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Electrocardiographic changes associated with experimental alterations in blood potassium in cats
ELECTROCARDIOGRAPHIC EXPERIMENTAL
CHANGES ALTERATIONS
POTASSIUM I?. L. CHAMBERLAIN, KU.,
IN
ASSOCIATED IN BLOOD
WITH
CATS
J. SCUDDER, ?ul.D., AND R. L. ZWEMER,PH.D. NEW YORK, N. Y.
T
HE increasing interest in electrocardiographic abnormalities which are not due to structural changes in the myocardium has prompted our study of the effect of potassium on the electrocardiogram. An intimate relationship of potassium to automatism and to bioelectric phenomena seemsfairly certain, in the light of current knowledge, and numerous investigators have studied the effects of potassium on heart muscle st,rips, the intact heart,, and heart-lung preparations. Electrocardiograms with concomitant pot,assium determinations on the intact, unanesthetized subject following potassium administration are rare. Wiggersl produced elect,rocardiographic changes similar to those due to coronary occlusion by applying wit,h a brush a 20 per cent solution of potassium chloride directly to the ventricle of the dog. Wiggers and his associates?,3 described electrocardiographic changes in dogs following intravenous and intracardiac injections of potassium chloride. These changes varied with the amount of potassium chloride injected and with the site and speed of injection. Concentrations of serum potassium were not determined. Harris and Levin4 noted slowing of the human heart and slight diminution in the height of the P waves following the administration of 5 cc. of 5 per cent potassium chloride solution. They conclude that there is no relation between electrocardiographic changes and concentration of potassium in the serum, but from the data presented this conclusion does not seem justified. In five experiments on four dogs, Winkler, Hoff, and Smith5 found marked changes in the electrocardiogram, with eventual cardiac arrest, following the intravenous administration of 1.12 per cent potassium chloride solution at the rate of 10 C.C.per minute. In the present study the potassium chloride was given intraperitoneally because Zwemer and TruszkowskiG had found that this procedure gave more predictable results and smoother blood potassium curves. I\mTERIALS
AlVD METHODS
Eight normal cats xvex preparedfor electrocardiographicobservation,using the three standard leads. One or two control electrocardiograxnswere taken, and From the Departments of Medicine, Surgical Pathology, Physicians and Surgeons, Columbia University. Received for publication May 28, 1939. 458
and Anatomy,
College of
CHAMBERLAIN
ET
AL.:
ELECTROCARDIOGRAPHIC
CHANGES
IN
CATS
459
whole blood was obtained for determination of potassium content by the Truszkowski-Zwemer method.7 Whole blood determinations are permissible in the cat, since the potassium contents of cells and plasma rise and fall together and are not so widely different as in other species.8 Pota’ssium chloride (10 per cent solution) was then injected intraperitoneally into seven of the animals, and 10 per cent sodium chloride solution into the eighth as a control. Repeated whole blood samplings and electrocardiograms were taken at intervals of from five to fifteen minutes until death or apparent recovery. If death ensued, blood from various vessels (cf. Zwemer and Pikes) and fluid from the pericardium and cerebrospinal system were collected for determination of potassium content. The specific gravity of the blood was measured by the falling-drop method of Barbour and Hamilton.iQ Three cats given potassium chloride recovered. One had been given a sublethal dose, another was treated with a large amount of physiologic saline, and the third was injected with eschatin.”
The outstanding results in the individual animals are given below, and the chief effects of potassium on the electrocardiogram are then briefly summarized. Specific data are given in Tables I and II, and illustrated by Figs. 1 to 5. 1. Cat 3732.-After the administration of 938 mg. of potassium chloride per kg. (in 10 per cent solution) intraperitoneally, the blood potassium content showed a gradual rise from 35.2 to 71 mg. per cent. Electrocardiograms taken at ten-minute intervals showed progressive inversion of the T waves in Leads II and III. These changes were marked; the waves, which had been normally upright, became deeply inverted. When the blood potassium content reached 47.9 mg. per cent (30 minutes after injection), intraventricular block appeared, and the QRS complexes assumed the appearance of those which are typical of bundle branch block. Subsequent records showed a marked increase in the intraventricular block, and what was probably complete auriculoventricular block with auricular asystole or auricular fibrillation. The intraventricular block increased, and the ventricular rate was very slow in the last record obtained before death, seventy minutes after injection. 2. Cat 3734.-After the administration of 963 mg. per kg. of potassium chloride intraperitoneally, in 10 per cent solution, the blood potassium content rose from 22.8 to 90 mg. per cent. Electrocardiograms taken at five- and ten-minute intervals showed, at first, flattening and a tendency to inversion of the T waves in Leads II and III. Partial intraventricular block was first noted when the blood potassium level was approximately 43 mg. per cent. When the blood potassium content rose above 66 mg. per cent, complete auriculoventricular block appeared, wit,h occasional paroxysms of ventricular *For
which
we take
this
opportunity
to thank
Parke,
Davis,
and
Company.
cont,rol maximum 9 deter.
death in 6 hours and 50 minutes
No. 3744 600 mg. KCl/Kg.
~~~
control maximum 9 deter.
death in a convulsion in 140 min.
No. 3743 800 mg. KCl/Kg.
~_~-
control maximum death 11 det.er.
death in 94 minutes
No. 3734 963 mg. KCl/Kg.
:11.8 90.2
-40.0 59.2
110.0
ti(i.0
“:i.cl
BLOOD R (am. % j 35.0 cont,rol maximum 72.0 4 deter.
NO. .&PTD RESULT PROCEDURE No. 3734 -cleatllin 70 min938 mg. utes KCl/Kg.
-~
max.
contr.
contro1 max. later 1.046 I.060
1.054 1.052
1.049
BLOOD SP. GR.
normal to aw. fib. to aw. and ven. stand.
normal to inc. A-V block to aw. fib. or standstill
normal to aur. asyst. to ven. tachysyst. to ven. iib.
160 to 900 to fib.
to 38
VEN.
175 to 190 to 44 181) to 16
~~..._.
plete A-V block and aur. fib. OT asyst.
RHYTHM
to ” ;I ” to -
1.3
to 3 to 0.2 1 to 1.3 to -
r
P-R
.08 to aur. fib.
.08 to inc. block
.O!I to .05 to
SE(‘. .I)li to fib.
none
rt. to P
AXIS
.i”2
.o::
. 0 :: to .nn
.04 to .14
QRS DUR. .I14 t0 .21 QRS
9 to .12
to ci to 19
iso. to -4.5
iso. to +9
SK
3
t.li to t0.8 to -4
tb Il.2
to
iso.
‘I’,
4.2 to 5 to 10-t
VOLT ti.5 10.7 to 15.6
$8
to +5
tl to -G
t’7.5
-7 to i” c)
tl to
+I.2 to to.7
tF t1.2 to
to t1.8 to
tl
to -. 5 to -16.2 t1.3 to t”.O to
t1.2
T,
to -. 8 to -13.3
t4.1
Tz
contr. max. final
‘3X 44.3 26.9
1.053 1 .OGO 1.042
contr . 1 . 05” <) max. 1.061 1.059 final 1 wk. 1.051
normal to uartial A-V blocl; to aur. stand. to A-V block to normal
ltii to 260 to 200
l;S(i -70 -280 to 95
180 to 260 to 170 170 t.0 210
I-COST
normal to partial A-V block, aur. stand. to ven. fib. to ven. tach. to aur. stand.
normal
1.053 1.055 1.053
23.7 49.0 43.7 29.8
normal to partial A-V blocl; to aur. or ven. tach. to normal
1.052 1.059 1.053
No. 3755 recovery control 600 mg. after 2 hr. maximum KCl/Kg. 45 min. final followed 1 week by 30 C.C. later adrenal cortex extract NO. 3754 almost corn- control 600 mg. plete remaximum KCl/Kg. covery in final followed -2 hr. 17 deter. by 500 C.C. phys. saline
eontr. max. final
conk. max. final
29.7 37.8 25.8
nearly reeovered after 1 hr. 37 min.
