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112 EFFECT OF PARATHYROIDECTOMY ON LEFT-VENTRICULAR FUNCTION IN HÆMODIALYSIS PATIENTS T. DRÜEKE J. FLEURY Y. TOURE P. DE VERNEJOUL M. FAUCHET P. LESOURD C. LE PAILLEUR J. CROSNIER Clinique Néphrologique, Laboratoire de Biophysique et de Médecine Nucléaire, and Clinique Cardiologique, Hôpital Necker, Paris, France Summary The effect of parathyroidectomy on left- ventricular function was evaluated in chronic-hxmodialysis patients with advanced hyperpar- athyroidism. Radionuclide angiocardiography (22 patients) and ultrasound echography (8 patients) revealed a significant increase in left-ventricular ejection fraction 1-2 weeks after parathyroidectomy. This im- provement was associated with an augmented cardiac index (radionuclide method) and with an increase in mean velocity of circumferential myocardial fibre shor- tening (echocardiography). Circulating blood volume and erythrocyte space, as well as arterial blood-pressure, had changed little after parathyroidectomy, whereas plasma calcium, phosphate, and immunoreactive para- thyroid hormone were significantly lower after surgery. Thus, correction of severe hyperparathyroidism led to a significant improvement in cardiac performance. Introduction CONGESTIVE heart-failure is a common complication in chronic-haemodialysis patients. Atheromatous coron- ary-artery disease, ansemia, chronic fluid-volume over- load, hypertension, arteriovenous shunting of blood, episodic extracorporeal circulation, and metabolic and electrolyte disturbances may all be implicated.l,2 That an excess of parathyroid hormone may play a part is suggested by our previous studies in vivo and in vitro. 3-6 In the present investigation we tested this hypothesis in severely hyperparathyroid ursemic patients. Left-ven- tricular function was evaluated, before and after para- thyroidectomy, with radionuclide angiocardiography and echocardiography. Patients 23 chronic-haemodialysis patients (14 men, 9 women) were studied. All had severe secondary hyperparathyroidism, and parathyroidectomy was indicated. The mean age was 39 years (range 19-71). Their mean time on dialysis was 78 months (range 1-120 months). A multilayer plate kidney was used for haemodialysis. All patients had arteriovenous fistula:. The haemodialysis schedules were 3 x 5 or 3 x 6 hours weekly in most cases and remained unchanged throughout the study. None of the patients had clinical evidence of heart-failure at the time of study. 2 of the 23 patients had intermittent or permanent arterial hypertension, and 1 was diabetic. Nearly half of the patients had blood-transfusion after surgery to correct the red- cell mass lost during the operation. Drug therapy was held constant except for oral or intravenous calcium supplemen- tation and reduction in oral phosphate binders after parathy- roidectomy. Methods Radionuclide angiocardiography and ultrasonic echocardio- graphy were done before and 6-14 days after parathyroidec- tomy. The studies were performed in the morning 1 or 2 days after a haemodialysis session. The patients were in the supine anterior position. Plasma parathyroid hormone was determined with an anti- carboxyl terminal antibody.8 All data are expressed as the mean ±SEM. Comparisons between groups were made with Student’s paired t test or Wil- coxon’s paired T test, as appropriate. Isotope Method Radionuclide angiography, with a method described else- were enabled the following heemodynamic parameters to be determined in a single non-invasive investigation-blood volume, red-blood-cell space, cardiac index, stroke volume, left-ventricular end-systolic and end-diastolic volume (LVESV and LVEDV), and left-ventricular ejection fraction (LVEF). These parameters allow a quantitative evaluation of cardiac function. The procedure has three stages: (1) determination of blood volume and red-cell space after injection of tranferrin labelled with indium-113m (100 Ci); (2) measurement of cardiac out- put and stroke volume (SV) from the transit curve in cardiac chambers of the same tracer (300 .Ci); and (3) measurement of LVEDV by planimetry derived from scintigraphy of cardiac cavities (5 mCi of "I-In-transferrin). The following calcula- tions were then made: LVEF = SV/LVEDV and LVESV = LVEVD-SV. The complete investigation lasts 30 min and requires three successive injections of tracer into one peripheral vein and withdrawal of a 2 ml blood sample from another vein. The short half-life of 113m1n (104 min) exposes the patient to neg- ligible irradiation. Echocardiography Left-ventricular performance was estimated by measuring the percentage of systolic shortening of the left-ventricular dia- meter, ejection fraction, and the mean velocity of circumferen- tial myocardial fibre shortening. The end-diastolic and end-systolic volumes were calculated from the left-ventricular-cavity dimensions of the echocardio- grams at the phase of end-diastole and end-systole. The ejec- tion time was measured directly from the left-ventricular endo- cardium. For the calculations, the heart was assumed to be a rotational ellipsoid. TABLE I-RADIONUCLIDE LEFT-VENTRICULAR PERFORMANCE AND BLOOD-VOLUME DATA BEFORE AND AFTER PARATHYROIDECTOMY IN 22 Results are mean ± SEM. NS = not significant. * Student’s paired t test.

