THE CARDIACOUTPUTAT REST IN LAENNEC'S CIRRHOSIS1

By HENRYJ. KOWALSKI2 ANDWALTERH. ABELMANN

(From the Thorndike Memorial Laboratory, Second and Fourth Medical Services [Harvard],and the Department of Medicine, Harvard Medical School, Boston, Mass.)

(Submitted for publication April 29, 1953; accepted June 12, 1953)

INTRODUCTION

Patients with Laennec's cirrhosis and those withoccidental beri-beri frequently have the commonbackground of consumption of alcoholic beveragesand inadequate diet of long duration. A short cir-culation time which may be found in occidentalberi-beri (1) and in Laennec's cirrhosis (2, 3) sug-gests an elevated cardiac output. In the case ofberi-beri, this has been verified (4, 5, 6, 7), but, toour knowledge, direct measurements of systemicblood flow have not been reported in chronic liverdisease. Increased flow of blood to the peripheryin patients with Laennec's cirrhosis is suggested bythe frequent occurrence of warm extremities, cu-taneous vascular spiders, wide pulse pressure, andcapillary pulsations in the nail beds.

The present study reports measurements of theresting cardiac output, blood pressure, and periph-eral resistance in patients with chronic alcoholismand disease of the liver.

MATERIALS ANDMETHODS

Selection of patientsTwenty-two hospitalized patients 8 with clinical and/or

laboratory evidence of chronic parenchymal disease of theliver were studied. Only patients without clinical evi-dence of co-existing heart disease and without evidenceof acute gastro-intestinal bleeding were included. Allsubjects gave a history of excessive intake of alcoholicbeverages and an irregular and inadequate diet of long-standing.

Of the 22 patients studied, three had "fatty liver," 11had Laennec's cirrhosis without fluid retention, andeight had Laennec's cirrhosis with either ascites or periph-eral edema or both. Of the 19 patients with Laennec's

1 Presented in part at the Eastern Section Meeting ofthe American Federation for Clinical Research, December5, 1952, New York, N. Y.

2 Postdoctoral Research Fellow, Life Insurance Medi-cal Research Fund.

8 Weappreciate the courtesy of Dr. Charles S. Davidsonand his associates, and of the various medical services ofthe Boston City Hospital for making their patients avail-able for study.

cirrhosis, all save one (No. 17) had enlargement of theliver, and all but two (Nos. 11 and 18) had cutaneous vas-cular spiders. All 22 patients had abnormally high Brom-sulfalein retention.

A diagnosis of "fatty liver" was made clinically whenthere was enlargement of the liver and laboratory evi-dence of hepatic dysfunction without the following: icterus,cutaneous vascular spiders, ascites, edema, splenomegaly,or prominent abdominal veins.

PROCEDURES

Each patient was studied early in the morning withoutany premedication, fasting and recumbent. An indwellingneedle was inserted into the left brachial artery and asimilar needle was placed into a right antecubital vein.The patient then was allowed to rest -for at least twentyminutes.

Cardiac outputThe cardiac output was determined by the dye-injection

method as described by Hamilton and his co-workers (8).Five mg. of a 0.5 per cent solution of Evans blue dye wereinjected rapidly through the venous needle from a tubercu-lin syringe previously calibrated by weighing. The deadspace of the indwelling needle was known and accountedfor in determining the amount of dye injected. Samplesof arterial blood were collected from the arterial needlethrough a short length of polyethylene tubing into hepari-nized tubes mounted along the rim of a circular lucite discequipped with funnels arranged so that spillage betweentubes was minimized. The disc was rotated about a cen-trally placed vertical shaft by a variable-speed electricmotor. The usual collection time for each tube was twoand one-half seconds. Samples of arterial blood were cen-trifuged for 20 minutes at 3,000 rpm. and the concentrationof dye in undiluted plasma was determined in micro-cellsof 0.5 cc. capacity at a wave length of 625 mu. using aBeckmann Model DU spectrophotometer. In most pa-tients duplicate estimations were made.

The cardiac index was calculated from the cardiac out-put and the body surface area using the height and weightat time of study irrespective of the presence or absence ofedema. In subjects with marked obesity and perhaps inthose with abnormal fluid retention, the body surface areacalculated according to Du Bois and Du Bois (9) mightdistort the predicted value for cardiac index (10, 11). Thecardiac output also was expressed in terms of oxygen con-sumption as a ratio by the formula:

Cardiac output L./min. X 100Oxygen consumption cc./min.

