Acta med. scand. Vol. 198, pp. 349-351, 1975
Creatine Phosphokinase Following Cardioversion G. Forssell, R . Nordlander, 0. Nyquist, E. Orinius and I . Styrelius From f h e D t p u r f m e n fqf Medic,irie, Koro/insha I n s f i f i t r e f( i f Hrttltlirige sjrtkhus, Niidditigt,, Swwfen
ABSTRACT. Serial estimations of total serum creatine phosphokinase (CPK) have been performed before and during 18-51 hours after cardioversion of supraventricular tachyarrhythmias in 12 patients without acute myocardial infarction (AMI). The maximal CPK rise was 78 mU/ml (110%) and the CPK did not exceed the upper normal limit (130 mU/ml) in more than two patients (149 respectively 156 mU/ml). The CPK rise we have observed in a series of AM1 patients varied between 101 (133 %) and 2 260 mU/ml (3 780 %), mean 900 mU/ml (1 184 %). Therefore, cardioversion performed as described seldom seems to interfere with diagnosing AM1 by serial estimations of serum CPK during the next 24 hours.
Serial estimations of serum creatine phosphokinase (CPK) is commonly regarded as a very sensitive test of myocardial damage and has therefore in recent years been used widely for diagnosing acute myocardial infarction (AMI). However, elevated C P K values have also been reported in association with large muscle mass (6),physical exercise ( I , 16, 18, 20, 27), skeltal muscle diseases (7, 21, 22), alcoholic muscular disease (13, 23), i.m. injections (2, 10, 15, 17, 28, 31). cardioversion of arrhythmias ( 5 , 8, 11,30) and cerebral diseases (4,9,23). Therefore, these situations have been said t o interfere with diagnosing AM1 by serum CPK analysis. Previous studies of the influence of cardioversion on the serum C P K have been performed with rather infrequent blood sampling, mostly only once a day. T h e aim of the present study was to investigate the effect of cardioversion on the total serum CPK activity during 24 hours after the DC shock, by frequent blood sampling.
One patient had three shocks, four patients had two and the remainder one shock each. No patient had an AM1 or any muscular disease. All patients but one were treated with digoxine. which treatment was interrupted three days before the cardioversion. Quinidine administration was started in I I patients one day before the DC shocks. All patients but one had been on oral anticoagulant therapy for at least three weeks. No i.m. injections had been given to any patient. The cardioversion was performed after i.v. administration of 10-35 mg (mean 20) diazepam (Valium@,Roche). No premedication was given and no other amnesic or anaesthetic drug. Electrodes were placed over the upper sternum and under the left scapula. The total electrical energy of all shocks to a patient varied from 100 to 650 Wsec (mean 270). Sinus rhythm was achieved in ten patients. Venous blood samples for total serum CPK analysis were drawn 30 min before. just prior to, immediately after, 30 min after, I hour after and continuously every 2nd-4th hour for 18-51 hours after the DC shock. No i.m. injections were given during this period. The blood sample was centrifuged and the serum was frozen to - 18°C for 1-27 days. All blood samples from one individual were analysed together, using the same CPK reagent for the whole batch. The CPK activity was measured at 37°C with a spectrophotometer (LKB Reaction Rate Analyzer, 8600) using a test pack (Boehringer@, 15721). The CPK activity is expressed in mU/ml (Enzyme nomenclature. Recommendations 1964 of the International Union of Biochemistry, Elsevier Publishing Company, Amsterdam. London and New York 1965). The maximal difference when analysing double samples varied from 0 to 56 mU/ml for CPK values between 16 and 2 186 mU/ml. Comparison of the CPK activity in samples analysed immediately and after freezing for 141 days (mean 8) showed a difference varying from 0 to 42 mU/ml for CPK values between 21 and I 1 2 5 mU/ml. These differences are not statistically significant @>0.05).
RESULTS M A T E R I A L A N D METHODS Twelve patients, aged 4 6 7 0 years (mean 62). received a total of 18 DC shocks because of atrial fibrillation/flutter.
