PHYLLIS FOSSHAGE. rabbit auricle (12). Dock and Lewis established. that thyroid feeding to rats increased the total

Transcription

1 THE HEMODYNAMICS OF THYROTOXICOSIS IN MAN WITH SPECIAL REFERENCE TO CORONARY BLOOD FLOW AND MYOCARDIAL OXYGEN METABOLISM1 By GEORGE G. ROWE, JOHN H. HUSTON,2 ARVIN B. WEINSTEIN, HERMAN TUCHMAN,. JOHN F. BROWN,8 AND CHARLES W. CRUMPTON WITH THE TECHNICAL ASSISTANCE OF AUDREY PETERSON, BERYL WELCH, AND PHYLLIS FOSSHAGE (Frm the Cardi-Pulmnary Research Labratry and the Department f Medicine, University f Wiscnsin Medical Schl, and the University Hspitals, Madisn, Wis.) (Submitted fr publicatin September 28, 1955; accepted Nvember 16, 1955) Fr many years the hemdynamics f thyrtxicsis have been f interest t clinicians. Bld flw thrugh the extremities was assumed t be increased in thyrtxicsis because f the high rate f heat eliminatin when the hand was placed in a calrimeter (1). Several wrkers fund an increase in cardiac utput in thyrtxic subjects using the xygen cntent f arm vein bld in the Fick frmula (2-). Similar findings were btained using the nitrus xide (5) and acetylene methds (6, 7). The velcity f circulatin, as determined by the rate f transit f radiactive materials thrugh the cardivascular system is accelerated in thyrtxicsis and becmes nrmal after effective treatment (8, 9). Circulatin time measured by sdium dehydrchlate in patients with thyrtxicsis is mre rapid than nrmal (). Blalck and Harrisn using xygen cntent f right ventricular bld in the Fick frmula shwed that in dgs thyrid feeding prduced an increase in cardiac utput while thyridectmy prduced a decrease in utput (11). Experiments cncerning the mycardium directly have shwn an increase in 02 uptake/gram f muscle. Direct measurement f 02 cnsumptin in the Warburg apparatus demnstrated an increase in xygen utilizatin by the thyrid stimulated mycardium as shwn in the islated beating ithis investigatin was supprted in part by grants t the Cardi-Pulmnary Research Labratry f the University f Wiscnsin frm the Wiscnsin Heart Assciatin, Wiscnsin Alumni Research Fundatin, and Natinal Heart Institute f the Natinal Institutes f Health, Public Health Service. 2Wiscnsin Heart Assciatin Research Fellw. 3 Heart Trainee f the Natinal Heart Institute, U. S. Public Health Service, rabbit auricle (12). Dck and Lewis established that thyrid feeding t rats increased the ttal bdy xygen cnsumptin (13). Then by cnverting the animals t a heart lung preparatin they demnstrated that the increased xygen cnsumptin by the heart and lungs was directly related t the cardiac rate and the xygen cnsumptin per beat remained unchanged. They cncluded that the increase in cardiac xygen metablism was explained by the increased cardiac rate and was nt therwise related t the hypermetablic state. In view f this rather cnsistent bdy f data the reprt f nrmal mycardial xygen cnsumptin in thyrtxic patients despite an increase in ttal metablism is surprising (1). It appeared that these bservatins might be re-evaluated in a larger number f patients, studying them befre and after treatment fr thyrtxicsis s that each patient culd serve as his wn cntrl. MATERIAL AND METHODS Hemdynamic studies were made f ten patients believed t have thyrtxicsis n the basis f clinical and labratry examinatin. The plan was t determine the cardiac utput and crnary bld flw f each patient in the thyrtxic state, t treat him with radiactive idine r surgery, and subsequent t clinical imprvement t repeat the hemdynamic studies. All patients were treated with radiactive idine except N. 6 (L. M.), wh had subttal thyridectmy. All studies were dne in the fasting, pst-absrptive state and every effrt was made t btain basal cnditins. Cardiac utput was determined by the Fick principle, crnary bld flw by the nitrus xide saturatin methd utilizing a bld-mycardial partitin cefficient f 1 (15). Pressures were recrded with Statham strain gauges and the direct writing Sanbrn ply-vis. The usual frmulae were used fr calculatin f cardiac wrk and peripheral resistance. 272