No. 3752 200 mg. KU/Kg*.
19.5 34.5 20.5
control maximum final F det.er.
apparent control recovery maximum after 4 hr. final 15 min. 10 deter.
No. 3752 400 mg. k-Cl/Kg.
TABLE 'D
1.2 to 3 to 1.5
0.7 to 2
2 to 3 to ?.a 2 to
2 to to 2
.:oo
.09 to .ll
.bo* to .OG .OQ to .14 to 0.11
.E .OG
.oi to .lO
-
rt. to left to rt.
none to left to none none to left to none
rt. to left
.k
.03 to .12
.04 to .20 to .04
.03
.03 to .07 to iso. iso. to f.3
to 7 7 to 3 to 5 5.5 to 12 to 5
iso. 20 to t.ti
8 to 9 to 7
iso. to -2.3 to t.5
+.5 -3
4
4: to
$2 to $5 to t1.3
t6.5 to -.6
tl.5 -. 8 to
t0
$2 to t8 to t2 t2 to t3
tl to $6 to tl
-1
t8 to
t2.4 to t10 to t1.5 t1.5 to t2.5 to tl -. s to
1.0601
45.4
Ih1
?O’
103' -
l”5’
-
1.0583 1.0613
~.
1.0583 1.0578
1.0581
1.0569
1.0526
(h)
UP‘
V.
Tad.
fib.
Aur. standstill Runs of $ V. tach.
115
170 to 120 to 100
75
103
134
136
RATE
EXPERIMENT
aur.
A-V
-Complete standstill a v. fib.
Partial bl. Slower
Tdl.
Tnch.
RHYTHM
PRWW~OI.
SP. GRAV. CAP. BLOOD
45.5
43.4 42.8
34.5
23.7
BLOOD K
50’ 55’ 57’
42’
30 min. 35’ 40'
-KC1 10 min. 15 min. 25 min.
Control
TIME AFTER INJECTION
DETAILED
.7
1.0
2.0
2.0
P
us
.09
.14
.09
.09
P-R
8.16
.14
.I” .16
.lti
.09
.05
.04
DUR.
QRS
CM~ No.
Lt. B
Lt.
Lt.
Lt.
No
No
No
II (tiO0
.ZSIS DEV.
3755
TABLE
3.3
t::
t2.0 -
t3.5
tl -. 5 t1.2 t.4
QKS I
Mc.
8-3
-3
tl -3
-6
4-12
+4
t4.7
QRS II
f-6
fl -8
-10
-7
-2.::
-2
-1.5
-1.7
0
t-l-2
t9 to t7
0
Tl
Trmn-
t5.5
QRS III
KC~/KILO,
?+4.5
t5
+4.5
t6.5
-4
-1
-.8
TX
hus~s~r,
$t2
t7
t8
ts
t.6 -4.0
-.8
-.8
T,
KC1
REMARKS
C.C. 10% traperitoneally.
EXTRACT)
injected
in-
Sinus rhythm has appeared again and bundle branch block is less marked. Marked improvement. intracardiac injection 10 C.C. eschatin. Ventricular fibrillation. Marked increase in EKG abnormalities. 10 C.C. esehatin intramuscularly.
Prolonged A-V and intraventrieular eonduct,ion. Marked changes. Left bundle branch block now present, with wide QRS, coupling, and questionable ventricular fibrillation. Marked increase in abnormalities. Lead III shows wider QRS with more rapid rates.
‘8
CORTEX
48.7 (8)
2”40’
1 week later
43.7
2’24’ 2’35’
1.0586
1.0595
stand-
Bradycardia
? hur. still
S.A.
fable Tach.
2”20’
(h)
tach.
1.0594
43.7
2’5’
hur. standstill
rent.
1.0585
45.8
l”55’ 2O
tach. or P. fib.
Aur. standstill
\-.
2O9’
1.0603
44.7
46.8
1°19’ l”31’
1”lO’
1"s'
95
160
280
230
120
140 to 180
090
-
2
82.6
.ll
.06
.20 or ._
.04
.OR
8-7
.I4
Var. R.
t
?.OO
TABLE
No
No
Lt.
Lt.
Lt.
Lt.
II-COX-T
t1.5 -0.7
f3.2
up
8t3.3
f-3
'D
t5
+s
$4.2
?tci
Variable
T-5
t.5
Q.J- -
?-3 tl
!-8
8-10
t.5
2
inverted
T-2.5
-2
t.5 -. 6
-4
-1.5
?-A.3
Variable
%6
t.5 -1
t2 -1.5
18
$+6
8t5.5
EKG similar, but not to, initial record.
identical
Slower rate, absence of P waves, shorter QRS duration and clearing of axis deviation. ImDroved. Cell volume 41.6. Plasma sp. Plasma pro. grav. 1.0296. 7.7%.
I
Complexes vary with rate, showing high-grade bundle branch block due to shorter rest periods. Coupling occasionally present. Cell volume 43.4. Plasma sp. grav. 1.0312. Plasma protein Intracardiac injec8.25%. tion 10 C.C. eschatin. Vent. tach. with shorter QRS Slight and regular rhythm. imnrovement in EKG. Sinus tach. probably present, with shorter QRS duration but rapid rate, In subsequent record P waves were absent and QRS much wider.
in and dy-
vent. fibril. or vent. with even more rapid EKG suggests dying
Bizarre complexes variable rhythm, size, shape, rhythmicity, suggesting ing heart.
Borderline tach., rate. heart.
464
THE
tachycardia. Ventricular injection and was followctl
AMERICAS
fibrillation by death.
HEART
JOURNAL
appearecl
ninety
minutes
after
3. Cat 3743.-The animal died in a convulsion two hours and twenty minutes aft,er an int,raperitoneal injection of 800 mg. per kilo. Gradual increases in the blood potassium level were accompanied by intraventricular block, followed by aurieulovent.ricular block with what was probably auricular flutter.
Fig. I.-Cat 3732. Records taken before and after intraperitoneal injection of 938 mg. of potassium chloride per kilo in 10 per cent solution show progressive inversion of T waves in Leads I and II, followed by intraventricular block and either auricular standstill or auricular fibrillation with complete auriculoventricular block. The tracings were taken with standard technique. The flne vertical lines fall every .04 second, and the flne horizontal lines represent a string deflection of 0.1 millivolt. Blood potassium levels were: control, 35.2 mg. per cent; 47.9 mg. per cent at 30 minutes; At death, the serum potassium was 72.2 mg. Per 71.2 mg. per cent at 55 minutes. cent.