EFFECT OF PARATHYROIDECTOMY ON LEFT-VENTRICULAR FUNCTION IN HÆMODIALYSIS PATIENTS

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112

EFFECT OF PARATHYROIDECTOMY ONLEFT-VENTRICULAR FUNCTION IN

HÆMODIALYSIS PATIENTS

T. DRÜEKEJ. FLEURYY. TOURE

P. DE VERNEJOUL

M. FAUCHETP. LESOURD

C. LE PAILLEURJ. CROSNIER

Clinique Néphrologique, Laboratoire de Biophysique et deMédecine Nucléaire, and Clinique Cardiologique, Hôpital

Necker, Paris, France

Summary The effect of parathyroidectomy on left-ventricular function was evaluated in

chronic-hxmodialysis patients with advanced hyperpar-athyroidism. Radionuclide angiocardiography (22patients) and ultrasound echography (8 patients)revealed a significant increase in left-ventricular ejectionfraction 1-2 weeks after parathyroidectomy. This im-provement was associated with an augmented cardiacindex (radionuclide method) and with an increase inmean velocity of circumferential myocardial fibre shor-tening (echocardiography). Circulating blood volumeand erythrocyte space, as well as arterial blood-pressure,had changed little after parathyroidectomy, whereasplasma calcium, phosphate, and immunoreactive para-thyroid hormone were significantly lower after surgery.Thus, correction of severe hyperparathyroidism led to asignificant improvement in cardiac performance.

Introduction

CONGESTIVE heart-failure is a common complicationin chronic-haemodialysis patients. Atheromatous coron-ary-artery disease, ansemia, chronic fluid-volume over-load, hypertension, arteriovenous shunting of blood,episodic extracorporeal circulation, and metabolic andelectrolyte disturbances may all be implicated.l,2 Thatan excess of parathyroid hormone may play a part issuggested by our previous studies in vivo and in vitro. 3-6

In the present investigation we tested this hypothesisin severely hyperparathyroid ursemic patients. Left-ven-tricular function was evaluated, before and after para-thyroidectomy, with radionuclide angiocardiographyand echocardiography.

Patients

23 chronic-haemodialysis patients (14 men, 9 women) werestudied. All had severe secondary hyperparathyroidism, andparathyroidectomy was indicated. The mean age was 39 years(range 19-71). Their mean time on dialysis was 78 months(range 1-120 months). A multilayer plate kidney was used forhaemodialysis. All patients had arteriovenous fistula:. The

haemodialysis schedules were 3 x 5 or 3 x 6 hours weekly in most

cases and remained unchanged throughout the study. None ofthe patients had clinical evidence of heart-failure at the timeof study. 2 of the 23 patients had intermittent or permanentarterial hypertension, and 1 was diabetic. Nearly half of thepatients had blood-transfusion after surgery to correct the red-cell mass lost during the operation. Drug therapy was heldconstant except for oral or intravenous calcium supplemen-tation and reduction in oral phosphate binders after parathy-roidectomy.

Methods

Radionuclide angiocardiography and ultrasonic echocardio-graphy were done before and 6-14 days after parathyroidec-tomy. The studies were performed in the morning 1 or 2 daysafter a haemodialysis session. The patients were in the supineanterior position.

Plasma parathyroid hormone was determined with an anti-carboxyl terminal antibody.8

All data are expressed as the mean ±SEM. Comparisonsbetween groups were made with Student’s paired t test or Wil-coxon’s paired T test, as appropriate.

Isotope MethodRadionuclide angiography, with a method described else-

were enabled the following heemodynamic parameters to bedetermined in a single non-invasive investigation-bloodvolume, red-blood-cell space, cardiac index, stroke volume,left-ventricular end-systolic and end-diastolic volume (LVESVand LVEDV), and left-ventricular ejection fraction (LVEF).These parameters allow a quantitative evaluation of cardiacfunction.The procedure has three stages: (1) determination of blood

volume and red-cell space after injection of tranferrin labelledwith indium-113m (100 Ci); (2) measurement of cardiac out-put and stroke volume (SV) from the transit curve in cardiacchambers of the same tracer (300 .Ci); and (3) measurementof LVEDV by planimetry derived from scintigraphy of cardiaccavities (5 mCi of "I-In-transferrin). The following calcula-tions were then made: LVEF = SV/LVEDV and LVESV =LVEVD-SV.The complete investigation lasts 30 min and requires three

successive injections of tracer into one peripheral vein andwithdrawal of a 2 ml blood sample from another vein. Theshort half-life of 113m1n (104 min) exposes the patient to neg-ligible irradiation.

EchocardiographyLeft-ventricular performance was estimated by measuring

the percentage of systolic shortening of the left-ventricular dia-meter, ejection fraction, and the mean velocity of circumferen-tial myocardial fibre shortening.The end-diastolic and end-systolic volumes were calculated

from the left-ventricular-cavity dimensions of the echocardio-grams at the phase of end-diastole and end-systole. The ejec-tion time was measured directly from the left-ventricular endo-cardium. For the calculations, the heart was assumed to be arotational ellipsoid.

TABLE I-RADIONUCLIDE LEFT-VENTRICULAR PERFORMANCE AND BLOOD-VOLUME DATA BEFORE AND AFTER PARATHYROIDECTOMY IN 22

Results are mean ± SEM. NS = not significant.* Student’s paired t test.

113

TABLE II-ECHOGRAPHIC LEFT-VENTRICULAR PERFORMANCE DATA BEFORE AND AFTER PARATHYROIDECTOMY IN 8 PATIENTS

Results are mean ± SEM.*Wilcoxon’s paired T test. NS=not significant.VCF = Velocity of circumferential myocardial fibre shortening.

Results

Radionuclide FindingsThe cardiac-performance data obtained with the

radionuclide method in 22 hsemodialysed patients beforeand after parathyroidectomy are shown in table i.

Whereas the heart rate remained unchanged, a signifi-cant increase in cardiac index was observed after para-thyroidectomy. Moreover, left-ventricular end-systolicvolume and, to a minor degree, end-diastolic volumediminished significantly after surgery. Thus mean left-ventricular ejection fraction increased significantly afterparathyroidectomy. These changes were observed in theabsence of significant changes in blood volume or redblood-cell mass. Systolic and diastolic blood pressurebefore (131±4-6 and 7 3 ±3 mm Hg) and after parathyroi-dectomy (128±3-3 3 and 73± 1-9 mm Hg) were comparable.

Echocardiographic FindingsIn 8 patients, cardiac performance was studied with

ultrasound echography before and after parathyroidec-tomy (table 11). A significant reduction in end-systolicdiameter and thus in left-ventricular end-systolic volumewas observed after surgery. However, , no significantchange in end-diastolic dimensions was noted. The per-centage of systolic shortening of the left-ventricular dia-meter and left-ventricular ejection fraction increasedsignificantly. Furthermore, the mean velocity of circum-ferential fibre shortening, which is a suitable parameterfor the assessment of basal left-ventricular contractility,also increased significantly after correction of the severehyperparathyroidism.

Biochemical FindingsThe concentration of plasma calcium in the 22 pa-

tients in the radionuclide study obtained at the time ofstudy fell from 255&plusmn;0043 before to 189&plusmn;0069mmol/1 after parathyroidectomy (p<0.001); plasmaphosphate fell from 1.95&plusmn;0-18 to 1.49&plusmn;0.13 mmol/l(p<0.02); and plasma immunoreactive parathyroid hor-mone fell from 247:1::51 to 30&plusmn;27 ng protein/ml (nor-mal, 4-8 ng protein/ml) (p<0-001). Plasma urea

(29.2+1.8 mmol/1 before, 32 .6&plusmn;2 mmol/1 after) andplasma creatinine (1-09&plusmn;0-07 mmol/1 before,1 16&plusmn;0-07 mmol/1 after) changed little with parathyroi-dectomy. ,

