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Creatine kinase and MB-fraction after a long distance race
Clintca Chrmtca Acra, 125 (1982) 307-310 Elsevier Biomedical Press
307
CCA 2303
Creatine kinase and MB-fraction distance race W.H. Department
Reinhart,
M. Sttiubli
*, H.P.
Kijchli
after a long and P.W. Straub
of Internal Medicine and Department o.f Cltnrcal Chemistry. Inselspital, Berne (Swttzerland) (Received
Umversity of Berrte,
May IOth, 1982)
Summary
In 18 well-trained athletes creatine kinase (CK) and the CK-MB isoenzyme were measured immediately after a 100 km race and 10 days later for control purposes. The CK was 1970 + 1505 U/l (mean + SD, range 481-5558 U/l) after the race and 50 + 23 U/l on the control day ( p < 0.001). The CK-MB fraction was 72 t_ 70 U/l (range 14-288 U/l) and 8.6 + 2.3 U/l (p < 0.01). The ratio CK-MB/CK was 3.4 k 1.1% and never exceeded 6%. The study indicates that elevated CK and CK-MB are a common finding after a long distance race. CK-MB/CK ratios up to 6% may be observed.
Introduction
Elevation of the total creatine kinase (CK) in the serum after long-term strenuous exercise is well known [l-5]. Nevertheless, there are only few reports about the pattern of the creatine kinase isoenzymes, the so called MM-, MB- and BB fractions [ 1,4,5]. The CK-MB-fraction is believed to be ‘heart-specific’, its elevation indicating myocardial damage in clinical medicine. However, it has been known for many years that the skeletal muscle too, contains a small and variable amount of MB-fraction [6,71. With increasing popularity of long distance races and with increasing age of participants, emergencies under such circumstances become more frequent. After a collapse during racing it may be particularly difficult to rule out a cardiac disorder, especially because normal ranges of the isoenzyme CK-MB during and after this kind of sport are not well known. Heinemann et al [4] reported on normal CK-MB levels in ice-hockey players, weight lifters and cross-country skiers after a normal training programme, whereas others described a substantial increase of the CK-MB * Address for correspondence: Bern. Switzerland.
0009-8981/82/000&0000/$02.75
Dr. M. Staubli,
Medizinische
-1982 Elsevier Biomedical
Universitatsklinik,
Press
Inselspital.
CH 3010
308
with a mean CK-MB/CK ratio of 6.6 + 2.9% SD [I] and 8.3 + 6.3% [5] after marathon running. In the present study we have investigated the CK and the CK-MB-isoenzyme in 18 healthy top athletes after a 100 km race and IO days later for control purposes. Methods Eighteen well trained male athletes were selected for the study. They all had obtained a top rank in the same race a year ago. They gave informed consent to the study. The 100 km race took place during the night, starting at 10 p.m. with most parts on the streets. During the race the runners were allowed to eat and drink unrestrictedly. Within 15 min after completion of the race, 5 ml of blood in sodium citrate (3.6%) was drawn from an antecubital vein without stasis together with samples for another study. The blood was centrifuged and the plasma deep frozen. Ten days after the race, the same amount of blood was taken again at the same time of day for control measurements. During these 10 days, the athletes did not participate in long distance races, but all of them maintained a basal running activity. Total CK activity was measured at 25°C with the N-acetylcysteine reactivated method using commercial reagents (Merck, Darmstadt, FRG). CK-B subunit activity was determined by use of inhibiting antibodies against the M-monomer (Merck, Darmstadt, FRG). Because CK and CK-MB values did not conform to a normal distribution, we used Wilcoxon’s signed rank sum test and Spearman’s rank order correlation for the analysis of paired data. A p < 0.05 was taken as level of statistical significance. Results All being Table later, using
TABLE
athletes completed the whole distance of 100 km, the average racing time 9 h (range 7.5-10 h). The CK and CK-MB-isoenzyme values are given in I. Mean CK was increased about 28-fold compared to control values 10 days and the MB-fraction about 6-fold. Fig. 1 shows the individual values of CK a logarithmic scale. The large variation of individual values at the end of the
I
MEAN VALUES&SD FOR CREATINE KINASE AND THE MB ISOENZYME FRACTION IN 18 ELITE RUNNERS AFTER A 100 KM RACE AND IO DAYS LATER FOR CONTROL PURPOSES Normal
range
After the race Control values P
*
n-9.
