Acta med. scand. Vol. 197, pp. 503-505, 1975
CREATINE PHOSPHOKINASE AFTER SUBMAXIMAL PHYSICAL EXERCISE IN UNTRAINED INDIVIDUALS G. Forssell, R. Nordlander, 0. Nyquist, E. Orinius and I . Styrelius From rhe Department of Medicine, Karolinska Institute at Huddinge Hospital, Huddinge, Sweden
MATERIAL AND METHODS
Absrract. Serial estimations of total serum creatine
phosphokinase (CPK) have been performed before and during 1849 hours after submaximal physical exercise in 17 untrained individuals, mean age 50 years. The maximal CPK increase after exercise was 32 mU/ml (73%). The serum CPK did not exceed the upper normal limit (130 mU/ml) except in one individual (150 mU/ml). The maximal CPK increase in patients with acute myocardial infarction (AMI) vaned between 101 mU/ml (133%) and 2 260 mU/ml(3 790%), mean 900 mU/ml ( I 184%). As the maximal CPK elevation in AM1 occurs within the same period, it seems that heavy physical work of short duration just before the onset of symptoms will very seldom impair the diagnosis of AMI with the CPK technique used,
Serial estimations of serum creatine DhosDhokinase . (CPK) have gained much importance in the diagnosis of acute myocardial infarcti0.n (AMU. As CPK rises earlier above normal level and reaches its maximum earlier than other commonly used enzymes, it provides a very valuable test in the early phase of AM1 (3, 11, 15, 19). CPK has been documented to have a very high sensitivity in AM1 and the CPK range is about double the GOT range in the same patients. However, there has been much argument about the specificity. Significant CPK elevations have been reported after e.g. physical exercise (1, 9, 1 1 , 12, 18), i.m. injections of various drugs (2), cardioversion of arrhythmias (6) and in muscular diseases (5). On the other hand, these studies have been performed with rather infrequent blood sampling, mostly only once a day. The aim of the present study was to investigate the change in total CPK after submaximal physical exercise in untrained individuals of different ages, by frequent blood sampling.
Seventeen untrained subjects, 15 men and 2 women, performed a stepwise increasing exercise on a bicycle ergometer. Their ages ranged from 32 to 73 years (mean 50). The starting load for the men was 50 W, with increments of 50 W every 6 min. The women started on 40 W with increments of 30 W every 6 min as far as possible. None had any history of angina pectoris or myocardial infarction and none experienced chest pain during their exercise test. No i.m. injections were given before or after the test’ for Serum CPK were taken 30 min before, just prior to the bicycle test, immediately after, 30 min after, 1 hour after and every 2nd4th hour for 18-49 hours. The blood sample was centrifuged and the serum was frozen to -18°C for 1-3 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 (Boehringerm, 15721). The CPK activity is expressed in mU/ml (Enzyme nomenclature. Recommendations 1964 of the International Union of Biochemistry, Elsevier, Amsterdam, London and New York 1%5).
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 1 4 1 days (mean 8), showed a difference varying from 0 to 42 mUI ml, for CPK values between 21 and 1125 mU/ml. These differences are not statistically significant (p>0.05).
RESULTS The 17 individuals stopped their exercise test on
40-300 W (mean 130+67), because of muscular fatigue. None experienced any chest pain. The CPK values are shown in Fig. 1. The maximal CPK elevation immediately after the exercise test was 21 Acra med. scand. 197
G . Forssell et a [.
504
,i!yL-
Physlcal exercise
,
100
-
I'
---.
--. ~
!
50-
OJ
JJ ,
0
12
24
36
"
"
'
I
48
Tlme , h o u r s
Fig. 1 . CPK following physical exercise (indicated by
arrow).
mU/ml (18%). The maximal CPK increase during the following 1849-hour period was 32 mU/ml (73%). In no subject did CPK rise above 150 mU/ml after exercise, and only one individual had a CPK value above the upper normal level (130 mU/ml with our technique). I n 92 consecutive AM1 patients the maximal CPK increase varied between 101 (133%) and 2 260 mU/ml (3 790%), mean 900 mU/ml ( I 184%). DISCUSSION The effect on serum CPK activity of various forms of physical exercise has been variously reported by different authors (1, 8-14, 16, 18,20). The conflicting results may be due to differences in age and physical state of the subjects, the nature and duration of the exercise, the intervals of blood sampling, the duration of the follow-up after exercise and different methods for CPK analysis. Most of the studies mentioned concern young healthy students, trained or untrained, and young athletes. In the present study the mean age (50 years) was not as far from that of patients with AM1 and only minimal CPK elevations were observed in each individual. Minimal CPK elevations are uncommon in AM1 diagnosed by history, ECG and serum GOT/GPT. Heavy physical exercise just before the onset of symptoms is also uncommon. So, diagnosing AM1 with the aid of serial CPK determinations will very seldom be impaired by heavy physical work of short duration prior to the admission. Assuming that the observed CPK elevations after exercise are due to the skeletal muscle release, it Acta med. scnnd. 197
should be possible for diagnostic purposes to differentiate this source from the myocardium by using the CPK isoenzymes. There are, however, divergent opinions about the proportion of CPK-MB in skelel~lmuscle, 0-20% (4, 17, 19), as well as about the proportion of CPK-MB as a percentage of total CPK in association with AMI, 0-38% (7, 19). There is accordingly a certain risk of afalse positive as well as a false negative diagnosis of AM1 even with the aid of CPK-MB isoenzymes. In conclusion, only insignificant elevations of total CPK occurred during 18-49 hours after submaximal physical exercise. Heavy exercise performed within this period will therefore apparently only seldom interfere with the diagnosis of AM1 by serial estimation of total CPK. ACKNOWLEDGEMENTS This study was supported by a grant from the Swedish National Association against Heart and Chest Diseases and was given technical support by LKB-produkter AB, Sweden.
REFERENCES 1 . 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. Coodlev, E.: Prognostic value of enzvmes in mvocardial infarction. J.A.M.A. 225: 597, 1973. 4. Dawson, D. & Fine, J.: Creatine kinase in human tissues. Arch. Neurol. 16: 175, 1967. 5. Hughes, B. P.: Creatine phosphokinase in facioscapulohumeral muscular dystrophy. Brit. med. J . 3: 464, 1971. 6. Konttinen, A., Hupli, V., Louhija, A. & Hartel, G.: Origin of elevated serum enzyme activities after direct-current counter-shock. New Engl. J. Med. 281: 231, 1969. 7. Konttinen, A . & Somer, H.: Determination of serum creatine kinase isoenzymes in myocardial infarction. Amer. J. Cardiol. 29: 817, 1972. 8. Ledwich, J.: Changes in serum creatine phosphokinase during submaximal exercise testing. Canad. med. Ass. J. 109: 273, 1973. 9. Loegering, D., Critz, J. &Wagner, J.: Serum creatine phosphokinase as a diagnostic aid. Minn. Med. 50: 1751, 1967. 10. Martin, K. J . & Nichols, G.: Serum creatine phosphokinase in man during diving training. Aerospace Med. 45: 67, 1974. 11. Nevins. M. A., Saran, M., Bright, M. & Lyon, L . J.: Pitfalls in interpreting serum creatine phosphokinase activity. J.A.M.A. 224: 1382, 1973. 12. Nuttall, F. & Jones, B.: Creatine kinase and glutamic ocalacetic transaminase activity in serum: Kinetics of
Creatine phosphokinase after exercise
13.
14.
15. 16.
17.
change with exercise and effect of physical conditioning. J. Lab. clin. Med. 71: 847, 1968. Pearce, J . , Pennington, R. & Walton, J.: Serum enzyme studies i n muscle disease. J. Neurol. Neurosurg. Psychiat. 27: I. 1964. Shapiro, Y . , Magazanik, A , , Sokar, E. & Reich, C.: Serum enzyme changes in untrained subjects following a prolonged march. Canad. J. Physiol. Pharmacol. 51: 271, 1973. Sobel, B. E. & Shell, W. E.: Serum enzyme determinations in the diagnosis and assessment of myocardial infarction. Circulation 45: 471, 1972. Swaiman, K . G. & Awad, E. A.: Creatine phosphokinase and other enzyme activity after controlled exercise. Neurology 14: 977, 1964. van der Veen, K. J. & Willebrands, A. F.:
505
lsoenzymes of creatine phosphokinase in tissue extracts and in normal and pathological sera. Clin. chim. Acta 13: 312, 1966. 18. Vejajiva, A. & Teasdale, G.: Serum creatine kinase and physical exercise. Brit. med. J. 1 : 1653, 1965. 19. 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. 20. Wolfson, S . , Rose, L., Bousser, J., Parisi, A., Acosta, A., Cooper, K. & Schechter, E.: Serum enzyme levels during exercise in patients with coronary heart disease: Effects of training. Amer. Heart J. 84: 478, 1972.
