The resis­
tivity e of the vessel wall is then calculated according 
to the formula 
R.A 
n =--,where R = Z-R 
~ I " , 
and I is the thickness of the vessel wall, A the internal 
cross-sectional area of the glass tube (1.3267 mm2), R. 
the resistance of the vessel wall and R, the resistance 
of the column of saline solution between the measuring 
electrodes. R. is determined by subtraction of R, from 
Z, the total resistance . The measurementS of the saline 
solutions were made at temperatu res ranging from 
23•c to body temperature, yielding resistiviry values of 
0.70 to 0.62 ohm-mat I to 10kHz, which is in good 
agreement with earlier values from the literature (8, 
22). Fig. XII: 12 shows amplitude curves at different 
frequencies for (a) saline solution, (b) fresh vein and 
(c) fresh anerial walls in situ. An example (d) is also I k lOOk IM 
Frequency(Hzl 
given of the effect on resistivity of an arterial wall in 
situ after the production of a visible local ischaemic 
tissue injury. The amplitude curves in Fig. XII: 12 show a rela­
tively rapid fall around 10 kHz, which is interpreted as 
caused by the lowering of the inductive resistance by 
high frequencies. Below 10 kHz lhe prominence of 
this effect decreases . The resistivities of the femoral arteries and veins in 
20 measurements of the 5 dogs were compared with 
the resistivity of 0.9% NaCl (0.62 ohm-m at 23•C). The immediate determinations of resistivities of the 
vessel walls, before obvious damage was produced by 
the glass tubes, showed values for the vein varying 
between 60 to 116 ohm-m at I kHz and 20 to 79 ohm­
m at 10 kHz and 37•c. For the artery, values of 
81-121 ohm-m were obtained at I kHz and 4S-67 
ohm-m at 10 kHz and 37°C. The variations depended partly on the difficulties of 
measuring the thickness of the vessel walls, which 
varied between 0.03-0.05 mm for the vein and 
0.10-0.15 mm for the artery. Two other factors were 
the injury necessitated by the dissection of the vessels 
free from surrounding tissues, which may have partly 
damaged the vasa vasorum, and the direct damage by 
the glass tubes. Values of resistivity decreased at the 
end of each examination . For example, examination of 
an artery which had a directly visible ischaemic region 
around the glass tube gave 36 to 54 ohm-m at I kHz 
and 8.0 to ll.5 ohm-mat 10kHz {Fig. XII: 12d). The results of these examinations indicate clearly 
that the resistivity of femoral arteries and veins is of an 
Biologicall y closed electric circuits 127 Applied voltage 
50 mil 
SBmv~ .. -...,11-Applied voltage 
ISOmV 
Fig. Xll: 13. In vivo de<ermination of resiSiivity to DC 
pulses across the wall of a dog's femoral artery. Method of 
Burger and van Milaan: amplitudes (11A) and potential dif· 
fcrcnccs (mV)when SO and ISO mV pulses were applied 
(pulse duration: O.S second). The distortions in the tracings 
are C'dused by polarization of the electrodes. Initial deflec. lions were used to obtain a relative measure of resistivity. order at least 100 to ISO times higher than the 
resistivity of saline solution, which in turn is known to 
have roughly the same order of resistivity as blood 
plasma, serum and interstitial fluid. b) Pulsed direct currem 
Resistivity studies with direct current are of consider· 
able interest, as this type of current represents electric 
transports in vivo. Attempts were therefore made to 
study resistivity of blood vessels with a technique 
developed by Burger and van Milaan (8). In this way, 
information on the resistance of walls of large vessels 
in comparison to resistance of the intravascular con· 
ducting medium, the plasma, should be possible to 
obtain. As in determinations of resistivity with alternating 
current, many sources of error can interfere in deter· 
minations of resistivity with direct current. It is evi· 
dent that an application of DC pulses will ionize the 
test material and change its relative conductivity dur· 
ing each pulse. The applied potential will furthermore 
produce ionic separations, providing electromotive 
forces in the opposite direction. This effect means that 
the test current builds up a galvanic potential. When potential difference is constant within cer· 
tain limits, the degree of i(mization is a dynamic event 
which initially increases exponentially the actual flow 
of current per unit time. This observation is well 
known since julius Tafel (72). On prolonged applica· 
tion of direct current, different counteracting reactions 
will contribute to decelerate the current. Moreover, 
the same technical difficulties are encountered in both 
DC and AC determinatio ns of resistivity of a vessel 
128 Biologically closed electric circuits wall, i.e., geometric measurements of specimens and 
avoidance of injury to tissue. These experiments were performed in five dogs, 
using the same rype of preparation of femoral vessels 
and electrodes in glass tubes as was employed in the 
determinatio ns of resistivity with alternating currents. A series of 10 DC pulses (0 .. 5-1.0 sec duration each) 
was applied over 25, 50, 100 and ISO mV through the 
vessel wall in one direction and then in the opposite 
direction. Polarizati on caused a dis·tortion of the measured 
deflections of potential. It is therefore necessary to 
define how the measuremen ts were obtained and the 
results analyzed. Fig. XII: 13 shows tracings of measured currents 
and potential differences through the vessel wall dur· 
ing application of 50 and !50 m V potential pulses over 
the current-supplying electrodes . The distortions of 
these potentiAls arc in principle eaSy to undetStand, 
despite the complicated nature of the underlying ki­
netic events. For the actual measurements the high initial potcn· 
tial and peaks of current have been used. In the well 
known formula 
I R=-·o A -
R = resistance, Q = specific resistance, I = length, 
A = cross-sectional area. R is determined by the 
simultaneous measurements of voltage drop and cur· 
rent flow through the specimen. In these experime nts (as well as in determinations 
with alternating current) no clear difference could be 
observed when current was passed from outside to 
inside or vice versa. Table XII: 5 presents the actual measureme nts and 
calculated resistivities of a daog's femoral artery in siru. The resistivity of femoral veins was of the same 
order of magnitude as that of the arteries (resistivity of 
0.9% NaCI gave values of0.70 ohm·m at n•c). The 
measured resistances to pulses of direct current 
through the walls of the femoral artery and vein were 
200 to 280 times higher in these experiments than in 
those through 0.9% NaCI solution. Table XII: S. Resistivity de~trminatio11s of femoral artery of dog 
by means of direct CU11'ent pulses 
Applied Obtained Vcs~ l wall Vessel wall 
voltage Current voltage resistance resistivity 
(mV) (I<A) (mV) (l<Q) (Qm) 
25 0.15 2.59 5.93 143 
50 0.30 5.79 7.96 192 
100 0.67 13.21 8.38 202 
ISO 0.92 18.06 8.29 200 C. Observations of 
a preferentia l electric 
pathway in vessels and 
tissues 
The experiments on resistivity of "large" vessel walls 
in relation to the relatively low resistivity of plasma 
and interstitial IUuid indicate the possibility that elec­
trochemical gradients in tissue may be levelled over 
the proposed VICC (vascular-interstitial closed cir­
cuit). If this hypothesis is correct, the vascular system 
must be acknowledged to possess a previously unre­
cognized function: the U.rge (i.e., macroscopic ) vessels 
act as electrically .conducting, insulated cables. The vessel 
walls thus insulate one branch of the conducting me­
dia, the plasma. from its surroundings , except at its 
transcapillary junctions with the other branch, the 
interstitial fluid. This hypothesis of a conducting 
VICC will now be tested in different ways. Consider an electric direct current, passing from the 
interior of a vessel to a distant region of tissue. After a 
sufficient quanti'ly of current has flowed, certain mor­
phologic (and presumably functional ) changes should 
develop in the preferential pathways for the current. Such changes appeared to be the actual case in experi-
Fig. XII: 14. O.Om<:>nstration of preferential pathway of cur­
rent from the lumen of the aorta to the vasa vasorum in a 
dog, indicating electrical insulating properties of the aortic 
walls. Direct current (I 700 coulombs at 10 volts) wa.< passed 
between a.n inuaaortic ca[hode {stainless steel wire, extend· 
ing 10 em beyond rhe t.ip of a plastic catheter) and platinum 
anode electrode in the shoulder muscles. (a) External surface 
o{ aorta. Oedema and brown-black discolouration arc seen in 
the adventitia in an area approximately 3 x2 em. Microscopi­
cally, the numerous vasa vasorum in this region were dark 
a 
2cm ments in which the changes were examined by direct 
visual inspection, in vivo microscopy and histolo­
gic techniques. These experimems will now be pre­
sented. l. Cathodic field 
A catheter was passed from a femoral vein or artery 
into a pulmonary artery or the aorta, respectively , of 
each of 15 anaesthetized dogs. Through the catheter an 
aneriographic guidewire of stainless steel was passed, 
and its tip positioned 5 t.o 10 em beyond the tip of the 
catheter. This guidewire was used as a cathode. A 
platinum string was used as an anode and placed 
percutaneously either in the lung tissue ~ em from 
the pulmonary arterial cathode, or in the shoulder 
muscles or in an intraabdominal organ, 10 to 15 em 
