A platinum electrode was inserted into the 
catheter, which was irrigated continuously with phys-
Fig. VI: 13. Artificial electric charging and discharging of 
li•;ng tissue of a dog. One platinum electrode was placed 
against the mesentery and one in the lumen of the aorta via a 
fe.moral catheter. A 23 volt potential, giving initially 6.5 mA 
current, was applied between the electrodes for 15 minutes. I. 8 volts were then measured between the electrodes. The 
c111rrent flow between the electrodes was then read by means 
of a digital microampc: rcmctcr in parallel with the voltrne~c .r. The initial part of the discharge took place very rapidly he­
tween the cessation of applying potential to the eltctrodes 
and the first measurement. Initial current values are there­
fore not included. 10 
5 
. . . 04---------~--------.-------~r- -. 0 5 10 IS tnt.n 
58 Electric potentials iologic saline solution. The abdomen was surgically 
opened. Another platinum electrode was directly 
placed against tissues of various organs, e.g., mesen­
tery. A direct current potential of predetermined mag­
nitude was applied between the electrodes for one to 
several minutes. The potential difference between the 
two electrodes was then measured with a millivolt­
meter immediately after interruption of current flow. The electrodes were then short circuited over a mi­
croamperemeter in parallel with the millivoltmeter. The values of current and potential were then read at 
regular intervals and plotted against time. These experiments revealed in the 5 dogs that in 
vivo an artificial electrical charging and discharging of 
a tissue was easily demonstrated. Thus, in the experiment illustrated in Fig. VI: 13 a 
potential of 23 volts at an initial current of 6.5 rnA was 
applied between the aorta and a mesenteric electrode 
in a dog. After 15 minutes, a potential of 1.8 V was 
measured between the electrode-s. The electrodes were 
then connected to each ot!her over the microampere 
meter. The current-time integral of the discharge is 
illustrated in Fig. VI: 13. The initial values are not 
included because initial discharge was very rapid. Differences of electric impedance and ionic concen­
tration in different tissues aUow local variations of 
electric charges. These charges can be artificially 
changed when the tissues are electrically connected to 
each other over electrodes and an external conductor. Thus, short circuiting between tissue regions of differ­
ent electric potentials can level that potential differ­
ence. Moreover, when an external source of direct 
current is connected into the circuit, an artificial local 
charging of tissues can be obtained. Different tissues 
such as fat, muscle, viscera, bone, blood, interstitial 
fluid, cell membranes, etc., are aJso known to have 
different resistivities (see Chapter X!D. It is therefore 
logical to regard tissues as composed of numerous 
galvanic cells with different capacity. A tumour or 
granuloma with an electric potential in relation to the 
surrounding tissues should therefore contain a surplus 
of cations or anions in relation to surroundi ng tissue. Why and how such ionic s-eparations occur in vivo is 
another problem, which will be considered later. E. Control studies of electric 
potentials of normal and 
pathological tissues 
At this stage of experimentation the existence of elec­
tric potential between a pulmonary lesion and sur­
rounding lung was checked with a modified technique. This part of the study was performed in a group of fifteen patient-volunteers . In these studies nonpolari­
zable Ag-AgCI electrodes with KCI-agar bridges were 
used. The electric potentials of normal lung, pleura 
and liver in dog will be described as a background to 
discussions of integrated influences by "reference" 
tissues. l. Electrodes, recording of potentials, 
and techniques of cell sampling 
Nonpolarizable Ag-AgCI electrodes with KCI bridges 
were used in order to explore the possibility that diffu­
sion potentials participate in the development of the 
observed electric potentials of lung lesions. Silver strings, ISS mm long and 0.25 mm thick, 
were each soldered to electrical cables. The site of 
soldering was protected with Araldite"' and a plastic 
tube. The strings were polished and chemically 
cleaned (CCI4 IS minutes, I M HN03 2 minutes, 
10% (COOH), 5 minutes). The surfaces of the silver 
strings were then coated with a layer of Teflon (954-
103) in liquid suspension. The Teflon was allowed to 
dry with the string in a vertical position. The string 
was then placed in an oven for 5 minutes at a tempera­
ture of 26<f. In this manner two Teflon layers were 
applied to the surface of the string. The distal 5 mm of 
the Teflon layers were then scratched off the string 
and the surface polished and cleaned chemically as 
described above. A chloride layer was applied to the 
0.04 em~ of silver surface (0.9% NaCI solution, cur­
rent of 0.4 mA between the string and an equally 
cleaned silver plate, duration SO seconds). Electrodes manufactured in this way were then kept 
in the dark in a 2 M KCI solution. Their electrical 
a Plain AgCI electrode 
Jo.1mV Smin 1 
b 
Io.rmv tmin cables were connected to each other and to a carbon 
rod, which was also placed in the KCI solution, as 
recommended by Cooper (2). Because carbon is slight­
ly cathodic with respect to silver-silver chloride, a 
small chloriding current was maintained . Electrodes 
treated in this way show good electrical stability, com­
parable to what has been reported by Cooper (2) and 
Geddes and Baker (4). Sale bridge carriers were manufactured from hard 
radiopaque Teflon tubes, Teflon coated cannulas (1.2 
mm thick), or in dog experiments, glass capillaries. They were filled with 3 M KCI solution in 2% agar. Cyrologica/ sampling followed by electric potential 
studies was performed through hard Teflon tubes. These tubes (165 mm long, 1.5 mm thick) were pro­
vided with a plastic three-way stopcock and an in­
dwelling, I mm thick, biopsy cannula. Each tube was 
inserted under local anaesthesia in the skin through a 3 
mm incision. The tube was advanced under fluo­
roscopic comrol to the edge of the lesion. Cytologic 
material was then sampled by means of a screw needle, 
0.55 mm thick, inserted through the cannula into the 
tissue, according to the technique previously described 
by the author (II). After removal of cellular material, 
a new needle was inserted through the plastic tube and 
advanced to the distal wall of the lesion, where again 
cellular material was sampled. The lumen of the plastic tube was then filled with 
the sterile agar-KCI solution, which shortly before was 
made liquid by placing the agar-KCI bottle in boiling 
water. The Ag-AgCI electrode was introduced into the 
plastic tube with the proximal part secured in the hub 
of the stopcock. Care was taken not to introduce air 
bubbles, both when filling the tube with the KCI-agar 
material and when inserting the electrode. A corresponding , grounded , reference electrode was 
also introduced into the subcutis of the chest wall. AgCI electrode with salt bridget 3M KCI in 2X agar) 
Fig. Vi: 14. Stability tests of Ag-AgCl electrodes in 0.9% 
NaCI. (a) Drift of 6 microvolts during a 30 minute period. Fluctuations <± 10 mjc:rovolt s. (b) Same electrodes in 0. 9 o/o NaCI with interconnected 3 M KCI-agar bridges. Po­
tential drift of 100 microvolts during a 30 minute period. Fluctuations < ±40 microvolts. Electric potentials 59 lung mediastinum lung pleura 
Fig. VI: 15. Profile of electric potential of tissue through the 
chest of a dog in re.lation to subcutaneous grounded refer­
ence electrode. Anteroposterior radiograph. Needle elec­
trode was inserted from the left side through the chest, an· 
terior and superior to the bean. While the exploring elc. ;­
tn>de was removed, 30 mV positive pOtentials arc seen when 
Elecrric potential of the tissues was recorded during 
withdr•wa l of the exploring electrode. When record­
ings were made during cineradiography (frame speed 
50/sec), the position of the electrode was determined 
by comparing the cine frames with the markings of the 
frame exposures on the same chart paper as the electric 
potentials. The impedan ce of the recording circuit was usually 
in the kiloohm range. The input impedance of the 
recording instrument (Grass Polygraph direct current 
recorder) is 10 megohms. Stability of the electrodes was tested repea ted!~· and 
found entirely satisfactory (Fig. VI: 14). After primary amplification of the input signal, the 
outgoing signal was fed back into parallel-coupled, 
secondary amplifiers. This arrangement permitted 
separate treatment of amplification and filtering of 
individual tracings, which appeared necessary because 
the acrualtissue potential profiles could not be predict­
ed. In instances when the tissues were fibrotic or o'hcr­
wi:se hard, salt bridges of higher mechanical stability 
than the Teflon tubes were used. Biopsy needles, 1.2 
60 Electric potentials the electrode traversed the left and right pleurae. Two posi­
cive tissue potenlials are also seen upon 1raversing the media· 
stinum. Small regular "spikes" represent a superimposed 
electrocardiogram. These are of lower amplitude in the chest 
wall than in the lungs. mm thick, were then coated with double Teflon layers 
on their inside and outside surfaces in the same way as 
the Teflon coating on the electrode surfaces. Salt 
bridges within the.se needles have shown excellent me­
chanical stability but preclude use of these needles for 
combined cytologic sampling and studies of electrical 
potential. On the other hand, several tracings of elec­
tric potential can be made during ins-ertion and with­
d.rawal of the instrument. 2. Electric potentials of pleura and lung 
The preliminary studies of electric potential of lung 
revealed certain characteristics of the profile of electric 
potentials of two specific tissues. These profiles could 
be identified as related to specific structures by means 
of high speed cineradiography. The electric potential of pleura and lung, studied in 
22 dogs, appeared as follows. Tr•cings were made with 
the polarizable stainless steel electrodes and with the 
nonpolarizable Ag-AgCI electrodes provided with a 
salt bridge in a glass capillary. In Fig. VI: 15, a frontal view is seen of the thorax of 
a dog with the exploring , Teflon-coated, polarizable, 
stainless steel electrode inserted through the anterior 
and superior part of botb lungs. The noninsulated tip 
of the electrode is situated in tbe soft tissues of tbe 
right thoracic wall. The grounded reference electrode 
is positioned in the subcutis of the left side of the 
tborax but is not seen in the radiograph. The exploring 
electrode was pulled as evenly as possible out of the 
chest as electric potential was traced continuously. A series of positive fluctuations of potential differ­
ences appeared in the chest wall or the pleura. The 
section of tracing corresponding tO lung shows a rela­
tively even level of potential. A superimposed electro­
cardiogram shows very small fluctuations in the chest 
wall compared witb tbe lung, where the amplitudes 
also increased as the tip of the electrode moved toward 
the heart. The potentials of chest wall-pleura were furtber 
investigated. When the electrode WJS passed through 
tbe pleura in a dog, positive fluctuations of potential 
are seen in Fig. VI: 16 before (upper tracing) and after 
(lower tracing) the introduction of some air into tbe 
pleural space. When the electrode was introduced and 
removed, about20 mV positive deflection s of potential 
were seen at the site of contact bctwee.n pleura and 
chest wall. After some air was put into the pleural 
space, the electrode was introduced and pulled out, 
but slowly. This tracing !bows a large positive deflec­
tion of potential before tbe tip of the electrode reached 
the air-filled pleural space. When the retracted tip 
reached the air in tbe pleura, rapid oscillations oc­
curred due to the open circuit. At the touch of tbe 
visceral pleura these oscillations disappeared. The po­
tential in the lung was approximately the same as 
observed previously in the chest wall. Positive deflec­
tions of potential of the type that occur on traversing 
tbe parietal pleura were not observed from the visceral 
pleura in dog or man. 7 
• 0. Lung 
0 
10 
Rtsp 
Fig. VI: 17. Electrical potentials at the pleura. upon four in· 
scrtioos and retractions of a Ag-AgCI<Iectrode in a thin 
glass capillary with KCI agar salt bridge. Grounded r<f<n:ncc 
electrode of tht same construction was positiontd in the sub­
cutis of the eh<st wall. Resp = pneumotaehygraphic r<eord· 
ing of respiration. The exploring electrode w11s inserted from cMtt 
I 10mV 
parietal 
pleura lung 
I uno chest 
parietal 
p~ra 
Fig. VI: 16. Demonstration of electric pot<ntial of pl<ura in 
dog. As the exploring electrode passed b<twecn the chest 
wall and lung, aboutlO mY of potential difT<rcne< was re· 
corded, correspooding to the pleura (upper t.racing). Wh<n 
air was present in th< pleural spa« (low<r tracing), the same 
manoouvre shows that the potential difT<r<nce is related to 
the parietal pleun. As the electrode is inserted or withdrawn 
through che air·fillcd pleural space, an open circuit is ere· 
atcd, causing rapid oscillations . Stainless steel electrodes. In Fig. VI: 17 a control study is shown of tbe elec­
tric potential of pleura and lung in the dog, using tbe 
same recording equipment and the nonpolarizing 
Ag-AgCl electrodes inserted into glass cnpillarics filled 
with KCl-agar. The grounded reference electrode was 
positioned in the subcutis of the rillht chest wall. The 
exploring electrode was inserted from the opened ab­
domina.! cavity through tbe diaphragm into tbe lung 
close to the costopbrenic sulcus. The glass capillary 
could then be mo,·ed repeatedly from the lung to the 
pkurae and chest wall. As in previous studies, positive 
deflection s of potential were obtained at the contact 
with the inner surface of the chest wall. These deflec­
tions, corresponding to the parietal pleura, have a 
magnitude of about 20 m V in relation to the pulmo-
1 
Ch 
the abdominal cnitv through the diaphiUffi into th<lung. and th<n mo,·ed from the lung to th• chest wall (Ch) and 
back. Each mo\·ement to and from the pari<l21 pl<ura caused 
two d<nection s of potential. These pleural pot<ntials were 
us<d in the studi<S of tissue potential profiles of pulmonary 
masses to localize the tip of the exploring cl<etrode. Electric potentials 61 nary parenchyma. The potential deflections of the 
pleura were present in all the twentytwo dogs and are 
also detectab le in man (see Fig. VI: 21). After repeated needlings in the same place, the tis­
sue profile of electric potential of the lung sometimes 
varies slightly, which may result from small haemor­
rhages in the track of the electrode. The superim­
posed electrocardiogram usually shows a lower ampli­
tude in the chest wall than in the pulmonary parenchy­
ma. Discussion. Agoston.i (I) published in 1972 an exten­
sive physiologic review of the pleura, including 268 
references. From this source and further search of 
more recent literature , it appears that pleural electro­
physiology has not been a subject of previous study. No attempts have been made here to evaluate the 
functional significance of the positive potential of the 
pleura. It seems possible, however, that the mecha­
nism for in vivo development of membranes and organ 
capsules which is proposed in Chapter XII is also valid 
for the development of the fibrous pleural membranes. The distinct.ive electrical changes observed upon 