Discussion

These non-invasive radionuclide and echocardio-graphic studies have demonstrated that parathyroidec-tomy is followed by an acute enhancement of ventricular

performance in ursemic patients with severe hyperpar-athyroidism before surgery. The increase in ejectionfraction after parathyroidectomy as demonstrated by theradionuclide study was associated with an increase incardiac index, and reductions in left-ventricular end-sys-tolic and end-diastolic volumes, whereas heart rate,blood pressure, and circulating blood and red-cellvolumes did not change significantly. The fall in end-systolic volume and the increase in ejection fraction ofthe left venticle could be confirmed by an independentstudy with ultrasound echography. This study alsoshowed an improvement in percentage circumferentialfibre shortening and in mean velocity of circumferentialfibre shortening, thus supporting the view of improvedmyocardial function after parathyroidectomy. However,the slight reduction in left-ventricular end-diastolicvolume found with the radionuclide study was not foundin this smaller group of patients. It must be noted thatthe reported changes are means for the group as a wholeand that in some patients no change or even a changeopposite in direction to that of the mean value wasobserved. In haemodialysis patients, numerous factorsthat influence cardiac function-such as blood volumeand blood pressure-undergo intermittent changes inmagnitude between dialysis sessions. Even so, correctionof the severe hyperparathyroid state could be shown toinduce an improvement in cardiac performance in themajority of patients studied. The mechanism by whichthe correction of severe hyperparathyroidism has led tothe observed rapid improvement in cardiac functionremains to be elucidated. The secondary hyperparathy-roidism of uraemia is characterised by multiple metabolicand electrolyte changes of the extracellular space as wellas of the cell interior.9.1O The effect of parathyroidec-tomy on calcium and phosphate metabolism could indir-ectly lead to changes in heart-muscle contractility. Themyocardial calcium ion and high-energy phosphatelevels, especially ATP, have a key role in the contractileperformance of the myocardial fibre." Besides such in-direct effects, parathyroid hormone could also exert di-rect effects on the myocardium. We have demonstratedin isolated guineapig auricles that synthetic parathyroidhormone reduces the stimulatory effect of isoproterenolon myocardial contractile force.6Whether the acute surgical correction of the hyper-

parathyroid state leads to a permanent improvement inheart function needs to be evaluated. It would also be ofinterest to know whether similar changes in cardiac per-formance occur in non-urxmic patients with primaryhyperparathyroidism who undergo parathyroidectomy.

Secondary hyperparathyroidism may play an impor-tant part in uraemic toxicity.12.I3 The present study sug-

114

gests that excessive parathyroid-hormone secretion

might also be harmful to the uraemic myocardium.We thank Mrs C. Cabibbo, Mrs E. Scalbert, and the nurses of the

haemodialysis unit of Necker Hospital; Dr B. Lafforgue and his col-leagues at the A.U.R.A. Home Dialysis Training Centre; Dr S. Delonsand her colleagues at the E. Rist Hsemodialysis Centre, Paris; andProf. C. Dubost, of the F. Widal Hospital, Paris, for their help. Wealso thank Mrs D. Mavroyannis for secretarial assistance.

Requests for reprints should be addressed to T. D., Hopital Necker,161 Rue de Sevres, 75730 Paris-Cedex 15, France.

REFERENCES

1, Pabico RC, Freeman RB. Pericarditis and myocardiopathy. In: Masry SG,Sellers AL, eds. Clinical aspects of uremia and dialysis. Springfield,Illinois: Charles C. Thomas, 1976:69-99.

2. Dr&uuml;eke T, Le Pailleur C, Jungers P. Uremic cardiomyopathy and pericar-ditis. In: Hamburger J, Crosnier J, Gr&uuml;nfeld J-P, Maxwell MH, eds. Advances in nephrology, vol. 9. Chicago: Year Book Medical Publishers(in press).

3. Ulmann A, Dr&uuml;eke T, Zingraff J, Crosnier J. Heart rate response to isopro-terenol infusion in hemodialyzed patients. Clin Nephrol 1977; 7: 58-60.

4. Lhoste F, Dr&uuml;eke T, Man NK, et al. Anti-beta adrenoceptor blockade acti-vity of plasma ultrafiltrate in two ur&aelig;mic patients: effect of parathyroidec-tomy. Biomedicine 1976; 25: 181-84.

5. Dr&uuml;eke T, Lhoste F, Larno S, et al. Cardiac interaction of parathyroid hor-mone and propranolol in ur&aelig;mia. Proc Eur Dial Transpl Ass 1976; 13:464-70.

6. Lhoste F, Dr&uuml;eke T, Larno S, Boissier JR. Cardiac interaction between para-thyroid hormone, beta-adrenoceptor agents, and verapamil in the guineapig in vitro. Clin Exp Pharmacol Physiol (in press).

