Serum Zinc Concentration in Acute Myocardial Infarction

Serum Zinc Concentration in Acute Myocardial Infarction Ali M. Handiani M.D., F.C.C.P.;· I. Cecil Smith, Ir., Ph.D.;·· lohn B. Herrmann, M.D.;·· and James A. Halsted, M.D.··

The serum zinc concentration was examined in 18 patients, 11 with weD documented myocardial infarction and 7 patients with chest pain caused by myocardial ischemia without infarction. 1be zinc level feU sharply in the myocardial infarction patients within a day of onset, then rose to nonnal values within seven to ten days. There was no comparable change from nonnal values in the serum zinc level in seven patients with myocardial ischemia,

I t appears that acute tissue damage from a variety

of causes may result in a rapid fall in serum zinc eoncentration.t" Included among these causes is myocardial infarction, a finding first reported by Wacker et al' and recently confirmed by Lindeman et aJ.2 The latter reported significant changes within two hours of the onset of symptoms. The decline in serum zinc concentration had been under investigation by us for some time. Of considerable interest was our finding that patients suffering from chest pain resulting from myocardial 'insufficiency failed to develop the markedly decreased concentration of serum prevailing in myocardial infarction, although certain of the signs and symptoms in the two conditions were similar. In this paper, we describe our findings in the two conditions. Further support for the occurrence of the striking effects of myocardial infarction on serum zinc concentration is provided by experimentally induced infarction in two dogs. METHODS

Eighteen patients in the Nemazee Hospital in Shiraz, Iran, were investigated, 11 while undergoing an episode of acute myocardial infarction, and 7 with chest pain caused by myocardial ischemia, without the electrocardiographic or enzyme changes characteristic of infarction. The 11 patients with a diagnosis of myocardial infarction fulfilled the usual criteria. Electrocardiographic changes were typical and increased serum glutamic oxaloacetic transaminase levels were present in all. Because the patients ·Department of Medicine, Nemazee Hospital, Pahlavi University Medical School, Shiraz, Iran. ··Veterans Administration Hospital, Washington, D.C. Manuscript received October 30, 1972; revision accepted July 6. Reprint requests: Dr. Handiani, Nemazee Hospital, Shiraz, Iran

CHEST, 65: 2, FEBRUARY, 1974

although two showed borderline values. In two dogs with experimentally induced infarction the serum zinc concentration level also declined markedly in a manner similar to that observed in patients with infarction. It is suggested that under appropriate conditions measurement of serum zinc concentration levels may be a useful aid for differentiation of myocardial ischemia from infarction.

were not always admitted to the hospital promptly, the serum samples are identified according to the number of days after the onset of chest pain. Blood was collected on admission and at one or two-day intervals thereafter, using polyethylene syringes with zincfree needles. After separating serum, the samples were frozen and shipped in dry ice from Iran to Washington D.C. The atomic absorption spectrophotometric method of Hackley et al. was used for measurement of zinc concentration. In two dogs, an experimental infarction was produced by ligation of the anterior descending coronary artery distal to the diagonal branch. Preinfarction zinc concentrations were established by analyzing plasma samples obtained weekly over periods of 15 and 20 weeks, respectively. Dog 1 died 48 hours after induction of the infarct. The second dog was killed 37 days after infarction. At autopsy, tissue samples were removed from both the areas with infarction and normal areas for zinc analyses. REsULTS

Human Studies Table 1 indicates the mean and standard deviation of normal serum zinc concentration in 28 healthy Iranians and in 89 healthy Americans. There was no significant difference between the two, the mean ± SD being 95 ± 12 and 96 ± 13 ",g/l00 ml respectively. . Table 2 shows the serum zinc levels in 11 patients Table I-Zine Concentration in Healthy Adul..• No.

Mean ± SD

American Men

62

96 ± 13

American Women

27

97 ± 11

Iranian

28

95 ± 13

Category

·~/100

ml

SERUM ZINC CONCENTRATION IN ACUTE INFARCTION 185

Table 2--Zinc: Ler,el. in. Acute Myocardial Inlaretion *

Days after Onset of Chest Pain

Patient, No. 2 1 2 3 4 5 6 7 8 9 10 11

50

Mean

±

60 64

3 64 60

4

5

6

7

10

11

58 42

64 62 62

64

90

96

96

92 104

66

92 70

102 76 74

110

100 102

78 92

72 110

76 64

74 80

88 94

78 76

72 78

90

92 96

8

9

76

90

64

64 78 96 66 52

70 76 46 72 64 78 96 74 46

63.2

65.0

68.2

65.6

74.7

75.6

88.0

80.3

89.2

4.3

5.4

5.7

6.5

5.5

6.3

7.0

6.9

6.2

7.1

9.1

6.8

8.3

8.4

9.9

7.3

8.3

8.0

8.6

7.0

7.4

9.5

64

52

64 72

70 70 62 78

66

SD Coefficient of variation

66

92 74 104

92 88 78 94 100 116 95.5

*"g/loo mI

Animal Studies

with clinically well documented myocardial infarction following the onset of chest pain. As will be noted, the level is below the normal mean by more than two standard deviations in all except one (second day) of the patients, or during the subsequent days early after onset. A gradual return to normal followed, with all exceeding the minimal normal (mean minus 2 SD) by the tenth day. One patient regained normal levels by the third day, two more on the fifth. However, the latter relapsed to subnormal concentration levels later. On the other hand, in seven cases of myocardial ischemia when infarction was not demonstrated, the mean serum zinc level remained normal (Table 3), although with borderline values in two. The distribution of values was characteristic of the relatively wide range of zinc concentration in a healthy population. The infarction group by contrast showed much less variability between patients as shown by its much smaller and more uniform coefficients of variation.

The serum zinc values in the two dogs were consistent with the findings in the patients (Table 4). In dog 1 it dropped from 67 ± 12 (mean ± SD) to 38 p.g/l00 ml within 24 hours. In dog 2 it fell from 74 ± 16 to 42 during the first 24-hour period following infarction. The serum zinc remained low, 50 -+- 6.0 for four days after infarction. However, after eight days it returned to normal. In dog 1 the tissue zinc concentration of the area with infarction was 18 compared to 19 p.g Znl gm fresh tissue for the normal heart muscle. For dog 2 the area with infarction contained 18 contrasted to 17 (p.g Znl gm fresh tissue) for the normal area. DISCUSSION

In 1956, Wacker et all described a decrease in serum zinc levels in eight patients who had suffered an acute myocardial infarction. However, their study was done before body fluid zinc measure-

Table 3-Zinc: Ler,e& in MyocardiallllChemia*

Patient, No.

Day after Onset of Chest Pain 2

1 2 3 4 5 6 7

92 72 88 74 118

104 82

90

90

3

5

92 lOS 84

74 96 94 74 92 102 74

74 90

90

60 98

4

96

82

88 98 74

Mean

90

87

87

90

87

SD Coefficient of variation

15.3

13.7

12.1

12.4

12.1

17.0

14.9

13.7

13.8

13.9

±

6

7

8

9

10

11 98 82 96

112 96 108

80 108 116

86

92

105

101

86

92

8.3

18.9

92 8.7

·pg/loo mI

186 HANDJANI ET AL

CHEST, 65: 2, FEBRUARY, 1974

Table 4--Elfed 01 Sur«ieaUy Indueed Myocardiallnlarction on Zine Let1eI.