CK (U/l)
O-60
1970+1505 50+ 23 < 0.00 I
CK-MB
(U/l)
72 _+70 8.6& 2.3 * < 0.01
< IO
309 10'000
-
T
6% ,
1'000
l
-
3 :: 100
10
0
4600
zobo
CK (U/I) Fig. 1. Creatine kinase (U/l, logarithmic scale) in 18 elite runners after a 100 km race and control 10 days later. The shaded area represents the normal range (O-60 U/l). Fig. 2. Correlation between CK (U/l) and the isoenzyme fraction CK-MB (U/l) Shaded areas represent normal ranges for CK (O-60 U/l) and CK-MB (O-10 represents a CK-MB/CK ratio of 6%.
values
in 18 100 km runners. U/l). The dotted line
race is noteworthy, since we investigated a very homogenous group of elite runners. A correlation between the running velocity and either the CK or the CK-MB concentrations could not be found. On the control day the mean value of CK was within normal limits (Table I), although one third of the runners still had increased levels. The highest CK value on the control day (117 U/l) was accompanied by an increased CK-MB-fraction (14.1 U/l). This runner felt absolutely well, he was the fastest of those runners who participated in our study and he won the same race one year later. When CK is plotted against the MB-fraction (Fig. 2) it becomes obvious that the CK-MB/CK ratio never exceeded 6% at any CK level (dotted line). The mean CK-MB/CK ratio was 3.4%. A highly significant correlation between CK and CK-MB was found (r, = 0.97. p < 0.0001). Discussion
The CK values observed in the present study were surprisingly high as compared to other investigations [2,4]. In only one study were CK values in a similar range reported after a 160 km race [ 11. From a clinical standpoint, the absolute values for the CK-MB-fraction are frightening and raise the question as to whether the MB-fraction is of muscular or cardiac origin. CK is a key enzyme in muscular
310
metabolism. Its presence in the plasma signifies damage to striated muscle leading to an efflux of CK from muscle cells. The CK-MB content of skeletal muscle varies between different muscle groups and ranges between O-20% of the total content [7,10]. The increased CK-MB after the race in comparison to control values may therefore reflect a leakage from skeletal muscles of both CK and CK-MB. This interpretation is supported by the highly significant correlation between CK and CK-MB in this study. The ratio CK-MB/CK, however, never exceeded 6%; the same limit was also observed for acute viral rhabdomyolysis [8] and for different types of surgery involving striated muscle other than the heart [9]. Although our data are therefore well explained by assuming exclusive skeletal muscle damage, the rather wide (absolute) inter-individual variation of CK-MB, particularly observed at high CK levels, is difficult to explain. It may be due to inter-individual differences of CK-MB and CK contents of analogous muscle groups in different individuals or to different running styles, since a variable content of CK-MB in different muscle groups is known [7,10]. Nevertheless myocardial damage contributing to the described enzyme pattern cannot be ruled out completely. However, as long as a ‘heart damage specific’ humoral indicator is lacking, it remains a matter of speculation whether repeated competitive long distance running causes repetitive myocardial damage, possibly resulting in the so-called athletic heart syndrome [ 11,121. For every-day clinical practice it may be concluded that the absolute values for the CK-MB isoenzyme may be grossly misleading and that CK-MB values should be given as percentage of CK. References I Kielblock AJ, Maqoo M, Booyens J, Katzeff IE. Creatine phosphokinase and lactate dehydrogenase levels after ultra long-distance running. S Afr Med J 1979; 55: 1061-1064. 