4. Cat 3744.-Progressively increasing intraventricular block, allricular fibrillation, and, finally, auricular and ventricular standstill were observed over a period of six hours and fifty minutes following the intraperitoneal injection of 600 mg. per kg. of potassium chloride solution. The electrocardiographic abnormalities increased in spite of a slight decrease in the blood potassium level after the first ninety minutes. 5. Cat 3752.-Sublethal doses of potassium chloride produced transient electrocardiographic changes. Injection of 400 mg. per kg.
CHAMBERLAIN
ET
AL.:
ELECTROCARDIOGRAPHIC
CHANGES
IN
CATS
465
produced intraventricular and auriculoventricular block and ventricular tachycardia, with a return to normal four hours and fifteen minutes after injection. Immediately after recovery, a second injection of 200 mg. per kilo caused a rise of 8.1 mg. per cent in the blood potassium level, which was associated with partial auriculoventricular block and minor T-wave variations.
Fig. 2.-&t 3734. After the intraperitoneal chloride solution per kilo, tracings show T-wave block, auricular standstill, irregular ventricular tion. A to H show control and tracings taken at Approximate potassium values for tracings A and 59.6 mg. per cent.
injection of 963 mg. of potassium changes, followed by intraventricular tachysystole. and ventricular flbrilla10. 20, 30, 50, 70, 80. and 90 minutes. to F were: 22.8, 28.5, 35.8, 35.2, 43,
Fig. t.-Cat 3752. Only Lead II is shown. After injection of 400 mg. of potassium chloride solution per kilo, tracings A to E show the development of partial auriculoventricular and intraventricular block, followed by return to normal. Subsequently, a smaller dose (200 mg. per kilo) caused only slight changes in rate, voltage, and P-R interval, again followed by return to normal (J to 0). Timing of tracings A to 0 is as follows: control, 5, 25, 60, 90. 115, 130. and 230 minutes: second con;I$;“‘,;;;~ 15.are: 30, 19.5, 45, 60, 23.6, and 30.7, 90 mmutes. 40, 32.9, 33.7, 34.2, and 30.3 mg. per cent.
34.5, Approximate 34.0,
30.0, corresponding 27.4, 20.5.
potassium 29.7, 37.8, levels, 33.0.
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THE
AMERICAN
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JOURN&
6. Cat 3755.-Injection of 600 mg. per kg. of potassium chloride solution caused intraventricular and partial auriculoventricular block, followed by complete auricular standstill and periods of ventricular fibrillation, tachycardia, and tachysystole. Recovery followed intramuscular injection of 10 c.c., and intracardiac injections of 20 KC., of adrenal cortical extract (Parke, Davis, and Company). 7. Cat 3754.-After the appearance of auriculoventricular and intraventricular block caused by injecting 600 mg. of potassium chloride solution per kg., 500 C.C. of physiologic saline were administeretl intraperitoneally. This was followed by a return almost to normal of both the blood potassium level and the electrocardiogram in less than two hours after the potassium chloride had been injected. A
D
c
E
H
F
G
J
K
After administration of 600 mg. of Fig. 4.-Cat 3755. Only Lead II is shown. potassium chloride solution per kilo, intraventricular block, partial auriculoventricular block, ventricular tachycardia. irregular ventricular tachysystole, auricular standstill, and the final return to normal are shown. This animal received 10 cc. of eschatin one hour after the potassium chloride injection, and another 10 cc. sixty-five minutes later, but with questionable beneflt. The tracmgs, in order, show control. 25, 40, 57, 63, 70, 91, 129, 140, 155 minutes, and 1 week after potassium chloride. The approxi40.4, 44.1, 45.4, 46.0, 45.1, 48.0, mate corresponding blood potassium levels are 23.7, 44.6, 43.7, and 29.8 mg. per cent.
8. Cat S-7.-As a control, 27 C.C. of 10 per cent sodium chloride solution (600 mg. per kg.) were injected intraperitoneally. Records taken at half-hour intervals showed no change other than a slight acceleration in rate. The blood potassium level stayed practically constant, varying only between 21.7 and 20.7 mg. per cent. The relation of potassium administration to changes in the electrocardiogram may be summarized as follows: Heart Rate.-The effect on the rate was inconstant before A-V block (slowing), or ventricular tachycardia, or sinoauricular tachycardia appeared. Early variations in rate could have been caused by nervous excitement.
CHAMBERLAIN
ET
AT,. :
ELECTROCARDIOGRAPHIC
CHANGES
IN
CATS
467
P Waves.-The P waves decreased in amplitude by about 1 mm., in two instances, before they disappeared. They disappeared in all cases in which the cat received 600 mg., or more, of potassium chloride per kg. The blood potassium level at the time of the disappearance of the P waves and appearance of auricular standstill was quite variable, ranging from 36.4 to 90.2 mg. per cent.
Fig. 5.-C& 5.-Cat 3754. Tracings A to F show reversal of T waves and development of intraventricular and partial’ auriculoventricu~ar block and ventricular tachysystole after injection of 600 mg. of Potassium chloride solution per kilo. Fifty minutes after the potassium chloride administration, an intraperitoneal infusion of 500 C.C. of physiologic saline was started. Tracings F to I show a fairly rapid subsequent recovery. In order, the records show: control, 8, 20, 30: 45, 63, 30, 94, and 110 minutes. and J, 1 week after potassium chloride. The approxunate corresponding blood potassium levels are: 23.9, 31.0, 35.5, 36.4, 40.2, 93.3, 37.0, 36.1, 33.1, and 26.9 mg. per 100 ml.
P-R Interval.-Partial A-V block occurred in all the experiments. It was first observed when the blood potassium level ranged from approximately 30.7 to 66 mg. per cent, with an average of about 45 mg. per cent. In the four recovery experiments it disappeared at varying levels, either higher or lower than that at which it was first observed.