from the cathode in the aorta or inferior vena cava. Teo volts were applied between the electrodes and the 
quantity of current was measured in coulombs. Insu­
lating properties of the aortic wall could be demon­
strated at I 0 volt potemial difference with doses of 
current as large as I 700 coulombs. After the animal was sacrificed, the external wall of 
the aorta (Fig. XII: 14a) was found to be oedematous 
and brown-blac k within a 3 x 2 em area. The sped-
brown. (b) Inside the aorta, opened lengthwise . The brown 
vasa vasorum were found to be a branchjng nerwork of twigs 
all supplied by a single dark brown artery (arrow) arising 
from the lumen of the aorta. The intraaortic cathode, which 
had been lightly touching the intima, caused a small ridge 
(white arrows) of focal oedema. This ridge passes close to the 
dark artery, which seems to have-served as a preferential 
pathway for the electric current. The media between the in­
jured intima and adventitia was not substantially injured (see 
Fig. XII: 16a). Biologically closed electric circuits 129 men was then opened by a longitudinal incision (Fig. Xll: 14b). It showed only minimal injury macroscopi ­
eally as a small ridge of oedema where the guidewire 
cathOde had been in contact with the aonicwaU (white 
arrows). This fmding is a clear discrepancy from the 
widespread oedema and diseolouration of the external 
aortic wall. A local dark spot (arrow) was also found, 
rcprc:scnting the orifice of an artery. By dis>e<:tiun , the 
anery was followed as a dark channel in a cranial 
direction to the discoloured section of the aona, where 
.it ramified into the dark brown vasa vasorum. In this 
case, the relatively minor intimal injuries at the site of 
the cathode an.d the widespread changes in the distti­
tltltion area of vasa vasorum arising from a single 
artery appear to indicate a preferential pathway in this 
vessel for the flow of electric current. A local, marked injury to the aortic wall can, on the 
other hand, also be provoked (Fig. XII: 15). In this 
case the stainless steel cathode was pressed firmly 
against the inside of the aortic wall while 500 coulombs 
at 10 volts potential difference were passed between 
130 Biologically closed electric circuits Fig. XII: IS. Serious injury 
provoked by direct current 
to <he aona in a dog. 500 
coulombs at 10 volts were 
passed between <he calhodc, 
pressed against <he aortic in­
tima, and the anode in the 
shoulder muscles. Alllayers 
of the aorta were necrotic 
(sec Fig. xn: 16b). the electrodes (intraaonic cathode and a platinum an­
ode in the prostate gland of each of 3 dogs). Externally 
the aorta showed no discolouration or obvious oedema. Arteries arising locally from the aorta showed no disco­
louration. Histologi c sections of cathodic injuries tO the aorta 
are illustrated in Fig. XII: 16. Fig. XII: 16a shows the 
left put of the aurti<: spcdmen in Fig. XII: 14 b. Co­
agulation injury and oedema were found mainly in the 
outer part of the media and in the adventitia. Foci of 
dark amorphous material were interpreted as repre­
senting destruction of blood and walls of the vasa 
vasorum. Fig. XII: 16 b shows the severe cathodic in­
jury seen in Fig. XII: IS of the intima (left), media and 
adventiti a at the site of direct contact of the electrode 
with the aortic wall. Thrombosis was not seen at the metal surface of the 
cathode. 1\s an electron emittor, the cathode does not 
corrode. Serious damage to the vessel wall appears to 
be avoidable if the electrode is kept away from the 
intimal surface. In the case illustrated in Fig. XII: 14, 
Fig. Xll: /6. Injuries by di­
rect current to the aortic 
wall: histologic sections. (a) Macroscopic iniurios local­
ized mainly in <he peripheral 
layers of <he aorta (left pan 
of Fig. XII: 14b). Foci of 
destruction of aortic wall tis· 
sue are seen (lower right) in 
the outer pan of the media 
and in the ad\•cntitia, which 
were oedematou s. In the in­
jured part of <he wall, foci of 
Uark atuur1Jhuu s mau:dal 
arc also present, interpreted 
as necrotic blood from <he 
vasa vasorum. b corresponds to <he injury 
shown in Fig. XII: IS. In­
tima to <he left. Marked co­
agulation necrosis exfends 
lhrough all the layers of the 
aortic wall. The specimen 
ruptured easily during histo­
logic preparation. Scllle 
same in each view. the current produced only minor injuries to the intima 
close to the electrode. In all the dogs, the experiments revealed that it was 
possible to pass direct current selectively over veins 
and arteries. This fmding was possible with vessels of 
a calibre down to less than one mm in width and 
voltages up to 10 volts. As potential difference in· 
creases, the resistive properties of the vessel walls 
become increasingly critical. Although little detailed 
information has yet been obtained on these importam 
correlations , at 40 volts electrode potential the pre­
requisites for selective transport in tissue seem, how­
ever, to he suspended (Fig. XVII: 14). The experiments of this section suggest that veins 
and arteries can serve as selective pathways for electric 
current, even when generated at energies well above 
wbat is commonly encountered in biology. 2. Anodic field 
As destruction of tissue is easily produced by direct 
current in the anodic region, the studies of morpholo­
gic changes were petforrned mainly under direct mi­
croscopic observation of dog mesentery in vivo. The 
abdomen of each of 5 anaesthetized dogs was opened 
and several different sections of mesemery were used. These experiments revealed that a preferential path­
way for the current could he recognized in macroscopi­
cally visible small arteries and veins even at electrode 
potential differences up to 10 volls. In these experi­
ments, one electrode (anode) was placed gently against 
the mesentery and one electrode (cathode) was placed 
in the aorta. The selective pathway for the electric 
current will he illustrated in the following way: 
In Fig. XII: 17, th.e edge of a 4x5 mm platinum 
electrode is seen to the lower left placed directly on a 
dog's mesentery . A constricted or thrombosed vein 
(arrow) is seen in Fig XII: 17 a before the application 
of one volt herween the electrodes. The adjacent, 
slightly smaller vessel is the corresponding artery. Upon application of one voll herween the electrodes , 
initial current of 1.8 microamperes passed through the 
circuit. Small arterial branches soon developed many 
regional contractions , the flow of blood became inter­
rupted and thrombi formed around the anodic elec­
trode against the mesentery. Diapedetic bleedings also 
appeared in multiple small areas. After 75 minutes about 0.08 coulombs bad passed 
hetwce.n the electrodes. The blood in the large artery 
thrombosed and became brown. The blood in the 
corresponding large vein flowed as before, retaining 
normal colour (Fig. XII: 17 b). The continued flow in the large vein could, of 
course, depend on supply of fresh blood from nonoc· 
eluded arterial branches and a washing out of venous Fig. XII: 17. Intraarterial effectSofthe passage of direct cur­
rent between electrodes in the aorta and mesentery of a dog. The aortic electrode is electronegath •e (cathodic). The me­
senteric electrode is electropositive (anodic) and visible in 
the lower left corners of the illustrations. (a) Before passage 
of current. The large vessel is a vein and the adjacent vessel 
an artery. Note that a small venous branch is blocked just 
before entering the large vein (arrow). (b) After passage of 
current (one voh potential difference ). Initial flow of current 
was 1.8 microamperes. Small arterial branches within a few 
minutes showed multiple rontract.ions , diapedetic bleedings 
and formation of thrombi. After 75 minutes about 0.08 cou­
lombs had passed and the large artery thrombosed and 
turned brov.n. Eventually the corresponding vein showed 
some discolouration (after about 3 hours). The venous 
branch, still blocked (arrow), rC>·eals no discolouration or 
other change. Consequentl y, the electric current can be in­
ferred to flow preferentially through the artery, which there­
by constitutes a major channel of communi cation between 
the electrodes . thrombocmboli. This explanation , however, appears 
unlikely because the blocked venous blood vessel 
branch (arrow) appeared unchanged even as the blood 
in the large artery turned brown. Blood was also flow­
ing through the vein at the site where it crossed under 
the artery and even where it was positioned between 
the anode and the artery. After about 3 hours, venous 
Biologically closed electric circuits 131 0 + 
\ 
~lood 
Fig. XII: 18. Demonstration of the same type of closed cir­
cuit reactions at rhe splenic surfa:e of an anaesthetized dog 
(Figs. o-c) as at the surface of an interpositloned electrode 
material (platinum foil) in the circuit of an in vitro experi· 
ment (Figs. d, e). (a) Direct current is passed in vivo be­
tween one platinum electrode (I) in the inferior vena cava of 
a dog and one electrode (II) in contact with KCI-agar-litmus 
in a glass tube cylinder resting against the exposed spleen. A 
glass tube cylinder with KCI-agar-litmus (Ill) without an 
electrode is used to check sponta.1eous diffusion at the con­
tact of the salt bridge and the organ. (b) Three specimens of 
1h~ cylindcn. ~re . (hown with electrode attachment~ tn thP 
right, t.'Qnlacl with spleen on left. Right speci~n : electrode 11 
anodic, after 10 volts and S coulombs. The agar cylinder 
shows a partially chlorine-bleached acid (red) reaction adja­
cent to the former site of the electrode and an alkaline (blue) 
reaction where the cylinder rested against the spleen. Middk 
tp<dnren: electrode II cathodic, after 10 volts and S cou­
lombs. Alkaline reaction is obtained adjacent to electrode II. Left spednren: no current, shows only some blood from the 
surface of the spleen. (c) The experiment performed as 
above, except with approximately 2S coulombs at 20 volts. Middle specimen: electrode II cathodic. A strong alkaline re­
action is obtained adjacent to the elect.rode. A thin, bright 
red, acidic reaction is seen where the cylinder rested against 
the splenic surface. Right specimen: electrode II anodic. Bleaching and acidity are evident at the anode. The site of 
contact with the spleen is alkaline. Left specimen: no currenc, 
no litmus reaction. (d, e) Illustration of behaviour of a bipo­
lar electrode (platinum foil) before (d) and after (e)applica­
tions of current berween platinum electrodes. The same: 
types of surfa~ reactions , depending on direction of current, 
are created at the surfaces of the foil as at the surface of the 
spleen. 132 Biologically closed electric circuits branches also thrombosed close to the electrode, but 
the tendency was clear for a considerab ly earlier 
brownish discolouration of the blood in the anery 
between the tissue electrode and tbe aortic electrode. Findings were similar in the other 4 dogs. These experiments, like those of the previous sec­
tion, suggest that electric current flows selectively in 
the blood vessel between an intravascular elemode 
and the region of an extravascular electrode. This 
selective electric transport in vessels was observed 
even when potential differences were as great as 10 
volts between the electrodes and the vessel was only 
one nun in diameter. The observations in the cathodic and the anodic 
areas each support the postulated principle that •1essels 
function as electrically insulated cables with internal 
conducting properties . D. Structuring of interfaces 
in BCEC systems: 
development of membranes 
and organ capsules 
In tissue between metal electrodes , closed circuit elec­
tric transports are accompanied by polarization phe­
nomena with deposition of material on electrode sur­
faces. For example, when direct current is applied 
between platinum electrodes in tissue, several kinds of 
material and structures can be identified at the sur­
faces of the electrodes. With this background, fibrous 
membrane s, including organ capsules, basement mem-
Fig. XII: !9. In vitro electrophoresis of fresh dog liver tissue 
in the mid· part of a glass tube and KCI-agar-litmus on both 
sides of the tissue sample. Electrodes at the open ends of the 
glass tube. (a) Before direct current was applied, (b) after 20 
volts, 0.35 coulombs, alkaline (left) and acidic (right) elec­
trode reactions were obrained. To the right of the specimen 
the reaction was alkaline, to the left acidic. These reactions 
at the surfaces of a specimen are less obvious than the corre­
sponding reactions in vivo illustrated in Fig. XII: 18. 
a 
--branes and cell membranes should be looked at anew. Filn'ous membranes can actually be produced easily not 
only at electrode surfaces but also between elecrrodes in 
tissue, as will be shown in Chapter XVI. The principle 
of existence of a biologic equivalent to an electrode · 
electrolyte interface will now be presented. Reactions at interfaces in BCEC systems can be 
anticipated to lead to a large variety of structural 
developments. To test the hypothesis that the develop­
ment of fibrous membranes, e.g., intraabdominal or­
gan capsules, may be a BCEC-induced phenomenon, 
the following experiment was performed in vivo in 
three dogs. A platinum electrode (I) was inserted via a catheter 
from a femoral vein into the inferior vena cava of the 
anaesthetized animal (Fig. XII: 18). Another platinum 
electrode (11), shaped like a small disc, was placed in a 
glass tube (8 em long and 0.8 em wide) filled one-third 
full with a mixture of 0.9% KCI+l% agar-litmus. The abdomen of the animal was opened so that the tip 
of the agar-salt bridge of electrode II could be placed 
against the surface of the liver, the spleen or a kidney. Fig. XII: 18 a shows the exposed surface of the spleen 
with electrode II to the left and a "blank" bridge Ill to 
the right, witl)out a platinum electrode. This salt 
bridge was used to check possible SDOntaneous diffu­
sion at the contact between the bridge and organ 
surface. Current was then led between electrode II in 
contact with the test organ and electrode I in the 
inferior vena cava. Potential differences between 2 to 
20 volts were tested between 10 to 30 minutes, each 
test with new salt bridges. Fig. XII: 18 b shows the colour changes of KCI­
Iitmus-agar cylinders after two experiments each with 
10 volts potential difference applied for 15 minutes. To the right, after the electrode bad been anodic ( + ), 
chlorine has partly bleached the otherwise acidic red 
electrode end of the cylinder. Its other end, which bad 
been in contact with the splenic surface, shows a blue 
alkaline reaction. The middle cylinder shows this ex­
periment after the electrode had been cathodic (-). The electrode end of the cylinder shows an alkaline 
reaction. The left salt bridge showed only some con­
tamination of blood on the contact surface against the 
organ, but no litmus reaction. The experiment s were then repeated with 20 volts 
potential between the electrode in the inferior vena 
cava and the electrode with a salt bridge interposi­
tioned against the splenic surface. The result is shown 
in Fig. XII: 18c. The right cylinder shows in principle 
the same reactions as the right cylinder in Fig. b. The 
middle cylinder, however, shows an additional inter­
esting reaction. The alkalinity at the cathode is accom­
panied by a bright, red zone of acidity, corresponding 
to the site of contact with the splenic surface. These 
fmdings were consistent in the three dogs studied, with application of the electrode bridges at different 
sites on the hepatic and splenic surfaces. These studies also showed a clear tendency for an 
alkaline reaction of the salt bridge to be more easily 
produced at the organ surface than an acidic reaction. Furthermore , it was found that when electrode II was 
made anodic, the organ surface under the salt bridge 
shrank and became dry. When the electrode was made 
cathodic, a profuse flow of tissue water appeared 
around the bridge. These findings appear to represent 
an expression of electroosmotic water transport. For comparison , Fig. XII: 18 d, e illustrates the de­
velopment of redox reactions at the surface of an 
electron conductor , a platinum foil, positioned in the 
mid-part of a KCI-litmus agar cylinder when current is 
led through the cylinder between two platinum elec­
trodes at either end. The same types of surface reac­
tions are created on the inserted foil as were created on 
the surface of the spleen. Electrophoretic experiments were also performed on 
fresh specimens of dog liver. Thus, Fig. Xll: J9a 
shows a liver specimen in the middle part of a glass 
tube with KCI-agar-litmus bridges and platinum elec­
trodes before treatment. After application of 20 volts 
between the electrodes (Fig. XII: 19 b), blue and red 
colouring developed adjacent to the platinum cathode 
and anode. Corresponding to the interface between 
specimen and salt bridge, blue colouring developed on 
the anodic side and red on the cathodic side. These reactions adjacent to biologic material should 
not be accepted without reservation as proofs of the 
existence of analogues to electrode reactions at the 
surfaces of various organs. Alkaline and acid com­
pounds may, for example, have been produced by 
tissue metabolism. Under the influence of the applied 
electric potential between the electrodes, such com­
pounds may have separated electrophoretically and 
therefore given the observed litmus reactions. It 
should be noted that these reactions were found to be 
more pronounced in vivo than in vitro. This finding is 
remarkab le in that the in vivo experiments should be 
influenced by the buffering capacity and circulation of 
the tissue fluids. The experiments do indicate, however, that inter­
phase transports may take place within a closed elec­
tric circuit, including the surface of an organ. If bio­
logically closed electric circuits become accepted as a 
biologic mechanism , the development of several im­
portant structural components , e.g., organ capsules 
and perhaps also basemem membranes and other fi­
brous membranes , may become explained. Let us anticipate for a moment that the functional 
activities of an organ such as the liver (Chapter VI, 
Fig. 19) cause it to polarize against a nearby structure, 
such as the abdominal wall. The abdominal muscles 
also produce metabolic polarization which shou ld flue-
Biologically closed electric circuits 133 potential 
between polarizing 
organs or structures 
Fig. XII: 20. Suggested principle for development of bio­
logical mcmbrnncs as organ capsules. Metabolic activities in 
nearby tissues or between adjacent organs create differences 
of potential, giving rise to a driving electromotive force 
through a biologically closed electric circuit (BCEC). Asyn· 
chronous times of polarization of adjacent tissues or organs 
ruate in intensity, asynchronously in relation to the 
