
into the bloodstream. Because the           rise in the AL-EBD as compared with            caused a subsequent increase in the
albumin was removed from the inter-         postinjection values, however, oc-             rate of lymphatic c ~ n t r a c t i o n . ~ ~
stitial space almost exclusively by the     curred at 1 hour postinjection in the

Physical Therapy/Volume 74, Number ll/November 1994                                                                         1044 / 53
The third mechanism by which lym-           lead to any differences in limb vol-       ing the time of stimulation, (3) con-
phatic flow is thought to increase is       ume between the control and experi-        tinuing the data collection for a
that SC-HVS enhances the contraction        mental groups (Fig. 2). This discrep-      longer time period, and (4) using a
of lymphatic smooth muscle indirectly       ancy between the increased uptake of       more sensitive device for measuring
via the autonomic nervous system. A         AL-EBD without a concurrent reduc-         limb volume.
previous study22 demonstrated that          tion in limb volume may be due to
under certain conditions (frequen-          the fact that the amounts of AL-EBD        Conclusion
cy=48-96 Hz, voltage=50 V, 0.3 milli-       taken up were measured with a spec-
seconds, 10 seconds' duration), lym-        trophotometer, which is approxi-           This study demonstrated a physiologi-
phatic nerves and smooth muscle             mately 10 times more sensitive than        cal mechanism by which SC-HVS may
could be directly stimulated to facili-     are plethysmographic measurements.         exert its effects on edema, because
tate the contractile rate. These electri-   In addition, although the 1 hour of        lymphatic uptake of AL-EBD was
cal stimulation settings are different      SC-HVS enhanced lymphatic flow, the        greater in the experimental group
from those used in our experiment.          time may not have been sufficient to       animals than in the control group
                                            create a significant volume change.        animals. A reduction in the rat limb
McGeown et a123found that stimula-          These results agree with those of          volume was not achieved in either the
tion of the sympathetic chain in-           Mohr et a1,12 who found no difference      experimental group or thc contrul
creased lymph flow and lymphatic            between control and SC-HVS-treated         group. Although SC-HVS may assist in
contraction frequency in sheep hind-        traumatized rat paws. Our results          edema reduction via the lymphatics,
limb lymphatics. Transmural stimula-        differed from those of other investiga-    further studies are needed to show
tion of the bovine mesenteric lym-          tionsSl0 in which SC-HVS was initi-        actual reductions in limb volume.
phatics directly excited the intramural     ated immediately following trauma o r
nerves of lymphatic smooth muscle.22        histamine injection. As demonstrated
In our study, however, we adminis-          by Reed,8 SC-HVS limits the perme-         References
tered electrical stimulation through        ability of capillaries to larger mole-     1 Heughan C, Niinikoski J, Hunt TIC Effect of
the skin, as utilized in physical ther-     cules, similar to albumin. In our          excessive infusion of saline solution on tissue
apy clinics. Electrical stimulation de-     study, labeled albumin was already in      oxygen transport. Sulg Gynecol Obsfet. 1972;
                                                                                       135257-260.
livered in this manner cannot directly      the interstitium prior to the electrical
                                                                                       2 Kline I, Miller A, Katz L. Cardiac lymph flow
stimulate lymph smooth muscle and           stimulation, which may have led to         impairment and myocardial fibrosis. Arch
autonomic nervous system fibers             the difference in results.                 Pathol. 1963;76:424433.
without activating skeletal motoneu-                                                   3 Harada S, Dannenberg A, Kajiki A, et al. In-
rons.I1 In addition, autonomic ner-         The fact that limb volume increased        flammatory mediators and modulators re-
                                                                                       leased in organ culture from rabbit skin le-
vous sytem fibers that innervate            over the course of the experiment in       sions produced in vivo by suIfur mustard, 11:
lymph smooth muscle share morpho-           both groups was possibly due to (1)        Evans blue dye experiments that determined
logical characteristics with pain fibers    an inadvertent inflammatory reaction       the rates of entry and turnover of serum pro-
                                                                                       tein in developing and healing lesions. Am J
(ie, small fiber diameter, unmyeli-         to the sterile injection procedure or      Pathol. 1985;121:2%38.
nated, low conduction velocity). If         (2) the oncotic force created by the       4 Olszewski W. On the pathomechanism of
stimulation were to elicit direct excita-   extremely high concentration of AL-        development of postsurgical lymphedema.
                                                                                       L ~ ~ P ~ 1973;6:35-51.
                                                                                                      O ~ O ~ .
tion of intramural lymphatic nerves,        EBD mixture in the interstitial space.
                                                                                       5 Ganong W. Review of Medical Physiology.
the pain would be intolerable to the        If the concentration of tagged albu-       Los Altos, Calif: Lange Medical Publications;
subjects and there would be un-             min had been the same as in plasma         1993.
wanted skeletal musde contractions.         (and therefore the oncotic force had       6 Henze E, Schelbert HR, Collins JD, et al.
                                                                                       Lymphoscintigraphy with Tc-99m-labeled dex-
Consequently, a hypothesized mecha-         been less), the SC-HVS may have led        tran. J Nucl Med. 1982;23:923-929,
nism by which AL-EBD uptake was             to a reduction in the limb volume          7 Ohtake E, Matsui K. Lymphoscintigraphy in
increased in this study is through          values.                                    patients with lymphedema: a new approach
transcutaneous stimulation of sensory                                                  using intradermal injections of technetium-
                                                                                       99m human serum albumin. Clin Nuc Med
neurons, which may have caused the          Based on the results of this study, we     1986;11:4744478.
autonomic nervous system to be stim-        believe that SC-HVS has the potential      8 Reed B. Effect of high voltage pulsed electri-
ulated. This stimulation may have led       to reduce edema. A 1-hour treatment,       cal stimulation o n microvascular permeability
to the release of adrenergic sub-           however, may not be sufficient in this     to plasma proteins: a possible mechanism to
                                                                                       minimizing edema. Phys T h m 1988;68:491-
stances, which are excitatory to lymph      model. Because a typical treatment         495.
smooth muscle cells and result in           protocol using SC-HVS for edema            9 Bettany JA, Fish DR, Mendel FC. Influence of
spontaneous propulsion of lymph.24          reduction is approximately 20 to 30        high voltage pulsed direct current on edema
                                                                                       formation following impact injury. Phys T h e
                                            minutes in duration, further clinical      1990;70:219-224.
Limb Volume                                 research on this modality is essential.    10 Taylor K, Fish DR, Mendel FC, Burton HW.
                                            Future studies should address (1)          Effect of single 30-minute treatment of high
The enhanced lymphatic drainage, as         creating a situation in which the inter-   voltage pulsed current on edema formation in
                                                                                       frog hind limbs. Pbys Ther. 1992;72:6348.
indicated by the increase in AL-EBD         stitial concentration of proteins would
concentration in the plasma, did not        be the same as in plasma, (2) increas-

                                                                   Physical Therapy / Volume 74, Number ll/November 1994
11 Alon G , De Domenico G. High Voltage           of the cat. Aust J Exp Biol Med Sci. 1950;28:     vine mesenteric lymphatics. Am J Physiol,
Stimulation:An Integrated Approach to Clini-      161-169.                                          1980;239:H8%H95.
cal Electrotherapy. Chattanooga, Tenn: Chatta-    1 7 Stearns S, Lee P. A rapid method for re-      22 Ohhashi T, McHale N, Roddie I, Thornbury
nooga Corp; 1987.                                 peated collection of blood from the tail vein     K. Electrical field stimulation as a method of
12 Mohr T, Akers T, Landry R. Effect of high      of rats. Lab Anim Sci. 1984;34:395-396.           stimulating nerve o r smooth muscles in iso-
voltage stimulation o n edema reduction in the    18 Courtice F, Simmonds W. Absorption of          lated bovine mesenteric lymphatics. PJIugers
rat hind limb. Phys Ther. 1987;67:1703-1707.      fluids from the pleural cavities of rabbits and   Arch. 1980;388:221-226.
13 Hargens A, Zweifach B. Contractile stimuli     cats.J Physiol (Lond). 1949;109:117-130.          23 McGeown JG, McHale NG, Thornbury KD.
in collectnng lymph vessels. A J Physiol. 1977;
                              m                   1 9 Stewart G, Gaunt JI, Croft DN, Browse NL.     The effect of electrical stimulation of the sym-
233:H57-.H65.                                     Isotope lymphography: a new method of in-         pathetic chain o n peripheral lymph flow in the
14 Mohr T, Akers T. Simplified plethysmo-         vestigating the role of the lymphatics in         anaesthetized sheep. J Physiol (Lond). 1987;
graphic technique. Biomed Sci Instrum. 1985;      chronic limb oedema. Br J Surg 1985;72:906        393:123-133.
21:l-3.                                           909.                                              24 McHale N, Roddie I, Thornbury K. Nervous
15 Cosgrove K, Alon G, Bell S, et al. The elec-   20 Reddy NP. Lymph circulation: physiology,       modulation of spontaneous contractions in
trical effect of two commonly used clinical       pharmacology, and biomechanics. Crit Rev          bovine mesenteric lymphatics. J Physiol
stimulators on traumatic edema in rats. Phys      Biomed Eng. 1988;14:45-89.                        (Lond). 1980;309:461472.
Ther. 199:!;72:227-233.                           21 Ohhashi T, Azuma T, Sakaguchi M. Active
16 Courtice F, Steinbeck A. The lymphatic         and passive mechanical characteristics of bo-
drainage of plasma from the peritoneal cavity




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