468
THE
AMERICAS
HEART
.JOURSAt,
QRS Complexes.-The voltage of QRS became lower in three experiments and higher in two, in the early stages of poisoning before intraThe blood potassium content at the time of ventricular block appeared. the changes in voltage ranged from 30.7 to approximately 44 mg. per cent. Intraventricular block was observed in all the experiments, appearing with a blood potassium range of approximately 31 to 55 mg. per cent, averaging about 42 mg. per cent. T Waves.-Flattening or inversion of the T waves (especially in Leads II and III) occurred in four experiments before the appearance of intraventricular block. In these animals the blood potassium ranged from 28.5 to approximately 44 mg. per cent, with an average of about 36 mg. per cent. Marked T-wave changes eventually occurred, as would be expected with the appearance of intraventricular block. Ventricular standstill, or so-called ventricular fibrillation,* was observed in four experiments, the blood potassium ranging from 55.3 to 109.7 mg. per Cent. Ventricular taehysyst.ole was observed in four experiments, with blood potassium levels varying from 40.2 to approximately 57 mg. per cent. COMMENT
Our results confirm the findings of Wiggcrs” and Winkler, et al.,” in respect to the abnormalities in the electrocardiogram following potassium administration. They estend the observation that many of the changes may be reversed. The sequence of the various electrocardiographic abnormalities is fairly uniform in each experiment, as are the potassium changes. However, the relative elevation of blood potassium above the control level showed a less close relationship t,o the electrocardiographic changes in the different experiments than did the actual blood potassium level. Neither the dosage of potassium chloride nor the rapidity with which electrocardiographic changes occurred seemed to be exactly related to the potassium level at which the changes took place. The similarities between the abnormalities shown in our electrocardiograms and those produced in muscle-strip preparations in which the potassium content of the perfusion fluid was the only variableI 8sb, r, dve suggest that our electrocardiographic changes may well have been due chiefly to hyperpotassemia. The actual responsibility of potassium for the changes in the electrocardiograms can only be estimated, with OLW present knowledge, since changes in the concentration of other ions during hyperpotassemia may play an important part. Blood concentration per se is probably not important, as we found no relationship between blood specific gravity and electrocardiographic changes in five of our experiments. The blood potassium levels reported in the present experiments are not purely of pharmacologic interest, since equally high levels have been
CHAMBERLAIN
ET
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ELECTROCARDIOGRAPHIC
CHANGES
IN
CATS
469
found in cats after the experimental production of intestinal obstruction,13 intestinal fistulae,14 shock,l” and adrenal insufficiency.‘6 Rvh, c In the last-named syndrome, Nicholson and Soffer17 noted slowing of the heart rate and auricular fibrillation in eight adrenalectomized dogs whose blood potassium levels were elevated. In two of the animals, normal rhythm was restored after the administration of 200 cc. of physiologic salt solution. In certain clinical conditions, changes in the electrocardiogram may be occasioned by potassium release from damaged cells, especially if the general condition of the individual be poor. Unpublished observat,ions by Chamberlain, and a report of a case of intestinal obstmction by Scudder, Zwemer. and Whipplels woald indicate that this is true. Addendum Since this paper was written, two papers hdl-e appeared palling attention to c?llanges in the electrocardiogram in adrenal insufficiency concomitant with elevations in serum potassium. Hall, G. E., and Cleghorn, R. A.: Cardiac Lesions in Adrenal Insufficiency, C. M. A. J. 39: 126, 3935. Thompson, TV. A. R.: Potassium and the T Wave of the Electrocardiogram, Lancaet 1: 805, 19.39. CONCLUSIONS
1. Experimental increases in the blood potassium content in the cat are associat,ed with abnormalities in the electrocardiogram. 2. In order of appearance, the usual changes are: lowering or inversion of T waves, decrease or increase of QRS voltage, auriculoventricular and intraventricular block, auricular standstill or auricular fibrillation, ventricular tachycarclia or tachysystole, ventricular fibrillation, and vent,ricular standstill. 3. The electrocardiographic abnormalities are Feversible, and parallel roughly the return of the blood potassium content to normal when a sublethal dose is given, or following the administration of physiologic saline or adrenal cortex extract. 4. The potassium levels at the time electrocardiographic changes appear vary in different cats. This suggests t,hat factors other t,han blood potassium may also be important. 5. Potassium administration produces marked abnormalities in the electrocardiogram when the blood potassium content is considerably below the level reached in experimental adrenal insufficiency, intestinal obstruction. or intestinal fistula. REFERENCES 1. Wiggers, C. J.: Monophasic and Deformed Ventricular Complexes Resulting From Surface Applications of Potassium Salts, AK HEART J. 5: 346, 1930. 2. Idem: Studies on Ventricular Fibrillation Produced by Electric Shock; Action of Antagonistic Salts, Am. J. Physiol. 93: 197, 1930. Studies of Ventricular Fibrillation 3. Wiggers, C. J., Bell, J. M., and Paine, M.: Caused by Electric Shock, AJ~. HEART J. 5: 351, 1930.
470
THE
AMERICAN
HEART
JOURNAL
4. Harris, I., and Levin, D. A.: The Effects Upon the Human Electrocardiogram of the Introduction of Ca and K Into the Blood, J. Physiol. 89: 153, 1937. 5. Winkler, A. W., Hoff, H. E., and Smith, P. K.: Electrocardiographic Changes and Concentration of Potassium in Serum Following Intravenous Injection of Potassium Chloride, Am. J. Physiol. 124: 478, 1938. 6a. Zwemer, R. L., and Truszkowski, R.: The Importance of Corticoadrenal Regulation of Potassium Metabolism, Endocrinology 21: 40, 1937. 6b. Truszkowski, R., and Zwemer. R. L.: Exaerimental Alterations in Blood Potassium,’ Acta Biol. Exper.‘12: 1, 1938. A 7. Truszkowski, R., and Zwemer, R. L.: Determination of Blood Potassium, Bioehem. J. 31: 229. 1937. 8. Truszkowski, R., and Zwemer, R. L.: Cortico-adrenal Insufficiency and Potassium Metabolism. II. Blood Potassium in Normal and Adrenalectomized Cats, Biochem. J. 30: 1345, 1936. 9. Zwemer, R. L., and Pike, F. H.: Effects of Nerve Excitation on Potassium in Body Fluids, Ann. of the New York Acad. Sci. 37: 257, 1938. 10. Barbour, H. G., and Hamilton, W. F.: The Falling Drop Method for Determining Specific Gravity, J. Biol. Chem. 69: 625, 1936. 11. Wiggers, C. J.: Physiology in Health and Disease, Ed. 2, Philadelphia, pp. 96, -lil, 1937, Lea and Febiger. 12a. Busquet, H., and Pachon; V.: Sur le mechanisme musculaire de l’aetion cardioinhibit,rice du potassium, Compt. rend. Sot. de Biol. Paris 62: 785, 1907. 1%. Busquet, H.: Le paradoxe du potassium sur Ie coeur isole de Lapin, Compt. rend. Sot. de Biol. Paris 85: 1142, 1921. The Autonomic Rhythm of the Turtle Heart 1%. Chu, H. P., and Sollman, T.: Strips as Influenced by the Regional Gradient and Various Conditions, Am. .J. Phvsiol. 74: 451. 19%. 12d. Howell: W.: an Analvsis of the Influence of Sodium, Pota,ssium and Calcium Salts of the Blood on the Automatic Contractions of Heart Muscle, Am. J. Physiol. 6: 181, 1902. Iieber die Bedeutung des Kaliums fur die 12e. Kolm, H., and Pick, E. P.: Selbsteuerung des Herzens. Pfluee. Arch. f. d. ges. Phvsiol. 185: 235, 1920. 13. Scudder, J., Zgemer, R. L., ‘and T&zkowski, Ry: Potassium in Acute 111. testinal Obstruction, Surgery 1: 74, 1927. 14. Scudder, J., and Zwemer, R. L.: The Effect of Complete Intestinal Fistula on Blood Potassium, Surgery 2: 519, 1927. Blood Potassium During Experimental 15. Zwemer, R. L., and Seudder, J.: Shock, Surgery 4: 510, 1928. 1Ga. Bauman, E. J., and Kurland, H.: Changes in Inorganic Constituents of Blood in Suprarenalectomized Cats and Rabbits, J. Biol. Chem. 71: 381, 1927. Effect of Bilateral Suprarenalectom) 16b. Hastings, A. B., and Compere, E. L.: on Clertain (lonstituents of the Blood of Dogs, Proc. Sot. Exper. Biol. and Med. 28: 376, 1931. Blood Chemistry of adrenal Insufficiency 16~. Zwemer, R. L., and Sullivan, Ruth: in Cats, Endocrinology 18: 97, 1934. Cardiac Brrhythmias in Experimental 17. Nicholson, W. M., and Soffer, L. J.: Suprarenal Insuthciencp in Dogs, Bull. Johns Hopkins Hosp. 56: 236, 1935. A. 0.: Acute Intestinal Obstruc18. Scudder, J., Zwemer, R. L., and Whipple, Evaluation of Results in 2150 Cases; With Detailed Studies of 25 tion. Showing Potassium as a Tasie Factor, Ann. Hnrg. 107: 161, 1938.