polarizations of other organs, including the liver. If 
such structural units are joined in a closed electric 
circuit, an electrophoretic interphase deposition of ma­
terial from the organs and the fluids positioned be­
tween the structures should take place. This deposi· 
tion is illustrated schematica lly in Fig. XII: 20. The 
asynchronicity of the metabolic polarizations of two 
adjacent organs, such as the liver and the abdominal 
wall, accounts for a two-way current. A kind of ebb 
and flow effect on material is thereby induced, which 
might be the prerequisite for a complete and suitable 
composition of the membranes of both organs. As 
material accumulates at polarizing organ surfaces or 
other structural interfaces, the polarizing current will 
diminish and eventually cease. Consequently, the 
thicknt'SS of the membranes should be determined by 
the driving force of the metabolic polarizations. An "evetyday observation" which may partly sup­
port this theory is the development of a fibrous capsule 
around cardiac pacemaker devices in the subcutis and 
around intracardiac pacemaker electrodes. In these 
instances part of the closed circuit is the wiring of the 
device and part is the electrically conducting material 
in the tissues. When the fibrous material has obtained 
a certain thickness, successful function of the pace-
134 Biologically closed electric circuits account for ebb and flow transpOrt. Materials then become 
depOsited against electrode-equivalent surfaces of the circuit, 
or are deposited by trapping and surface adsorPtion in adja· 
cent tissue matrices. When the membrane has obtained a 
certain thickness , the polarizing current may be anticipated 
to cease .. 
maker requires either the driving potential difference 
to be increased or one has to replace the pacemaker 
and the inrracardiac electrode. Circular membrane -like structures will also be 
shown (Chapter XVI) to develop from interPhase de­
position of material between "A" and "B" zones 
around polarizing breast cancers. Funhcrmore, it will 
be seen that such interphase structures can be pro­
duced by closed circuit transports between electrodes 
and against electrode surfaces in tissue. Mixed anodic 
and cathodic fibrous material produced in this way 
adjacent to platinum electrodes in tissue will be seen to 
be strikingly similar histologically to fibrous mem­
branes which develop endogenously. It is important to 
point out, however, that mechanisms of adsorption of 
material to the surfaces of tissue matrices must be 
involved in these processes. E. Capillaries and VICC 
1. Biologic transfer of electrons 
Long distance transport of material in biological sys­
tems is currently regarded as a function of mechanical 
transport mechanisms and diffusion. Long distance transport of electric energy can be induced over cables 
by an electric sou.rce witb electrodes inserted into 
living tissue or an electrolyte. The electrode surfaces 
and adjacent electrolyte then serve as conversion sites 
between electronic and ionic electric charges. How 
does this picture correspond to tbe possibilities of a 
BCEC system without obvious electrode surfaces? First, there is no disagreement about the fact tbat 
short distance electron transfer takes place between 
molecules in biology as an expression of redox reac­
tions. But the processes themselves are remarkable 
because most organic molecules behave as dielectrics. Bockris and Dratic (5) discussed the possibility of 
electronic charge transfer by rotation of such mole­
cules, but rejected tbe possibility. Instead tbey re­
ferred to the fact that large protein and enzyme mole­
cules are semiconductors, as pointed out by Szent­
Gyorgyi (71). The high activation energy in semicon­
duction seemed, however, to make this mechanism 
unlikely until it was found that the protein cytochrome 
oxidase could give kinetic evidence of semiconduction 
(10, II, 12). The activation energy of semiconduction 
of this enzyme molecule was also found by Straub (69) 
to be approximate ly equal to the activation energy of 
tbe enzymatic reaction catalyzed by the molecule . It 
bas also been shown by Trukhan (75) that electron 
conduction within molecules may be considerably 
higher than conduction across interfaces between par­
ticles. This effect is explained as electronic tunneling 
or a microwave Hall effect on mobility of electrons 
(54). As pointed out by Bockris and Orotic (5), a signifi­
cant mobility of electrons can be understood in the 
case of many enzymes having conjugated double bonds 
I I I I 
(-<:=C-<:=C -). The resonance effect of excited 
electrons then produces huge orbitals along the chain. In protein molecules without long conjugated dou­
ble bonds but with cross-linked polypeptide bonds, 
0 H 
II I -e-N-
gives the following form of the chain 
HHOHHOHHOHHO 
I I II I I II I I II I I II -N-c-c-N-c-c-N-c-c-N-c-c-
1 I I I 
R, R2 R3 R. 
The orderly repetition of the peptide bond should then 
be able to produce an electronic conduction band, as 
in ordinary semiconducto r crystals. Anotber possibility is that the close connectio n be­
tween tbe electron-donat ing NH and electron-accept· 
ing CO groups may permit electron tunneling through 
the peptide chain ( 11 ). Different other models have also been suggested ( 4, 
23) which indicate the existence of different electron 
transport systems in biologic material involving intra­
and intermolecular transfer of charges. Rosenberg 
(54), for example, has shown that wet crystalline hae­
moglobin is an electron conductor. The reason for referring to the works above should 
be evident: the function of a BCEC, such as tbe VICC, 
will require an electrode-electrolyte analogue allowing 
regional transfer of electrons. Only in this way can tbe 
ionic conduction, transport and recombinations of a 
BCEC be activated and lead to purposeful biologic 
structuring and function. Experimental studies of electron exchange systems 
between molecules represent one important approach 
to tbese problems. Another approach may be to look 
for possible re~ction sites in organized living systems. We are here particularly interested in the VICC. Where should redox-steps most likely be located in 
tbis circuit? The answer would probably be; some­
where in the capillary wall, as tbis serves as an inter­
mediate partition for the exchange of material between 
blood and tissue. 2. The capillary wall 
Gases, water, ions, and compounds of low molecular 
weight pass over the capillary membranes by diffu­
sion, filtration and osmosis, according to prevailing 
opinions (24, 25). In tbese transports , transmural hy· 
drostatic pressure differences, colloid osmotic pres­
sures and concentration differences across the mem­
branes play important roles. The endothelial cells 
themselves are permeable for lipophilic substances 
such as gases, but not for hydrophilic substances (53). The latter pass through the capillary walls through 
interepithelial spaces (82), called stomata, pores or 
leaky junctions. Anotber type of transport is called 
micropinocytos is or cytopempsis (29), in which small 
vesicles transport material tbrough the endothelial 
cells (47). Morphologi c studies and studies with radio­
active tracers have led 10 the hypothesis that the vesicles 
may to some extent transport proteins and colloidal 
particles across the endothelium (7, 47). The function 
of the vesicles is, on the whole, not very well under­
stood. Their function must also be distinguished from 
tbat of transport through the channels of the "leaky 
junctions" (82). Before we discuss an additional possi­
ble mechanism, electTogenic closed circuit transpon 
over the capillary membrane , a short survey of the 
morphology of capillaries is necessary. A lengthwise section of a capillary is illustrated 
schematica lly in Fig. XII: 21 a. It contains six layers 
(13). On tbe outside is the basement membrane. Be­
tween tbe basement membrane and the periphety of an 
endothelial cell is the so-called exoendothe lial space. Biologically closed electric circuits 135 a 
Leaky junction Mobile portion Plasmatic 
----J,~~---_-_-...;;lin;;.:. ;.m:;.o:;;:;b ;. ;i 1-r:e..:l.-a....-e-~r.....-:z:. ;o :;.n;,;e-. __ 
0 Terminal 
b 
Fig. Xll: 21. A capillary wall: schematic presentation, (a) 
lengthwise , and (b)crosswisc sections. Six layers are recog· 
nized: basement membrane: , exoendothclial space, endotheli · 
al cells (EC}, endothelia l fibrin film, immobile and mobile 
layers of the plasmatic zone. Adhesion lines (AL} between 
adjoining endothelial cells form leaky junctions for water, 
electrolytes and large molecules and probably also for blood 
cells in diapedetic transport. Additional mechanisms of 
The endothelial cell has an endothelial fibrin film, 
which bordrers the lumen of the vessel. Next to the 
fibrin film is the plasmatic zone containing a layer of 
more or less immobile plasma and finally a mobile 
plasmatic portion (50). In the walls of capillaires the endothelial cells make 
contact only at specific adhesion lines (82). According 
to this view, the nonadherent parts of adjacent epithe­
lial walls form "leaky junctions". Such junctions (sto­
mata), seen in a plane through the adhesion lines are 
shown in Fi.g. XII: 21 b. Tortuous distensible channels 
or clefts are formed in this way. Peroxidase, with a 
136 Biologically closed electric circuits EC 
trans-port include diffusion, filtration and pinocyto-
sis (via vesicles) through the endothelial cell. The pericyte 