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HENRYJ. KOWALSKI AND WALTERH. ABELMANN

TABLE I

Cardiac index-"normal" values*

Standard deviationMean 4 of sample

No. Cardiac output L./min. X 100Authors subjects Method Cardiac index Oxygen consumption cc./min.

Cournand et al.(J. Clin. Invest., 30 Fick 3.31 4 0.54 2.32 41 0.32

1945, 24, 106.)

Stead et al.(J. Clin. Invest., 18 Fick 3.27 0.57 2.52 + 0.39

1945, 24, 326.)

Ebert et al.(J. Clin. Invest., 12 Fick 3.59 d0.72 2.64 :1: 0.34

1949, 28, 1134.)

Chapman et al.(J. Clin. Invest., 7 Fick 3.27 : 0.62 2.67 h 0.43

1950, 29, 651.)Dexter et al.J. Applied Physiol., 7 Fick 3.79 - 0.83 2.77 :4: 0.37

1951, 3, 439.)

Doyle et al.U. Clin. Invest. 10 Fick 3.52 4 0.79 2.41 1 0.35

1951, 30, 345.) Dye 2.85 4 0.40 1.97 4 0.87

Freis et al.(J. Clin. Invest., 8 Dye 4.19 4 0.81

1952, 31, 131.)

Present Authors 12 Dye 3.76 i 0.65

* Calculated by us from data in sources listed. Subjects with "anxiety" excluded as in individual reports.or more observations on the same subject were averaged, and the mean was used in these calculations.

Two

Table I indicates values of cardiac index as reported byothers and as determined in this laboratory using the dye-injection method in subjects who were considered es-sentially normal. Also shown are values for the ratio ofcardiac output to oxygen consumption.

Oxygen consumptionOxygen consumption was determined over a six-minute

period by means of a closed circuit water spirometerfilled with oxygen, after the cardiac output studies werecompleted.

Arterial pressure

Phasic and mean arterial pressures were measured di-rectly by means of an electromanometer of the condenser-microphone type and recorded on a direct writing oscil-lograph.4

Peripheral resistanceThe formula used was (12):

Resistance -Mean arterial pressure mm. Hg X 1332Cardiac output cc./sec.

4 Made by Sanbomn Company, Cambridge, Massachusetts.

Venous pressureVenous pressure was estimated by means of a saline

manometer attached to the indwelling needle located inthe antecubital vein, and referred to a zero point 5 cm.below the angle of Louis.

RESULTS

The data are found in Table II.

Cardiac output (Figure 1)

The mean cardiac index of patients with diseaseof the liver was 4.26 L. per min. per M2, and thestandard deviation of the sample was ± 2.73 L. permin. per M2. Values below the normal range werenot seen, and in seven patients they were above thenormal range.

As indicated in Figure 1, elevations of outputwere noted in one of the three patients with "fattyliver" as well as in patients with cirrhosis, irrespec-tive of the presence or absence of abnormal fluidretention or of jaundice.

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THE CARDIAC OUTPUT IN LAENNECS CIRRHOSIS

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1028

THE CARDIAC OUTPUTIN LAENNECS CIRRHOSIS

FAT TY CIRRHOSISLIVER DRY WET

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Although one patient (No. 15) had a very highcardiac index, 11.2 L. per min. per M2, this appar-ently did not unduly influence the mean of 4.76 sincethe median value for the series lay between 4.62and 4.24 L. per min. per M2. (This individual wasrestudied six weeks later at which time his cardiacindex was 16.3 L. per min. per M2and his oxygenconsumption was 263 cc. per min.)

The mean value of the ratio,cardiac output L./min. x 100

Peripheral resistance

Values ranged from 367 to 1965 dynes-cm.-seconds-5 with a mean of 955, a value within ac-cepted normal standards (13). Peripheral re-sistance was inversely related to cardiac output asseen in Figure 3. The mean resistance of the sevenpatients with high cardiac outputs was 596, a lowvalue.

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Figure 2 is a plot of cardiac index against the car- A slightdiac output-oxygen consumption ratio. Those pa- feature oftients with the highest value of cardiac index had though thethe highest ratios, suggesting that where the cardiac to have fastoutput is elevated such elevations are not accom- ation betwpanied by parallel increases in oxygen consumption. stroke volu

immediateArterial pressure tions in out

Values for mean arterial pressure ranged from 66to 120 mm. Hg. Patients with the higher pressures Heart sizegenerally had normal outputs with one exception With the(No. 15), whose mean pressure was 111 mm. Hg at and 22), alla time when his cardiac index was 11.2 L. per min. No chamb4per M2. vigorous c

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elevation of resting heart rate was amost patients with liver disease. Al-patients with the highest outputs tendedter rates, there was no consistent associ-'een output and rate. Elevations ofme as opposed to tachycardia were themechanism which produced the eleva-tput.

e exception of two individuals (Nos. 17[ patients were examined by fluoroscopy.er enlargement was noted. Unusuallyardiac pulsations were conspicuous in

1029

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The transverse diameter of the heartfrom teleoroentgenograms averaged 11of predicted values. (Normal rangecent to 110 per cent.) The mean transveter in the seven patients with elevataveraged 105 per cent of predicted valusize, then, was not abnormal.