T h e serum CPK values are shown in Fig. I . All patients had CPK values below 110 mU/ml before the cardioversion. T h e maximal increase immeAcra med. scand. I98
350
G. Forssrll et ul.
In the study by Konttinen et al. ( I I ) , blood samples for CPK determination were drawn 3 hours before the shock and on 3 successive mornings afterwards. The maximal CPK increase occurred in the morning after the DC shock. In our study there was no tendency to elevation of the CPK curves towards the end of the period. Even if an increase does occur after the first 24 hours, it will not interfere with diagnosing AMI, since the CPK peak is reached 12-24 hours after the onset of symptoms (19, 25). I n the present series of 12 patients, only two had a CPK rise above the normal level, which in our experience is considered to be 130 mU/ml. This incidence does not differ from the corresponding figures, 8 of 37 patients, reported by Konttinen et al. (11). The great difference is that our maximal CPK increase of 110 5% was much lower than their lowest of 450 5%. Using our techniques of cardioversion and CPK analysis, a diagnostic dilemma will very seldom occur as both a slightly abnormal CPK maximum and especially a DC shock during the first hours after onset of symptoms are uncommon in A M I . A DC shock after the initial phase of AM1 may in a minority of patients give a minimal CPK rise which, however, would cause diagnostic difficulties only in patients with recurring ischemic pains. Explanations of the different results in the present study compared with others ( 5 , 8 , 1 I , 30) may be different cardioversion procedures, including methods for anaesthesia and sites of injections, and differences in the frequency of blood sampling as well as in methods of CPK analysis. These possibilities cannot be further evaluated because of lack of information in these reports. It has previously been discussed whether the enzyme elevations observed after cardioversion are caused by heart muscle damage or skeletal muscle damage (because of contraction of the skeletal muscles caused by the DC shock) ( 1 1, 30). Using CPK isoenzymes, it has been shown that the elevation of total CPK in 15 of 40 electroconversions was of skeletal type (CPK-MM) (14). There are, however, divergent opinions about the proportion of CPK-MB in skeletal muscle, 0-20% (3, 26, 29), as well as about the percentage of CPK-MB in total CPK in association with AMI, 0-38% (13, 29). Therefore, there is a certaih risk of both false positive and false negative diagnosis of AMI, even with the aid of CPK isoenzymes.
._ .
ll
01
8 0
6
12
18
24
30
36
42
48
Tlme. h o u r s
Fig. I . Serum CPK curves following cardioversion.
diately after the DC shock was 14 niU/ml (29%). The maximal CPK rise during the 18-51-hour period was 78 mU/ml (110%). In no case did the CPK exceed 156 mU/ml during the period of investigation. The CPK rise showed no correlation with either the discharged energy or the number of DC shocks. DISCUSSION Cardioversion of supraventricular and ventricular tachyarrhythmias is a routine method for treating these complications in AMI. If cardioversion influences the serum CPK activity, e.g. by release of CPK from thoracic muscles, this procedure impairs the diagnosis of AM1 by CPK estimations. Increased serum CPK values above the upper normal level have in fact been reported after cardioversion ( 5 , 8, 1 1, 30). Konttinen et al. ( I I ) found a CPK increase in 8 of 37 patients. The CPK rose 1.2-29 times the normal level and the maximal increase occurred one day after the DC shock. The patients were anaesthetized with sodium thiopental, 0.5 mg of atropine being used as premedication. I t cannot be concluded from this report or from any of the others (S, 8, 30), whether i.m. injections had been given before or during the investigation period. 1.m. injections have been reported to induce elevations of serum CPK, with a maximum 24 hours after the injection (2, 10, 15, 17, 28, 31). Acta med. scond. 198
Creatine phosphokinase ,fullowing curdioversion
35 1
ACKNOWLEDGEMENTS
15. Kiister, J . : Herzinfarkt und intramuskulk appliziertes
This study was supported by a grant from the Swedish National Association against Heart and Chest Diseases and received technical support from LKB-produkter AB, Sweden.