CHANGES ALTERATIONS
POTASSIUM I?. L. CHAMBERLAIN, KU.,
IN
ASSOCIATED IN BLOOD
WITH
CATS
J. SCUDDER, ?ul.D., AND R. L. ZWEMER,PH.D. NEW YORK, N. Y.
T
HE increasing interest in electrocardiographic abnormalities which are not due to structural changes in the myocardium has prompted our study of the effect of potassium on the electrocardiogram. An intimate relationship of potassium to automatism and to bioelectric phenomena seemsfairly certain, in the light of current knowledge, and numerous investigators have studied the effects of potassium on heart muscle st,rips, the intact heart,, and heart-lung preparations. Electrocardiograms with concomitant pot,assium determinations on the intact, unanesthetized subject following potassium administration are rare. Wiggersl produced elect,rocardiographic changes similar to those due to coronary occlusion by applying wit,h a brush a 20 per cent solution of potassium chloride directly to the ventricle of the dog. Wiggers and his associates?,3 described electrocardiographic changes in dogs following intravenous and intracardiac injections of potassium chloride. These changes varied with the amount of potassium chloride injected and with the site and speed of injection. Concentrations of serum potassium were not determined. Harris and Levin4 noted slowing of the human heart and slight diminution in the height of the P waves following the administration of 5 cc. of 5 per cent potassium chloride solution. They conclude that there is no relation between electrocardiographic changes and concentration of potassium in the serum, but from the data presented this conclusion does not seem justified. In five experiments on four dogs, Winkler, Hoff, and Smith5 found marked changes in the electrocardiogram, with eventual cardiac arrest, following the intravenous administration of 1.12 per cent potassium chloride solution at the rate of 10 C.C.per minute. In the present study the potassium chloride was given intraperitoneally because Zwemer and TruszkowskiG had found that this procedure gave more predictable results and smoother blood potassium curves. I\mTERIALS
AlVD METHODS
Eight normal cats xvex preparedfor electrocardiographicobservation,using the three standard leads. One or two control electrocardiograxnswere taken, and From the Departments of Medicine, Surgical Pathology, Physicians and Surgeons, Columbia University. Received for publication May 28, 1939. 458
and Anatomy,
College of
CHAMBERLAIN
ET
AL.:
ELECTROCARDIOGRAPHIC
CHANGES
IN
CATS
459
whole blood was obtained for determination of potassium content by the Truszkowski-Zwemer method.7 Whole blood determinations are permissible in the cat, since the potassium contents of cells and plasma rise and fall together and are not so widely different as in other species.8 Pota’ssium chloride (10 per cent solution) was then injected intraperitoneally into seven of the animals, and 10 per cent sodium chloride solution into the eighth as a control. Repeated whole blood samplings and electrocardiograms were taken at intervals of from five to fifteen minutes until death or apparent recovery. If death ensued, blood from various vessels (cf. Zwemer and Pikes) and fluid from the pericardium and cerebrospinal system were collected for determination of potassium content. The specific gravity of the blood was measured by the falling-drop method of Barbour and Hamilton.iQ Three cats given potassium chloride recovered. One had been given a sublethal dose, another was treated with a large amount of physiologic saline, and the third was injected with eschatin.”
The outstanding results in the individual animals are given below, and the chief effects of potassium on the electrocardiogram are then briefly summarized. Specific data are given in Tables I and II, and illustrated by Figs. 1 to 5. 1. Cat 3732.-After the administration of 938 mg. of potassium chloride per kg. (in 10 per cent solution) intraperitoneally, the blood potassium content showed a gradual rise from 35.2 to 71 mg. per cent. Electrocardiograms taken at ten-minute intervals showed progressive inversion of the T waves in Leads II and III. These changes were marked; the waves, which had been normally upright, became deeply inverted. When the blood potassium content reached 47.9 mg. per cent (30 minutes after injection), intraventricular block appeared, and the QRS complexes assumed the appearance of those which are typical of bundle branch block. Subsequent records showed a marked increase in the intraventricular block, and what was probably complete auriculoventricular block with auricular asystole or auricular fibrillation. The intraventricular block increased, and the ventricular rate was very slow in the last record obtained before death, seventy minutes after injection. 2. Cat 3734.-After the administration of 963 mg. per kg. of potassium chloride intraperitoneally, in 10 per cent solution, the blood potassium content rose from 22.8 to 90 mg. per cent. Electrocardiograms taken at five- and ten-minute intervals showed, at first, flattening and a tendency to inversion of the T waves in Leads II and III. Partial intraventricular block was first noted when the blood potassium level was approximately 43 mg. per cent. When the blood potassium content rose above 66 mg. per cent, complete auriculoventricular block appeared, wit,h occasional paroxysms of ventricular *For
which
we take
this
opportunity
to thank
Parke,
Davis,
and
Company.
cont,rol maximum 9 deter.
death in 6 hours and 50 minutes
No. 3744 600 mg. KCl/Kg.
~~~
control maximum 9 deter.
death in a convulsion in 140 min.
No. 3743 800 mg. KCl/Kg.
~_~-
control maximum death 11 det.er.
death in 94 minutes
No. 3734 963 mg. KCl/Kg.
:11.8 90.2
-40.0 59.2
110.0
ti(i.0
“:i.cl
BLOOD R (am. % j 35.0 cont,rol maximum 72.0 4 deter.
NO. .&PTD RESULT PROCEDURE No. 3734 -cleatllin 70 min938 mg. utes KCl/Kg.
-~
max.
contr.
contro1 max. later 1.046 I.060
1.054 1.052
1.049
BLOOD SP. GR.
normal to aw. fib. to aw. and ven. stand.
normal to inc. A-V block to aw. fib. or standstill
normal to aur. asyst. to ven. tachysyst. to ven. iib.
160 to 900 to fib.
to 38
VEN.
175 to 190 to 44 181) to 16
~~..._.
plete A-V block and aur. fib. OT asyst.
RHYTHM
to ” ;I ” to -
1.3
to 3 to 0.2 1 to 1.3 to -
r
P-R
.08 to aur. fib.
.08 to inc. block
.O!I to .05 to
SE(‘. .I)li to fib.
none
rt. to P
AXIS
.i”2
.o::
. 0 :: to .nn
.04 to .14
QRS DUR. .I14 t0 .21 QRS
9 to .12
to ci to 19
iso. to -4.5
iso. to +9
SK
3
t.li to t0.8 to -4
tb Il.2
to
iso.
‘I’,
4.2 to 5 to 10-t
VOLT ti.5 10.7 to 15.6
$8
to +5
tl to -G
t’7.5
-7 to i” c)
tl to
+I.2 to to.7
tF t1.2 to
to t1.8 to
tl
to -. 5 to -16.2 t1.3 to t”.O to
t1.2
T,
to -. 8 to -13.3
t4.1
Tz
contr. max. final
‘3X 44.3 26.9
1.053 1 .OGO 1.042
contr . 1 . 05” <) max. 1.061 1.059 final 1 wk. 1.051
normal to uartial A-V blocl; to aur. stand. to A-V block to normal
ltii to 260 to 200
l;S(i -70 -280 to 95
180 to 260 to 170 170 t.0 210
I-COST
normal to partial A-V block, aur. stand. to ven. fib. to ven. tach. to aur. stand.
normal
1.053 1.055 1.053
23.7 49.0 43.7 29.8
normal to partial A-V blocl; to aur. or ven. tach. to normal
1.052 1.059 1.053
No. 3755 recovery control 600 mg. after 2 hr. maximum KCl/Kg. 45 min. final followed 1 week by 30 C.C. later adrenal cortex extract NO. 3754 almost corn- control 600 mg. plete remaximum KCl/Kg. covery in final followed -2 hr. 17 deter. by 500 C.C. phys. saline
eontr. max. final
conk. max. final
29.7 37.8 25.8
nearly reeovered after 1 hr. 37 min.