(see Fig. XU: 22) makes contact with some of the endothelial 
cells by ramificatio ns of primary· and secondary (tertninal} 
processes. The endothelial cells measure in thickness about 
I pm. The thickness of the basement membrane is about 600 
A, which in actuality is much less than as depicted in the 
f~gure . molecular diameter of 20 A, has been found to pass 
through these channels, of a presumed cylindrical dia­
meter of 90 A (82). Even under normal conditions, 
white blood cells pass by diapedesis through stomata 
without rupturing their walls (35). Diapedesis takes 
place by means of pseudopods. Part of the leukocyte 
moves as an extension through a stoma, which widens. The content of the blood cell then "flows" successively 
through the stoma into the surrounding tissue. Trans­
capillary transport of red blood cells also takes place 
by diapedesis, mainly during venous stasis (35). An interesting component of capillaries is the peri-a 
Fig. X/I: 22. (a) The peri­
cyte (after K. W. Zimmer­
mann, 1923) is a ceJllocated 
at scanered sites adjacent 
to capillary walls. (b) It 
usually gives off two pri­
mary processes along the 
vessels. Secondary pro· 
cesscs are arranged per· 
pendicularly to the length 
of the capillary and make 
contact at cenain points 
with endothelial cells. The 
pccicytes are be-lieved to be 
part of the mechanism of 
contraction of the capillar­
ies. Their distribution in 
intervals along the capillar­
ies suggests that segmenta l 
capillary contractions arc 
possible. Pericytes are also 
thought to possess some 
phagocytic activiry. Capillary wall ~rieyte Primary precast ':;r.rx, K ~-"" ,-\. : 
Nucleus of endothelia l cell 
(c) The capillaries are also 
pro\rided with a delicate 
network of nerve fibres, 
wbkh make contact with 
the periphery of the capil­
lary walls. c 
cyte, a cell known since 1873 (57). Its shape is de­
scribed as an ellipsoid, usually with two main pro­
cesses (Fig. XII: 22a) (83). These processes follow the 
capillary in its longitudinal directions, giving off sec­
ondary processes in a crosswise direction around the 
vessels (Fig. XU: 22b). The secondary processes make 
contact with the endothelial cells at certain points (78). The processes of pericytes are also described (35) to 
appear as intermediate forms of muscle fibres of veins 
and arteries. Pericytes are described as involved in the mecha­
nism of contraction of arterioles, venules and capillar­
ies (36, 70, 76, 77). They may also have some phagocy­
tic functions ( 40). Pericytes have now been found in all 
capillaries of mammals (78). They are remarkably few 
in the lung and in the capillaries of small animals such 
as the shrew, which has exceeding ly thin capillary 
walls (78). The basement membrane is of considerable interest 
in this connection. It consists of a collection of materi­
al outside the endothelial cells and forms a layer of 
lrn:l'ular t.hkkm:ss . It is funhc:r separated from lhe 
endothelial cells by the so-called exoendothelial space 
(13). The distal extensions of the pericytic processes 
cross the basement membrane. A layer of the base­
ment membrane of relatively low electron density (which seems to be identical with the exoendothelia l 
space) has been described toward both the endotheli­
um and toward an adjacent pericyte and its processes 
(39, 78). The blood capillaries are further provided 
with a ftne reticulum of neurofibrils (Fig. XII: 22c) 
located at the outer side of the endothelial tube (2, 35, 
52). The control of blood flow to a tissue region depends 
on pre-and post-capillary resistance (1). Precapillar y 
sphincters (84) and arteriolar smooth muscle adapt 
their activity to the metabolism of the tissue and to 
signals from central sympathetic influences (2, 17, 52). How does this picture of the structure and known 
functions of the capillaries fit with a presumed VICC, 
permitting selective closed circuit electrogenic trans­
ports of material between blood and tissues? At a first 
glance it may seem unlikely or even impossible to 
assume the existence of simultaneous redox reactions 
and closed circuit ionic transports in the presence of 
leaking pores of the capillary walls. Reversible redox 
sites adjacent to leaky junctions in the capillary wall 
slloul\.1 pc:rlnaps at Llu: tnost pcmtit small and rather 
inefficient circuits. For further insight into these prob­
lems, we will first tum to direct in vivo studies of the 
behaviour of small vessels and capillaries, exposed to 
electric fields. Biologically closed electric circuits 137 3. Capillary reactions in electric fields 
Direct in vivo microscopy and microphotography were 
performed of vessels of the mesentery of eleven dogs. One platinum electrode was gently placed against the 
mesentery, one was placed in the aorta and one in the 
inferior vena cava. Four possibilities to vary the elec· 
tric field around the mesenteric electrode were then 
available. Direct current voltages of 100 mV, I, 2 or S 
V were applied between the electrodes. The following 
results were obtained on microscopic in vivo inspec­
tion of small vessels (about 0.1 mm in diameter). When the mesenteric electrode was electropositive 
or electronegative in relation to the electrode in the 
aorta or the vena cava, small arteries contracted imme­
diately in various sites around the mesenteric electrode 
(Fig. XIV: I a) at each of the potential differences test­
ed. Blood flow was then completely interrupted in 
many small arteries. Sometimes they suddenly opened 
and let the blood flow through. Some small arterial 
branches showed no contractions, while some showed 
diapedetic leaking of red blood cells (Fig. XIV: 16). In 
each of the combinations of polarity and voltages, 
small arteries were regionally nearly always empty of 
blood cells. Rarely, veins were slightly more narrow 
than the adjacent artery. Local contractio ns over rela­
tively short distances were also seen in small arteries 
but occasionally also in veins (Fig. XII: 23). The immediate regional effects of electric fields on 
calibre of small vessels of the mesentery were then 
extended tO the study of arterioles, venules and capil­
laries. A standard dose of 1.2 coulombs at 5 volt potential 
difference for 20-30 minutes was applied in the four 
combinations of polarity and electrode positions men­
tioned above. Platinum electrodes were used. The 
mesenteric electrode was a 4x4 mm plate gently posi­
tioned against the mesentery without causing tissue in· 
jury. The electrodes in the aorta and the vena cava 
were introduced through vascular catheters. A small 
glass partition was used as a support for the mesentery 
(plastic material was unsuitable as it easily produced 
spontaneous diapedetic bleedings ). After 1.2 cou­
lombs were applied, pieces of the mesenteries were 
excised, ftxed in formalin, stained (haematoxylin -eo­
sin) and examined microscopically. The relative appearances of small arteries and veins, 
arterioles, venules and capillaries could now be in­
spected .. While it is evident that results from instanta­
neous and prolonged exposure of vessels to electric 
fields may differ, the actual results are nonetheless 
informative. In general, small arteries appeared empty and often 
very narrow compared to the accompanying relatively 
wide veins, which contained large amounts of granulo­
cytes. This tendency was present in all four combioa-
138 Biologically closed electric circuits Fig. XII: 23. Regional contractions were commonly ob­
served in smaU arteries (A) exposed to an electric field. Sometimes a small vein (V) appeared slightly narrower than 
the accompanying artery as seen in this figure. Mesentery of 
dog, haematoxylin..eosin. tions of polarity and electrode positions (Fig. XII: 24). Around the mesenteric anode, granulocytes accumu­
lated in veins in increasing number up to the electrode 
and even beneath it. Around the mesenteric cathode, 
an area ofaboun 10-15 mm in diameter was completely 
free of cellular elements in the arteries and veins. Immediate ly peripheral to the cell-free zone, granulo­
cytes were collected in veins in increasing amounts up 
to the cell-free zone. The locations of granulocytes and the relative cali­
bres of arterioles, capillaries and venules are illustrated 
in Fig. XII: 25. These studies showed a clear tendency 
in all four combinations of polarity and electrode posi­
tion. The arterioles and arterial portions of capillaries 
were all narrow and empty of blood cells in regions of 
variable size. The corresponding venules and venous 
capillaries were wide and contained occasionally large 
amounts of granulocytes . These cells also appeared 
often in the in~erst itial tissue. In three experime nts in dogs, two 4 x4 mm plati­
num electrodes were placed 2.5 em from each other 
against the mesentery. These experiments showed the 
same tendency as the previous experiments with re­
gard to the calibre of arterioles, capillaries and venules 
and to the local accumulat ion of granulocytes. Even 
after application of voltages between the electrodes of 
as lillie as 100 mV (10 pA, 30 minutes, 0.018 cou­
lombs), granulocytes collected selectively in small 
veins, venules and venous capillaries (Fig. XII: 26). 4. Selective distribution of granulocytes in a 
closed circuit 
How is it possible that granulocytes accumulate in 
veins, venules and venous capillaries when corre­
sponding small arteries, arterioles and arterial capillar-.-. .· 
• .. . ; ' . . .._ .... . .. 
