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Effects of long-distance running on hemostasis and fibrinolysis
Fibrinolysis (1990)4. Supp:2.99-101
0268-9499/90/0004-0099/$10.00
Q LongmanGmup UK Ltd 1990
Effects of Long-Distance Running on Hemostasis and Fibrinolysis
P. Hellstem, D. Seiler, M. Heiden, S. Golf, D. Nagel, K. Oberfrank, M. Kilhler SUMMARY. The effect of chronic physical exercise on hemostasisand thrombosis was studied in 35 long-distance runners who took part in an 1.000~kmrace lasting for 20 days and divided into daily portions of about 50 km. The following parameters were measured on the day before the race (day 0) and on days 1,3,6,8,11, and 19: factor VII activity, fibrinogen, t-PA, PAI-1, plasminogen, antiplasmin, D-dhners, and thrombinantithrombin-III complexes (TAT). During the race there was a rapid drop of factor VII and a continuous increase of fibrinogen. t-PA rapidly increased on day 1 and returned to baseline values on days 6 and 8. PAIand antiplasmin were not influenced. Plasminogen decreasedsignificantly on day 3 and returned to initial levels on days 11 and 19. D-Dimers continuously increased reaching the maximum levels on day 19. TAT levels were only significantly increased on day 19. KEYWORDS. Long-distance running. Physical exercise. