Trace elements in relation to cardiovascular disease

Title

Creator

dela Cruz, Benjamin

Lansangan, Luningning

Asprer, Gloria

Paradero, Revelinda

Language

English

Source

The Journal of the Philippine Medical Association Volume 52 (Issue Nos. 9-10) September-October 1976

Year

1976

Rights

In Copyright - Educational Use Permitted

Fulltext

Trace Elements in Relation to Cardiovascular Disease * * BENJAMIN DELA CRUZ, M.D.+, LUNINGNING LANSANGAN, B.S.+ GLORIA ASPRER, B.S.+ and REVELINDA PARADERO, B.S.+ CARDIOVASCULAR disease may be con sidered as a public health problem in the Philippines. Reports of the Disease In telligence Center, Department of Health show that diseases of the heart has a five year average mortality rate of 35.2 per 100,000 population and constitute 5.1% of the total deaths in the Philip pines. In the search for the etiologic factors of cardiovascular disease one has to consider the role of trace elements. In our previous reports1 2 we reported an increase in the mean values of man ganese and copper and a decrease in the mean levels of zinc in the serum of pa tients with hypertension, old myocardial infarct and diabetes mellitus. Kanabrocki3 and Wacker4 also suggested the possible relationship of copper, zinc and manganese to cardiovascular disease. In the present report we shall present find ings on the concentration of copper, zinc and molybdenum in the heart, liver and •Supported in Part By The Cardiovascular Unit, World Health Organization.. Geneva, Switzerland. Biomedical Research Division, Philip pine Atomic Energy Commission, Diliman, Quezon City. •Second Prize PMA-Abbott Research Award on Basic Science 1776. kidneys of 20 normal male healthy sub jects that met accidental death and from 25 male patients who died of myocardial infarction. MATERIALS AND METHODS Samples that were analyzed for their trace elemental contents were taken from the anterior wall of the left ventri cle, the superior anterior surface of the right lobe of the liver, and the cortex of the kidney. During the collection of the samples, extreme care was taken to prevent metallic contamination with the use of glass or silica knives. Prepara tion of irradiation standards for copper, zinc and molybdenum, as well as the bio logical reference materials to check the accuracy of our analytical procedures has been previously described2. Prepa ration of the tissue samples for irradia tion and the determination of its trace metals contents by neutron activation technique has already been reported5. RESULTS AND DISCUSSION Figures I, II and III will show the gamma ray spectrum of zinc, copper and molybdenum in the heart, liver and kid ney. The results in Tables I to HI in dicate the values of copper, zinc and 275 Sept .-Oct., 1976 J. P. M. A. 276 dela Cruz, et al. molybdenum in the heart, liver and kid ney of normal male subjects that met accidental death. The results in Table IV show that the mean values of zinc, copper and molybdenum in the heart, li ver and kidneys of Pilipinos are agreeable to the mean values reported in litera ture. The results in Tables I to III also indicate that the normal values of cop per, zinc and molybdenum in the heart, liver and kidneys of the normal subjects do not vary with their age and occupa tion. Figures IV to XII will show the scattergram of zinc, copper and molyb denum levels obtained from heart, liver and kidney tissues of normal healthy sub jects and patients with myocardial infarc tion. The results in Table V indicate that the mean concentration of rinc in the heart and liver of patients who died of myocardial infarction, 28.85 4- 2.07 ug/g and 37.57 4- 8.38 ug/g respective ly were lower than the normal mean values of 30.35 4- 2.33 ug/g and 47.30 4- 7.72 ug/g. Our data on the decrease of zinc concentration in the infarcted heart tissue is in good agreement with the report of Wester6, who reported a significant decrease of zinc level in the injured heart tissues. This decrease might perhaps be related to the disap pearance of lactic dehydrogenase, a zinc enzyme from the infarcted heart tissue with an increase in the level of its ac tivity being observed in the serum of pa tients with acute myocardial infarction7. Zinc has been reported to be beneficial to cardiovascular health. Schroeder6 found that the administration of zinc will reverse the hypertensive effect of cad mium in rats. The mean level of copper in the liver of patients with myocardlai infarction of 3.95 4-. 0.82 ug/g was lower than the normal value of 5.01 l-9b ug/g. Hartman9 has reported the athe rogenic effect of copper. Reinhold10 found that a deficiency in copper would * also result in the ^defective synthesis o? collagen and elastin in the aorta anc. blood vessels. The mean concentration of molybdenum, 0.83 4-_ 0.13 ug/g, 0.76 0.36 ug/g and 0.74 4- 0.31 ug/g in the heart, liver and kidney respectively of patients with myocardial infarction were higher than the normal values of 0.32 4 0.13 ug/g. 0.52 4. 0.16 ug/g and 0.41 4 0.20 ug/g. Our data on the molybdenum content of the infarcted heart tissue does not agree with the re sults obtained by Wester7 who reported a decrease in the concentration of mo lybdenum in the injured heart tissue, and relate the concentration of this trace ele ment to the degree of fibrosis present in the infarcted heart tissue. The data that we have obtained our 5 years investigation indicate changes in the concentration of copper, zinc and molybdenum in the heart, liver and kid ney of cardiac subjects occuring in as sociation with myocardial infarction. We do hope that the tissue mineral concen tration changes that we detected will add significant data to the growing evid ence that certain trace elements are as sociated with degenerative cardiovascu lar diseases, such as hypertension, athe rosclerosis and their sequela. The re sults that we obtained would not only help in establishing the elemental com position of a “Standard Man” but this study might give us a due on the bio chemical assodation of the certain trace elements with cardiovascular disease, which would offer information of im portance in the control of this public health problem. SUMMARY Heart, liver and kidney specimens from 45 adult male subjects were an alyzed for their zinc, copper and molybVolume 52 Not. 9-10 Cardiovascular Disease 277 Energy, MeV Fig. 1 — Gamma-ray spectrum of Zinc, Copper and Molybdenum in Heart. Sept.-Oct., 1976 J. P. M. A. 278 dela Cruz, et al 64 1000 Counts/min 800 600 400 200 20 10 1208 0. 0 0.8 Energy, MeV Fig. 2- Gamma-ray spectrum of Zinc, Copper and Molybdenum in Liver 40 0. .0 * o.: 0, Volume 52 Nos. 9-10 Cardiovascular Disease 279 280 dela Cruz, et al Sept.-Oct., 1976 J. P. M. A. I II Fig. 4 — Scattergram of zinc levels obtained from heart tissues of normal sub jects and patients with old myocardial infarct. Volume 52 Nos. 9-10 Cardiovascular Disease 281 I II Fig. 5 — Scattergram of zinc levels obtained from liver tissues of normal sub jects and patients with old myocardial infarct. Sept.-Oct., 1976 J. P. M. A. 282 dela Cruz, et al I II Fij*. 6 — Scattergram of zinc levels obtained from kidney tissues of normal sub jects and patients with old myocardial infarct. Volume 52 Nos. 9-10 Cardiovascular Disease 283 i n Fig. 7 — Scattergram of copper levels obtained from heart tissues of normal sub jects and patients with old myocardial infarct. Sept .-Oct., 1975 i. P. M. A 284 dela Cruz, et al. I II Fig. 8 — Scattergram of copper levels obtained from liver tissues of normal sub jects and patients with old myocardial infarct. Volume 52 Nos. 9-10 Cardiovascular Disease 285 I n Fig. 9 — Scattergram of copper levels obtained from kidney tissues of normal subjects and patients with old myocardial infarct. Sept .