~· . . " Fig. XII: 24. Overview of dog rruosenteries with different 
electrode positions and polarities, each exposed to 1.2 cou­
lombs at 5 V between the electrodes. In each of the electrode 
combinations smallan.eries were empty of blood cells. Small 
vcins contained varying degrees of increased numbers of 
granulocytes outside a cell·free zone around the electronega -
ies are narrow and empty of blood cells? This problem 
is further considered in Chapter XIV, Sections 1-K, 
where an alternative theory to so-called chemotactic 
accumulation of leukocytes and charged compounds in 
tissue is presented. A preliminary brief explanation 
will be given in this connection. tivc mesenteric electrode (a and,) and directJy up tO lhe elec­
tropositive mesenteric electrode (band t!). A = "small" arte­
ries, V = "small" veins (approx. 0.1 mm in diameter ). M.es • mesentery, Ao • aorta, V. cava • vena cava inferior. Scale same in each view. Haematoxylin-c os-in. All mammalian cells, including blood cells, are 
known to carry a surplus of fixed electronegative 
charges on their surfaces (79). Under the inllue.nce of 
an electric field of suitable strength in relation to the 
charged cells, and considering the factors of cell size, 
steric characteristics of cellular charges and matr~x 
Biologically closed electric circuits 139 ~';.-·· .. -. \ ,~ . -....... " .. . 
' . ,. -· . ' . .. ., , -.. 
~ 
Fig. XII: 25. Distribution of granulocytes in four different 
combinations of electrode posidons ~nd combinations of vol· 
tagcs in dog mesentery. In each combination arterioles and 
arteda_l capillaries (Ac) are e.mpty and narrow while the ven· 
140 BiologicaUy closed electric circuits • . \, . . ' -......... 
ulcs and \'enous capillaries (Vc) arc relatively wide ~md con· 
tain granulocytc.-s , some of which also appear in the dssue. Mcs ;s; mesentery, Ao:;:; aorta, V. cava= vena cava inferior. Scale same ln each ''iew. HaematOx yJin.eosin. • .... Fig. XII: 26. Meoentery of dog. Narrow small anery (A) is 
vinually empty of cells and widened small ••ein (V) contains 
selectively accumulated granulocytes peripheral to the zone 
free of cells around the cathode. Anode positioned on the 
mesentery 3 em away from the cathode. 100 mV, IO!lA, 30 
minutes, 0.018 coulombs. Haematoxylin-eosin . properties oftissue, the charged cells will be attracted or 
repelled depending on the polarity of the electric field. The electronegative granulocytes will consequently be at­
tracted to an anode and repelled by a cathode like any 
charged particle in an electrophoretic process. This pro­
cess requires an activated closed electric circuit, which 
in the present experiments was created by an external 
source of electric power, cables, electrodes and the 
conducting media in the tissue. We are therefore still 
only simulating the existence of a BCEC in our experi­
ments. This is one of the reasons we must wait until 
later (Chapters XIV, XVI) for discussion of bow gran­
ulocytes can accumulate electrophoreticaUy over an 
endogenou s, activated closed circuit (the VICC). The accumulation of granulocytes in vessels toward 
the anode, positioned against the mesentery, is readily 
explained as an electrophoretic attraction of the granu­
locytes. Around the cathode, however, electronegative 
particles and cells should be repelled. A cell-free zone 
was therefore also regularly observed around the cath­
ode. Nevertheless , outside this zone large amounts of 
granulocytes accumulated in ves.els (Fig. Xll: 21\). The mechanism of this phenomenon is explained in 
Chapter XIV (and illustrated in Fig. XIV: 18). 5. Mechanisms of regional contraction of 
arterioles and arterial capillaries 
Is there any mechanism which can explain the local 
regions of field induced contractions of small arteries, 
arterioles and arterial capillaries while corresponding 
venous vessels are wide? The capillaries , small vessels 
arteries and veins are provided with nerve fibres which 
evidently offer one possibility for neurogenous im­
pulses of contraction. Another or an as$0datcd mecha­
nism may be connected to the pericytes, which fur­
thermore are described to be involved in the contrac-
ll-814586 NorrkJUtmm tion of capillaries. We may now focus our attention to 
the remarkable fact that pericytes are sparsely found in 
the lungs and in the vessels of very small animals (78). Let us anticipate that the pericytes are involved in a 
mechanism of segmental small vessel contractions in­
duced by electric fields of a closed circuit (identified as 
a VICC system). In this case pericytes should not 
cover the entire capillary net as this should jeopardize 
a segmental mode of contractions. Consequently , pos­
sibilities of modulating selective closed circuit, "long· 
or short-distance" electrogenic transports should not 
be possible (see also Fig. Xll: 30a). Small animals as 
the shrew (smallest mammal, weight 2 g) should need 
very few pericytes because their capillary membranes 
are exceedingly thin. The shrew may get along well 
simply by diffusion through the thin capillary mem­
branes. The sparse extent of pericytes in the human 
lung is perhaps similarly explained. Gas exchange , the 
main function of the lungs, is sufficiently well covered 
by diffusion. There is consequently not a very large 
need in the lungs for an additional mechanism of long 
distance electrogenic transport. 6. Search for redox sites: possible origin of the 
basement membrane and the endothelial fibrin film 
In attempts to fmd the sites for the necessary redox 
steps of the VICC, we must take a second look at the 
components of the capillary membrane. Certain details 
of interest are shown in electron micrographs (Figs. XII: 27-29), kindly placed at my disposal by Prof. E. 