inserting and retracting an electrode through the chest 
wall and the lung have become a helpful landmark for 
topographic localization of the electrodes during trac­
ing of electric potentials of normal and pathological 
lungs. The thickness of an air layer in the pleura can easily 
be measured directly with an exploring needle elec­
trode. The ele<:trode is slowly pulled out from the 
lung. When an open circuit with high frequency dis­
turbances is observed, the external position of the 
needle in relation to the skin is noted. After further 
retraction of the needle, the circuit will close when the 
parietal pleura is reached. Assuming the needle was 
approximately perpendicular to the pleural surface, 
the distance the needle was pulled across the open 
circuit indicate$ the t.hickness of the air layer in the 
pleura. 3. Fluctuating '"demand potential " 
of a "reference tissue" (liver) 
Considerab le te<:hnieal difficulties were encountered in 
the study of normal variations of pulmonary electric 
potentials in vivo. To investigate the possibility that 
such variations. might be caused by outside events, 
e.g., metabolic· changes in an organ or "reference" 
tissue, any organ or tissue might be studied. The liver, 
more easily accessible than the lung, was chosen for 
these studies. The experiments shortly to be described suggest the 
concept that physicochemical potential of a normal 
tissue changes during different phases of its metabolic 
activities. These changes represent what might be 
62 Electric potentials called physiological "demand potentials" (see further 
Chapter XII). As previousl y stated, a tissue may be regarded as 
composed of multiple galvanic cells of variable charge. During different functional states they may be 
charged or discharged. In such events the nervous 
system may integrate metabolic activities and the func­
tions of ignition and balancing. Individual cells and 
grouped populations of cells may then, by their "phy· 
sicochemical, metabolic demand potential", influence 
their surroundings. Accordingly, demand potentials 
may be traced to partial functions within a ceU, a 
whole cell, a group of cells or a seemingly arbitrary 
large part of a utissue region" sucb as an organ. It 
follows that a recording of an electric demand potential 
of a tissue also depends on geometry , size and location 
of the electrod~. These relationship s include the inte­
grated electro(-physico )-chemical pOtentials of the tis­
sue components around the "exploring" electrode, 
around the "reference" electrode and interconnected 
Fig. VI: 18. Eleetrical potentials from the gastric a.nd hepatic 
parenchyma of a 24 kg dog. The potentials were measured in 
relation to a grounded sponge, soaked in saline solution in 
the abdomina l cavity. (a) Rhythmic fluctuations of potential 
from the liver. Their frequency is similar but their amplitude 
lower and of a slightly different pattern than that of the 
stomach. These rhythmic fluctuations are independent of 
respiration and of cardiac electrical activity. The maxima of 
the fluctuations of potential of the liver and the stomach var· 
ied from (a) out of phase to (b) almost in phase. Low or high 
amplitude s of the fluctuations of gastric potential were not 
accompanied by corresponding changes of amplitude in flue· 
tuations of hepatic potential. Rhythmic fluctuations of h.e· 
patic potential have not been previously described. a ~~ 
liver [ 1mV 
b 
( tmV conducting tissues. A short report has previously been 
presented on this problem by the author (9). In 18 experiments (IS dogs, three rabbits), laparo­
tOmy was performed. An Ag-AgCI electrode was 
placed under the hepatic capsule through a polyethyl­
ene tube (2 mm thick, filled with 3 M KCI solution in 
2% agar). The grounded reference electrode was 
placed either in the subcutis or connected to a sponge 
sheet soaked in 0.1 M KCl solution and placed in the 
abdomen between the stomach and liver. An exploring 
electrode was also placed under the serosa of the stom­
ach, which is known to produce rhythmic fluctuations 
of potential , induced by the nervous system (7, 12-13, 
15-18). Respiration was recorded as pressure changes 
in a corrugated rubber rube, slightly stretched and tied 
around the lower part of the chest. Fig. VI: 18 shows representative electric potentials 
of dog liver and stomach, compared to a grounded 
subcutaneous electrode. These experiments revealed rhythmic fluctuations 
of electric potential from the liver, usually at a fre­
quency of 3-5 per minute. The fluctuations, previous­
ly undescribed, were not produced by respiration, 
cardiac activity or bowel movements. Sometimes these 
fluctuations were almost synchronous with those of the 
stomach (Fig. VI: 18 b). Sometimes they were asyn­
chronous (Fig. VI: 18a). The waxing and waning pat­
tern from the stomach is interpreted as an imerference 
phenomenon of superimposed transmiued impulses. The electric poten rial fluctuations in the stomach are 
known to be of neurogenic origin (7, 12-13, 15-18). As in the stomach, fluctuations of potential in the liv­
er parenchyma are probably also of neurogenic ori­
gin. Most likely they represent secretory electric im­
pulses to the organ. The hepatic electric potentials 
could be altered by pharmacological agents. In the 
experiment illustroted in Fig. VI: 19, one electrode 
was inserted into the liver and one connected to a 
grounded sponge sheet soaked in 0.1 M KCI between 
leplnephr 
0.1mg 
lepinepht 
O.OSmg ~1mV 
llsopre.naline 
lmo 
150ml vamin 
Fig. VI: /9. Electrical acti\1ity in a dog liver, recorded in lepinepht 
0.025mg 
vivo with Ag-AgCI electrodes over KCI bridges. An abdomi­
nal reference ele. :trode was grounded. The rhythmic electri­
cal fluctuations of the liver show a frequency of about 4.5 per the liver and the stomach. After intravenou s injection 
of pharmacological agents as morphine, epinephrine, 
glucagon, histamine , antihistamine and others, differ­
ent changes of amplitude were produced in the rhyth­
mic fluctuations of hepatic potential. Previously unde­
sc;ribed slow waves of electric potential were also pro­
duced (Fig. VI: 19). Epinephrine drove the potential 
in a downward ly positive direction (note relatively low 
amplification and slow sp<.>ed of the recording ). The 
time-voltage integral is roughly dose-related. Isoprena­
line gave a slow wave in the electronegative direction, 
while glucagon and the amino acid nutri·tion com­
pound Yamin® also produced electropositive deflec­
tions. Usually the 3-5 per minute fluctuations changed 
their frequency and amplitude after administration of 
the agents which produced the slow waves. Other organs, e.g., pancreas and kidney, have also 
sltown fluctuations of electric potential similar to those 
sltown in the liver. The rhythmic 3-5 poer minute 
potential fluctuations and the accompanying slow po­
tential wave, artificially induced by different metaboli­
cally active agents, represent examples of "demand 
potentials" of a normal tissue. It is evident that "de­
mand potentials" of any tissue will influence gradients 
of potential in relation to locally injured tissue as well 
as to adjacent, but differently activated, normal tis­
SI.!Ies. 4. Electric potentials of pulmonary 
carcinomas 
In these studies the electric potentials were recorded 
with the Grass Polygraph DC instrument and the de­
scTibed Ag-AgCI electrodes. Thus, a technique differ­
ent from the preliminary was used. Difficulties were encountered in obtaining a suffi­
ciently large number of patients for detailed analysis of 
tissue polarization in different lung lesions. Permission 
~gluc.aQon 
,1mg leplnephr 
0.05mg 
lepinephr 
o.0125mg 
minute. Intravenous injections of different pharmacological 
agents were each followed by a slow electrical wave, also pre .. 
