THE HEMODYNAMICS OF THYROTOXICOSIS IN
MAN WITH SPECIAL REFERENCE TO
CORONARY BLOOD FLOW AND MYOCARDIAL
OXYGEN METABOLISM
George G. Rowe, … , Beryl Welch, Phyllis Fosshage
J Clin Invest. 1956;35(3):272-276. https://doi.org/10.1172/JCI103273.
Research Article
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SPECIAL REFERENCE TO CORONARY BLOOD FLOW AND
MYOCARDIAL OXYGEN
METABOLISM1
By GEORGE G. ROWE, JOHN H. HUSTON,2ARVIN B. WEINSTEIN, HERMAN
TUCHMAN,.
JOHN F. BROWN,8 AND CHARLES W. CRUMPTON WITH THE TECHNICAL ASSISTANCE OFAUDREYPETERSON, BERYL WELCH, ANDPHYLLIS FOSSHAGE
(FromtheCardio-Pulmonary ResearchLaboratoryandtheDepartmentofMedicine, University of Wisconsin Medical School, and the University Hospitals, Madison, Wis.)
(Submitted for publication September 28, 1955; accepted November 16, 1955)
For many years thehemodynamicsof thyrotoxi-cosis have been of interest to clinicians. Blood
flow through the extremities was assumed to be increasedin thyrotoxicosisbecauseof the high rate
ofheat eliminationwhen the handwas placedina
calorimeter (1). Several workers found an in-crease in cardiac output in
thyrotoxic
subjects using the oxygen content of arm vein blood in the Fick formula (2-4). Similarfindings
wereobtained using the nitrous oxide (5) and
acetyl-ene methods (6, 7). The velocity of circulation,
asdetermined by the rate of transit of radioactive
materials through the cardiovascular system is
accelerated in thyrotoxicosis and becomes normal
after effective treatment (8, 9). Circulation time
measured by sodium
dehydrocholate
inpatients
with thyrotoxicosis is more
rapid
than normal(10).
Blalock and Harrison
using
oxygen content ofright ventricular bloodintheFick formula showed that indogs
thyroid
feeding produced
an increase incardiac output whilethyroidectomy produced adecreaseinoutput
(11).
Experiments
concerning
themyocardium
di-rectlyhave shown an increase in 02
uptake/gram
of muscle. Direct measurement of 02 consump-tion in the Warburg apparatus demonstrated an
increase in oxygenutilization bythe
thyroid
stimu-latedmyocardium
asshown in the isolatedbeating
iThis
investigation was supported in part by grantsto the Cardio-Pulmonary Research Laboratory of the
University of Wisconsin from the Wisconsin Heart As-sociation, Wisconsin Alumni Research Foundation, and
National Heart Institute of the National Institutes of
Health, Public Health Service.
2Wisconsin Heart Association Research Fellow.
3Heart Trainee of the National Heart Institute, U. S.
Public Health Service, 1955.
rabbit auricle (12). Dock and Lewis established that thyroid feeding to rats increased the total body oxygen consumption (13). Then by con-verting the animals to a heart lung preparation
they demonstrated that the increased oxygen
con-sumption by the heart and lungs was directly re-lated to the cardiac rate and the oxygen con-sumption per beat remained unchanged. They concluded that the increase in cardiac oxygen metabolism was explained by the increased cardiac rate and was not otherwise related to the
hyper-metabolic state.
In view of this rather consistent body of data the report of normal myocardial oxygen consump-tion in thyrotoxic patients despite an increase in total metabolism is surprising (14). It appeared that these observations might be re-evaluated ina
larger number of patients, studying them before and aftertreatment forthyrotoxicosis sothat each patient could serve as his own control.
MATERIAL AND METHODS
Hemodynamic studies were made of ten patients be-lieved to have thyrotoxicosis on the basis of clinical and
laboratory examination. The plan was to determine the cardiac output and coronary blood flow of each patient in thethyrotoxic state, to treat him with radioactive
io-dine or surgery, and subsequent to clinical improvement
to repeat the hemodynamic studies. All patients were
treated with radioactive iodine except No. 6 (L. M.), who hadsubtotal thyroidectomy.