No. 3752 200 mg. KU/Kg*.
19.5 34.5 20.5
control maximum final F det.er.
apparent control recovery maximum after 4 hr. final 15 min. 10 deter.
No. 3752 400 mg. k-Cl/Kg.
TABLE 'D
1.2 to 3 to 1.5
0.7 to 2
2 to 3 to ?.a 2 to
2 to to 2
.:oo
.09 to .ll
.bo* to .OG .OQ to .14 to 0.11
.E .OG
.oi to .lO
-
rt. to left to rt.
none to left to none none to left to none
rt. to left
.k
.03 to .12
.04 to .20 to .04
.03
.03 to .07 to iso. iso. to f.3
to 7 7 to 3 to 5 5.5 to 12 to 5
iso. 20 to t.ti
8 to 9 to 7
iso. to -2.3 to t.5
+.5 -3
4
4: to
$2 to $5 to t1.3
t6.5 to -.6
tl.5 -. 8 to
t0
$2 to t8 to t2 t2 to t3
tl to $6 to tl
-1
t8 to
t2.4 to t10 to t1.5 t1.5 to t2.5 to tl -. s to
1.0601
45.4
Ih1
?O’
103' -
l”5’
-
1.0583 1.0613
~.
1.0583 1.0578
1.0581
1.0569
1.0526
(h)
UP‘
V.
Tad.
fib.
Aur. standstill Runs of $ V. tach.
115
170 to 120 to 100
75
103
134
136
RATE
EXPERIMENT
aur.
A-V
-Complete standstill a v. fib.
Partial bl. Slower
Tdl.
Tnch.
RHYTHM
PRWW~OI.
SP. GRAV. CAP. BLOOD
45.5
43.4 42.8
34.5
23.7
BLOOD K
50’ 55’ 57’
42’
30 min. 35’ 40'
-KC1 10 min. 15 min. 25 min.
Control
TIME AFTER INJECTION
DETAILED
.7
1.0
2.0
2.0
P
us
.09
.14
.09
.09
P-R
8.16
.14
.I” .16
.lti
.09
.05
.04
DUR.
QRS
CM~ No.
Lt. B
Lt.
Lt.
Lt.
No
No
No
II (tiO0
.ZSIS DEV.
3755
TABLE
3.3
t::
t2.0 -
t3.5
tl -. 5 t1.2 t.4
QKS I
Mc.
8-3
-3
tl -3
-6
4-12
+4
t4.7
QRS II
f-6
fl -8
-10
-7
-2.::
-2
-1.5
-1.7
0
t-l-2
t9 to t7
0
Tl
Trmn-
t5.5
QRS III
KC~/KILO,
?+4.5
t5
+4.5
t6.5
-4
-1
-.8
TX
hus~s~r,
$t2
t7
t8
ts
t.6 -4.0
-.8
-.8
T,
KC1
REMARKS
C.C. 10% traperitoneally.
EXTRACT)
injected
in-
Sinus rhythm has appeared again and bundle branch block is less marked. Marked improvement. intracardiac injection 10 C.C. eschatin. Ventricular fibrillation. Marked increase in EKG abnormalities. 10 C.C. esehatin intramuscularly.
Prolonged A-V and intraventrieular eonduct,ion. Marked changes. Left bundle branch block now present, with wide QRS, coupling, and questionable ventricular fibrillation. Marked increase in abnormalities. Lead III shows wider QRS with more rapid rates.
‘8
CORTEX
48.7 (8)
2”40’
1 week later
43.7
2’24’ 2’35’
1.0586
1.0595
stand-
Bradycardia
? hur. still
S.A.
fable Tach.
2”20’
(h)
tach.
1.0594
43.7
2’5’
hur. standstill
rent.
1.0585
45.8
l”55’ 2O
tach. or P. fib.
Aur. standstill
\-.
2O9’
1.0603
44.7
46.8
1°19’ l”31’
1”lO’
1"s'
95
160
280
230
120
140 to 180
090
-
2
82.6
.ll
.06
.20 or ._
.04
.OR
8-7
.I4
Var. R.
t
?.OO
TABLE
No
No
Lt.
Lt.
Lt.
Lt.
II-COX-T
t1.5 -0.7
f3.2
up
8t3.3
f-3
'D
t5
+s
$4.2
?tci
Variable
T-5
t.5
Q.J- -
?-3 tl
!-8
8-10
t.5
2
inverted
T-2.5
-2
t.5 -. 6
-4
-1.5
?-A.3
Variable
%6
t.5 -1
t2 -1.5
18
$+6
8t5.5
EKG similar, but not to, initial record.
identical
Slower rate, absence of P waves, shorter QRS duration and clearing of axis deviation. ImDroved. Cell volume 41.6. Plasma sp. Plasma pro. grav. 1.0296. 7.7%.
I
Complexes vary with rate, showing high-grade bundle branch block due to shorter rest periods. Coupling occasionally present. Cell volume 43.4. Plasma sp. grav. 1.0312. Plasma protein Intracardiac injec8.25%. tion 10 C.C. eschatin. Vent. tach. with shorter QRS Slight and regular rhythm. imnrovement in EKG. Sinus tach. probably present, with shorter QRS duration but rapid rate, In subsequent record P waves were absent and QRS much wider.
in and dy-
vent. fibril. or vent. with even more rapid EKG suggests dying
Bizarre complexes variable rhythm, size, shape, rhythmicity, suggesting ing heart.
Borderline tach., rate. heart.
464
THE
tachycardia. Ventricular injection and was followctl
AMERICAS
fibrillation by death.
HEART
JOURNAL
appearecl
ninety
minutes
after
3. Cat 3743.-The animal died in a convulsion two hours and twenty minutes aft,er an int,raperitoneal injection of 800 mg. per kilo. Gradual increases in the blood potassium level were accompanied by intraventricular block, followed by aurieulovent.ricular block with what was probably auricular flutter.
Fig. I.-Cat 3732. Records taken before and after intraperitoneal injection of 938 mg. of potassium chloride per kilo in 10 per cent solution show progressive inversion of T waves in Leads I and II, followed by intraventricular block and either auricular standstill or auricular fibrillation with complete auriculoventricular block. The tracings were taken with standard technique. The flne vertical lines fall every .04 second, and the flne horizontal lines represent a string deflection of 0.1 millivolt. Blood potassium levels were: control, 35.2 mg. per cent; 47.9 mg. per cent at 30 minutes; At death, the serum potassium was 72.2 mg. Per 71.2 mg. per cent at 55 minutes. cent.
4. Cat 3744.-Progressively increasing intraventricular block, allricular fibrillation, and, finally, auricular and ventricular standstill were observed over a period of six hours and fifty minutes following the intraperitoneal injection of 600 mg. per kg. of potassium chloride solution. The electrocardiographic abnormalities increased in spite of a slight decrease in the blood potassium level after the first ninety minutes. 5. Cat 3752.-Sublethal doses of potassium chloride produced transient electrocardiographic changes. Injection of 400 mg. per kg.