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DISCUSSION

terse diam- The data indicate that the cardiac output deter-ed outputs mined at rest and in recumbency may be normal orLes. Heart distinctly elevated in patients with chronic alcohol-

ism and parenchymal disease of the liver.When the output is increased, it is out of pro-

portion to the oxygen consumption or, by impli-i eight pa- cation from the Fick formula (C.O. = oxygend Hallaran consumption/arterio-venous oxygen difference),

the arterio-venous oxygen difference must be de-creased. The increase in blood flow is mainly ac-complished by a larger output per beat. Since thearterial pressures are essentially normal, the in-creased blood flow is associated with decreasedtotal vascular resistance. The hemodynamic pic-ture in these subjects with elevated outputs re-sembles the high output state as seen in beri-beriheart disease (4, 5, 6, 7) and in the "shunt circu-lation" of arterio-venous fistulae (15, 16) orPaget's disease (17).

Several factors might be involved in producingthe elevated outputs seen in one-third of the presentseries:

2to -2so Anxiety, which may elevate the cardiac output(13, 18, 19), does not appear responsible for theincrease in blood flow since the subjects were re-

DIAC OUTPUT laxed, indifferent, and without overt resentment.

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6t

THE CARDIAC OUTPUT IN LAENNECS CIRRHOSIS

Anemia, a frequent feature of parenchymal dis-ease of the liver, is associated with an elevation ofcardiac output when the hemoglobin falls to about7 Gm. per 100 cc. or the hematocrit to about 20per cent (20). Anemia of such degree was notseen in these patients, and since high values forcardiac output were seen in subjects with normalor near normal hematocrits, anemia does not ade-quately explain the elevated output.

All subjects gave a history of longstanding con-sumption of alcohol combined with a poor dietaryintake. This background is similar to that of pa-tients with occidental beri-beri as reported byWeiss and WiLkins (1) and by Blankenhorn (21).However, in our patients, clinical evidence of thi-amine deficiency, such as neuritis, was absent, ve-nous pressure was not elevated, cardiac enlarge-ment was not evident, and heart failure was notseen. Four of the seven subjects with elevated out-puts (Nos. 4, 5, 6, and 15) had been hospitalized22 days or longer before study, and during thistime they consumed nutritious diets under super-vision. Two of these four patients (Nos. 42 and5), in addition, were given supplementary thiaminechloride parenterally (Table II). In view of thesefacts, occidental beri-beri seems unlikely as anexplanation of the elevated outputs seen in somepatients.

Elevated concentrations of blood pyruvic andlactic acid have been noted in some patients withcirrhosis (22, 23, 24). This raises the possibilityof impaired utilization of thiamine even in the pres-ence of adequate amounts of the vitamin.

The high output state noted in some patients maybe related to a deficiency state other than beri-beri.However, Howarth (25) studied the resting car-diac output in 20 severely malnourished individualswith hunger edema, and without evidence of vita-min deficiencies. The outputs were normal or low.The nutritional heart disease described in associa-tion with liver disease in the South African Bantu(26) also appears associated with normal or lowcardiac outputs at least at the stage of the diseaseobserved.

The existence of arterio-venous communicationsin normal as well as in cirrhotic livers has beendemonstrated by Herrick, by Prinzmetal and hisco-workers, and by Dock (27, 28, 29). The roleof these communications in producing elevations of

cardiac output would not seem great since estimatesof hepatic blood flow and splanchnic arterio-ve-nous oxygen difference (30, 31 ) suggest theformer is decreased and the latter increased in sub-jects with cirrhosis.

The site of the increased blood flow thus wouldseem to lie in the periphery of the body, and wefall back on the concept suggested by Weiss andWilkins (1) in explanation of the circulatorychanges in beri-beri, namely that there exists gen-eralized peripheral arteriolar dilatation, acting ineffect like multiple arterio-venous shunts in parallel.

