Case ReportBritish Heart Journal, 1972, 34, I I 3-I I 6.

Cardiomyopathy accompanying industrialcobalt exposureM. Barborik and J. Dusek'From First Medical Clinic and the Pathological Institute, Palacky University,Olomouc, Czechoslovakia, and Pathological Institute, McGill University,Montreal, Quebec, Canada

A case of cardiomyopathy in a 4I-year-old metal worker is described. High concentration ofcobalt in the organs and the morphologicalfindings in the heart suggest cobalt cardiomyopathy tobe the underlying disease.

The toxicity of cobalt has recently been dis-cussed in association with the so-called beerdrinkers' cardiomyopathy. This disease was

reported first from Quebec City where 48cases were observed clinically with 20 fatalities(Bonenfant, Miller, and Roy, I967; Journal ofthe American Medical Association, I966;Canadian Medical Association J7ournal, I967).Similar cases were published from Omaha,Nebraska (McDermott et al., I966), and fromBelgium (Kesteloot et al., I968). It was feltthat cobaltous sulphate added to the beer was

mainly responsible for the myocardial damage(Morin and Daniel, I967). In animal experi-ments, it was possible to produce acutemyocardial damage by treatment with exces-

sively high doses of cobalt compounds (Griceet al., I969a,b; Kasperek, Siller, and Knieriem,I969; Knieriem and Herbertz, I969). Nu-tritional factors appeared to predispose tocobalt toxicity (Alexander, I969).

In medical practice, cobalt salts were usedfor the treatment of anaemias with con-

siderable success (Berk, Burchenal, andCastle, I949; Fountain and Dales, I955).Undesired side effects have been reported(Wintrobe, I967); cardiomyopathy, however,did not appear. Neither have there been anyreports of cobalt-induced cardiomyopathy inindustry, in spite of the intensive and long-lasting exposure to cobalt of workers withhard metal alloys. The disease has beenreported so far only as cardiomyopathy ofbeer drinkers.The following is a case of fatal disease in a

metal worker who had been exposed to

1 Research Fellow of Medical Research Council ofCanada.

cobalt for some time. The necropsy findings,together with the results of the determinationof cobalt in the tissues, indicate a causalrelation.

Case reportA 4i-year-old man was admitted to the hospitalon 6 March I966, with the symptoms of a generalmalaise, non-productive cough, and oppressivepain below the left costal margin. During pre-vious medical checkups he had always beenreported as healthy, with normal chest x-rays androutine laboratory value examinations, exceptslightly raised RBC count (around 5,8oo,ooo), Hbvalues (I7-20 g/Ioo ml), and haematocrit (50%).

Physical examination on admission showedcongestion of the conjunctivae, auscultatory ralesover the chest, and enlargement of the heart. Achest x-ray showed enlargement of the heart toboth sides (Fig. I). Laboratory findings: RBC6,700,000, Hb 20 g/IOO ml, WBC 6,8oo, + +proteinuria with granular casts. Non-proteinnitrogen was 33 mg/ioo ml on the day of admis-sion, rising to 55 mg/Ioo ml on the second day.Serum aspartate and alanine transferases werewithin normal limits. Electrocardiogram showedsinus rhythm with low voltage in the extremityleads, high and widened P in leads II and III, andbiphasic P in V. PR interval 0oI4 sec, QRSo-o8 sec, right axis deviation, and transition zonein the chest leads in V5. The electrocardiographicpattern was described as suggestive of rightventricular hypertrophy.On the second day of admission the patient

complained of oppressive pain under the leftcostal margin. He vomited and became irritated.There was cyanosis, increased filling of thecervical veins, tachycardia 120/min, and softpulse. Blood pressure dropped to immeasurablevalues and right-sided hemiparesis developed.

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114 Barborik and Dusek

FIG. I Chest x-ray taken 2 days beforedeath. The heart appears very enlarged.

Temporary improvement resulted from norepine-phrine infusion, and injections of strophanthinand aminophylline; however, further deteriorationled to death on 9 March, 3 days after admittanceto hospital.

Necropsy findings Heart weighed 490 g. Bothatria and ventricles were dilated, the left ven-tricular wall was thickened (I3 mm), the rightventricular wall showed trabecular hypertrophy.Myocardium of both ventricles was pale. Cardiacvalves were normal, and coronary arteries were

patent with only a few atherosclerotic plaques.Minimal atherosclerotic changes were found inthe aorta. The lungs showed congestion and slightoedema. The thyroid gland was moderatelyenlarged. There were effusions in both pleuralcavities (500 right and i5o ml left side) and in thepericardial sac (500 ml).

Microscopical examination Histological studyof several areas from the ventricles showed a

similar pattern: the myocardial fibres weremostly thickened, fragmented, with obvious focalvacuolar change. The interstitial connective tissueseparating the fibres was diffusely increased andoedematous (Fig. 2). There was no inflammatoryreaction in any of the areas studied. The endo-cardium showed diffuse thickening, with occa-sional small parietal thrombi. The intramural

FIG. 2 Representative area of the leftventricular myocardium. Note irregularity,thickening, and vacuolar degeneration of themuscle fibres and the loose interstitial connec-

tive tissue. (H and E. X 250.)

coronary branches were patent. Histology of thethyroid showed normal structure except severalareas where the alveoli were small, lined withcolumnar epithelium, and contained little colloid.The lungs were congested. Histology of the liver,kidneys, and spleen revealed both acute andchronic congestion. Examination of sternum, rib,and vertebral body showed normal pattern ofhaemopoietic tissue.

In summary, the necropsy revealed cardio-megaly with cardiomyopathy of an unknownorigin. The myocardial changes could not beattributed to the minimal atherosclerotic changespresent in the coronary arteries. There were no

valvular deformities and, microscopically, no

signs of inflammation. Thyroid gland showedfocal signs of activation. The cause of death wascardiac insufficiency.A sample from the left ventricular myocardium

was analysed for the content of cobalt. The valuefound was 37 ,ug/Ioo g wet weight of the heartmuscle or I40 FLg/100 g dry tissue weight (Table).

TABLE Organ concentrations of cobalt in case of cardiomyopathy and in two control cases

Organ Cardiomyopathy Controls

pLg/boo ml ±g/Iroo ml Uraemia Cor pulmonalewet weight dry weight

glg/Ioo ml Lg/10oo ml gg/Ioo ml [Lg/Ioo mlwet weight dry weight wet weight dry weight

Heart 37 I40 5 20 2 10Lung I7 107 7 40 3 20Liver 34 135 3 I0 3 I0Spleen I9 87 4 20 I I0Kidney 29 I40 3 I0 I I0

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Cardiomyopathy accompanying industrial cobalt exposure iI5

DiscussionThis report describes a case of cardiomyo-pathy in a patient who had been exposed for4 years to cobalt. Clinical features (age,sudden manifestation of the disease, shortclinical course with a fatal outcome, clinicalsigns of cardiac insufficiency, electrocardio-graphic findings) resembled beer drinkers'cardiopathy. Low serum enzyme values(SGOT, SGPT) were not in disagreementwith the diagnosis of cardiomyopathy; in theQuebec cases high levels of serum enzymewere ascribed more to the secondary liverdamage than to the myocardial involve-ment. Postmortem chemical analysis showedmassive accumulation of cobalt in tissues. Inthe myocardium the concentration exceededthe values given by Sullivan, Parker, andCarson (I968) in fatal cases of beer drinkers'cardiopathy. Necropsy findings also corre-sponded with the pathological findings in

cases of beer drinkers' cardiopathy (Bonenfantet al., I967; Grinvalsky and Fitch, I969;McDermott et al., I966; Rona, I968).The toxic effect of cobalt is known since the