2 HEMODYNAMICS OF THYROTOXICOSIS 273 The final series cnsists f eight acceptable cmplete studies. The ninth patient, (F. K.) had the lwest initial I' uptake in the series, 9 per cent, and althugh the radiactive idine uptake decreased fllwing therapy he did nt attain a satisfactry clinical respnse. He failed t gain weight and cntinued t experience his symptms f nervusness, tachycardia, palpitatin and dyspnea. Additinal investigatin at this time revealed a severe anxiety tensin state assciated with a very difficult hme situatin. This patient's data are shwn at the bttm f the table but are excluded frm the averages because it is felt that his primary disease was nt thyrtxicsis. Hwever, statistical calculatins were made with these data included and excluded (Table I) withut prducing significant differences in the ver-all pattern. The tenth patient was a 22-year-ld wman with mderately severe thyrtxicsis and mild hypertensin wh returned t the hspital in the euthyrid state subsequent t treatment. Hwever, because she was pregnant and had develped mre severe hypertensin, it was felt that data cllected frm her wuld serve n purpse fr this series s re-study was nt dne. In patient G. A. a satisfactry initial determinatin f crnary bld flw was impssible frm the first nitrus xide curves but since he was still thyrtxic at the time f his return t the hspital hemdynamic studies were repeated befre and after he had respnded t further treatnent. Results in this case will be cited later. Cmparisns were als made between hyperthyrid, treated hyperthyrid and nine nrmal subjects studied in ur labratry. RESULTS Results f the study are summarized in Table I. It is apparent that these patients respnded t treatment f thyrtxicsis in the usual fashin with a gain f weight, decrease in heart rate and xygen cnsumptin per square meter bdy surface and a lessening f radiactive idine uptake by the thyrid. Althugh n significant change ccurred in the systemic mean arterial bld pressure, there was a fall in the pulnnary arterial bld pressure (p < 0.01). This differing respnse in the tw circulatins resulted in a significant increase in ttal peripheral resistance (p < 0.05) with n change in the pulmnary resistance. There was a 50 per cent decrease in right ventricular wrk index (p < 0.01) but, althugh the left ventricular wrk index decreased 28 per cent, this was nt significant (p < 0.1). Hwever, the majr change in cardiac utput in patient G. A. ccurred after his initial, but nly partially successful, treatment. Althugh this study was incmplete, the cardiac utput data are satisfactry. If the secnd study be replaced by this determinatin, statistical analysis reveals a significant decrease in left ventricular wrk index fr the entire grup (p < 0.05). The decrease in rate (-28 per cent) was s similar t the fall in cardiac index (37 per cent) that n significant change in strke index ccurred. Observatins n the mycardial metablism revealed that successful treatment was fllwed by significant changes in the crnary vascular resistance (+ 70 per cent p < 0.01), crnary bld flw (- 38 per cent p < 0.01), cardiac metablic rate fr xygen per 0 grams f mycardial tissue (- 37 per cent p < 0.01) and the cardiac metablic rate fr xygen per beat (- 17 per cent p < 0.05). When the patients with thyrtxicsis were cmpared t nrmal subjects, see Table I, there were significant increases in heart rate (p < 0.01), xygen cnsumptin (p < 0.02), mean pulmnary arterial pressure (p < 0.05), cardiac index (p < 0.05), left and right ventricular wrk index (p < 0.02), crnary bld flw (p < 0.05), and cardiac xygen utilizatin (p < 0.05) in the frmer. Our data cncerning the nrmal crnary bld flw and mycardial xygen extractin and utilizatin cmpare favrably with Bing's 18 nrmal subjects (1). Cnversely, fllwing treatment, cmparisn f pst-thyrtxic patients with nrmals revealed n significant differences in the hemdynamic and metablic state. DISCUSSION This study indicates that cntrary t previusly published bservatins (1) the mycardium participates in the increase in xygen cnsumptin characteristic f all bdy tissues in thyrtxicsis. This hypermetablism is accmpanied by an increase in crnary bld flw, a decrease in crnary vascular resistance, and an increase in xygen cnsumptin per beat. It seems clear since there is an increase in xygen cnsumptin per beat that the cardiac xygen utilizatin is related nt nly t the increase in cardiac rate but t the general hypermetablism f the mycardium as well. If the left ventricular wrk r left ventricular wrk index be divided by the mycardial xygen cnsumptin per 0 grams f tissue, an index f efficiency is btained. Althugh these indices did nt change, cmparisn f figures btained by this methd wuld be subject t errrs inherent in

3 27 ROWE, HUSTON, WEINSTEIN, TUCHMKAN, BROWN, AND CRUMPTON.,:.w N 6 ).i ;A r\.t- -0 0_m \ Ok e Ch. li R V W.V ' I V O. V V ' 0 0-,a0 O-t- _ 0in" t_0 d rvi C;en 0 t'i *ti tl. 0 C! +- V -< f Iq'DROVAq Cl ESft V> OS0nO _e It ( 0.z MM0 rr0 In s0 v ) C _t c Oi 1. i Ṟ t- -. ci el 1. t. Z! Tb.. G. "e ;t ra lj.. Q lll;., v I- wz. -c..a, m P > _n P t In C..a, 1 C v 1 C -a,0, " N0 V V c V 00 i I w." 0 *a " m iz..g.%). tta qz 31- ;'It t..) i. r,?.t lya Q e ;:q cd ) Cd z.. cd MS 0e '0_ a S^a 0N -N b00 N "_ Wa &ns W) "N 0% 00 O- - k- v00 -e 00 N _) *..- r a rv MM WV U.m tn 0- UX 0 0U) n CtS CS 0 a00 svzo0 0_t O -%. - _ +w ++ C O % 0s N 0M ei 11.1 c 8Cs t >b la 0.0 NO CS S0v W- t0..0 U)Nq0V a CSS c O % c... NOMetk I.. uzr V r> - V) U Cd ll:. -b _ 0 0 s0 a 0 zl5 z >,-z.ztz-b C "i Ui %6 V: 0 0 c 0 > N> >

4 HEMODYNAMICS OF THYROTOXICOSIS 275 Mai 0n 0 C @0 O~ O0 O@~' Of' I O' O' O O O '0 d ~ 80 W0 00 HIW tc 00 V _ V dd ; dd d dd d d dd r w+ + V0-eq - i 0 V - -+v 0tt' eq d 0~ V U H b0p C~~~~0+ ~ I *0 a> Ct_ a> OR +O+, av b 0 sc,i ev, t- _e^, e- 8 es,w, 0> >> ffi C@0 i8 +V we _" v _ a;a I 9A' g 0600 t "e" "3 f + +a- V O..> v ch~ av R ~ O~ an~q M b e X>X N X N X s~niq - > - s 0s "N t NU.0 n wiq0; in C') wi'jd C. c 1H '0 iti 0 '00' c Pa) )f- 'Ut N0 swa a_qt r W - 0 UOO -N el! 01 aq -t - n tel C O, W) -sta' a ss W W N-I eq el -'00 eq V) eqe-. '~h 0 0'> O -0d d C 03 'U '0 eq U) C- ' '0W N W)~~~~~~~~~~~~~~~~~~~0 U)U)~@0U ~U) C') W) -)r W) --0 -"m - Vq V.e C-.% eq@0-0 C..0' C~ eq C'0O' k NO. NO "~O gi ~ g ~ + 0' a ZO ZOLiZO >:z --~.Iz u;z -~z 9.z 0C - e C') ' U) Is '0 C~ >

5 276 ROWE, HUSTON, WEINSTEIN, TUCHMAN, BROWN, AND CRUMPTON estimatin f left ventricular weight shuld any change in mycardial weight have ccurred during the interim between studies (average 3.9 mnths). Withut such specific and presently unbtainable infrmatin, n speculatin cncerning relative efficiency f nrmal and thyrtxic heart muscle is justified. Althugh there was a slight increase in bdy respiratry qutient in the secnd as cmpared t the first study, this change was nt statistically significant. This trend may be related t the fact that these patients were studied at the end f a 15-hur fasting perid, and wing t their hypermetablism, had mre nearly exhausted their