Lidocain. Med. Klin. 68: 1079, 1973. 16. Loegering, D., Critz, J . &Wagner, J . : Serum creatine phosphokinase as a diagnostic aid. Minn. Med. 50: 1751, 1967. 17. Meltzer, H. Y . , Mrozak, S . & Boyer. M.: Effect of intramuscular injections on serum creatine phosphokinase activity. Amer. J . med. Sci. 259:42, 1970. 18. Nevins, M. A,, Saran, M., Bright, M. & Lyon, L. J . : Pitfalls in interpreting serum creatine phosphokinase activity. J.A.M.A. 224: 1382, 1973. 19. Nordlander, R.: Serum creatine phosphokinase in acute myocardial infarction. To be published. 20. Nuttall, F. & Jones, B.: Creatine kinase and glutamic oxalacetic transaminase activity in serum: Kinetics of change with exercise and effect of physical conditioning. J. Lab. clin. Med. 71:847, 1968. 21. Okinaka, S . , Kumagai, H., Ebashi, S., Sugita, H., Monoi, H., Toyokura, Y . & Fujie, Y . : Serumcreatine phosphokinase. Arch. Neurol. 4: 520, 1961. 22. Pearce, J . , Pennington, R. & Walton, J . : Serum enzyme studies in muscle disease. J . Neurol. Neurosurg. Psychiat. 27: 96, 1964. 23. Perkorr, G . T.: Alcoholic myopathy. Amer. Rev. Med. 22: 125, 1971. 24. Schiavone, D. J . h Kaldor, J.: Creatine phosphokinase levels and cerebral disease. Med. J . Aust. 2:790, 1965. 25. Sobel, B. E. & Shell, W. E.: Serum enzyme determinations in the diagnosis and assessment of myocardial infarction. Circulation 45:471, 1972. 26. van der Veen, K. J . & Willebrands, A. F.: Isoenzymes of creatine phosphokinase in tissue extracts and in normal and pathological sera. Clin. chim. Acta 13: 312, 1966. 27. Vejajiva, A. & Teasdale, G.: Serum creatine kinase and physical exercise. Brit. med. J. I: 1653, 1965. 28. Vorburger, C., Fassler, B. & Kohl, P.: Serumkreatinphosphokinase und intramuskuliire Injektion. Schweiz. med. Wschr. 103: 927, 1973. 29. Wagner,G. S., Roe. C. R., Limbird, L. E., Rosati, R. A. &Wallace. A . G.: The importance of identification of the myocardial-specific isoenzyme of creatine phosphokinase (MB form) in the diagnosis of acute myocardial infarction. Circulation 47: 263, 1973. 30. Warbasse. R., Wesley, J . E., Connolly, V . & Galluzzi, N. J.: Lactic dehydrogenase isoenzymes after electroshock treatment of cardiac arrhythmias. Amer. J . Cardiol. 21:496, 1968. 31. Zener, J. C. & Harrison, D. C.: Serum enzyme values following intramuscular administration of lidocaine. Arch. intern. Med. 134:48. 1974.
REFERENCES I . Ahlborg, B. & Brohult, J . : Metabolic changes after exercise. Lancet 1: 1272, 1966. 2. Cacace, L.: Elevated serum CPK after drug injections. New Engl. J . Med. 287:309, 1972. 3. Dawson, D. & Fine, J.: Creatine-kinase in human tissues. Arch. Neurol. 16: 175, 1967. 4 . Dubo, H., Park, D. C., Pennington, R. J. T., Kalbag, R. M. & Walton, J . N.: Serumcreatine-kinase in cases of stroke, head injury, and meningitis. Lancet 2:743, 1967. 5 . Eshchar. J . & Zimmerman, H. J.: Creatine phosphokinase in disease. Amer. J. med. Sci. 253: 272, 1967. 6 . Garcia, W.: Elevated creatine phosphokinase levels associated with large muscle mass. J.A.M.A. 228: 1395, 1974. 7. Hughes, B. P.: Creatine phosphokinase in facioscapulohumeral muscular dystrophy. Brit. med, J . 3:464, 1971. 8. Hunt, D. & Bailie, M. J . : Enzyme changes following direct current countershock. Amdr. Heart J . 76: 340, I 968. 9. Hunt, D., McRae, C. & Zaph, P.: Electrocardiographic and serum enzyme changes in subarachnoid hemorrhage. Amer. Heart J . 77: 479, 1969. 10. Klein, M., Shell, W. & Sobel, B.: Serum creatine phosphokinase (CPK) isoenzymes after intramuscular injections, surgery, and myocardial infarction. Cardiovasc. Res. 7:412, 1973. I I . Konttinen, A,, Hupli, V., Louhija, A. & Hartel, G.: Origin of elevated serum enzyme activities after direct-current countershock. New Engl. J . Med. 281:231, 1969. 12. Konttinen, A,, Hartel, G . & Louhija, A,: Multiple serum enzyme analyses i n chronic alcoholics. Acta med. scand. 188:257. 1970. 13. Konttinen, A. & Somer, H.: Determination of serum creatine kinase isoenzymes in myocardial infarction. Amer. J. Cardiol. 29: 817, 1972. 14. - Specificity of serum creatine phosphokinase isoenzymes in diagnosis of acute myocardial infarction. Brit. med. J . 1:386. 1973.