2 Magazanik A, Shapiro Y, Meytes D. Meytes I. Enzyme blood levels and water balance during a marathon race. J Appl Physiol 1974; 36: 214-217. 3 Bunch TW. Blood test abnormalities in runners. Mayo Clin Proc 1980: 55: 113- 117. 4 Heinemann G, Pabst H, Schievelbein H. Die Aktivitat der Creatinkinase und des Isoenzyms CK-MB im Serum van Hochleistungssportlern. Dtsch Z Sportmed 1978; 29: 33-37. 5 Siegel AJ, Silverman LM, Holman L. Elevated creatine kinase MB isoenzyme levels in marathon runners. J Am Med Assoc 1981; 246: 2049-205 1. 6 Van der Veen KJ, Willebrands AF. Isoenzymes of creatine phosphokinase in tissue extracts and in normal and pathological sera. Clin Chim Acta 1966; 13: 312-316. 7 Tsung SH. Creatine kin&e isoenzyme patterns in human tissue obtained at surgery. Clin Chem 1976: 22: 173-175. 8 Vladutiu AO, Venuto RC. Creatine kinase MB and lactate dehydrogenase 5 isoenzymes in rhabdomyolysis. Clin Chem 1977; 23: 1366. 9 Prellwitz W. Creatine kinase isoenzymes in direct skeletal muscle damage. In H. Lang, ed. Creatine kinase isoenzymes. Springer 1981; 171-173. 10 Wilhelm AH, Alkers KM, Todd JK. Creatine phosphokinase isoenzyme distribution in human skeletal and heart muscle. IRCS Med Sci 1976; 4: 418. 1 I Gott PH. Roselle HA, Crampton RS. The athletic heart syndrome. Arch Intern Med 1968: 122: 340-344. 12 Noakes TD, Rose AG. Opie LH. Hypertrophic cardiomyopathy associated with sudden death during marathon racing. Br Heart J 1979; 41: 624-627.
307
CCA 2303
Creatine kinase and MB-fraction distance race W.H. Department
Reinhart,
M. Sttiubli
*, H.P.
Kijchli
after a long and P.W. Straub
of Internal Medicine and Department o.f Cltnrcal Chemistry. Inselspital, Berne (Swttzerland) (Received
Umversity of Berrte,
May IOth, 1982)
Summary
In 18 well-trained athletes creatine kinase (CK) and the CK-MB isoenzyme were measured immediately after a 100 km race and 10 days later for control purposes. The CK was 1970 + 1505 U/l (mean + SD, range 481-5558 U/l) after the race and 50 + 23 U/l on the control day ( p < 0.001). The CK-MB fraction was 72 t_ 70 U/l (range 14-288 U/l) and 8.6 + 2.3 U/l (p < 0.01). The ratio CK-MB/CK was 3.4 k 1.1% and never exceeded 6%. The study indicates that elevated CK and CK-MB are a common finding after a long distance race. CK-MB/CK ratios up to 6% may be observed.
Introduction
Elevation of the total creatine kinase (CK) in the serum after long-term strenuous exercise is well known [l-5]. Nevertheless, there are only few reports about the pattern of the creatine kinase isoenzymes, the so called MM-, MB- and BB fractions [ 1,4,5]. The CK-MB-fraction is believed to be ‘heart-specific’, its elevation indicating myocardial damage in clinical medicine. However, it has been known for many years that the skeletal muscle too, contains a small and variable amount of MB-fraction [6,71. With increasing popularity of long distance races and with increasing age of participants, emergencies under such circumstances become more frequent. After a collapse during racing it may be particularly difficult to rule out a cardiac disorder, especially because normal ranges of the isoenzyme CK-MB during and after this kind of sport are not well known. Heinemann et al [4] reported on normal CK-MB levels in ice-hockey players, weight lifters and cross-country skiers after a normal training programme, whereas others described a substantial increase of the CK-MB * Address for correspondence: Bern. Switzerland.