-Oct., 1976 J. P. M. A. 286 dela Cruz, et al. I II Fig* — Scattergram of molybdenum levels obtained from heart tissues of normal subjects and patients with old myocardial infarct. Volume 52 Nos. 9-'O Cardiovascular Disease 287 I II Fl#. 11 — Scattergram of molybdenum levels obtained from liver tissues of normal subjects and patients with old myocardial infarct. Sept .-Oct., 1976 J. P. M A. 288 dela Cruz, et al. I II Fig. 12 — Scattergram of molybdenum levels obtained from kidney tissues of normal subjects and patients with old myocardial infarct. Volume 52 Nos. 9-10 Cardiovascular Disease 289 Table 1. VALUES OF ZINC IN HEART. LIVER AND KIDNEY OF 20 NORMAL MALE SUBJECTS: ug/g WET TISSUE Name Age Occupation : Cause of Death Heart : Liver : Kidney G. D. 40 Soldier : Vehicular accident 30.50 : 44.50 : 39.30 R. J. 10 Vendor : Stabbing 29.50 : 46.00 : 33.55 Unknown 40 N. A. : Gunshot wound 28.55 : 40.67 : 31.83 Unknown 40 N. A. : Stabbing 32.70 : 49.00 : 33.20 F. S. 43 Butcher Stabbing 30.07 : 45.40 : 33.89 K. S. 45 Businessman Stabbing 29.04 : 42.30 • 37.10 L. S. 15 Patrolman : Stabbing 30.50 : 57.45 : 31.64 F. C. 45 Scavenger : Vehicular accident 26.86 : 47.80 : 36.78 H. C. 1-5 Laborer Vehicular accident 29.64 : 28.13 : 35.48 J. B. i-5 Employee . Stabbing 29.64 : 54,41 : 35.03 A. P. 15 Driver : Vehicular accident 33.60 : 41.60 : 32.53 M. L. Employee Stabbing 35.29 : 30.66 : 37.69 N. C, 17 Driver : Vehicular accident 28.26 : 55.30 : 31.68 M. J. 43 Security : Gunshot 33.00 : 57.64 : 30.20 Guard A. T. 48 Employee : Vehicular accident :: 30.19 : 51.61 : 34.26 P. D. 48 Security : Karate blow :: 28.60 : 32.20 : 34.40 Guard S. T. 48 None ; Vehicular accident : 34.80 : 13.63 ; 40.27 A. D. 48 Employee : Gunshot : 27.82 : 46.90 : 37.69 M. L. 50 Realtor : Gunshot : 29.26 : 57.41 : 34.68 A. C. 54 Operator : Stabbing 1 «! 29.10 : 49.20 : 39.20 Table II. VALUES OF COPPER IN HEART, LIVER AND KIDNEY OF 20 NORMAL MALE SUBJECTS; ug/g WET TISSUE Name ; Age Occupation Cause of Death : Heart Liver Kidney O. D. 40 Soldier Vehicular accident 3.10 2.80 3.40 R J. 40 Vendor Stabbing 2.02 7.41 2.15 Unknown 40 N. A. Gunshot 2.19 8 <00 2.48 Unknown 10 N. A. Stabbing 1.62 3.10 2.00 F. S. 43 Butcher Stabbing 2.20 7.60 2.54 R. S. 45 Businessman Stabbing 2.43 6.20 2.99 L. S. 15 Patrolman Stabbing 3.20 5.66 2.01 F. C. 45 Scavenger Vehicular accident 4.54 5.49 2.72 H. C. 15 Laborer Vehicular accident 3.26 3.79 1.71 J. B. 15 Employee Stabbing 1.60 4.14 2.54 A, P. 45 Driver Vehicular accident 3.40 5.13 3.15 M. L. 16 Employee Stabbing 3.86 5.14 2.69 N. S. 47 Driver Vehicular accident 2.84 6.02 2.46 Security Gunshot 3.45 4.00 3.44 M. J. 18 : Guard A. T. : 48 : Employee Vehicular accident : 2.45 : 4.49 ! 2.15 P. D. : 48 : Security Guard Karate blow 2.30 : 5.90 : 1.10 S. T. . 48 : None Vehicular accident 3.62 : 5.32 3.51 A. D. 48 : Employee Gunshot 2.40 : 4.12 2.32 M. L. 50 : Realtor Gunshot 2.52 : 2.12 2.48 A. C. 54 : Operator Stabbing 3.52 : 3.75 : 3.19 Sept.-Oct., 1976 J. P. M. A. 290 dela Cruz, et al. Table IH. VALUES OF MOLYBDENUM IN HEART, LIVER AND KIDNEY OF 20 NORMAL MALE SUBJECTS ug/g WET TISSUE Name : Age : Occupation : Cause of Death Heart Liver : Kidney O. D. : 40 : Soldier : Vehicular accident : 0.15 : 0.12 : 0.48 R. J. : 40 . Vendor : Stabbing 0.23 : 0.87 : 0.60 Unknown : 40 : N. A. : Gunshot 0.21 : 0.47 : 0.25 Unknown : 40 : N. A. Stabbing 0.48 : 0.97 : 0.52 F. S. : 4i : Butcher Stabbing 0.70 : 0.56 : 0.51 R. S. : 45 : Businessman : Stabbing 0.54 : 0.65 0.57 L. S. : 45 : Patrolman : Stabbing : 0.31 0.2S : 0.20 F. C. : 45 : Scavenger : Vehicular accident : 0.31 : 0.29 : 0.12 H. C. : 45 : Laborer : Vehicular accident : 0.50 : 0.45 0.27 J. B. : 45 : Employee : Stabbing : 0.24 : 0.21 0.34 A. P. : 45 : Driver : Vehicular accident : 0.27 : 0.52 : 0.44 L. : 46 : Employee Stabbing 0.27 : 0.13 0.24 N. C. : 47 : Driver : Vehicular accident : 0.36 : 0.35 : 0.38 M. J. : 48 : Security : Guard : Gunshot 0.09 : 0.86 : 0.35 A. T. : 48 : Employee Vehicular accident : 0.37 : 1.22 0.94 P. D. : 48 : Security : Guard : Karate blow : 0.53 : 0.64 0.55 S. T. : 48 : None : Vehicular accident 0.26 : 0.28 0.27 A. D. : 48 : Employee : Gunshot 0.20 : 0.65 0.44 M. L. : 50 : Realtor : Gunshot 0.16 : 0.28 : 0.25 A. C. : 54 : Operator : Stabbing 0.26 : 0.52 : 0.40 Cardiovascular Disease 291 Volume 52 Nos. 9-10 K id n e y 14-67(5) CD in cd 8 o «“s co § 1 8 o fa Z—s ® s d > 00 in T—1 •** CD co CD i CD in r-i CO <+• fa s 2 fl co CO © CO 20 d r-< o in o d • * • • s CO CD 8 © fl ci d o •fl -H Hl -H s co in i-H o .in in co d co b; CD O'. 8 fa b-‘ T—i o ve + + +. •P4 o rH co J co o in b- m d TH co X CO co b- t-H +■> co d o fl O ■H -H .1 “1 s in X co co X co o (bl d •• co on fl me: fl fl © fl s fa © 75 © JD CJ Q< & >» fl o O N O § ® fl *4 ® > 2 • • *4 65 M to 9 fl •M a fa ® > •M J fa fl ® a •• •• * • CO co o o CD co co d o -H 41 CO in 1—* o m TH in co d co •• •• •• co CD CD t- o> i—1 t> 1—1 o +. +, + o 1—1 co co o in b-’ in d co X co co b- i—< co o d -H -H -H in X CO co 00 co d co d co E o c N T5 >» O % 292 dela Cruz, et al. Sept.-Oct., 1976 J. P. M. A. denum contents. The normal mean values of zinc, copper and molybdenum in the heart, liver and kidney of male adult Filipinos was determined and found be agreeable with the normal mean values reported in literature. The mean concentration of zinc in the heart and liver of patients who died of myo cardial infarction, 28.85 -4- 2.07 ug/g and 37.57 -k 8.38 ug/g respectively were lower than the normal values of 30.35 4- 2.33 ug/g and 47.30 + 7.72 ug/g. The mean level of copper in patients with myocardial infarction of 3.95 4- 0.82 ug/ g was lower than the normal value of 5.0i 1.96 ug/g. The mean concen tration of molybdenum of 0.83 4- 0.13 ug/g, 0.76 + 0.36 ug/g and 0/74 40.31 ug/g in the heart, liver and kidney respectively of patients with myocardial infarction were higher than the normal values of 0.32 4- 0.13 ug/g, 0.52 4-_ 0.1& ug/g and 0.41 -£ 0.20 ug/g. The results and importance of our in vestigation was discussed. REFERENCES 1. B. dela Cruz et ala “The Manganese Concentration in Red Blood Cells and Serum of Filipinos." Jour nal of the Philippine Medical Association Vol. 49, No. 6, pp. 313-320 June 1973. 2. B de1h Cruz’et al,’“The Concentration of Cop per, Zinc and Molybdenum in Serum and Red Blood Cells of Filipinos." The Journal of the Philippine Medical Association Vol. 51, Nos. 7-8 pp. 173-188 July-August 1975. 3. E. L. Kanabrocki dt at, Neutron activation studies of biological fluids, manganese and copper. I nt. J. Applied Radiation 15:175, 1964. 4. W. E. Wacker et el. The relation of copper to cerrloplasmin activity and zinc to malic and lac tic dehydrogenase activity in acute myocardial in farction J. Clinical Investigation 35:741, 1956. 5. B. dela Cruz et at, "Trace Elements in Heart and Other Tissues of Filipinos Determined by Neutron Activation Analysis". The Journal of the Philippine Medical Association. V. 47, pp. 90-98’ August 1971. 6. P. O. Wester, Trace Elements in Human Myocar dial Infarction determined by neutron activation analysis. Acta Med. Scand. 178:765, 1965. 7. F. Wroblenski and S. La. Doo, Lactic Dehydroge nase activity in blood. Pure Soc. Exp; Bini 90r 210. 8. H. A. Schroeder and J. Buckman, Arch, of Envir onment and Health 14 (1967) 693. 9. D. Harman, Circulation 28, 658. 10. J. G. Reinhold, Radioisotopes in animal nutritionand physiology. Vienna, International Atomic Ener gy Agency, pp. 267-232, 1964.

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275-292

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