7. De Vernejoul P, Fauchet M, Rimbert JN, Barritault L, Gambini D, MetzgerJP. M&eacute;thode de mesure de la fraction d’&eacute;jection ventriculaire gauche effec-tive par association radiocardiographie-scintigraphie cardiaque. Son in-t&eacute;r&ecirc;t pour le calcul des r&eacute;gurgitations aortiques et mitrales. Int J ApplRadiat Isotopes 1976; 27: 643-51.

8. Dubost C, Bordier Ph, Ferry J, Gu&eacute;ris J. Le dosage de la parathormone dansl’hyperparathyro&iuml;die. Nouv Presse M&eacute;d 1978; 7: 21-25.

9. Massry SG, Coburn JW. Divalent ion metabolism and renal osteodystrophy.In: Massry SG, Sellers AL, eds. Clinical aspects of uremia and dialysis.Springfield, Illinois: Charles C. Thomas, 1976: 304-87.

10. Guisado R, Arieff AI, Massry SG. Muscle water and electrolytes in uremiaand the effects of hemodialysis. J Lab Clin Med 1977; 80: 322-31.

11. Katz AM. Congestive heart failure. Role of altered myocardial cellular con-trol, New Engl J Med 1975; 293: 1184-91.

12. Massry SG, Goldstein DA. The search for uremic toxin(s) "X". "X"=PTH.Clin Nephrol 1979; 11: 181-89.

13. Dr&uuml;eke T, Ulmann A. Ost&eacute;odystrophie r&eacute;nale: r&ocirc;le de la vitamine D et dela parathormone. Nouv Press M&eacute;d 1979; 8: 1901-03.

ALBUMIN AND NUTRITIONAL &OElig;DEMA

MICHAEL H. N. GOLDEN BARBARA E. GOLDENALAN A. JACKSON

Tropical Metabolism Research Unit, University of the WestIndies, Mona, Kingston 7, Jamaica

Summary The nature of the association between

plasma albumin and nutritional &oelig;demahas been examined by observing the changes in albuminduring loss of &oelig;dema in patients on a restricted diet.Since there was no difference in the concentration ofplasma albumin before and after loss of &oelig;dema, the as-sociation is not causal. These results provide no supportfor the assertion that nutritional &oelig;dema should betreated with a high-protein diet or an albumin infusion.

Introduction

HYPOALBUMII3lMIA is widely accepted as the cause ofoedema when the two are present together,I,2 particu-larly in kwashiorkor and nephrotic syndrome. If the as-sociation is causal a rise in albumin concentrationshould precede the loss of oedema. One might furtherexpect a relation between the albumin concentrationand both the degree of oedema and the rate at which it

is cleared. We have tested these predictions in childrenwith kwashiorkor.

Patients and Methods

Twelve children with kwashiorkor or marasmic-kwashior-kor3 were studied (see accompanying table). None of the childrenwas in cardiac failure and all had normal serum- sodium concen-trations. On admission the degree of oedema was estimated clini-cally, and each child was offered a diet appropriate for whathis or her weight was thought to be if the child was normallyhydrated.4- The diet was made up from an infant formula(’Pelargon’, Nestle 27 g/1), white cane sugar (100 g/1),and arachis oil (20 g/1) to provide 0.6 g protein/kg/day and400 kj/kg/day. This diet maintains body-weight in non-rede-matous malnourished children without permitting new tissue

synthesis; it is inadequate for normal children.s The diet wassupplemented with potassium chloride, 4 mmol/kg/day; mag-nesium chloride, 1 mmol/kg/day; folic acid, 5 mg/day; and amultivitamin preparation (’Tropivite’, Federated Pharmaceu-tical), 0.5 5 mvday. Appropriate antibiotics were given. No childreceived intravenous fluids.

Plasma albumin was measured by a bromocresol-green bind-ing method.6 This method, which gives higher values thanother methods owing to globulin binding,7 has a normal rangeof 40-53 g/1. Human albumin-was used as standard.The quantity of oedema fluid was assessed as the difference

between the weight of the child on admission and the lowestweight maintained for three days after the loss of clinicaloedema (expressed as percentage of admission weight).The results were analysed by a one-tailed, paired Student’s

t-test.

Results

Mean plasma-albumin concentration did not changewith the loss of oedema (fig. 1). Only one child had a sub-stantial rise in albumin as oedema was lost. Otherwise,not only is the range of values (15-30 g/1) similar beforeand after loss of oedema, but also there is no differencein values for individual children. There was no sugges-tion that a critical albumin concentration had to bereached before oedema was lost. The degree of oedemadid not correlate with plasma-albumin concentration:the rate of oedema clearance, expressed either as g/kg/

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