viously undescribed. The time-voltage integral of these 
waves was found co be dose· related, within certain limits. Electric potentials 63 Fig. VI: 20. Poorly differentiated myosarcomatous metasta· 
sis in the left lower lobe of a 63-year-old woman. Cellular 
material was obtained via a needle chrough a percutaneously 
inserted plastic tube. The tube was next advanced through 
the tumour into the I eng tissue and filled with 3M KCI in 
2% agar. An t\g-AgCI elecuode was then inuoduced into 
lhe tube. During retnction oflbe electrode, with bridge, the 
elecuic potential was recorded (Fig. VI: 21) against a corre­
$ponding grounded nonpolari7.able elecErode imroduced into 
the subcutis of the chest wall. nowadays must be obtained from a patient only after it 
has been explained that the procedure is part of a 
research program and not exclusively to his or her own 
be.nefit. In twelve patients from whom permission 
could be obtained, the actual technique of examination 
has given essentially the same main information as was 
obtained in the preliminary study: tumours in the lung 
in 
Fig. VI: Zl. Elecuic potential profile through the lung and 
the tumou_r shown in Fig. Vl: 20. Two s-imuhaneous rracings 
obtained with different amplifica tions and cut-off filters. When the exploring electrode was retracted from the lung 
behind the tumour, small elecuocardiographic (ecg) tluctu· 
ations can be seen superimposed on the left in the lower trac· 
ing. Upon en1ering me rumour surface (! ),the electrode re· 
vealed a positive electric potential. Compared to the leve-ls of 
64 Electric powntials Oul do sometimes (8 patients) show an e.lectric potential 
difference in relation to mrrounding lung pare.nchy· 
rna. This potential difference is sometimes electroposi · 
tive, sometimes electronegative in relation to a ground· 
ed subcutaneous reference electrode. A poorly differentiated myosarcomatous metastasis 
in the lung is seen in Fig. VI: 20. The rumour was 
surrounded by an "A" zone, 2 em broad. Two trac· 
ings of electric potential were simultaneously obtained 
from the tumour (Fig. VI: 21). Filters of differe.nt 
frequency were used. The tracings show from left to 
right the electric potential difference in lung behind 
the tumour, then differences of about 5 mV of poten· 
tial in three portions of the tumour, a region of in· 
creased amplitudes of ecg fluctuations in the "A" zone 
and lowered ecg amplitudes in the "B" zone, an elec· 
tropositive "pleural spike" and finally the potential of 
the chest wall. It should also be noted that in at least 
one part of the tumour the electric potential was nega· 
tive in relation to that of the surrounding lung. The appearance of a higher amplirude of the super· 
imposed ecg in the "A" zone compared with the "B" 
zone is of certain interest. As will be seen later (Chap· 
ter XVI), it is possible to produce "A" and "B" zones 
experimentally. A tracing of the electric potential 
across such zones during the production of superim· 
posed pulses simulating an ecg can also produce the 
sudden change of amplitude between the "A" and 
"Bu zones. This phenomenon can be explained as a change of 
conductivity depending , for instance, on differences in 
ionic composition or concentration between the "A" 
and "B" zones. The uA" and .. 8" zones seem in this 
way to be characterized by bioelectrical eorrespon· 
dences tO their radiographi c appearances. Fig. VI: 22 illustrates a squamous cell carcinoma 
Lung 
Pleura 
Chest wall 
potential in the surrounding pulmonary parenchyma, are· 
gion of relatively negative po1emial can be seen inside the ru­
mour. When the elecuode entered the "A'• zone of the lung, 
increased ecg fluctuations are seen until the "8" zone ( J) 
was entered, where the magnitude of ecg fluctuations is ap­
proximatel y halved until the pleura was reached. After the 
exploring electrode uaversed the pleura ( J ), the ecg Ouctu· 
ations from the chest wall are relatively very small. Fig. VI: 22. Squamous cell carcinoma, right upper lobe of a 
64·ycaro()ld woman. (a) Posteroanterior projection . The tu· 
mour is surrounded by a trad.iolucent ''A" zone. Irregular 
structures are at the surface of the rumour. An arcade (ar· 
rows) is suggested at the edge of the "B" zone. (b) Shallow 
surrounded by a radiolucent "A" zone. Arrows in Fig. VI: 22 a indicate a row of small arches at the interface 
between an "A" and "B" zone. Fig. Vl:22b shows 
the tumour and the surrounding parenchyma after the 
development of a pneumothorax 1.5 em broad. The 
electric potential difference was measured berween the 
inserted exploring electrode and the grounded refer­
ence electrode in the subcutis. The exploring electrode 
Fig. VI: 23. Electric potentials in the tumour shown in Fig. VI: 22. (a) Posteroanterior view of tumour and electrode. (b-J) Lateral views of tumour and electrode with corrc· 
spooding parts of the rcoordings of electrical potential. Elc· 
a 
2 mv] 
6-824586 NOfdnu.rriim right anterior oblique projection after needle biopsy. A 1.5 
em pneumothorax is prese-nt. The pleura is thin and the 
pleural space open. The "B" zone has :partly disappeared. See also Fig. VI: 23. 
was then slowly pulled out. During this retraction of 
the electrode, the exact position of the electrode tip 
was determined by cineradiogr aphy (Fig. VI: 23). At 
the posterior and anterior partS of the tumour the 
tracing reveals an electropositive deflection of poten­
tial in relation to the surrounding lung. The interior of 
the tumour, on the other hand, shows a relatively 
electronegative potential. vation of elemical potential is seen in the posterior and an· 
terior parts of the tumour in relation to both surrounding 
lung and the interior of the tumour. Grounded reference 
electrode in subcutis. Elect.-ic potentials 65 smv] 
Fig. VJ: Z4. Two inflammatory granulomas (arrows) in a 56-
year-old man. The electric potential of the upper lesion 
shows a IS mV negative deflection in relation to the sur­
rounding lung. Fig. VI: 24 shows two pulmonary nodules in the 
right lung of a patient who was referred for diagnostic 
needle biopsy. The exploring needle electrode was 
inserted through the upper of the two lesions ( diame­
ter 1.5 em). Tracings of potential were obtained, re­
vealing a I 5 m V negative potential difference in rela­
tion to the surrounding lung. Two samplings of cells 
were taken from the upper and three from the lower 
lesion. Histologically the material from aU samplings 
showed macrophages, some inflammatory cells and 
tissue debris, but no neoplastic cells. The cytologic 
results indicated that the lesions were inJJammatory 
granulomas. Electric potential differences also were found in 
nonneoplastic pulmonary masses (30 of 36 patients, 
84 %) (see Section A. 3). F. Summary and conclusions 
These studies of electric potentials, especially in differ­
ent pulmonary lesions in relation to a grounded refer­
ence electrode in the subcutis of the chest wall, have 
revealed: 
66 Electric potentials I) Repeated insertion and retraction of the exploring 
electrode usually produced reproducible differences of 
potential between t~e lesion and the surrounding lung. This has been the case with polarizable metal elec­
trodes as well as with nonpolarizable electrodes. 2) In certain neoplasms and inflammatory lesions, 
the potential of the periphery of the lesion was elevat­
ed or lowered in relation either to the surrounding 
lung or to the centre of the tumour. In other lesions no 
potential difference was present between the lesion 
and the surrounding lung in comparison with the ref­
erence electrode. These findings have shown no corre­
lation to the cellular type or bacteriologic nature of the 
lesion. 3) The cause for this seeming disparity has been 
suspected to depend on the presence or absence of 
local tissue injury. When regions in a lesion showed 
potential differences (positive or negative) in relation 
to the surrounding lung, sampled cytologic material 
was often necrotic and therefore unsuitable for specific 
diagnosis. Statistical proof of such a correlation is 
hampered by many predictable and unpredictable 
variables and would therefore require a very large ma­
terial, which is yet not available. 4) The complex but reproducible appearances of the 
electric potentials in different lung lesions allow only 
preliminary assumptions about their possible origin. Neoplasms and granulomas frequently develop sponta­
neous bleeding or necrosis, a finding common in any 
case material. Such local injuries should have electro­
physiological correspondence in an electric injury po­
tential (a well established concept). The occasional 
finding of polarized lesions in the lung appears to 
support this assumed correlation. Discussion in subse­
quent chapters of physicochemical polarization of in­