Acfa mtd. srund. 198
Creatine Phosphokinase Following Cardioversion G. Forssell, R . Nordlander, 0. Nyquist, E. Orinius and I . Styrelius From f h e D t p u r f m e n fqf Medic,irie, Koro/insha I n s f i f i t r e f( i f Hrttltlirige sjrtkhus, Niidditigt,, Swwfen
ABSTRACT. Serial estimations of total serum creatine phosphokinase (CPK) have been performed before and during 18-51 hours after cardioversion of supraventricular tachyarrhythmias in 12 patients without acute myocardial infarction (AMI). The maximal CPK rise was 78 mU/ml (110%) and the CPK did not exceed the upper normal limit (130 mU/ml) in more than two patients (149 respectively 156 mU/ml). The CPK rise we have observed in a series of AM1 patients varied between 101 (133 %) and 2 260 mU/ml (3 780 %), mean 900 mU/ml (1 184 %). Therefore, cardioversion performed as described seldom seems to interfere with diagnosing AM1 by serial estimations of serum CPK during the next 24 hours.
Serial estimations of serum creatine phosphokinase (CPK) is commonly regarded as a very sensitive test of myocardial damage and has therefore in recent years been used widely for diagnosing acute myocardial infarction (AMI). However, elevated C P K values have also been reported in association with large muscle mass (6),physical exercise ( I , 16, 18, 20, 27), skeltal muscle diseases (7, 21, 22), alcoholic muscular disease (13, 23), i.m. injections (2, 10, 15, 17, 28, 31). cardioversion of arrhythmias ( 5 , 8, 11,30) and cerebral diseases (4,9,23). Therefore, these situations have been said t o interfere with diagnosing AM1 by serum CPK analysis. Previous studies of the influence of cardioversion on the serum C P K have been performed with rather infrequent blood sampling, mostly only once a day. T h e aim of the present study was to investigate the effect of cardioversion on the total serum CPK activity during 24 hours after the DC shock, by frequent blood sampling.
One patient had three shocks, four patients had two and the remainder one shock each. No patient had an AM1 or any muscular disease. All patients but one were treated with digoxine. which treatment was interrupted three days before the cardioversion. Quinidine administration was started in I I patients one day before the DC shocks. All patients but one had been on oral anticoagulant therapy for at least three weeks. No i.m. injections had been given to any patient. The cardioversion was performed after i.v. administration of 10-35 mg (mean 20) diazepam (Valium@,Roche). No premedication was given and no other amnesic or anaesthetic drug. Electrodes were placed over the upper sternum and under the left scapula. The total electrical energy of all shocks to a patient varied from 100 to 650 Wsec (mean 270). Sinus rhythm was achieved in ten patients. Venous blood samples for total serum CPK analysis were drawn 30 min before. just prior to, immediately after, 30 min after, I hour after and continuously every 2nd-4th hour for 18-51 hours after the DC shock. No i.m. injections were given during this period. The blood sample was centrifuged and the serum was frozen to - 18°C for 1-27 days. All blood samples from one individual were analysed together, using the same CPK reagent for the whole batch. The CPK activity was measured at 37°C with a spectrophotometer (LKB Reaction Rate Analyzer, 8600) using a test pack (Boehringer@, 15721). The CPK activity is expressed in mU/ml (Enzyme nomenclature. Recommendations 1964 of the International Union of Biochemistry, Elsevier Publishing Company, Amsterdam. London and New York 1965). The maximal difference when analysing double samples varied from 0 to 56 mU/ml for CPK values between 16 and 2 186 mU/ml. Comparison of the CPK activity in samples analysed immediately and after freezing for 141 days (mean 8) showed a difference varying from 0 to 42 mU/ml for CPK values between 21 and I 1 2 5 mU/ml. These differences are not statistically significant @>0.05).
RESULTS M A T E R I A L A N D METHODS Twelve patients, aged 4 6 7 0 years (mean 62). received a total of 18 DC shocks because of atrial fibrillation/flutter.
T h e serum CPK values are shown in Fig. I . All patients had CPK values below 110 mU/ml before the cardioversion. T h e maximal increase immeAcra med. scand. I98
350
G. Forssrll et ul.
In the study by Konttinen et al. ( I I ) , blood samples for CPK determination were drawn 3 hours before the shock and on 3 successive mornings afterwards. The maximal CPK increase occurred in the morning after the DC shock. In our study there was no tendency to elevation of the CPK curves towards the end of the period. Even if an increase does occur after the first 24 hours, it will not interfere with diagnosing AMI, since the CPK peak is reached 12-24 hours after the onset of symptoms (19, 25). I n the present series of 12 patients, only two had a CPK rise above the normal level, which in our experience is considered to be 130 mU/ml. This incidence does not differ from the corresponding figures, 8 of 37 patients, reported by Konttinen et al. (11). The great difference is that our maximal CPK increase of 110 5% was much lower than their lowest of 450 5%. Using our techniques of cardioversion and CPK analysis, a diagnostic dilemma will very seldom occur as both a slightly abnormal CPK maximum and especially a DC shock during the first hours after onset of symptoms are uncommon in A M I . A DC shock after the initial phase of AM1 may in a minority of patients give a minimal CPK rise which, however, would cause diagnostic difficulties only in patients with recurring ischemic pains. Explanations of the different results in the present study compared with others ( 5 , 8 , 1 I , 30) may be different cardioversion procedures, including methods for anaesthesia and sites of injections, and differences in the frequency of blood sampling as well as in methods of CPK analysis. These possibilities cannot be further evaluated because of lack of information in these reports. It has previously been discussed whether the enzyme elevations observed after cardioversion are caused by heart muscle damage or skeletal muscle damage (because of contraction of the skeletal muscles caused by the DC shock) ( 1 1, 30). Using CPK isoenzymes, it has been shown that the elevation of total CPK in 15 of 40 electroconversions was of skeletal type (CPK-MM) (14). There are, however, divergent opinions about the proportion of CPK-MB in skeletal muscle, 0-20% (3, 26, 29), as well as about the percentage of CPK-MB in total CPK in association with AMI, 0-38% (13, 29). Therefore, there is a certaih risk of both false positive and false negative diagnosis of AMI, even with the aid of CPK isoenzymes.
._ .
ll
01
8 0
6
12
18
24
30
36
42
48
Tlme. h o u r s
Fig. I . Serum CPK curves following cardioversion.
diately after the DC shock was 14 niU/ml (29%). The maximal CPK rise during the 18-51-hour period was 78 mU/ml (110%). In no case did the CPK exceed 156 mU/ml during the period of investigation. The CPK rise showed no correlation with either the discharged energy or the number of DC shocks. DISCUSSION Cardioversion of supraventricular and ventricular tachyarrhythmias is a routine method for treating these complications in AMI. If cardioversion influences the serum CPK activity, e.g. by release of CPK from thoracic muscles, this procedure impairs the diagnosis of AM1 by CPK estimations. Increased serum CPK values above the upper normal level have in fact been reported after cardioversion ( 5 , 8, 1 1, 30). Konttinen et al. ( I I ) found a CPK increase in 8 of 37 patients. The CPK rose 1.2-29 times the normal level and the maximal increase occurred one day after the DC shock. The patients were anaesthetized with sodium thiopental, 0.5 mg of atropine being used as premedication. I t cannot be concluded from this report or from any of the others (S, 8, 30), whether i.m. injections had been given before or during the investigation period. 1.m. injections have been reported to induce elevations of serum CPK, with a maximum 24 hours after the injection (2, 10, 15, 17, 28, 31). Acta med. scond. 198
Creatine phosphokinase ,fullowing curdioversion
35 1
ACKNOWLEDGEMENTS
15. Kiister, J . : Herzinfarkt und intramuskulk appliziertes
This study was supported by a grant from the Swedish National Association against Heart and Chest Diseases and received technical support from LKB-produkter AB, Sweden.