All studies were done in the fasting, post-absorptive state and every effort was made to obtain basal condi-tions. Cardiac output was determined by the Fick
prin-ciple, coronary blood flow by the nitrous oxide satura-tion method utilizinga blood-myocardial partition coeffi-cient of 1 (15). Pressures were recorded with Statham strain gauges and the direct writing Sanborn poly-viso. The usual formulae were used for calculation of cardiac work and peripheral resistance.
HEMODYNAMICS OF THYROTOXICOSIS
The final series consists of eight acceptable complete studies. The ninth patient, (F. K.) had the lowest ini-tialI' uptake in theseries, 49percent, andalthoughthe radioactive iodine uptake decreased following therapy he did notattain a satisfactory clinical response. Hefailed
togain weightand continuedto experiencehis symptoms
of nervousness, tachycardia, palpitationanddyspnea. Ad-ditional investigation at this time revealeda severe anx-iety tension state associated with a very difficult home situation. This patient's data are shown at the bottom
of the table butare excluded from the averages because
itis felt that his primary disease wasnotthyrotoxicosis.
However, statistical calculations were made with these
data included and excluded (Table I) without producing significant differences in the over-all pattern. The tenth
patientwas a22-year-old woman with moderately severe
thyrotoxicosis and mild hypertension who returned to the hospital in the euthyroid state subsequent to treat-ment. However, because she was pregnant and had
de-veloped more severe hypertension, it was felt that data collectedfromher would serve no purpose for this series so re-study was not done. In patient G. A. a satisfactory
initial determination of coronary blood flow was impos-sible from the first nitrous oxide curves but since he was still thyrotoxic at the time of his return to the hospital hemodynamic studies were repeated before and after he had responded to further treatnent. Results in this case will becitedlater. Comparisons were also made between hyperthyroid, treated hyperthyroid and nine normal
sub-jects studied inour laboratory.
RESULTS
Resultsof thestudy are summarized in Table I. It is apparent that these patients responded to treatment of thyrotoxicosis in the usual fashion with a gain of weight, decrease in heart rate and oxygen consumption per square meter body
sur-face and a lessening of radioactive iodine uptake
by the thyroid. Although no significant change occurred in the systemic mean arterial blood pres-sure, there was a fall in the pulnonary arterial blood pressure (p < 0.01). This differing re-sponse in the two circulations resulted in a
sig-nificant increase in total peripheral resistance
(p
<0.05)
with nochange
in thepulmonary
re-sistance. There was a 50 per cent decrease in
right ventricular work index (p < 0.01) but,
al-though the left ventricular work index decreased 28 per cent, this was not significant (p < 0.1).
However, the major change in cardiac output in patient G. A. occurred after his initial, but only
partially successful, treatment. Although this
study was incomplete, the cardiac output data are
satisfactory. If the second study be replaced by
this determination, statistical analysis reveals a
significant decrease in left ventricular work index forthe entire group (p <0.05). The decrease in rate (-28 per cent) was so similar to the fall in cardiac index (37 per cent) that no significant change in stroke index occurred.
Observations on the myocardial metabolism
re-vealed that successful treatment was followed by significant changes in the coronary vascular re-sistance (+ 70per cent p <0.01), coronaryblood flow (- 38 per cent p < 0.01), cardiac metabolic rate foroxygen per 100 grams of myocardial tissue (- 37 per cent p < 0.01) and the cardiac meta-bolic rate for oxygen per beat (- 17 per cent
p <0.05). When the patients with thyrotoxicosis were compared to normal subjects, see Table I, there were significant increases in heartrate (p <
0.01),oxygenconsumption (p < 0.02),mean pul-monary arterial pressure (p < 0.05), cardiac in-dex (p < 0.05), left and right ventricular work index (p < 0.02), coronary blood flow (p<
0.05), and cardiac oxygen utilization (p < 0.05)
in the former. Our data concerning the normal coronary blood flow and myocardial oxygen ex-traction and utilization compare favorably with
Bing's 18 normal subjects (14). Conversely, fol-lowing treatment, comparison of post-thyrotoxic patients with normals revealed no significant dif-ferences in the hemodynamic and metabolic state.