jured tissue will provide explanations for variations of 
electric polarity of the lesions and their relation to 
structural modifications inside and outside lesions. The idea is advanced that different regions in cells 
and tissues can be regarded as conglomerations of 
galvanic cells of different capacity and charge. Thus, short circuiting of different parts of normal 
subcutis in the dog produced marked local decrease of 
electronegative potential. The application of an exter­
nal direct current between two subcutaneous elec­
trodes produced marked local accumulation of charges 
in the tissues, which discharged relatively slowly after 
a short circuit was established . This finding led to 
studies of spontaneous electric activity in other organs. These studies are of principal interest because normal 
metabolism in the tissue surrounding a lesion should 
inOuence the internal physicochemical gradients be­
tween the tissues. More easily accessible tissues than 
the lung were therefore selected for these studies. 5) Rhythmic Ouctuations of potential in dog livers 
(frequency about ;..5 per minute, amplitude about I m V) were measured against a grounded reference elec­
trode in the abdomen or subcutis. These fluctuations 
of electric potential have not been described previous­
ly, except for a preliminary report (9), and most likely 
are of neurogenic origin. After intravenous injection of 
pharmacologic agents (epinephrine, histamine, iso­
prenaline, glucagon and others) dose-related waves of 
slowly changing potentials could be induced. These 
findings, also previously undescribed, show how a 
normal tissue apparently may develop electric poten­
tial gradients in relation to a surrounding tissue. It is 
suggested that the rhythmic endogenous waves of the 
liver represent neurogenic potentials which trigger 
metabolic events of the organ, e.g., secretion. The su­
perimposition of rhythmic potentials and slow poten­
tial waves then represent a "demand potential" in the 
organ. The appearance of such demand potentials can 
be expected to depend on factors including size and 
shape of activated tissue, size, shape and location of 
the electrodes. 6) Parietal pleura, but not visceral, demonstrates a 
high "spike" of positive potential ( 15-20 m V) when an 
exploring electrode is passed through the chest wall 
into the lung. This spike was found to be a reliable 
landmark in studying the electric potentials of pulmo­
nary lesions. 7) Electrocardiograms superimposed on the tracings 
of the lung tissue potential profile show higher ampli­
tude in the "A" than in the "B" zones. The explana­
tion for this finding depends not simply on spatial 
location of the electrodes but also on differences of 
conductivity between these zones. 8) The metabolic activities of lung, stomach, liver 
and probably many other tissues may vary local electri­
cal charge, here identified by the presence of waves of 
slowly changing potential. Furthermore, local injury 
in an organ will produce a local accumulation of 
charges ("injury potential" ), e.g., by diffusion of ionic 
products of decomposition. A potential is then created 
between the injured tissue and the surrounding nonin­
jured tissues, each possessing their own metabolic po­
tentials. This concept is important because the differ­
ences of potential between injured and surrounding 
noninjured tissue, in the author's opinion, provide the 
energy necessary to drive the processes of healing. The existence of physiological polarization of tissues 
or organs should, however, also lead to the develop­
ment of normal structura l modifications. With the 
latter possibility in mind, the presence of well-defined 
spikes of electrical potential, such as described for the 
pleura, are of interest. As illustrated in Fig. VI: 25, 
well-defined potential differences are also observab le 
when the exploring electrode passes the peritoneal 
membrane and liver capsule and the reference elec­
trode is positioned in the subcutis of the abdominal 
wall. Associated problems will be treated in Chapter Subcuti.s Subcutis + liver 
(oomv 1min 
I I I I I I I I 
Fig. VI: 25. Tracing of potential of abdominal wall and liver 
in dog. The exploring electrode was inserted from subcutis 
through abdominal wall into liver and back to subcutis. A 
grounded refe.rcnce electrode was placed subcutaneously. A 
negative and then positive deflection was obtained between 
the subcutis and the liver parenchyma, showing regular fluc­
tuations of potential (frequency about 4-5 per minute). In 
the subcutis smaller fluctuations of the same frequency are 
seen (arrows), presumably transmitted from the liver. On re­
traction, electrode passes an air gap between the liver and 
the abdominal wall. The hepatic capsule showed a positive 
deflection of potential. XII, where a mechanism for development of mem­
branes is outlined. The information collected in this chapter is prelimi­
nary but indicates that electro(-chemical) energy gradi­
ents may be identified between different tissues. These 
gradients appear to express differences of local meta­
bolic activities of normal tissue or differences between 
normal and injured tissue. The utilization of such 
energy gradients depends largely on the suggested 
system of selective transport of material which is here 
called biologically closed electric circuits (BCEC). This system will be particularly considered in Chapter 
XII. Chapter XIII outlines the driving energy of this 
system. An understanding of the function of BCEC 
systems requires, however, further studies of its com­
ponents, which will be presented in Chapters VII-XI. References 
1. A.gostoni, E.: Mechanics of the pleural spQce. Physiological 
Reviews 52: 57, 1972. 2. Cooper, R.: Storage of silve.r chloride electrodes . EEG Clin. Neurophysiol. 8:692, 1956. 3. f.>ahlgren , S., and Nordenstr6m , 8.: Transthoracic needle biop­
sy. Stockholm , Almqvist & Wiksell, 1966. 4. Geddes, L.A., and Baker, l. E.: Chloridc:d silver electrodes. Med. Res. Eng. 6:33, 1967. 5. Geddes, L.A., Da CostaJ C. P., and Wi~ , G.: The impedance 
of stainless steel electrodes . Med. Bioi. Engng. 9: Sll, 1971. 6. Grundfest , H., Seng:sl•k~, R. W.1 Oettinger, W. H., and 
Gurry, R. W.: Stainle$5 steel microneedle electrodes made by 
electro-pointing . Rev. Sci. lnstr. 21:360, 1950. 7. Mond, R.: Ober die elektromotorischen Kriifle der Magen· 
schleimhaut vom Frosch. PflUgers Arch. Ges. Physiol. 215:468, 
192611927. 8. Nordenstr 6m, B.: Eloclric potentials in pulmonary lesions. Acta 
Radiol. Diagn. IJ: I, 1971. 9. NordenstrOm, 8.: Electric potential fluctuations in the liYer. IRCS 2: 1666, 1974. Electric potentials 67 10. Nordenstrom, B.: New instruments for biopsy. Radiology 
117:474, 1975. 11. Nordenstr6m, B., and Sinner, W. N.: Needle biopsies of pul­
monary lesions. Fortschr. ROntgenstr. 129:414, 1975. 12. Quigley, j. P., Bar<roft, j., Adair, G. S., and Goodman, E. N.: 
Tbe difference in potential across gastric membranes and cer­
tain factors modifying the potential. Am. J. l)hysiol. 147:67, 
1946. 13. Rehm, W. S.: Evidence that the major portion of the ganric 
potential originates berween the submucosa and mucosa. Am. j. 
Physiol. 147:69, 1946. 14. Riddick, T. M.: Control of oolloid subility tbrough uta poten· 
tial. New York ~ Zeta-Mete r Inc., 1720 Fint Avenue, New 
York, N.Y. 10028, 1968. 68 Electric potentials IS. Satre, H.: Bniehungen de5 Eigenpotcntials der Magenscb.leim­
haut des WannbiOters z.u.r Salzsiuresek.retion . z. Bioi. 9S: 13S~ 
1934. 16. Swyngedauw, j.: Sur l'existencc d'une difference de potentiel 
variable entre Ia boucbe et l'estomac au cours de Ia s6crltion 
gastrique . Cornpt. Rend. Soe. Bioi. 9S: 1431, 1928. 17. Swyngeda uw, j.: Variations du potentiel d~·elop,X dans Ia 
muqueuse ganrique au cours de Ia secretion. Compt. Rend. Soc. Bioi. 98: 1433, 1928. 18. Swyngedauw , J.: Evolution du potentiel d'un «tomac a jeun. Compt. Rend. Soc. Bioi. 99:796, 1928. 19. Weinman, j., and Mahler ~ j.: An analysis of electrical proper­
ties of metal dec.trodes. Mecl. Elect. Bioi. Eng. 2:299, 1964. VII. Spontaneous development 
of a fluctuating injury 
potential in tissue 
The incidence of necrosis in pulmonary cancers is 
difficult to estimate. According to Byrd et a!. (2), 
cavitation develops in approximately 10 per cent of 
primary pulmonary neoplasms. Found almost exclu­
sively in squamous cell carcinomas, cavitation is rare 
in undifferentiated and alveolar cell carcinomas (3, 5). Because necrotic material is not always replaced by air 
wh.ich is radiographically evident in cavitation, the 10 
per cent value probably represents a low estimate for 
the incidence of necrosis in pulmonary neoplasms. In 
the author's experience, adenocarcinoma s and meta­
staticcancers in lung may also be necrotic, but the lung 
tumours wh.ich are most frequently necrotic are defi­