R. Weibel, University of Berne, Switzerland (78). The basement membrane is a structure about which 
little is still known of its origin and function. These 
membranes were recognized as early as 1848 by Kopf 
and Bowman. They are described as consisting of 
connective tissue elaborated by cells of mesenchymal 
origin (Deseemet's membrane ) or of ectodermal origin 
(the basement membrane of the lens) (37). Basement 
memhrane~ are cnmrosed of an amorpho us marrix, 
which contains a fine network of partially oriented 
fibres (37). Chemically , basement membranes contain 
various sequences of amino acids and carbohydrates. They also contain a low molecular weight glycoprotein 
and collagen (33) and antigenic protein (6). Strangely enough, the basement membranes are de­
scribed as covering the lumens of the anticipated chan­
nels of transport, the stomata and the places where 
vesicles must empty their content into the tissue (13, 
48). However , an exoendothelial space (Figs. XII: 21, 
27-29) is also described (13, 48), which could represent 
a space for escape of materials transported through the 
capillary walls. Colloids of blood arc normally excluded from the 
interendothelial clefts which are occupied by ground 
substance contiguous with basement membrane (40, 
Biologically closed electric circuits 141 Fig. XII: 28. Capillary of rat cardiac muscle. Magnifica· 
tion 18 700x. Observe a zone of low electron density (Ap) 
between endothelium and basement membrane (B) and an· 
other broader zone of low elect.ron density (A;) between en· 
dothelium and content of capillary. These findings sug-Fig. XII: 27. Elemon micro­
graph of capillary (C) from rat 
cardiac muscle with pericyte 
(P). Magnification 20 500x. Basement laminae (B) sur· 
round the pericyte and the in· 
terstitial side of the endotheli · 
um. Note a zone of low eiC(:· 
tron density (A) betwC(:n 
basement laminae on one 
· hand and pericyte and endo· 
thelium on the other. It is sug· 
gested that the basement 
membrane represents an ap· 
position of material and not 
primariJy a structural element 
of the capillary waU. gesr that similar forces may be involved in the creation of 
zones of low elec-tron density such as shown fo.r the creation 
ofHA" zones in a contracting movable precipitate adjacent ro 
a fixed "matrix" (see Figs. XU: 1, 4 and 1 and Chapter X). A 
pericyte process (P) is enframed (see also Fig. XII: 29). ~~~~~~~~~~~~~~~~~~~ ~-
142 Biologically closed electric circuits Fig. XII: 29. (a) Pericyte pro· 
cess (P), cnframed in Fig. XII: 28, shows a web of cyto· 
plasmic filaments (f) and pino­
cytotic vesicles (pv). Capillary 
(C). Material of basement mem· 
brane (B) surrounds the peri­
cyte process but is separated 
from its surface by a zone of low 
electron density (A). Magnifica· 
tion 52 670x. (b) Smooth mus· 
cle cell (M) on venule (V) shows 
filaments (f) and vesicles (pv) 
located predominantly under its 
right-hand surface. Vesicles in 
the endothelial cell (E) arc more 
randomly dispersed. Both sides 
of the basement membrane (B) 
located between the venule and 
the muscle cell show zones of 
low c.lecuon density (A). Mag· 
nificarion 38 300 x . 48). It has been suggested that the basement mem­
brane constitutes the major permeability barrier of 
blood vessels ( 48). Why is then the partially amorphous , partially 
structured basement membrane separated from the 
wall of the endothelial cells? Is it possible that the 
material of rhe basement membrane represents a pro­
duct of nearby "electrode reactions" at the endothelial 
membrane facing the interstitium? An electron micro· 
scopic observation of Low and Weibel (39, 78) now 
becomes of interest: a zone of low electron density 
corresponds to the exoendot helial space. Moreover 
trus zone also can be recognized along the surface of 
pericytes , includiog their processes. Fig XII: 27 shows r 
a pericyte (P) and one of its processes in contact with 
the endothelium of a capillary (C) of rat cardiac mus· 
cle. The basement membrane (B) is seen not only 
against the endothelium but also around the body of 
the pericyte. Beneath the basement membrane is a.lso 
seen the 7-0ne of low electron density (A). Fig. XII: 28 
shows this zone between the basemenr membrane and 
the periphery of the endothelium (Ap). However, it 
should also be noted that a similar bUI broader zone of 
low electron density is presem be~en the material inside 
the capillary and the inner endothelial wall (A;). Finally, 
Fig. XII: 29a shows higher magnification of the peri· 
cyte process (P) from the enframed section of Fig. XII: 28. The pericyte process is located within the 
Biologically closed electric circuits 143 basement membrane. A zone of low electron density 
(A) is apparent. Fig. XII: 29 b shows endothelium (E) 
and a smooth muscle cell (M) on venule (V). Between 
them is the basement membrane material (B), concen· 
trated in the middle between two zones of low electron 
density to each side (A). The basement membrane can 
further be seen as a collection of "fibrous" material of 
varying thickness. The origin of basement membranes now become of 
inter~l ~s pOssible prQducrs of rhe endothelial cell~. If the redox sites for electron transfer are located, e.g., 
to the endothelial cell membranes , then the basement 
membranes may have developed from products of de· 
position at an electrode equivalent surface, as such 
depositions develop at any electrode surface of a 
closed circuit. Fibrous membranes of different compo­
sition can also be produced experimentally adjacent to 
electrodes as an effect of electrophoresis in vivo and in 
tissue samples (see Chapter XVI). A logical consequence of such a view is apparent. The endothelial cell should not very likely appear as an 
interpositioned barrier, carrying anticipated redox me­
diators e.g. enzyme particles only at the "outer" (in· 
terstitial) membrane of the endothelial cell. An expla­
nation is also required for the development of the 
endothelial fibrin film, described by Copley (13). This 
fllm may also devdup from proc.luc. :ts of d.c:po:sitiou at 
an electrode equivalent "inner" surface of the endo­
thelial membrane facing the blood stream. If, indeed 
the basement membrane develops from material of 
deposition at the outer (interstitial ) electrode equiv· 
alent surface of the endothelial cell, the exoendothelial 
space (13), which seems to be identical with the zone 
of low electron density, according to Low and Weibel 
(39, 78), can also get an explanation. Collected "elec· 
trode material" adjacent to a surface should physically 
behave like the basement membrane under the infiu· 
ence of its internal concentration forces. We have 
encountered this situation earlier (see Figs. XII: I and 
4) in the creation of "A" and "B" zone effects by 
products of deposition in tissue adjacent to a metal in 
in vivo corrosion. A corresponding zone of low density 
of electrons is also seen in Fig. XII: 28 between the 
contents of the capillary and the inner surface of the 
capillary wall. This zone is probably a result of post· 
mortem contraction of material in the lumen of the 
capillary (see also effects of concentration forces, Fig. XII: 7). The endothelial fibrin film is a structure, 
continuously exposed to forced convection and should 
therefore appear differently as compared to the base­
ment membrane and the material inside the capillary, 
as seen in Fig. XII: 28. Up to this point we have tried to localize the neces­
sary redox sites in the VICC by looking for electrode 
equivalent products of deposition as membrane-like 
structures. In this view, the basement membrane on 
144 Biolocically closed electric circuits a 
loni<: trlntports 
b Ionic trantporh 
EC ~~~ EC 
\ .. --:::-____ , 
Fig. Xll: 30. Suggested mechanism of electric t.ransfer be­
tween ,-.scular and intentitial branches of VICC. The sur· 
faces of endothelial cells (EC) possess electrode equivalent 
sites (X) for reversible redox reactions. Ionic transports 
through the endothelial cell connect relatively anodic and ea· 
thod.ic .. inti:mal" electrode surfaces. ''External'' electrode 
surfaces against blood stream and interstitial tissue:: arc con­
nected <lectrically over blood plasma, leaking pores (sto­
mata) and interstitial tissue fluid. (a) When arterial stomata 
are selectively closed by contraction , conditions for long dis­
tance Stlective transports are created, e.g., over leaking di­
lated venules and venous capillaries . (b) When arterial StO· 
mata are open, short~istance transports take place through 
adjacent arterial stomata. the outer surface of the endothelial tube and the endo­
thelial fibrous fUm on its inner surface may indicate 
the positions of such sites. Fig. XII: 30a, b illustrates 
how electrode equivalent sites may be located at the 
surfaces of the capillary endothelium. A long distance 
electron transfer between the "electrodes " is evident· 
ly not very likely because this should require an 
electron conducting pathway through the endothelial 
cell. More likely this connection is covered by ionic 
transports as indicated in Fig. XII: 30. One particular 
component of transport in the presented view of capil­
lary VICC-functions , the vesicle of Palade, will next be 
considered . 7. Search for redox sites: the vesicles 
The knowledge of the morphologic appearance of vesi­
cles is based on electron micrographs (47, 78, 80). For 
example, multiple vesicles are seen in the capillary 
membranes, in a pericyte process and in a smooth 
muscle cell in Fig. XII: 29. The possibility of transport 
of proteins through the endothelial cells by means of 
vesicles has been discussed intensively during the last 
two decades (53). Vesicles are further thought to trans· 
port water through the endothelial cell, a process 
named pinocytosis. Very little is still known about !heir origin and functional role and, e.g., what makes 
vesiculation start or stop (29). Vesicles are described to 
move randomly in !he cytoplasm ( 47, 48), in a manner 
which is compared wilh Brownian motions (9, 66). A 
different explanation will soon be presented of their 
sometimes random appearance (as in the venule V, 
Fig. XII: 29 b) and of !heir sometimes regular appear­
ance (to !he right in the smoolh muscle cell M, Fig. XII: 29b). This explanation will suggest an electro­
genic mechanism of the development and mode of 
transport of vesicles. The presence of vesicles is well known from other 
biological fields and particularly from !he transmission 
of nervous impulses . The study of neurophysiology 
tells us !hat electrical impulses do not directly activate 
an organ. Instead, the electrical impulses over axons 
release transmitter substances, which are carried by 
vesicles (31, 46). In experimental studies it will be 
shown (Fig. XIV: 8) that a weak electric current, flow­
ing between two platinum elettrodes in blood produces 
bud-like bubbles of gaseous material extending in 
dendritic formations from the electrode surfaces. When 
electrolysis of water is performed in the presence of a 
matrix, small bubbles of anodic 02 and cathodic H2 
are virtually pumped far out into the matrix, where 
these bubbles are retained. There they can be energeti­
cally recovered over an experimental fuel cell arrange­
ment. These experiments (Chapter XIII) represem 
8 
b initial attempts to simulate t.be principle of develop­
ment, transport and behaviour of vesicles, as well as to 
simulate some of the actual events connected with the 
transcapillary transfer of energy in the VICC. Some of the most important energetic compounds in 
tissue metabolism are nonionic, e.g., oxygen and glu· 
cose. A selective and enhanced closed circuit exchange 
of compounds between blood and a metabolizing re­
gion of tissue must not r.ecessarily be limited to an 
exchange of ions. Possibilities also exist for electro­
genic transport of nonionic materials in the presence of 
suitable matrices.