Postinfarction, Days

Preinfraction Mean ± SD Dog, No. 167 274

± ±

12 (15)··

38

16 (20)··

42

2

3

4

8

9

48

56

52

100

96

37

10

80

±

12

.pg Zn/l00 ml ··Number of analyses.

ments reached their present state of refinement. Recent studies have shown that plasma zinc concentrations also decrease in a wide variety of disorders including acute infectious diseases.v" active liver disease," mongolism," uremia," growth retardation,8.9 pregnancy, 10 during administration of oral contraceptives,'! and after major surgery.t Moreover, it was shown to drop sharply within four hours of the administration of endotoxin in two patients in a dose sufficient to produce fever and leukoeytosis.P Lindeman" has also shown that in experimental infarction in the dog, zinc concentration is unchanged in the area with infarction compared with normal heart muscle. However, there was a significantly increased radioactive-zinc uptake in mitochondrial and microsomal fractions and a decrease in nuclear fractions. Although there may be a redistribution of zinc in damaged tissue, this cannot account for the zinc that disappears from serum which probably is taken up by the liver and perhaps other visceral organs. Such a redistribution could be brought about by the release of the substance from leukocytes described by Pekarek and Beisel.13 A similar decrease in serum iron concentration following acute myocardial infarction" and after endotoxin injection in man suggests that a common mechanism may be responsible for alteration in both of these metals. In the present state of technology, determination of zinc concentration, although simple to accomplish, requires that there be a laboratory available for trace element analysis and that those involved be aware of the precautions that must be taken to avoid contamination. The data suggest a potentially useful test in diHerentiating myocardial ischemia from infarction. However, further studies will be needed to evaluate its pathophysiologic significance.

1 Wacker WEC, Ulmer DD, Vallee BL: MetaIloenzymes and myocardial infarction. 11. Malic and lactic dehydrogenase activities and zinc concentrations in serum. N Engl J Med 255:449, 1956 2 Lindeman RD, Bottomley RG, Cornelison R, et al: influence of acute tissue injury on zinc metabolism in man. J Lab Coo Med 79:452, 1972 3 Halsted JA, Smith JC Jr: Plasma-zinc in health and disease. Lancet 1:322, 1970 4 Hackley BM, Smith JC Jr, Halsted JA: A simplified method for plasma zinc determination by atomic absorption spectrophotometry. Clin Chern 14:1, 1968 5 Halsted JA, Hackley B, Rudzki C, et al: Plasma zinc concentration in liver disease. Comparison with normal controls and certain other chronic diseases. Gastroenterology 54:1098, 1968 6 Milunsky A, Hackley BM, Halsted JA: Plasma, erythrocyte and leucocyte zinc levels in Down's syndrome. J Ment Deflc Res 14:99, 1970 7 Mansouri K, Halsted JA, Gombos EA: Zinc, copper, magnesium, and calcium, in dialyzed and nondialyzed uremic patients. Arch Intern Med 125:88,1970 8 Halsted JA, Ronaghy HA, Abadi P, et al. Zinc deficiency in man: The Shiraz experiment. Am J Med 53:277, 1972 9 Prasad AS, Miale A Jr, Farid Z, et al: Zinc metabolism in patients with the syndrome of iron deficiency anemia, hepatosplenomegaly, dwarfism and hypogonadism. J Lab Clin Med 61:537,1963 10 Johnson NC: Study of copper and zinc metabolism during pregnancy. Proc Soc Exp BioI Med 108:518, 1961 11 Halsted JA, Hackley BM, Smith JC Jr: Plasma zinc and copper in pregnancy and after oral contraceptives. Lancet 2:278,1968 12 Smith JC Jr, McDaniel EG, McBean LD, et al: Effect of micro-organisms upon zinc metabolism. Proc Western Hemisphere Nutri Congr, Bal Harbour, Fla. (abstr) (in press),1971

ACKNOWLEDGMENTS: I gratefully acknowledge the help and criticism of Dr. J. G. Reinhold, Director of the PahlaviPennsylvania Nutrition Research project at Pahlavi University, Shiraz, Iran.

13 Pekareh RS, Beisel WR: Characterization of the endogenous mediator( s) of serum zinc and iron depression during infection and other stresses. Proc Soc Exp BioI Med 133:728, 1971 14 Handjani AM, Banihashemi A, Raflee R: Serum iron in acute myocardial infarction. Blut 23:363, 1971

CHEST, 65: 2, FEBRUARY, 1974

SERUM ZINC CONCENTRATION IN ACUTE INFARCTION 187