Acta med. scand. 197
CREATINE PHOSPHOKINASE AFTER SUBMAXIMAL PHYSICAL EXERCISE IN UNTRAINED INDIVIDUALS G. Forssell, R. Nordlander, 0. Nyquist, E. Orinius and I . Styrelius From rhe Department of Medicine, Karolinska Institute at Huddinge Hospital, Huddinge, Sweden
MATERIAL AND METHODS
Absrract. Serial estimations of total serum creatine
phosphokinase (CPK) have been performed before and during 1849 hours after submaximal physical exercise in 17 untrained individuals, mean age 50 years. The maximal CPK increase after exercise was 32 mU/ml (73%). The serum CPK did not exceed the upper normal limit (130 mU/ml) except in one individual (150 mU/ml). The maximal CPK increase in patients with acute myocardial infarction (AMI) vaned between 101 mU/ml (133%) and 2 260 mU/ml(3 790%), mean 900 mU/ml ( I 184%). As the maximal CPK elevation in AM1 occurs within the same period, it seems that heavy physical work of short duration just before the onset of symptoms will very seldom impair the diagnosis of AMI with the CPK technique used,
Serial estimations of serum creatine DhosDhokinase . (CPK) have gained much importance in the diagnosis of acute myocardial infarcti0.n (AMU. As CPK rises earlier above normal level and reaches its maximum earlier than other commonly used enzymes, it provides a very valuable test in the early phase of AM1 (3, 11, 15, 19). CPK has been documented to have a very high sensitivity in AM1 and the CPK range is about double the GOT range in the same patients. However, there has been much argument about the specificity. Significant CPK elevations have been reported after e.g. physical exercise (1, 9, 1 1 , 12, 18), i.m. injections of various drugs (2), cardioversion of arrhythmias (6) and in muscular diseases (5). On the other hand, these studies have been performed with rather infrequent blood sampling, mostly only once a day. The aim of the present study was to investigate the change in total CPK after submaximal physical exercise in untrained individuals of different ages, by frequent blood sampling.
Seventeen untrained subjects, 15 men and 2 women, performed a stepwise increasing exercise on a bicycle ergometer. Their ages ranged from 32 to 73 years (mean 50). The starting load for the men was 50 W, with increments of 50 W every 6 min. The women started on 40 W with increments of 30 W every 6 min as far as possible. None had any history of angina pectoris or myocardial infarction and none experienced chest pain during their exercise test. No i.m. injections were given before or after the test’ for Serum CPK were taken 30 min before, just prior to the bicycle test, immediately after, 30 min after, 1 hour after and every 2nd4th hour for 18-49 hours. The blood sample was centrifuged and the serum was frozen to -18°C for 1-3 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 (Boehringerm, 15721). The CPK activity is expressed in mU/ml (Enzyme nomenclature. Recommendations 1964 of the International Union of Biochemistry, Elsevier, Amsterdam, London and New York 1%5).
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 1 4 1 days (mean 8), showed a difference varying from 0 to 42 mUI ml, for CPK values between 21 and 1125 mU/ml. These differences are not statistically significant (p>0.05).
RESULTS The 17 individuals stopped their exercise test on
40-300 W (mean 130+67), because of muscular fatigue. None experienced any chest pain. The CPK values are shown in Fig. 1. The maximal CPK elevation immediately after the exercise test was 21 Acra med. scand. 197
G . Forssell et a [.
504
,i!yL-
Physlcal exercise
,
100
-
I'
---.
--. ~
!
50-
OJ
JJ ,
0
12
24
36
"
"
'
I
48
Tlme , h o u r s
Fig. 1 . CPK following physical exercise (indicated by
arrow).
