The Electrourogram III. Experimental Work in Dogs

THE JOURNAL OF UROLOGY

Vol. 77, No. 3, March 1957 Printed in U.S.A.

THE ELECTROUROGRAM III. EXPERIMENTAL WORK IN DOGS ALFRED W. KNEUCKER From the Department of Si,rgery, Chicago Medical School, Chicago, Ill.

This is the third of a series of papers on the Electrourogram. In the first we showed its existence.* The second communication, describing experiments on rabbits, demonstrated that each part of the kidney produces a specific curve. t It was shown further that the curves of the renal parenchyma are entirely distinct fro1n those of the hollow structures, i.e. pelvis and ureter.t It was also shown that the curves of the renal parenchyma are influenced by the action of diuretic and antidiuretic measures. The present report deals with experimental work performed on dogs TECHNIQUE

The experiments were performed under general anesthesia. Nembutal intravenously, in doses of 10 mg. per lb. of body weight, was found to be the anesthetic of choice. The volume of solution injected must be limited in order to avoid excessive diuresis from larger infusion which profoundly affects the curves. Morphine or demerol premedication should not be used because they are antidiuretic. One of the major problems is the elimination of confusion from respiratory curves. This can be accorn.plished in various ·ways: a) Some dogs breathe slowly and superficially under anesthesia. These are ideal for the experiments but, unfortunately, they are very rarely encountered. b) Artificial respiration with a mechanical resuscitator is the principal method employed to deviate the curves produced by breathing. Only pure oxygen should be used. A tracheostomy should be performed and a Foley-type tracheal tube inserted. This diminishes respiratory effort but does not completely abolish it. c) In order to eliminate it completely, phrenicotomy through the opened thorax may be performed. However, in many animals, after a brief period of cessation, some respiratory movements are resumed. d) Tubocurarin, 0.1 mg. per pound of body weight, slowly injected, is often helpful, but some animals react badly and succu111.b rapidly. e) Anectin (succinyl choline chloride) intravenously in 0.4 cc doses will stop the breathing for some time. It may be repeated if necessary. In our hands, mechanical respiration with tracheostomy and anectin gave the best results, and the complicating influence of the respiratory curve was almost negligible. The animals are starved for at least 8 hours before survery. Immediately before the experiment starts, 50 to 100 cc physiological salt solution is administered subcutaneously to provide adequate diuresis. In dogs the right kidney usually lies just below the twelfth rib, whereas the left kidney is located a little lower in the retroperitoneal space. It is, therefore,

,r Accepted for publication * J. Urol., 69: 458, 1953.

t J. Urol., 75: 250, t Author has found

September 29, 1956.

1956. out from many personal communications that the electrourogram has quite often been mistaken for the electroureterogram. 537

538

ALFRED W. KNEUCKER

helpful to resect the twelfth rib on the right side. The exposure of the organ is generally similar to that in human beings. Care should be taken not to displace the kidney which might distort its circulation. A Sanborn Twin Viso apparatus* which permits the simultaneous registration of electric potentials from two organs (both kidneys, kidney and adrenal, kidney and ureter) was used in the experiments. It should be mentioned that curves obtained through different techniques look different. t A single channel machine in which the speed can be adjusted may also be used; however, registration of only one organ or one part of an organ at a time is often not satisfactory for experimental work. Either uni- or bipolar registration may be made. After a considerable number of experiments in dogs and rabbits, the bipolar registration became the method of choice. As electrodes, needles are used, which can be introduced either superficially into the renal parenchyma to register the potentials from the cortex (electrofliogram); or more deeply into the renal substance to register the potentials of the medulla (electromyelogram). If the needles do not snugly fit the metallic ends of the cable, adapters must be used.t If curves are registered percutaneously, as is the rule in man,§ only the tips of the needles should conduct electricity; thus 3 to 5 mm. of the needle remains uncovered while the rest is insulated, preferably with baked-on enamel. ,-r The two needles inserted into the renal parenchyma represent the active electrodes for bipolar registration. Other needles serve as inactive electrodes; they are inserted deeply into the adjacent muscles. Concerning the leads there are the following possibilities: a) Unipolar registration. In the rare cases where the registered curves are to be unipolar, the patient's cable which has 5 wires may be used in the following manner: Four inactive electrodes (needles) are inserted somewhere into the muscles; the active electrodes connected to the chest wire (colored brown) are inserted into the renal tissue. If unipolar registration of both kidneys simultaneously is desired the one-wire cable, also colored brown, is connected to the needle which is thrust into the second kidney. The machine has to be set on the V-lead after speed and sensitivity have been adjusted. b) If we want to register bipolar potentials from one kidney, which is the usual technique, we take the RA and LA wires (colored black and white, respectively), connect them to two needles inserted into the kidney and set the machine on Lead I. The inactive electrodes, attached to the other three wires (red, green, brown), are placed as before, somewhere in the adjacent muscles. c) The Sanborn Company modified their Twin Viso apparatus for our purpose in the following way:

* Sanborn Company, Cambridge 39, Mass. t When, as it will be pointed out later, the electrogastrogram was registered these curves

differed considerably from the curves Goodman demonstrated in his work with the stomach. See Goodman, E. N., et al.: Gastroenterology, 29: 598 (October) 1955. t Manufactured by Sanborn Company. § See EUG IV in this issue of J. Urol., pp. 543-548. ~ Such needles are manufactured by Cameron Surgical Specialty Company, 666 W. Division St., Chicago 10, Ill.