CHAMBERLAIN
ET
AL.:
ELECTROCARDIOGRAPHIC
CHANGES
IN
CATS
465
produced intraventricular and auriculoventricular block and ventricular tachycardia, with a return to normal four hours and fifteen minutes after injection. Immediately after recovery, a second injection of 200 mg. per kilo caused a rise of 8.1 mg. per cent in the blood potassium level, which was associated with partial auriculoventricular block and minor T-wave variations.
Fig. 2.-&t 3734. After the intraperitoneal chloride solution per kilo, tracings show T-wave block, auricular standstill, irregular ventricular tion. A to H show control and tracings taken at Approximate potassium values for tracings A and 59.6 mg. per cent.
injection of 963 mg. of potassium changes, followed by intraventricular tachysystole. and ventricular flbrilla10. 20, 30, 50, 70, 80. and 90 minutes. to F were: 22.8, 28.5, 35.8, 35.2, 43,
Fig. t.-Cat 3752. Only Lead II is shown. After injection of 400 mg. of potassium chloride solution per kilo, tracings A to E show the development of partial auriculoventricular and intraventricular block, followed by return to normal. Subsequently, a smaller dose (200 mg. per kilo) caused only slight changes in rate, voltage, and P-R interval, again followed by return to normal (J to 0). Timing of tracings A to 0 is as follows: control, 5, 25, 60, 90. 115, 130. and 230 minutes: second con;I$;“‘,;;;~ 15.are: 30, 19.5, 45, 60, 23.6, and 30.7, 90 mmutes. 40, 32.9, 33.7, 34.2, and 30.3 mg. per cent.
34.5, Approximate 34.0,
30.0, corresponding 27.4, 20.5.
potassium 29.7, 37.8, levels, 33.0.
466
THE
AMERICAN
HEART
JOURN&
6. Cat 3755.-Injection of 600 mg. per kg. of potassium chloride solution caused intraventricular and partial auriculoventricular block, followed by complete auricular standstill and periods of ventricular fibrillation, tachycardia, and tachysystole. Recovery followed intramuscular injection of 10 c.c., and intracardiac injections of 20 KC., of adrenal cortical extract (Parke, Davis, and Company). 7. Cat 3754.-After the appearance of auriculoventricular and intraventricular block caused by injecting 600 mg. of potassium chloride solution per kg., 500 C.C. of physiologic saline were administeretl intraperitoneally. This was followed by a return almost to normal of both the blood potassium level and the electrocardiogram in less than two hours after the potassium chloride had been injected. A
D
c
E
H
F
G
J
K
After administration of 600 mg. of Fig. 4.-Cat 3755. Only Lead II is shown. potassium chloride solution per kilo, intraventricular block, partial auriculoventricular block, ventricular tachycardia. irregular ventricular tachysystole, auricular standstill, and the final return to normal are shown. This animal received 10 cc. of eschatin one hour after the potassium chloride injection, and another 10 cc. sixty-five minutes later, but with questionable beneflt. The tracmgs, in order, show control. 25, 40, 57, 63, 70, 91, 129, 140, 155 minutes, and 1 week after potassium chloride. The approxi40.4, 44.1, 45.4, 46.0, 45.1, 48.0, mate corresponding blood potassium levels are 23.7, 44.6, 43.7, and 29.8 mg. per cent.
8. Cat S-7.-As a control, 27 C.C. of 10 per cent sodium chloride solution (600 mg. per kg.) were injected intraperitoneally. Records taken at half-hour intervals showed no change other than a slight acceleration in rate. The blood potassium level stayed practically constant, varying only between 21.7 and 20.7 mg. per cent. The relation of potassium administration to changes in the electrocardiogram may be summarized as follows: Heart Rate.-The effect on the rate was inconstant before A-V block (slowing), or ventricular tachycardia, or sinoauricular tachycardia appeared. Early variations in rate could have been caused by nervous excitement.
CHAMBERLAIN
ET
AT,. :
ELECTROCARDIOGRAPHIC
CHANGES
IN
CATS
467
P Waves.-The P waves decreased in amplitude by about 1 mm., in two instances, before they disappeared. They disappeared in all cases in which the cat received 600 mg., or more, of potassium chloride per kg. The blood potassium level at the time of the disappearance of the P waves and appearance of auricular standstill was quite variable, ranging from 36.4 to 90.2 mg. per cent.
Fig. 5.-C& 5.-Cat 3754. Tracings A to F show reversal of T waves and development of intraventricular and partial’ auriculoventricu~ar block and ventricular tachysystole after injection of 600 mg. of Potassium chloride solution per kilo. Fifty minutes after the potassium chloride administration, an intraperitoneal infusion of 500 C.C. of physiologic saline was started. Tracings F to I show a fairly rapid subsequent recovery. In order, the records show: control, 8, 20, 30: 45, 63, 30, 94, and 110 minutes. and J, 1 week after potassium chloride. The approxunate corresponding blood potassium levels are: 23.9, 31.0, 35.5, 36.4, 40.2, 93.3, 37.0, 36.1, 33.1, and 26.9 mg. per 100 ml.
P-R Interval.-Partial A-V block occurred in all the experiments. It was first observed when the blood potassium level ranged from approximately 30.7 to 66 mg. per cent, with an average of about 45 mg. per cent. In the four recovery experiments it disappeared at varying levels, either higher or lower than that at which it was first observed.