nitely primary squamous cell carcinomas. The low incidence of cavitation in such highly ma­
lignant tumours as undifferentiated bronchogenic car­
cinomas is difficult to explain. One possible explana­
tion would be that such cancers tend to obstruct cen­
tral bronchi by rapid and continuous overgrowth so 
that endobronchial evacuation of the necrotic material 
is seldom possible. Rapid growth of a malignant tumour is generally 
thought to cause imbalance between nutritional supply 
and demand, leading to necrosis. Compression or inva­
sion of an artery supplying the tumour may also pro­
duce necrosis. Erosion of a nutrient vessel also may produce internal bleeding and thereby increase inter· 
nat pressure, inducing necrosis. A thrombus in a blood 
vessel in a lung cancer may be regarded as a metaboli­
cally isolated tissue wh.ich will be subject to autolytic 
changes. Injury of tissue may be produced by circulatory, 
metabolic, mechanical, chemical and electrical factors, 
heat or radiation. From a physical point of view, any 
of these sources can produce an electrical injury poten­
tial. Consider hepatic autolysis as an example of necrosis. Almost no light microscopic changes can be seen dur­
ing the first six hours (I). Thereafter , cell membranes 
gradually disintegrate and nuclei start to show pykno· 
sis. Mitochondria then begin to sweU and vacuoles 
appear in the cytoplasm (II). After about 24 hours 
karyolysis is observed. After 48 to 72 hours most cells 
are necrotic. Electron microscopica lly, changes c.an be 
observed soon after· hypoxia. Saladino and Trump 
(13), studying slices of mouse liver, observed the earli­
est autolytic changes in mitochondria after a mere S 
minutes of hypoxia. When lack of oxygen injures a tissue, lysosomes 
liberate soluble hydrolytic enzymes (7). These en­
zymes are most active in an acidic environment , spread 
into different parts of the cell, and reach a maximum 
Fluctuati ng injury potential 69 intracellular concentration afrer 3 to 4 hours (7). Lyso­
somal enzymes appear to be of central importance in 
proteolytic degradation of cells, a point recently 
stressed by Marzella (12). After lysosomal enzymatic 
digestion is established, other cellular enzymes are 
then continually liberated in the tissue (1, 10, 14). Hydrolases initiate lysosomal action in the liver of 
starVed rats exposed to carbon tetrachloride, according 
to De Duve, et al. (8). The soluble hydrolytic enzymes 
are Feleased across the lipoprotein membrane of the 
lysosome in a primary attack which appears to derive 
from ischaemic injury to the cenrre of the lysosome. In 
addition to the release of lysosomal hydrolases, autoly­
sis is accomplished also by acid pbosphatases, cathep­
sin, P-gJucuronidase, acid ribonuclease and acid des­
oxyribonuclease (8, 9). Studies in organs other than the liver further indi­
cate that the liberation of lysosomal enzymes is one of 
the earliest reactions in the development of autolysis 
(12). In its early stages, autolysis includes an increase in 
tissue weight and then an accumulation of intracellular 
calcium. Dawkins, et al. (6) have attributed the in­
crease in weight to an oomotic effect. This osmotic 
weight increase is also an indication of the ongoing 
destruction of molecules, which as a physical process 
can be characterized as a catabolic liberation of energy. As cells die, they lose their metabolic functions and 
become more acid in reaction ( 4). They change their 
permeability characteristics for ions and macromole­
cules. Inllux of water swells their protoplasm. Granu­
lar bodies appear. Cytoplasm and nuclei coagulate and 
disintegrate into debris (4). The studies of electric potential of lung tumours and 
granulomas (Chapter VI) revealed that potential gradi­
ents of varying magnitude and polarity may be present 
in lung lesjons, relative to a surrounding reference 
tissue. These gradients may be electronegative, elec­
tropositive or even zero. Usually, reproducible profiles 
of potential could be obtained from any particular kind 
of lesion. No correlation could be found between the tissue 
profiles of electric potential in different tumours of 
corresponding size, location or histologic type. The 
variability of the profiles of potential among different 
tumours (and sometimes in different parts of the ru­
mours) nullified attempts at quantitative correlation. Empirically, however, it became evident eventually 
that necrotic material could be obtained by aspiration 
biopsy from most of the polarizing lesions. This preliminary empirical information was next 
turned into directed research attempting to explain the 
finding of inconsistent electrical potential in histologi­
cally similar lesions. Tumours are known sometimes to 
contain internal bleeding or necrotic regions of varying 
extent (2, 3, 5). These changes are a form of injury to 
70 Fluctuating injury potential tissue, which should produce electrochemical injury 
potentials. Necrosis or haemorrhage may well explain 
why a tumour of particular histologic type, size and 
location presents electric polarization in relation to 
surrounding noninjured tissue in one patient while a 
seemingly corresponding rumour in another paticm 
does not show such changes. Furthermore , focal autolysis in a lesion might be 
expected to cause local variations in electrochemical 
potential. Age of the locally degrading process may 
also be a factor. Controlled research on these problems 
would be extremely difficult to carry out in vivo in the 
lung. As focal internal haemorrhage in a lesion is very 
probably involved in the process of polarization, blood 
was chosen as a readily accessible tissue to study in 
attempting to explain the possible origin of electrical 
polarization of lung lesions. A. Degradation of blood 
The development of local necrosis in a surviving sub­
ject is not reStricted to hours or a few days. The whole 
process may be found to modify the tissues during 
months or even years. In the present in vitro experi­
ments, the spontaneous degradation of blood during 
hypoxia was studied over the relatively long time peri­
ods of one to eight weeks. These studies were arranged 
to simulate, at least approximately, the spontaneous 
degradation of clotted blood inside a tumour. Fresh human blood was studied under sterile condi­
tions with regard to spontaneous pH and changes of 
electric diffusion potential (Fig. VII: 1). Twenty to SO 
ml of fresh sterile blood were placed in a sterile collo­
dium bag which was suspended in a jar containing 
I 000 ml of circulating Ringer's solution at 37•c. Three Ag-AgCl electrodes with KCl bridges and three 
pH electrodes were placed through holes in a rubber 
stopper, fitted to the bag opening. A grounded refer­
ence (Lazaran) Ag-Ag Cl electrode with KCl bridge 
was inserted in the Ringer·'s solution. The surface of 
the blood and the Ringer's solution was covered with a 
2 em thick layer of sterile liquid paraffin to prevent 
contact of air with the fluids. The entire apparatus was 
then kept inside a sterilized plastic cover. The pH of the blood and its change of diffusion 
potential in relation to the grounded reference elec­
trodes were recorded intermittently during the experi­
mental periods, which var:ed from one to eight weeks. Experiments on six different samples of human blood 
and two samples of dog blood were performed. Sam­
ples of the blood were taken at different times to 
confirm bacteriologic sterility. The results of these studies showed that pH of the 
blood decreased rapidly during the first days (Fig. VII: 2). The three separate pH electrodes showed 
some internal differences despite careful calibration 
before the experiments. Control calibrations after the 
experiments usually showed some differences among 
the c:lectrodes, panicularly after they had been im­
mersed in the blood over several weeks. These dispari­
ties probably are a function of different adsorptions of 
vatious proteins on the glass surface of the electrodes, 
an unavoidable aspect of the experiment . A spontaneous lowering of the pH during the first 
days took place equally in human and in dog blood. Measurements of pH and simultaneous electric po-
Fig. VII: I. Apparatus for de<ermination of pH and electric 
diffusion potential of spontaneously degrading blood. A col· 
lodlum bag is filled with blood (I) without citrate or heparin 
and suspended in Ringer's solution (2) circulating at 37"C. 
Three pH electrodes (3) and three Ag-AgCJ electrodes (4) 
(one of esc:h illustrated) pass throogh a rubber stopper (5) 
and arc immetsed in the blood. A grounded Lazaran refer­
ence electrode (6) is placed in the Ringer's solution. A cover· 
ing tltick la)·cr of liquid paraffin (oot illustrated ) prevents 
contact of air with the blood and Ringer's solution. A stirrer 
(7) circulates the Ringer's solution. ... 