ELECTROUROGRAM IIL EXPERIMENTAL 1VORK

539

The standard 3-wire input cable is connected to the AC an1plifier jack on the Sanborn Twin Viso DC amplifier and recorder. By this means the signals from the organ being measured are fed directly to the standard input circuit of the Sanborn electrocardiograph amplifier. The white and the black wires represent the active electrodes, the green wire the inactive electrode. Since we have two 3-wire input cables for the two channels of the Twin Viso machine, simultaneous bipolar records of both kidneys can be made, which is the ideal method of registration. The speed of the machine must be adjusted to the needs of the experiment. For short examinations (and especially if the curves are to be studied as to whether they are influenced by action potentials from the heart or lungs; or in order to measure the distances between the peaks of the waves), the recommended speed is 5 mm../sec., or one-fifth of the regular speed of the electrocardiograph. For long registration, as is the case with human beings, a speed 0.5 mm./ sec. is desirable. The question of sensitivity has not yet been answered. The standard sensitivity of 1 mv = 10 mm. on the paper is usually sufficient, but there are conditions under which an increased sensitivity, as for example 1 mv = 15 mm., seems to give better results. RESULTS

A) The following observations confirm beyond doubt that it is the renal parenchyma from which potentials are registered: I) If both ureters are exposed, severed from the bladder, and cannulated with vinyl tubes, the excreted urine is readily observed. If curves from both kidneys are registered at the same time it becomes obvious that diuresis and writing are parallel.* In addition, if the quantity of excreted urine is measured it will be seen that the larger the amount of excreted urine the higher are the amplitudes of the curve. 2) If the diuresis is increased or if diuretics arc administered, the amplitudes of the curves are increased; if antidiuretics are applied the amplitudes of the curves decrease. If the renal pedicle is tied~which is a surgical antidiuretic measure--the curves flatten. t ~1) If the ureter is tied at the ureteropelvic junction the kidney stops working; accordingly the kidney stops writing. The curves either fade out or change into curves from neighboring organs (see later, influence of curves on each other) . The same is true if the ureteral cannula is blocked by a blood clot. When the blood clot is removed and the urinary flow is restored, the kidney begins ·writing immediately, unless there is another reason for non-registration. 4) Referring to the previously mentioned electrofliogram and electroniyclogram, we see that shortly after diuresis has been induced the curves of the electrofliogram have higher amplitudes than the electromyelogram, because the princi* It takes some time for a drop of urine to travel from the renal papilla to the end of the cannula. Therefore, it may be that the kidney "writes" and no urine seems to appear However, a slight twist of the cannula, or a different position of the kidney reHults in an immediate urinary flow, t This phenomenon was already mentioned in the EUG II.

540

ALFRED W. KNEUCKER

1+:r1. ,: 1 .·"T''T~·~~~ "•:: :

I

!

'.

-"7'"

i

!Tl .,I

'·

'

--

I

.. -~·--r-.-,

,.

!

i :

i

1;:1:,_:1rl

;iJI i:j1) lllilll ,1, ,i::

1[·,111

i

1

11

~n"' ... ,

I-

H

.

11F1f'i'!l1'il I' ''"' li!lilli!lli!III illl, li 11:1,111::Jl;:i! ,, ':i ·' ., ,._ 1

161111

.

~

1

1

,.

·:

I

·1, I I '1:·,

U. 11.L

,; :,,,,,

.

l Fm. 1. EENG

1

j-.

·;

.,

!

I I

'

-~

.1

,.,

,

I

'

..

,

_,.'...'._ --· ___:_;_:_.._ :...c_,,

electroepinephrogram; EUC

=

!ii:

I

,,,

::::;rii

i!!

ii

l[I _1;

:,,iil ;

electrourogram

=

'R+~+.cl~-h-11"'¥ i''i+'+''H++-JJ''.:..J' 2'+,.'+-1+·'+'"+··'.µ'·~1'.-..'+''4' +H++II,-+-t-++t-+c-t·J I i 1:, i ,,,,, i

i..cr:+.+1-++.cil-+llH·,

I '-1

1

,,

,

,.,,

:, ,;;.

.

:.

'

'

.

·.

.