Lidocain. Med. Klin. 68: 1079, 1973. 16. Loegering, D., Critz, J . &Wagner, J . : Serum creatine phosphokinase as a diagnostic aid. Minn. Med. 50: 1751, 1967. 17. Meltzer, H. Y . , Mrozak, S . & Boyer. M.: Effect of intramuscular injections on serum creatine phosphokinase activity. Amer. J . med. Sci. 259:42, 1970. 18. Nevins, M. A,, Saran, M., Bright, M. & Lyon, L. J . : Pitfalls in interpreting serum creatine phosphokinase activity. J.A.M.A. 224: 1382, 1973. 19. Nordlander, R.: Serum creatine phosphokinase in acute myocardial infarction. To be published. 20. Nuttall, F. & Jones, B.: Creatine kinase and glutamic oxalacetic transaminase activity in serum: Kinetics of change with exercise and effect of physical conditioning. J. Lab. clin. Med. 71:847, 1968. 21. Okinaka, S . , Kumagai, H., Ebashi, S., Sugita, H., Monoi, H., Toyokura, Y . & Fujie, Y . : Serumcreatine phosphokinase. Arch. Neurol. 4: 520, 1961. 22. Pearce, J . , Pennington, R. & Walton, J . : Serum enzyme studies in muscle disease. J . Neurol. Neurosurg. Psychiat. 27: 96, 1964. 23. Perkorr, G . T.: Alcoholic myopathy. Amer. Rev. Med. 22: 125, 1971. 24. Schiavone, D. J . h Kaldor, J.: Creatine phosphokinase levels and cerebral disease. Med. J . Aust. 2:790, 1965. 25. Sobel, B. E. & Shell, W. E.: Serum enzyme determinations in the diagnosis and assessment of myocardial infarction. Circulation 45:471, 1972. 26. van der Veen, K. J . & Willebrands, A. F.: Isoenzymes of creatine phosphokinase in tissue extracts and in normal and pathological sera. Clin. chim. Acta 13: 312, 1966. 27. Vejajiva, A. & Teasdale, G.: Serum creatine kinase and physical exercise. Brit. med. J. I: 1653, 1965. 28. Vorburger, C., Fassler, B. & Kohl, P.: Serumkreatinphosphokinase und intramuskuliire Injektion. Schweiz. med. Wschr. 103: 927, 1973. 29. Wagner,G. S., Roe. C. R., Limbird, L. E., Rosati, R. A. &Wallace. A . G.: The importance of identification of the myocardial-specific isoenzyme of creatine phosphokinase (MB form) in the diagnosis of acute myocardial infarction. Circulation 47: 263, 1973. 30. Warbasse. R., Wesley, J . E., Connolly, V . & Galluzzi, N. J.: Lactic dehydrogenase isoenzymes after electroshock treatment of cardiac arrhythmias. Amer. J . Cardiol. 21:496, 1968. 31. Zener, J. C. & Harrison, D. C.: Serum enzyme values following intramuscular administration of lidocaine. Arch. intern. Med. 134:48. 1974.
REFERENCES I . Ahlborg, B. & Brohult, J . : Metabolic changes after exercise. Lancet 1: 1272, 1966. 2. Cacace, L.: Elevated serum CPK after drug injections. New Engl. J . Med. 287:309, 1972. 3. Dawson, D. & Fine, J.: Creatine-kinase in human tissues. Arch. Neurol. 16: 175, 1967. 4 . Dubo, H., Park, D. C., Pennington, R. J. T., Kalbag, R. M. & Walton, J . N.: Serumcreatine-kinase in cases of stroke, head injury, and meningitis. Lancet 2:743, 1967. 5 . Eshchar. J . & Zimmerman, H. J.: Creatine phosphokinase in disease. Amer. J. med. Sci. 253: 272, 1967. 6 . Garcia, W.: Elevated creatine phosphokinase levels associated with large muscle mass. J.A.M.A. 228: 1395, 1974. 7. Hughes, B. P.: Creatine phosphokinase in facioscapulohumeral muscular dystrophy. Brit. med, J . 3:464, 1971. 8. Hunt, D. & Bailie, M. J . : Enzyme changes following direct current countershock. Amdr. Heart J . 76: 340, I 968. 9. Hunt, D., McRae, C. & Zaph, P.: Electrocardiographic and serum enzyme changes in subarachnoid hemorrhage. Amer. Heart J . 77: 479, 1969. 10. Klein, M., Shell, W. & Sobel, B.: Serum creatine phosphokinase (CPK) isoenzymes after intramuscular injections, surgery, and myocardial infarction. Cardiovasc. Res. 7:412, 1973. I I . Konttinen, A,, Hupli, V., Louhija, A. & Hartel, G.: Origin of elevated serum enzyme activities after direct-current countershock. New Engl. J . Med. 281:231, 1969. 12. Konttinen, A,, Hartel, G . & Louhija, A,: Multiple serum enzyme analyses i n chronic alcoholics. Acta med. scand. 188:257. 1970. 13. Konttinen, A. & Somer, H.: Determination of serum creatine kinase isoenzymes in myocardial infarction. Amer. J. Cardiol. 29: 817, 1972. 14. - Specificity of serum creatine phosphokinase isoenzymes in diagnosis of acute myocardial infarction. Brit. med. J . 1:386. 1973.
Acfa mtd. srund. 198