Shorr, Zweifach, Furchtgott, and Baez (32)have demonstrated that a vasodilator material,VDM, is produced by the liver under anaerobicconditions, and that it is inactivated by normal butnot by anoxic liver tissue. Moreover, VDMwasnot inactivated under aerobic conditions by thelivers of cirrhotic rats (33). It is thus conceivablethat in human cirrhosis VDMis increased, or thereis an imbalance in the VDM-VEMsystem infavor of VDM. This, then, could be a mechanisminvolved in the production of peripheral vaso-dila-tation.

In the final analysis, we do not know whether theelevated outputs are related specifically to hepaticdisease, or to a form of chronic malnutrition, oreven whether they may represent the circulatoryresponse of certain patients with chronic alcohol-ism to the laboratory situation.

The high incidence of prolongation of the Q-Tinterval is of interest in relation to similar electro-cardiographic findings observed in occidental beri-beri (1), and in general deficiency states not re-lated to thiamine deficiency (34). Prolongationof the Q-T interval has been noted by other workersin cirrhosis (35, 36).

SUMMARY

Observations made in 22 patients with a historyof alcoholism, and inadequate diet, and cirrhosisof the liver indicate that the resting cardiac outputwas elevated in one-third of the patients and wasassociated with a large stroke volume, normal bloodpressure, and low peripheral vascular resistance.Where the cardiac output was high, it was ele-vated out of proportion to the oxygen consumption,indicating a decreased arterio-venous oxygen dif-ference.

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HENRYJ. KOWALSKI AND WALTERH. ABELMANN

It is suggested that dilatation of the peripheralvascular bed is, responsible for the increased bloodflow.

ACKNOWLEDGMENTS

We are grateful for the technical assistance of MissBernice E. Fingerman.

Weexpress our gratitude to Dr. Laurence B. Ellis forhis encouragement and advice throughout this investigation.

REFERENCES

1. Weiss, S., and Wilkins, R. W., The nature of thecardiovascular disturbances in nutritional deficiencystates (beri-beri). Ann. Int. Med., 1937, 11, 104.

2. Dock, W., Present concepts regarding the mechanismof heart failure. Bull. St. Francis Sanatorium,1951, 8 (no. 3), 1.

3. Abelmann, W. H., Unpublished observations, 1950-1951.

4. Porter, R. R., and Downs, R. S., Some physiologicalobservations on the circulation during recovery fromVitamin B1 deficiency. Ann. Int. Med., 1942, 17,645.

5. Burwell, C. S., and Dexter, L., Beri-beri heart dis-ease. Tr. A. Am. Physicians, 1947, 60, 59.

6. Campbell, J. A., Selverstone, L. A., and DonQvan,D. L., Studies on the high output cardiac failureof occidental beriberi. J. Clin. Invest., 1951, 30,632.

7. Lahey, W. J., Arst, D. B., Silver, M., Kleeman, C. R.,and Kunkel, P., Physiologic observations on a

case of beriberi heart disease, with a note on theacute effect of thiamine. Am. J. Med., 1953, 14, 248.

8. Hamilton, W. F., Riley, R. L., Attyah, A. M., Cour-nand, A., Fowell, D. M., Himmelstein, A., Noble,R. P., Remington, J. W., Richards, D. W., Jr.,Wheeler, N. C., and Witham, A. C., Comparisonof the Fick and dye injection methods of meas-

uring the cardiac output in man. Am. J. Physiol.,1948, 153, 309.

9. DuBois, D., and DuBois, E. F., Clinical calorimetry.X. A formula to estimate the approximate surfacearea if height and weight be known. Arch. Int.Med., 1916, 17, 863.

10. Tanner, 3. M., Fallacy of per-weight and per-surfacearea standards, and their relation to spurious cor-

relation. J. Applied Physiol., 1949, 2, 1.11. Taylor, H. L., Brozek, J., and Keys, A., Basal cardiac

function and body composition with special refer-ence to obesity. J. Clin. Invest., 1952, 31, 976.

12. Cournand, A., Riley, R. L., Bradley, S. E., Breed,E. S., Noble, R. P., Lauson, H. D., Gregersen, M.I., and Richards, D. W., Jr., Studies of the cir-culation in clinical shock. Surgery, 1943, 13, 964.

13. Stead, E. A., Jr., Warren, J. V., Merrill, A. J., andBrannon, E. S., The cardiac output in male sub-jects as measured by the technique of right atrialcatheterization. Normal values with observations

on the effect of anxiety and tilting. J. Clin. Invest.,1945, 24, 326.