I

'

I.•·: i ii

i1·II '1:'1,.''Ii' l'iIii' ·; tl[i i 1:...'

I

i

l!I

,.

·1: r'

I,

:ii

:1.

f!!

'i

l

I' ----

!

', 1

1, :'

'

....

,.,

,:,,,,

,,

'

lil!llil I

l lil!llll/11!III

·, 1,1'·,1

ii

'I

,i' Iii 11,·i

,,,,i''.lii

I

i

',_1.

i

\J:>i..:

'

I'

"- :..:.:::·'"

,

"c':c ,, >, ,, ,. ..-,," Fm. 2. RT= right testicle; LT= left testicle; A= artefact. In this registration, functions of testicles alternate. i

'

,

,

,

I,

:

Fm. 3. RK

=

right kidney; LK

.· , ,,

=

left kidney

pal work of the kidney at that time is done by the cortex (glomeruli). About 10 minutes later, the medulla has to do the greater work and the curves of this part of the kidney (tubuli) show the higher amplitudes. Still later, the curves of the renal pelvis and the ureter have the highest amplitudes.* 5) The excised kidney which has neither circulation nor nervous impulses continues to write for 10 to 15 minutes (see EUG II). Parenthetically, the excised kidney keeps writing longer than any other excised parenchymatous organ, such as the liver. B) Tracings of organs of the same tract resemble each other. Thus, the curves from the adrenals which are histogenetically akin to the kidneys, resemble

* See EUG II.

ELECTROUROGRAM III. EXPERIMENTAL WORK

54:1

the renal curves (fig. 1). If a kidney is removed and tracings are taken after the wound has properly healed, curves from the adrenal of the same side can be registered percutaneously. These curves cannot be registered as long as the kidney is present. For the reasons for this phenomenon see under E, 4. Finally, curves can be easily traced from the testicles, be it that the organ is exposed surgically, or that the curves are registered with needles inserted percutaneously, or taken with flat plates placed outside the scrotum over the testicles (electro-orchidogram, fig. 2)* The testicular curves resemble the renal curves, too. C) As described in EUG II, the two kidneys often function alternately (fig. 3). Concurrently, the amplitudes of the renal curves also alternate. At a given time the left kidney, for instance, is more active than the right and, accordingly, the left kidney shows higher amplitudes. Ten minutes later the right kidney is more active and the amplitudes of this kidney increase. The same phenomenon can be observed very often when both testicles or both adrenals are registered simultaneously. t D) It may be that from one organ or, in rare cases, from both organs, no tracings can be recorded, although the machine is hooked up properly and there are no other technical errors.t E) Functional activity of neighboring organs exert a definite influence on the renal curves. 1) Mention has been made above, and also in earlier reports, of the influence of respiration upon the renal curves. 2) Similarly, the motion of the heart, the diaphragm, and the large vessels exerts an influence on the renal curves particularly during percutaneous registration of renal curves in human beings. However, the spikes of the superimposed electrocardiogram are easily detected and can be avoided if the electrodes (needles) are either placed away from the large vessels (renal artery, aorta) or in the vicinity of such high vascularized organs as the kidney (pararenal) and not into the organ itself.§ 3) If the animal is fed a large meal just before the experiment starts, an electrogastrogram may be obtained. 4) Potentials from the kidney suppress the registration of the adrenal curve in the living animal (electroepinephrogram = EENG). The larger organ is electrically more powerful. Therefore, the larger kidney overcomes the potentials of the small adrenals as, under rare circumstances, the immense size and electrical strength of a full stomach overpower the renal curves. Therefore, it can be said that the electrical competition between organs depends * In consequence, but of no interest for the urologist, electric potentials can be traced from all organs including the skin. One is, therefore, entitled to speak of Electrosplanchnography or Electrohistiography. t Figure 2 shows the curves from both kidneys taken simultaneously; the left kidney is more active during the time of registration. t For reasons see EUG IV in this issue. § See EUG IV, pararenal position of needles in the human EUG. In the animal experiment the needles may be inserted into the renal parenchyma and yet spikes from the electrocardiogram are seldom seen, most likely since the kidney is dislocated and the circulation additionally changed somewhat on account of narcosis and surgery.

542

ALFRED W. KNEUCKER

upon the size or functional strength of the organs involved, their position in the neighborhood, and their movement. It is sometimes difficult to exclude these influences in order to get the genuine, unaltered curve of an organ. SUMMARY

The nephron itself and its parts are the carriers and sources of renal potentials. Curves of organs of the same tract resemble each other. Curves can be registered from all organs. The function of paired organs and, accordingly, the height of the amplitudes of their curves, alternate. The curves usually influence each other; special ways had to be found to get pure curves from the organs under investigation. The technique of the experimental EUG in dogs is described in detail.

3001 W. 19th St., Chicago 23, Ill.