glycgen stres than at the time f the secnd study. When bth treated and untreated thyrtxic patients are gruped, significant direct crrelatins emerge between Il31 uptake and the cardiac index (p < 0.05), left ventricular wrk index (p < 0.01), and crnary bld flw (p < 0.02). The relatin between Il31 uptake and mycardial xygen uptake was nt significant (p < 0.1). Since the xygen cnsumptin per square meter is the numeratr f the cardiac index equatin, it is nt valid t calculate the crrelatin between BMR and cardiac index; the arterivenus xygen difference remained cnstant and bviusly a direct relatin has t exist. A significant crrelatin between cardiac utput and crnary bld flw existed (p < 0.05) with the fractin f cardiac utput which perfused each 0 grams f left ventricular muscle remaining 2.1 per cent in bth treated and untreated patients. SUMMARY AND CONCLUSIONS 1. Hemdynamic bservatins in patients with thyrtxicsis are reprted. In eight patients studies were made befre and after treatment. The results were cmpared with thse frm nine nrmal subjects. 2. Evidence is presented that the hypermetablic state f thyrtxicsis includes the mycardium since there is a significant increase in crnary bld flw and cardiac metablic rate fr xygen. 3. Fllwing specific treatment, the cardiac utput, cardiac wrk, crnary bld flw and mycardial xygen cnsumptin returned t nrmal, and the crnary vascular resistance increased. REFERENCES 1. Stewart, G. N., Studies n the circulatin in man. The bld flw in the hands and feet in nrmal and pathlgical cases. Harvey Lect., , 8, Davies, H. W., Meakins, J., and Sands, J., The influence f circulatry disturbances n the gaseus exchange f the bld. V. The bld gases and circulatin rate in hyperthyridism. Heart, 192, 11, Rabinwitch, I. M., and Bazin, E. V., The utput f the heart per beat in hyperthyridism. Arch. Int. Med., 1926, 38, Burwell, C. S., Smith, W. C., and Neighbrs, DeW., The utput f the heart in thyrtxicsis, with the reprt f a case f thyrtxicsis cmbined with primary pernicius anemia. Am. J. M. Sc., 1929, 178, Fullertn, C. W., and Harrp, G. A., Jr., The cardiac utput in hyperthyridism. Bull. Jhns Hpkins Hsp., 1930, 6, Liljestrand, G., and Stenstr6m, N., Clinical studies n the wrk f the heart during rest: I. Bld flw and bld pressure in exphthalmic giter. Acta. med. Scandinav., 1925, 63, Bthby, W. M., and Rynearsn, E. H., Increase in circulatin rate prduced by exphthalmic giter. Arch. Int. Med., 1935, 55, Blumgart, H. L., The velcity f bld flw in health and disease. The velcity f bld flw in man and its relatin t ther measurements f the circulatin. Medicine, 1931,, Blumgart, H. L., Gargill, S. L., and Gilligan, D. R., Studies n the velcity f bld flw. XIII. The circulatry respnse t thyrtxicsis. J. Clin. Invest., 1931, 9, 69.. Tarr, L., Oppenheimer, B. S., and Sager, R. V., The circulatin time in varius clinical cnditins determined by the use f sdium dehydrchlate. Am. Heart J., 1933, 8, Blalck, A., and Harrisn, T. R., The effects f thyridectmy and thyrid feeding n the cardiac utput. Study number fur n the regulatin f circulatin. Surg., Gynec. & Obst, 1927,, Andrus, E. C., and McEachem, D., The cardiac manifestatins f hyperthyridism. Am. J. M. Sc., 1932, 183, Dck, W., and Lewis, J. K., The effect f thyrid feeding n the xygen cnsumptin f the heart and f ther tissues. J. Physil., 1932, 7, Bing, R. J., The crnary circulatin in health and disease as studied by crnary sinus catheterizatin. Bull. New Yrk Acad. Med., 1951, 27, Eckenhff, J. E., Hafkenschiel, J. H., Harmel, M. H., Gdale, W. T., Lubin, M., Bing, R. J., and Kety, S. S., Measurement f crnary bld flw by the nitrus xide methd. Am. J. Physil., 198, 152, 356.