experimental work of Webb (I962, I964).Cobalt apparently inhibits several enzymes,most probably by competition with magnes-ium and calcium ions that are necessary forthe enzymatic activity. It thus interferes withthe breakdown of metabolites in the Krebscycle, with the metabolism of pyruvate, fattyacids, and with the terminal electron transportmechanism (Dingle et al., I962; Hall andSmith, I968; Levy, Levinson, and Schade,I950; Webb, I962, I964; Wiberg, Munro,and Morrison, I967). Enzymatic inhibitionmay be combined with partial replacement ofcalcium on sites where it is necessary formuscular contraction. As stressed by Kauf-mann and Fleckenstein (I965), this leads tomyocardial insufficiency characterized by adefective utilization of the high energyphosphates.The interference of cobalt with the cardiac

metabolism causes obvious myocardial weak-ness with dilatation of the heart and secondaryparietal thrombosis, a picture similar to thedescription of the acute fulminating formof beri beri heart disease. Light micro-scopical findings are similar (Grinvalsky andFitch, I969).

Histochemical studies of Hall and Smith(I968) in animals intoxicated with cobaltoussulphate or chloride showed an abundance ofglycogen, some increase in the overallenzymatic activity of beta-hydroxybutyricdehydrogenase, and decrease in activity ofsuccinic dehydrogenase. The findings have

been interpreted as a sign of metabolicchanges in the heart muscle caused by cobalt.However, an obvious loss of body weight wasreported in this study dealing with the kisto-chemical changes after poisoning with cobalt.It seems that, in addition to the toxic effect ofcobalt, accumulation of glycogen and enzym-atic changes may have resulted from starva-tion.

Ultrastructural changes after an experi-mental intoxication with cobalt (Grice et al.,I969a, b; Hall and Smith, I968; Knieriem andHerbertz, I969) show severe damage to thecardiac muscle cells with disappearance of themyofibrils, aggregation of mitochondria, fattydegeneration, and final disappearance of thecells and fibrosis. Similar findings werereported in human cases examined with theelectron microscope (Alexander, I968; Augerand Chenard, I967). The ultrastructuralobservation of one case by Wellman (I968),though it resembles findings in experimentalcobalt intoxication, lacks some importantinformation (intake of cobalt). Clinical find-ings and the electron microscopical pattern inthis case also differ slightly from the Quebeccases.

Little is known so far about the conditionsresponsible for the individual differences intoxicity of cobalt for man. It seems thatcobalt alone is not responsible for the cardio-toxicity, and that additional features such asdeficient diet, alcohol, viral infection, andelectrolyte imbalance (Wiberg et al., I969)sensitize the tissues to excessive intake ofcobalt. This would explain the appearance ofbeer drinkers' cardiomyopathy in only a smallpercentage of the population consuming highquantities of beer with increased concentra-tion of cobaltous sulphate and the apparentlyrare occurrence of cobalt cardiomyopathyamong metal workers. Lung fibrosis may bemore frequent as a complication in workerswith hard alloys (Bech, Kipling, and Heather,I962), and it may cause secondary heartinsufficiency.

In the history of the case presented it isdifficult to specify any possible contributoryfactor. There is no indication of an excessivealcohol (beer) intake and an inadequate diet.The findings in the heart and thyroid aresimilar to those found in cases of beer drinkers'disease. It is felt that, because of the highcontent of cobalt found in the organs,especially in the heart muscle, and be-cause of the lack of any other causal factorfor the myocardial lesion, the case maywell be an example of cobalt cardiomyo-pathy secondary to an industrial exposure tothis metal.

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Ix6 Barborik and Dusek

The authors thank Dr. G. Rona and Mrs. W.Cisneros for their help in the preparation of themanuscript, and Mr. H. Coletta for the photo-graphs.

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Rona, G. (I968). Endemic cardiomyopathy of beerconsumers. Acta morphologica Academiae Scienti-arum Hungaricae, I6, 103.

Sullivan, J. F., Parker, M., and Carson, S. B. (I968).Tissue cobalt content in 'beer drinkers' myo-cardiopathy.' Journal of Laboratory and ClinicalMedicine, 71, 893.

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Requests for reprints to Dr. M. Barborik, IstMedical Clinic, Faculty Hospital, I.P. Pavlova 6,Olomonc, Czechoslovakia.

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