468
THE
AMERICAS
HEART
.JOURSAt,
QRS Complexes.-The voltage of QRS became lower in three experiments and higher in two, in the early stages of poisoning before intraThe blood potassium content at the time of ventricular block appeared. the changes in voltage ranged from 30.7 to approximately 44 mg. per cent. Intraventricular block was observed in all the experiments, appearing with a blood potassium range of approximately 31 to 55 mg. per cent, averaging about 42 mg. per cent. T Waves.-Flattening or inversion of the T waves (especially in Leads II and III) occurred in four experiments before the appearance of intraventricular block. In these animals the blood potassium ranged from 28.5 to approximately 44 mg. per cent, with an average of about 36 mg. per cent. Marked T-wave changes eventually occurred, as would be expected with the appearance of intraventricular block. Ventricular standstill, or so-called ventricular fibrillation,* was observed in four experiments, the blood potassium ranging from 55.3 to 109.7 mg. per Cent. Ventricular taehysyst.ole was observed in four experiments, with blood potassium levels varying from 40.2 to approximately 57 mg. per cent. COMMENT
Our results confirm the findings of Wiggcrs” and Winkler, et al.,” in respect to the abnormalities in the electrocardiogram following potassium administration. They estend the observation that many of the changes may be reversed. The sequence of the various electrocardiographic abnormalities is fairly uniform in each experiment, as are the potassium changes. However, the relative elevation of blood potassium above the control level showed a less close relationship t,o the electrocardiographic changes in the different experiments than did the actual blood potassium level. Neither the dosage of potassium chloride nor the rapidity with which electrocardiographic changes occurred seemed to be exactly related to the potassium level at which the changes took place. The similarities between the abnormalities shown in our electrocardiograms and those produced in muscle-strip preparations in which the potassium content of the perfusion fluid was the only variableI 8sb, r, dve suggest that our electrocardiographic changes may well have been due chiefly to hyperpotassemia. The actual responsibility of potassium for the changes in the electrocardiograms can only be estimated, with OLW present knowledge, since changes in the concentration of other ions during hyperpotassemia may play an important part. Blood concentration per se is probably not important, as we found no relationship between blood specific gravity and electrocardiographic changes in five of our experiments. The blood potassium levels reported in the present experiments are not purely of pharmacologic interest, since equally high levels have been
CHAMBERLAIN
ET
AL. :
ELECTROCARDIOGRAPHIC
CHANGES
IN
CATS
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found in cats after the experimental production of intestinal obstruction,13 intestinal fistulae,14 shock,l” and adrenal insufficiency.‘6 Rvh, c In the last-named syndrome, Nicholson and Soffer17 noted slowing of the heart rate and auricular fibrillation in eight adrenalectomized dogs whose blood potassium levels were elevated. In two of the animals, normal rhythm was restored after the administration of 200 cc. of physiologic salt solution. In certain clinical conditions, changes in the electrocardiogram may be occasioned by potassium release from damaged cells, especially if the general condition of the individual be poor. Unpublished observat,ions by Chamberlain, and a report of a case of intestinal obstmction by Scudder, Zwemer. and Whipplels woald indicate that this is true. Addendum Since this paper was written, two papers hdl-e appeared palling attention to c?llanges in the electrocardiogram in adrenal insufficiency concomitant with elevations in serum potassium. Hall, G. E., and Cleghorn, R. A.: Cardiac Lesions in Adrenal Insufficiency, C. M. A. J. 39: 126, 3935. Thompson, TV. A. R.: Potassium and the T Wave of the Electrocardiogram, Lancaet 1: 805, 19.39. CONCLUSIONS
1. Experimental increases in the blood potassium content in the cat are associat,ed with abnormalities in the electrocardiogram. 2. In order of appearance, the usual changes are: lowering or inversion of T waves, decrease or increase of QRS voltage, auriculoventricular and intraventricular block, auricular standstill or auricular fibrillation, ventricular tachycarclia or tachysystole, ventricular fibrillation, and vent,ricular standstill. 3. The electrocardiographic abnormalities are Feversible, and parallel roughly the return of the blood potassium content to normal when a sublethal dose is given, or following the administration of physiologic saline or adrenal cortex extract. 4. The potassium levels at the time electrocardiographic changes appear vary in different cats. This suggests t,hat factors other t,han blood potassium may also be important. 5. Potassium administration produces marked abnormalities in the electrocardiogram when the blood potassium content is considerably below the level reached in experimental adrenal insufficiency, intestinal obstruction. or intestinal fistula. REFERENCES 1. Wiggers, C. J.: Monophasic and Deformed Ventricular Complexes Resulting From Surface Applications of Potassium Salts, AK HEART J. 5: 346, 1930. 2. Idem: Studies on Ventricular Fibrillation Produced by Electric Shock; Action of Antagonistic Salts, Am. J. Physiol. 93: 197, 1930. Studies of Ventricular Fibrillation 3. Wiggers, C. J., Bell, J. M., and Paine, M.: Caused by Electric Shock, AJ~. HEART J. 5: 351, 1930.
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4. Harris, I., and Levin, D. A.: The Effects Upon the Human Electrocardiogram of the Introduction of Ca and K Into the Blood, J. Physiol. 89: 153, 1937. 5. Winkler, A. W., Hoff, H. E., and Smith, P. K.: Electrocardiographic Changes and Concentration of Potassium in Serum Following Intravenous Injection of Potassium Chloride, Am. J. Physiol. 124: 478, 1938. 6a. Zwemer, R. L., and Truszkowski, R.: The Importance of Corticoadrenal Regulation of Potassium Metabolism, Endocrinology 21: 40, 1937. 6b. Truszkowski, R., and Zwemer. R. L.: Exaerimental Alterations in Blood Potassium,’ Acta Biol. Exper.‘12: 1, 1938. A 7. Truszkowski, R., and Zwemer, R. L.: Determination of Blood Potassium, Bioehem. J. 31: 229. 1937. 8. Truszkowski, R., and Zwemer, R. L.: Cortico-adrenal Insufficiency and Potassium Metabolism. II. Blood Potassium in Normal and Adrenalectomized Cats, Biochem. J. 30: 1345, 1936. 9. Zwemer, R. L., and Pike, F. H.: Effects of Nerve Excitation on Potassium in Body Fluids, Ann. of the New York Acad. Sci. 37: 257, 1938. 10. Barbour, H. G., and Hamilton, W. F.: The Falling Drop Method for Determining Specific Gravity, J. Biol. Chem. 69: 625, 1936. 11. Wiggers, C. J.: Physiology in Health and Disease, Ed. 2, Philadelphia, pp. 96, -lil, 1937, Lea and Febiger. 12a. Busquet, H., and Pachon; V.: Sur le mechanisme musculaire de l’aetion cardioinhibit,rice du potassium, Compt. rend. Sot. de Biol. Paris 62: 785, 1907. 1%. Busquet, H.: Le paradoxe du potassium sur Ie coeur isole de Lapin, Compt. rend. Sot. de Biol. Paris 85: 1142, 1921. The Autonomic Rhythm of the Turtle Heart 1%. Chu, H. P., and Sollman, T.: Strips as Influenced by the Regional Gradient and Various Conditions, Am. .J. Phvsiol. 74: 451. 19%. 12d. Howell: W.: an Analvsis of the Influence of Sodium, Pota,ssium and Calcium Salts of the Blood on the Automatic Contractions of Heart Muscle, Am. J. Physiol. 6: 181, 1902. Iieber die Bedeutung des Kaliums fur die 12e. Kolm, H., and Pick, E. P.: Selbsteuerung des Herzens. Pfluee. Arch. f. d. ges. Phvsiol. 185: 235, 1920. 13. Scudder, J., Zgemer, R. L., ‘and T&zkowski, Ry: Potassium in Acute 111. testinal Obstruction, Surgery 1: 74, 1927. 14. Scudder, J., and Zwemer, R. L.: The Effect of Complete Intestinal Fistula on Blood Potassium, Surgery 2: 519, 1927. Blood Potassium During Experimental 15. Zwemer, R. L., and Seudder, J.: Shock, Surgery 4: 510, 1928. 1Ga. Bauman, E. J., and Kurland, H.: Changes in Inorganic Constituents of Blood in Suprarenalectomized Cats and Rabbits, J. Biol. Chem. 71: 381, 1927. Effect of Bilateral Suprarenalectom) 16b. Hastings, A. B., and Compere, E. L.: on Clertain (lonstituents of the Blood of Dogs, Proc. Sot. Exper. Biol. and Med. 28: 376, 1931. Blood Chemistry of adrenal Insufficiency 16~. Zwemer, R. L., and Sullivan, Ruth: in Cats, Endocrinology 18: 97, 1934. Cardiac Brrhythmias in Experimental 17. Nicholson, W. M., and Soffer, L. J.: Suprarenal Insuthciencp in Dogs, Bull. Johns Hopkins Hosp. 56: 236, 1935. A. 0.: Acute Intestinal Obstruc18. Scudder, J., Zwemer, R. L., and Whipple, Evaluation of Results in 2150 Cases; With Detailed Studies of 25 tion. Showing Potassium as a Tasie Factor, Ann. Hnrg. 107: 161, 1938.