14. Shipley, R. A., and Hallaran, W. R., The four-leadelectrocardiogram in two hundred normal men andwomen. Am. Heart J., 1936, 11, 325.

15. Ellis, L. B., and Weiss, S., The local and systemiceffects of arterio-venous fistula on the circulationin man. Am. Heart J., 1930, 5, 635.

16. Warren, J. V., Nickerson, J. L., and Elkin, D. C.,The cardiac output in patients with arteriovenousfistulas. J. Clin. Invest., 1951, 30, 210.

17. Edholm, 0. G., Howarth, S., and McMichael, J.,Heart failure and bone blood flow in osteitis defor-mans. Clin. Sc., 1945, 5, 249.

18. Grollman, A. P., Physiological variations in thecardiac output of man. IV. The effect of psychicdisturbances on the cardiac output, pulse, bloodpressure, and oxygen consumption of man. Am. J.Physiol., 1929, 89, 584.

19. Hickam, J. B., Cargill, W. H., and Golden, A., Cardio-vascular reactions to emotional stimuli. Effect onthe cardiac output, arteriovenous oxygen differ-ence, arterial pressure, and peripheral resistance.J. Clin. Invest., 1948, 27, 290.

20. Brannon, E. S., Merrill, A. J., Warren, J. V., andStead, E. A., Jr., The cardiac output in patientswith chronic anemia as measured by the techniqueof right atrial catheterization. J. Clin. Invest.,1945, 24, 332.

21. Blankenhorn, M. A., The diagnosis of beriberi heartdisease. Ann. Int. Med., 1945, 23, 398.

22. Weiss, S., and Ellis, L. B., Oxygen utilization andlactic acid production in the extremities during reptand exercise in subjects with normal and in thosewith diseased cardiovascular systems. Arch. Int.Med., 1935, 55, 665.

23. Williams, R. H., and Bissell, G. W., Thiamine metabo-lism with particular reference to the role of theliver and kidneys. Arch. Int. Med., 1944, 73, 203.

24. Amatuzio, D. S., and Nesbitt, S., A study of pyruvicacid in the blood and spinal fluid of patients withliver disease with and without hepatic coma. J.Clin. Invest., 1950, 29, 1486.

25. Howarth, S., Cardiac output and the peripheral cir-culation in malnourished subjects. (Wuppertal,B.A.O.R., 1946) Proc. Physiol. Soc., 17-18 Dec.1948, abstracted, J. Physiol., 1949, 109, 14P.

26. Gillanders, A. D., Nutritional heart disease. Brit.Heart J., 1951, 13, 177.

27. Herrick, F. C., An experimental study into the causeof the increased portal pressure in portal cirrhosis.J. Exper. Med., 1907, 9, 93.

28. Prinzmetal, M., Ornitz, E. M., Jr., Simkin, B., andBergman, H. C., Arterio-venous anastomoses inliver, spleen, and lungs. Am. J. Physiol., 1948, 152,48.

29. Dock, W., The ro.le of increased hepatic arterial flowin portal hypertension of cirrhosis. Tr. A. Am.Physicians, 1942, 57, 302.

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THE CARDIAC OUTPUT IN LAENNECS CIRRHOSIS

30. Bradley, S. E., Ingelfinger, F. J., and Bradley, G. P.,Hepatic circulation in cirrhosis of the liver. Cir-culation, 1952, 5, 419.

31. Myers, J. D., The hepatic blood flow in Laennec's cir-rhosis with an estimate of the relative contributionsfrom portal vein and hepatic artery. J. Clin. Invest.,1950, 29, 836. 1

32. Shorr, E., Zweifach, B. W., Furchtgott, R. F., andBaez, S., Hepatorenal factors in circulatory homeo-stasis. IV. Tissue origins of the vasotropic prin-ciples, VEMand VDM, which appear during evolu-

tion of hemorrhagic and tourniquet shock. Circu-lation, 1951, 3, 42.

33. Shorr, E., and Zweifach, B. W., Hepato-renal factorsin circulatory homeostasis. XIX. VEMand VDMmechanisms in nutritional cirrhosis in rats. Fed-eration Proc., 1948, 7, 115.

34. Ellis, L. B., Electrocardiographic abnormalities in

severe malnutrition. Brit. Heart J., 1946, 8, 53.35. Hegglin, R., L'insuffisance cardiaque energeto-dyna-

mique. Cardiologia, 1949, 15, 65.36. Oppenheim, M., Die Myokardose bei Lebercirrhose.

Schweiz. med. Wchnschr., 1950, 80, 795.

1033