631928626-Biologically-Closed-Electric-Ci-Bjorn-Nordenstrom-pdf.txt
Summarize the following text section accurately and concisely. Maintain specific details and numerical information, and use anti-repetition mechanisms:

        The resis­
tivity e of the vessel wall is then calculated according 
to the formula 
R. A 
n =--,where R = Z-R 
~ I ", 
and I is the thickness of the vessel wall, A the internal 
cross-sectional area of the glass tube (1. 3267 mm2), R. the resistance of the vessel wall and R, the resistance 
of the column of saline solution between the measuring 
electrodes. R. is determined by subtraction of R, from 
Z, the total resistance. The measurementS of the saline 
solutions were made at temperatu res ranging from 
23•c to body temperature, yielding resistiviry values of 
0. 70 to 0. 62 ohm-mat I to 10kHz, which is in good 
agreement with earlier values from the literature (8, 
22). Fig. XII: 12 shows amplitude curves at different 
frequencies for (a) saline solution, (b) fresh vein and 
(c) fresh anerial walls in situ. An example (d) is also I k lOOk IM 
Frequency(Hzl 
given of the effect on resistivity of an arterial wall in 
situ after the production of a visible local ischaemic 
tissue injury. The amplitude curves in Fig. XII: 12 show a rela­
tively rapid fall around 10 kHz, which is interpreted as 
caused by the lowering of the inductive resistance by 
high frequencies. Below 10 kHz lhe prominence of 
this effect decreases. The resistivities of the femoral arteries and veins in 
20 measurements of the 5 dogs were compared with 
the resistivity of 0. 9% NaCl (0. 62 ohm-m at 23•C). The immediate determinations of resistivities of the 
vessel walls, before obvious damage was produced by 
the glass tubes, showed values for the vein varying 
between 60 to 116 ohm-m at I kHz and 20 to 79 ohm­
m at 10 kHz and 37•c. For the artery, values of 
81-121 ohm-m were obtained at I kHz and 4S-67 
ohm-m at 10 kHz and 37°C. The variations depended partly on the difficulties of 
measuring the thickness of the vessel walls, which 
varied between 0. 03-0. 05 mm for the vein and 
0. 10-0. 15 mm for the artery. Two other factors were 
the injury necessitated by the dissection of the vessels 
free from surrounding tissues, which may have partly 
damaged the vasa vasorum, and the direct damage by 
the glass tubes. Values of resistivity decreased at the 
end of each examination. For example, examination of 
an artery which had a directly visible ischaemic region 
around the glass tube gave 36 to 54 ohm-m at I kHz 
and 8. 0 to ll. 5 ohm-mat 10kHz {Fig. XII: 12d). The results of these examinations indicate clearly 
that the resistivity of femoral arteries and veins is of an 
Biologicall y closed electric circuits 127 Applied voltage 
50 mil 
SBmv~. -. ,11-Applied voltage 
ISOmV 
Fig. Xll: 13. In vivo de<ermination of resiSiivity to DC 
pulses across the wall of a dog's femoral artery. Method of 
Burger and van Milaan: amplitudes (11A) and potential dif· 
fcrcnccs (mV)when SO and ISO mV pulses were applied 
(pulse duration: O. S second). The distortions in the tracings 
are C'dused by polarization of the electrodes. Initial deflec. lions were used to obtain a relative measure of resistivity. order at least 100 to ISO times higher than the 
resistivity of saline solution, which in turn is known to 
have roughly the same order of resistivity as blood 
plasma, serum and interstitial fluid. b) Pulsed direct currem 
Resistivity studies with direct current are of consider· 
able interest, as this type of current represents electric 
transports in vivo. Attempts were therefore made to 
study resistivity of blood vessels with a technique 
developed by Burger and van Milaan (8). In this way, 
information on the resistance of walls of large vessels 
in comparison to resistance of the intravascular con· 
ducting medium, the plasma, should be possible to 
obtain. As in determinations of resistivity with alternating 
current, many sources of error can interfere in deter· 
minations of resistivity with direct current. It is evi· 
dent that an application of DC pulses will ionize the 
test material and change its relative conductivity dur· 
ing each pulse. The applied potential will furthermore 
produce ionic separations, providing electromotive 
forces in the opposite direction. This effect means that 
the test current builds up a galvanic potential. When potential difference is constant within cer· 
tain limits, the degree of i(mization is a dynamic event 
which initially increases exponentially the actual flow 
of current per unit time. This observation is well 
known since julius Tafel (72). On prolonged applica· 
tion of direct current, different counteracting reactions 
will contribute to decelerate the current. Moreover, 
the same technical difficulties are encountered in both 
DC and AC determinatio ns of resistivity of a vessel 
128 Biologically closed electric circuits wall, i. e. , geometric measurements of specimens and 
avoidance of injury to tissue. These experiments were performed in five dogs, 
using the same rype of preparation of femoral vessels 
and electrodes in glass tubes as was employed in the 
determinatio ns of resistivity with alternating currents. A series of 10 DC pulses (0. 5-1. 0 sec duration each) 
was applied over 25, 50, 100 and ISO mV through the 
vessel wall in one direction and then in the opposite 
direction. Polarizati on caused a dis·tortion of the measured 
deflections of potential. It is therefore necessary to 
define how the measuremen ts were obtained and the 
results analyzed.
R.A n = --, where R = Z - R, and I is the thickness of the vessel wall, A the internal cross-sectional area of the glass tube, and R, the resistance of the column of saline solution between the measuring electrodes.
What is the formula used to calculate the resistance of the vessel wall?
The experiment aims to study the resistivity of the femoral arteries and veins in dogs and to examine the possibility of electric current flowing selectively through the vessel walls.
What is the purpose of the experiment involving the application of 10-20 volts between the electrodes?
The results indicate that the resistivity of the femoral arteries and veins is higher than that of the saline solution, and the findings suggest that the vessel walls may serve as electrically insulated cables.
What is the significance of the results of the resistivity measurements?
The experiment aims to study the effects of direct current on the vessel walls and to investigate the possibility of selective transport of material through the capillary walls.
What is the purpose of the experiment involving the application of direct current between the electrodes in the aorta and mesentery?
The proposed mechanism is that the granulocytes are attracted to the anode and repelled by the cathode due to the electric field, which is consistent with the observed results.
What is the proposed mechanism for the accumulation of granulocytes in the capillary walls?