7.00 
Fig. VII: 2. Spontaneous changes of pH in degrading human 
blood (without cittate or heparin) during 40 days. Initially, 
pH lowered rapidly. Tracings are from each of the three 
electrodes . tential of diffusion in the blood in relation to the 
Ringer's solution are illustrated in a representative 
example in Fig. VII: 3. The diffusion potential of the 
blood showed considerably greater fluctuations than 
the pH. The changes of potential spanned as much as 
200 mV during the first days and 250 mV between the 
maximum and ntinimum fluctuations during the ex­
periment . The pH fluctuated in this experimeot about 
one pH unit (equivalent to 61.54 mV at 37"C). The 
arrow "sterile" shows the time when a Satnple of blood 
was taken for bacteriological culture. This sample was 
sterile. Some hours after the sampling, the pH and the 
electric potential showed large fluctuations. A new 
blood. sample taken 8 days later showed the growth (X) 
of nonfermenting, gram-negative , aerobic rods. Early development of acidity in the spontaneously 
degrading blood has been a constant finding in these 
experiments . Initially, the corresponding electric dif­
fusion potential has shown large electropositive fluctu­
ations. Later, a varying pattern of fluctuations of pH 
and diffusion potential has been observed , including a 
tendency toward increasing stabilization . Inlet of air or 
infection of the blood has always disturbed this ten­
dency immediately. These experiments have been performed to obtain 
information about electrical changes of blood degrad­
ing over a relatively long period of time. It is apparent 
that control of the experimemal conditions could be 
improved , e.g., with regard to glucose level and oxy­
gen coment of the blood at the beginning of the experi­
ments. Deviations from in vivo conditions apply in 
these experiments also to several other variables, e.g., 
Fluctuating injury potential 71 mV 
•SO 
pH 
6.S 
1.0 o'~---
7.5 
-so 
-100 
0 pH 
EL. POTENTIAL 
HOURS 
s 10 10 
Fig. VI/: 3. Spontanoous fluctuations of pH and elc:ctric dif· 
fusion potential of spontaneously degrading human venous 
blood. The fluctuations of the "total., diffusion potential are 
considerably more pronounced than the changes of pH. The 
early electropos itive a.1d electronegat ive fluctuations of the 
diffusion potential cover a span of about 200 mV. The last 
composition of the surround ing medium and the simu· 
lation of a tumour barrier by the semipermeab le collo· 
dium membrane. Furthermore, immersion of elec"' 
trodes for several weeks in blood causes apposition of 
material on their surfaces, which must disturb their 
sensitivity. Besides the pH and the difference of "to­
tal" diffusion potential, redox potentials should also be 
studied in this way, but were not included in the 
present initial study. In performing an experiment on 
hypoxic degradation of blood we have, however, aJ. ready by defmition , this important additional factor in 
mind. So far we may limit ourselves to conclude that 
the actual experiments support the view that the spon· 
taneous hypoxic degradation of blood includes a focus 
of electric "injury" polarization in relation lO a "nor· 
mal" surrounding medium. Evidently this is also a 
dynamic process characterized by considerable electri· 
cal fluctuations in the early phases, followed by even· 
tual attenuation as the reactions drive toward equilibri· 
urn. 72 Fluctuating injury potential STERILE l 
DAYS 
20 30 40 50 
sterile bacteriological test sample was obtained after 40 days. Mter this sampling, the pH and electric potential suddenly 
moved in an electronegative direction. New sampling of the 
blood showed bacterial growth (gram-negative aerobic rods), 
presumabl y caused by bacterial contamination during the 
previous sampling. B. The fluctuating 
electrochemical potential of 
an injured tissue 
The spontaneo us changes in electric potential of hy­
poxic blood can be regarded as a degrading molecular 
process in which an ele-ctrochemical injury potential' 
develops. This process is catabolic; it liberates energy. Its progress in one direction will, as in all spontaneous 
r-eactions!> induce counter .. reactions. EventuaJly this 
combination will lead to a fluctuating attenuation 
toward equilibrium. The actual electric (physicoche· 
mical) potential should therefore vary depending on 
the phase of development of the degrading tissue. This mechanism may explain the observed variety in 
electric potentials of lung tumours in vivo. Cell death is known to be accompanied by a series of 
events in which the lysosomes play an imponan t role. Lysosomal liberation of different enzymes leads to 
decompos ition and splitting of cellular molecules. The necrotic mass may liquify by the action of hydrolytic 
enzymes. Energy produced by the degrading processes now 
becomes of particular interest. To explain the changes 
of electrical activity and pH illustrated in Fig. VII: 3, 
the following synthesis of known facts may be offered. Many well-known chemical reactions participate in 
the early production of acidity in autolysis. During 
hypoxia, oxidation of glucose ro C02 and water will 
deplete locally available resources of oxygen. Contin­
ued glucolysis will proceed as anaerobic production of 
lactic acid, a main compound responsible for local 
tissue acidity. Experiments of Gallagher, et at. (9) 
suggest that one of the first manifestations of tissue 
injury is a loss of A TP. As oxygen levels in autolysing 
tissue progressively diminish, the Krebs cycle de· 
creases in quantitative importance. As ATP diminish· 
es, the ATP·ADP system turns into an irreversible 
hydrolytic reaction, 
ATP+ H2Q-.AOP+phosphate + H+ +energy. The initial phase of low pH (Fig. VII: 3) only repre· 
sents a minor part of the early electrOpositive potential 
difference between degrading blood and a surrounding 
reference medium. A multitude of reactions are known 
to take place in autolysis of tissue (9, IS). It is, howev­
er, here beyond the intentions or even necessary to 
discuss many of the complex, possible series of bio­
chemical events described in autolysis. It may be suffi. cient to establish that degrading tissue develops an 
early electropositive transient phase which is partly 
caused by acidity. The early acidity (Fig. VII: 2) is evidently explain· 
able as a statistical , intermediate phenomenon between 
the production and disappearance of acidic products 
by diffusion, migration and recombination. Because protons among all ions possess the fastest 
rates of diffusion and a high tendency to recombine 
with counterions , the relative loss of prorons is prob· 
ably the leading reaction in the events which subse· 
quently drive the tissue in an electronegative direction. The tendency of the degrading blood to change from 
electropositive to electronegative is further enhanced 
by hypoxic production of anions, e.g., phosphate ions, 
which gradually appear as ATP undergoes hydrolysis. Other sources for the production of phosphate ions are 
phosphocreatinin , phosphoarginine and polymeta· 
phosphate. An accumula tion of phosphate ions is of 
particular interest for tbc eventual development of 
calcifications in tissue injury. When degrading tissue turns electronegative , differ· 
cnt cations will be anracted to the accumulating an· 
ions. In particular, ea++ and Mg•+ will be attracted 
to the accumulating phosphate ions and should preci· 
pitate as calcium and magnesium phosphate when the appropriate isodectric regions for these compounds 
have been reached. In this way the development of 
apatite, which is the most common calcium-conta ining 
salt deposited in injured tissue, can be explained. As 
apatite forms and anions then become depleted, the 
overall reaction might then be anticipated to drive 
again in the electropositive direction. An overview now must consider the observed elec­
trical events as applying to a large number of ions of 
different sizes, electrical charges, concentrations and 
specific activities. Thermal factOrs, pressure, gravity, 
externally superimposed electromagnetic fields, con­
vection, diffusion and local circulation must further 
interact with this behaviour. One factor which will be 
particularly considered in this work is the effect of 
biologically clostd electric circuits between a pathologi· 
cal injured tissue and the surrounding normal tissue, 
electrochemically polarizing against each other. It is easy to understand that a local injury of any 
kind represents a region with a level of entropy, which 
under the influence of factors, such as those men­
tioned above, must drive toward a higher level. Af· 
ter the injury has healed macroscopically , a pseudo· 
equilibrium is reached (as further transformations of 
tissue will take place, but at a slow rate). The differ· 
ences in speed and intensity of the partial reactions 
during different stages of their development can be 
anticipated to result in a fluctuating but anenuating 