mU/ml (18%). The maximal CPK increase during the following 1849-hour period was 32 mU/ml (73%). In no subject did CPK rise above 150 mU/ml after exercise, and only one individual had a CPK value above the upper normal level (130 mU/ml with our technique). I n 92 consecutive AM1 patients the maximal CPK increase varied between 101 (133%) and 2 260 mU/ml (3 790%), mean 900 mU/ml ( I 184%). DISCUSSION The effect on serum CPK activity of various forms of physical exercise has been variously reported by different authors (1, 8-14, 16, 18,20). The conflicting results may be due to differences in age and physical state of the subjects, the nature and duration of the exercise, the intervals of blood sampling, the duration of the follow-up after exercise and different methods for CPK analysis. Most of the studies mentioned concern young healthy students, trained or untrained, and young athletes. In the present study the mean age (50 years) was not as far from that of patients with AM1 and only minimal CPK elevations were observed in each individual. Minimal CPK elevations are uncommon in AM1 diagnosed by history, ECG and serum GOT/GPT. Heavy physical exercise just before the onset of symptoms is also uncommon. So, diagnosing AM1 with the aid of serial CPK determinations will very seldom be impaired by heavy physical work of short duration prior to the admission. Assuming that the observed CPK elevations after exercise are due to the skeletal muscle release, it Acta med. scnnd. 197
should be possible for diagnostic purposes to differentiate this source from the myocardium by using the CPK isoenzymes. There are, however, divergent opinions about the proportion of CPK-MB in skelel~lmuscle, 0-20% (4, 17, 19), as well as about the proportion of CPK-MB as a percentage of total CPK in association with AMI, 0-38% (7, 19). There is accordingly a certain risk of afalse positive as well as a false negative diagnosis of AM1 even with the aid of CPK-MB isoenzymes. In conclusion, only insignificant elevations of total CPK occurred during 18-49 hours after submaximal physical exercise. Heavy exercise performed within this period will therefore apparently only seldom interfere with the diagnosis of AM1 by serial estimation of total CPK. ACKNOWLEDGEMENTS This study was supported by a grant from the Swedish National Association against Heart and Chest Diseases and was given technical support by LKB-produkter AB, Sweden.
REFERENCES 1 . 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. Coodlev, E.: Prognostic value of enzvmes in mvocardial infarction. J.A.M.A. 225: 597, 1973. 4. Dawson, D. & Fine, J.: Creatine kinase in human tissues. Arch. Neurol. 16: 175, 1967. 5. Hughes, B. P.: Creatine phosphokinase in facioscapulohumeral muscular dystrophy. Brit. med. J . 3: 464, 1971. 6. Konttinen, A., Hupli, V., Louhija, A. & Hartel, G.: Origin of elevated serum enzyme activities after direct-current counter-shock. New Engl. J. Med. 281: 231, 1969. 7. Konttinen, A . & Somer, H.: Determination of serum creatine kinase isoenzymes in myocardial infarction. Amer. J. Cardiol. 29: 817, 1972. 8. Ledwich, J.: Changes in serum creatine phosphokinase during submaximal exercise testing. Canad. med. Ass. J. 109: 273, 1973. 9. Loegering, D., Critz, J. &Wagner, J.: Serum creatine phosphokinase as a diagnostic aid. Minn. Med. 50: 1751, 1967. 10. Martin, K. J . & Nichols, G.: Serum creatine phosphokinase in man during diving training. Aerospace Med. 45: 67, 1974. 11. Nevins. M. A., Saran, M., Bright, M. & Lyon, L . J.: Pitfalls in interpreting serum creatine phosphokinase activity. J.A.M.A. 224: 1382, 1973. 12. Nuttall, F. & Jones, B.: Creatine kinase and glutamic ocalacetic transaminase activity in serum: Kinetics of
Creatine phosphokinase after exercise
13.
14.
15. 16.
17.
change with exercise and effect of physical conditioning. J. Lab. clin. Med. 71: 847, 1968. Pearce, J . , Pennington, R. & Walton, J.: Serum enzyme studies i n muscle disease. J. Neurol. Neurosurg. Psychiat. 27: I. 1964. Shapiro, Y . , Magazanik, A , , Sokar, E. & Reich, C.: Serum enzyme changes in untrained subjects following a prolonged march. Canad. J. Physiol. Pharmacol. 51: 271, 1973. Sobel, B. E. & Shell, W. E.: Serum enzyme determinations in the diagnosis and assessment of myocardial infarction. Circulation 45: 471, 1972. Swaiman, K . G. & Awad, E. A.: Creatine phosphokinase and other enzyme activity after controlled exercise. Neurology 14: 977, 1964. van der Veen, K. J. & Willebrands, A. F.:
505
lsoenzymes of creatine phosphokinase in tissue extracts and in normal and pathological sera. Clin. chim. Acta 13: 312, 1966. 18. Vejajiva, A. & Teasdale, G.: Serum creatine kinase and physical exercise. Brit. med. J. 1 : 1653, 1965. 19. 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. 20. Wolfson, S . , Rose, L., Bousser, J., Parisi, A., Acosta, A., Cooper, K. & Schechter, E.: Serum enzyme levels during exercise in patients with coronary heart disease: Effects of training. Amer. Heart J. 84: 478, 1972.
Acta med. scand. 197