DISCUSSION
This study indicates that contrary to previously published observations (14) the myocardium
par-ticipates in the increase in oxygen consumption
characteristic of all bodytissues in thyrotoxicosis. This hypermetabolism is accompanied by an
in-crease in coronary blood flow, a decrease in
coro-nary vascularresistance,andanincrease in oxygen
consumptionper beat. Itseemsclear since there is
an increase in oxygen consumption per beat that
the cardiac oxygen utilization is related not only
to the increase in cardiac rate but to the general
hypermetabolism of the myocardium as well. If the left ventricular work or left ventricular work
index be divided by the myocardial oxygen
con-sumption per 100 grams of tissue, an index of
efficiency isobtained. Although these indices did
not change, comparison of figures obtained by
thismethod would be subjectto errors inherent in
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estimation of left ventricular weight should any
changeinmyocardial weight haveoccurredduring
the interim between studies (average 3.9 months). Without such specific and presently unobtainable
information, no speculation concerning relative
efficiency of normal and thyrotoxic heart muscle isjustified. Although there wasa slight increase inbody respiratory quotient inthesecond as
com-paredtothe first study, this changewasnot
statis-tically significant. This trend may be related to
the factthat thesepatientswere studiedatthe end of a 15-hour fasting period, and owing to their
hypermetabolism, had morenearly exhausted their glycogen stores than at the time of the second study.
When both treated and untreated thyrotoxic patients aregrouped, significantdirect correlations emerge between Il31 uptakeand the cardiac index
(p<
0.05),
left ventricular work index(p
<0.01), and coronary blood flow (p<
0.02).
The relation between Il31 uptake andmyocardial
oxy-gen uptake was notsignificant (p
<0.1).
Since the oxygen consumption per square meter is the numerator of the cardiac indexequation,
it is notvalid to calculate the correlation between BMR and cardiac
index;
the arteriovenous oxygendif-ference remained constant and
obviously
a direct relation has to exist. Asignificant
correlationbe-tween cardiacoutput and coronary blood flow ex-isted (p<
0.05)
with the fraction of cardiacout-put which
perfused
each 100 grams of left ven-tricularmuscle
remaining
2.1 per cent in both treated anduntreated patients.SUMMARY AND CONCLUSIONS
1. Hemodynamic observations in patients with
thyrotoxicosis are reported. In eight patients studies were made before and after treatment. The results were compared with those from nine normal subjects.
2. Evidence is
presented
that the hypermeta-bolic state ofthyrotoxicosis
includes the myo-cardium since there is asignificant
increase in coronary blood flow and cardiac metabolic ratefor oxygen.
3. Following specifictreatment, the cardiac
out-put, cardiac work, coronary blood flow and myo-cardial oxygen
consumption
returned tonormal,
and the coronary vascular resistance increased.REFERENCES
1. Stewart, G. N., Studies on the circulation in man.
The blood flow in the hands and feet in normal and pathological cases. Harvey Lect., 1912-13, 8,
86.
2. Davies, H. W., Meakins, J., and Sands, J., The in-fluence of circulatory disturbances on the gaseous
exchange of the blood. V. The blood gases and
circulation rate in hyperthyroidism. Heart, 1924,
11,299.
3. Rabinowitch, I. M., and Bazin, E. V., The output of the heart per beat in hyperthyroidism. Arch. Int.
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4. Burwell, C. S., Smith, W. C., and Neighbors, DeW.,
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5. Fullerton, C. W., and Harrop, G. A., Jr., The cardiac output in hyperthyroidism. Bull. Johns Hopkins Hosp., 1930, 46, 203.
6. Liljestrand, G., and Stenstr6m, N., Clinical studies on the work of the heart during rest: I. Blood flow and blood pressure in exophthalmic goiter. Acta. med. Scandinav., 1925, 63, 99.
7. Boothby, W. M., and Rynearson, E. H., Increase in circulation rate produced by exophthalmic goiter. Arch. Int. Med., 1935, 55, 547.
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9. Blumgart, H. L., Gargill, S. L., and Gilligan, D. R.,
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