sum of the partial reactions. This perspective gives an 
explanation for the sometimes electronegative, some· 
times electropositive polarity of an injured tissue in 
relation to its surroundings. The injured tissue pre· 
sents different phases in its development. As a conse­
quence of this view, it can be seen that sampling of 
material for measurements of electric potential (and 
chemical analysis) of injured tissue is rather meaning· 
less unless the results are related to the momentary 
phase of the natural history of the injury. Thus far the presentation has mainly been con· 
cerned with electrical factors in tissue polarization, 
while concentration-activity , pressure-volume and 
gravity have as yet received only passing mention. The 
important chemical forces will next be briefly dis· 
cussed (Chapter Vlll), followed by an experimental 
demonstration of interactions between electrical and 
chemical forces (Chapters X, XI). Reference s 
l. Bc:renbom , M.: Chang, P. L, lkl:z, H. E., and Stowell, R. E.: 
Chemical and enzymatic changes aS$0Ciatcd with mouse liver 
necrosis in vitro. Cancer Res. 15: 1, 1955. 2. 8)•rd, R. B., Miller, W. E., Carr, D. T., et al. : The roc-ntgeno· 
graphic appcanncc of squamous cell carcinoma of the bron· 
c:hus. Mayo Clin. Proc. 43: 327, 1968. Fluctuating injury potential 73 3. Byrd, R. 8., Miller, W. E., Carr, D. T., et al. : The roentgen~ 
gra;phic appearance of small cdJ carcinoma of the bronchus. Mayo Clin. Proc. 43: 337, 1968. 4. Cameron, G. R., and Spector, W. G.: The chemistry of the 
injured cell. Springfield , Ul., Charles C. Thomas Publ., 1961. S. Cttaudhuri, M. R.: Primary pulmonary cavitating: carcinomas. Thorax 28: 354, 1973. 6. Dawkins, M. J. R., Judah, J. D., and Rees, K. R.: Factors 
inRuencing the survival of liver cells during autolysis. J. Path. Bact. n: 257, 1959. 7. De Duve, C., and Beaufay, H.: Tissue fractionation studies. 10. Influence of ischaemia on the state of some bound enzymes in 
rat fiver. Biochern. J. 73:610, 1959. 8. De: Duve, C., Wauiaux, R., and Baudhui.n , P.: Distribution of 
enZ)'ITIC$ between subcellular fractions in animal tissues. AdV1n. En.zymol. 24:291, 1962. 9. GaJLagher, C. H., Judah, J. 0., and Rccs, K. R.: Enzyme 
cha113es during liver autol)"is. J. Path. Bact. 72: 247, 1956. 74 Fluctuating injury potential 10. Gossn.c-r, W.: Untenuchu.n.gen ii.ber das Verhalten dc:r Pbospha­
tascn und Esterascn wihrend der Autolyse. Arch. Path. Anat. 327: 304, 1955. 11. Holle, G., Burkhardt, R., Arndt, S., and BJ6dorn, M.: Obt:r 
manometrische, histochemische, his-tologi.sc.he und phasenop­
tische Befunde bei ischimischer Hypoxydose . Virchows Archiv 
327: 150, 1955. 12. Marzella, L.: SlUdies on mechanisms of intracc.lluJar degrada­
tion with special reference to lysosomes. A biochemical and 
elecuon microscopic study. Thesis, Dept. of Pathology, Hud· 
dinge Hospital, Huddinge, Sweden, 1979. 13. Sa1adino, A. J., and Trump, F.: lon movements in ttll injury. Am. J. Pathol. 52:737,1968. 14. Wah.i, P. N., Tandon, H. D., and Bharadwaj, T. P.: Acute 
carbon teuuhloride hepatic injury. Acta Patb. Mk:robiol . Scand. 37:305, 1955. 15. Van Lancker, j. L.: Molecular and cellular m.ec-banisms in 
disease. Berlin, Springer, 1976. vm. Concentration-dispersion forces 
A brief review of intermolecular 
physical behaviour 
Present knowledge of concentration and dispersion 
forces is incomplete in many respects (7, II). Still, 
their importance can often be recognized , even if only 
indirectly. This chapter offers a shon survey of these 
forces. Some physical models will be presented in 
Chapters IX and X. Implications of these models will 
then be illustrated in further experimental studies of 
structural development in vivo (Chapter XI). The concentration -dispersion forces are long-range 
or short-range (3, 4), depending on the presence or 
absence of exchange of electrons among molecules. Long-range forces are of three main types: electrostat­
ic, induction and dispersion (2, 3, 5). The short-range 
forces are of two main types: overlap repulsion (van 
der Waals' forces) and fixed-cha rge electrostatic 
forces. They all constitute extremely complex, inter­
acting variables , even in relatively "simple" and uni­
form systems such as water. These forces, still obscure 
in many respects, are of fundamental importance to 
the physit. :aJ bc::haviour of mauer. The interactions of concentration forces constitute a 
basis for understanding the development of structure 
in normal and pathological tissues. The structural 
changes around the pulmonary and mammary lesions 
presented in this book may be regarded as induced by 
local degeneration of tissue, a rather specific situation in which these forces come into play. Before some of 
these aspects of structural development of tissue are 
considered, physical aspects of concentration and dis­
persion forces will be briefly surveyed (3, 6-10, 
12-16). The interaction between two particles or molecules 
A and 8 may be written as a potential energy function 
U_,8• The force between A and 8 depends on their 
separation d and the spatial orientation of their polar 
moments, which may be induced or permanent. Be­
tween A and 8 the force F!V., is written: 
F . = +kA8 
AH -dup 
where the function is negative when the net force is 
attractive and positive when the net force is repulsive 
(4). The constant k is specifically determined by A8, 
and the exponential function of d by the rotational or 
stationary potential energy of particles. For an infinite separation of panicles the U AB ap­
proaches zero. When rwo particles approach each oth­
er within a distance of, e.g., some molecular diameters, 
the UAB is either positive, zero, or negative. For most 
particles the observed value is negative, as in condens­
ing water, or zero, as in clustered water molecules with 
a fmite volume. The low compressibility of ice shows 
Concentration-dispersion forces 75 F 
REPULS ION 
b 
R 
d 
ATTRACTION 
Fig. VIII: I. Besides "ordinary" electrostatic forces, attrac· 
tivc and repulsive forces of the van der Waals' type are im­
portant for structural development.
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:

        A platinum electrode was inserted into the 
catheter, which was irrigated continuously with phys-
Fig. VI: 13. Artificial electric charging and discharging of 
li•;ng tissue of a dog. One platinum electrode was placed 
against the mesentery and one in the lumen of the aorta via a 
fe. moral catheter. A 23 volt potential, giving initially 6. 5 mA 
current, was applied between the electrodes for 15 minutes. I. 8 volts were then measured between the electrodes. The 
c111rrent flow between the electrodes was then read by means 
of a digital microampc: rcmctcr in parallel with the voltrne~c. r. The initial part of the discharge took place very rapidly he­
tween the cessation of applying potential to the eltctrodes 
and the first measurement. Initial current values are there­
fore not included. 10 
5. 04---------~--------. -------~r- -. 0 5 10 IS tnt. n 
58 Electric potentials iologic saline solution. The abdomen was surgically 
opened. Another platinum electrode was directly 
placed against tissues of various organs, e. g. , mesen­
tery. A direct current potential of predetermined mag­
nitude was applied between the electrodes for one to 
several minutes. The potential difference between the 
two electrodes was then measured with a millivolt­
meter immediately after interruption of current flow. The electrodes were then short circuited over a mi­
croamperemeter in parallel with the millivoltmeter. The values of current and potential were then read at 
regular intervals and plotted against time. These experiments revealed in the 5 dogs that in 
vivo an artificial electrical charging and discharging of 
a tissue was easily demonstrated. Thus, in the experiment illustrated in Fig. VI: 13 a 
potential of 23 volts at an initial current of 6. 5 rnA was 
applied between the aorta and a mesenteric electrode 
in a dog. After 15 minutes, a potential of 1. 8 V was 
measured between the electrode-s. The electrodes were 
then connected to each ot. her over the microampere 
meter. The current-time integral of the discharge is 
illustrated in Fig.
6.5 mA
What was the initial current between the electrodes in the experiment illustrated in Fig. VI: 13?
1.8 V
What was the potential difference measured between the electrodes after 15 minutes in the experiment illustrated in Fig. VI: 13?
Non-polarizable Ag-AgCI electrodes with KCI bridges
What type of electrodes were used in the studies of electric potentials in the chest wall, lung, and other tissues?
To investigate the possibility of diffusion potentials participating in the development of electric potentials in tissues
What was the purpose of the study on the electric potentials of normal and pathological tissues?
To investigate the potential differences between the lesion and the surrounding lung tissue
What was the goal of the study on the electric potentials of lung lesions?