0009-8981/82/000&0000/$02.75
Dr. M. Staubli,
Medizinische
-1982 Elsevier Biomedical
Universitatsklinik,
Press
Inselspital.
CH 3010
308
with a mean CK-MB/CK ratio of 6.6 + 2.9% SD [I] and 8.3 + 6.3% [5] after marathon running. In the present study we have investigated the CK and the CK-MB-isoenzyme in 18 healthy top athletes after a 100 km race and IO days later for control purposes. Methods Eighteen well trained male athletes were selected for the study. They all had obtained a top rank in the same race a year ago. They gave informed consent to the study. The 100 km race took place during the night, starting at 10 p.m. with most parts on the streets. During the race the runners were allowed to eat and drink unrestrictedly. Within 15 min after completion of the race, 5 ml of blood in sodium citrate (3.6%) was drawn from an antecubital vein without stasis together with samples for another study. The blood was centrifuged and the plasma deep frozen. Ten days after the race, the same amount of blood was taken again at the same time of day for control measurements. During these 10 days, the athletes did not participate in long distance races, but all of them maintained a basal running activity. Total CK activity was measured at 25°C with the N-acetylcysteine reactivated method using commercial reagents (Merck, Darmstadt, FRG). CK-B subunit activity was determined by use of inhibiting antibodies against the M-monomer (Merck, Darmstadt, FRG). Because CK and CK-MB values did not conform to a normal distribution, we used Wilcoxon’s signed rank sum test and Spearman’s rank order correlation for the analysis of paired data. A p < 0.05 was taken as level of statistical significance. Results All being Table later, using
TABLE
athletes completed the whole distance of 100 km, the average racing time 9 h (range 7.5-10 h). The CK and CK-MB-isoenzyme values are given in I. Mean CK was increased about 28-fold compared to control values 10 days and the MB-fraction about 6-fold. Fig. 1 shows the individual values of CK a logarithmic scale. The large variation of individual values at the end of the
I
MEAN VALUES&SD FOR CREATINE KINASE AND THE MB ISOENZYME FRACTION IN 18 ELITE RUNNERS AFTER A 100 KM RACE AND IO DAYS LATER FOR CONTROL PURPOSES Normal
range
After the race Control values P
*
n-9.
CK (U/l)
O-60
1970+1505 50+ 23 < 0.00 I
CK-MB
(U/l)
72 _+70 8.6& 2.3 * < 0.01
< IO
309 10'000
-
T
6% ,
1'000
l
-
3 :: 100
10
0
4600
zobo
CK (U/I) Fig. 1. Creatine kinase (U/l, logarithmic scale) in 18 elite runners after a 100 km race and control 10 days later. The shaded area represents the normal range (O-60 U/l). Fig. 2. Correlation between CK (U/l) and the isoenzyme fraction CK-MB (U/l) Shaded areas represent normal ranges for CK (O-60 U/l) and CK-MB (O-10 represents a CK-MB/CK ratio of 6%.
values
in 18 100 km runners. U/l). The dotted line
race is noteworthy, since we investigated a very homogenous group of elite runners. A correlation between the running velocity and either the CK or the CK-MB concentrations could not be found. On the control day the mean value of CK was within normal limits (Table I), although one third of the runners still had increased levels. The highest CK value on the control day (117 U/l) was accompanied by an increased CK-MB-fraction (14.1 U/l). This runner felt absolutely well, he was the fastest of those runners who participated in our study and he won the same race one year later. When CK is plotted against the MB-fraction (Fig. 2) it becomes obvious that the CK-MB/CK ratio never exceeded 6% at any CK level (dotted line). The mean CK-MB/CK ratio was 3.4%. A highly significant correlation between CK and CK-MB was found (r, = 0.97. p < 0.0001). Discussion
The CK values observed in the present study were surprisingly high as compared to other investigations [2,4]. In only one study were CK values in a similar range reported after a 160 km race [ 11. From a clinical standpoint, the absolute values for the CK-MB-fraction are frightening and raise the question as to whether the MB-fraction is of muscular or cardiac origin. CK is a key enzyme in muscular
310
metabolism. Its presence in the plasma signifies damage to striated muscle leading to an efflux of CK from muscle cells. The CK-MB content of skeletal muscle varies between different muscle groups and ranges between O-20% of the total content [7,10]. The increased CK-MB after the race in comparison to control values may therefore reflect a leakage from skeletal muscles of both CK and CK-MB. This interpretation is supported by the highly significant correlation between CK and CK-MB in this study. The ratio CK-MB/CK, however, never exceeded 6%; the same limit was also observed for acute viral rhabdomyolysis [8] and for different types of surgery involving striated muscle other than the heart [9]. Although our data are therefore well explained by assuming exclusive skeletal muscle damage, the rather wide (absolute) inter-individual variation of CK-MB, particularly observed at high CK levels, is difficult to explain. It may be due to inter-individual differences of CK-MB and CK contents of analogous muscle groups in different individuals or to different running styles, since a variable content of CK-MB in different muscle groups is known [7,10]. Nevertheless myocardial damage contributing to the described enzyme pattern cannot be ruled out completely. However, as long as a ‘heart damage specific’ humoral indicator is lacking, it remains a matter of speculation whether repeated competitive long distance running causes repetitive myocardial damage, possibly resulting in the so-called athletic heart syndrome [ 11,121. For every-day clinical practice it may be concluded that the absolute values for the CK-MB isoenzyme may be grossly misleading and that CK-MB values should be given as percentage of CK. References I Kielblock AJ, Maqoo M, Booyens J, Katzeff IE. Creatine phosphokinase and lactate dehydrogenase levels after ultra long-distance running. S Afr Med J 1979; 55: 1061-1064. 2 Magazanik A, Shapiro Y, Meytes D. Meytes I. Enzyme blood levels and water balance during a marathon race. J Appl Physiol 1974; 36: 214-217. 3 Bunch TW. Blood test abnormalities in runners. Mayo Clin Proc 1980: 55: 113- 117. 4 Heinemann G, Pabst H, Schievelbein H. Die Aktivitat der Creatinkinase und des Isoenzyms CK-MB im Serum van Hochleistungssportlern. Dtsch Z Sportmed 1978; 29: 33-37. 5 Siegel AJ, Silverman LM, Holman L. Elevated creatine kinase MB isoenzyme levels in marathon runners. J Am Med Assoc 1981; 246: 2049-205 1. 6 Van der Veen KJ, Willebrands AF. Isoenzymes of creatine phosphokinase in tissue extracts and in normal and pathological sera. Clin Chim Acta 1966; 13: 312-316. 7 Tsung SH. Creatine kin&e isoenzyme patterns in human tissue obtained at surgery. Clin Chem 1976: 22: 173-175. 8 Vladutiu AO, Venuto RC. Creatine kinase MB and lactate dehydrogenase 5 isoenzymes in rhabdomyolysis. Clin Chem 1977; 23: 1366. 9 Prellwitz W. Creatine kinase isoenzymes in direct skeletal muscle damage. In H. Lang, ed. Creatine kinase isoenzymes. Springer 1981; 171-173. 10 Wilhelm AH, Alkers KM, Todd JK. Creatine phosphokinase isoenzyme distribution in human skeletal and heart muscle. IRCS Med Sci 1976; 4: 418. 1 I Gott PH. Roselle HA, Crampton RS. The athletic heart syndrome. Arch Intern Med 1968: 122: 340-344. 12 Noakes TD, Rose AG. Opie LH. Hypertrophic cardiomyopathy associated with sudden death during marathon racing. Br Heart J 1979; 41: 624-627.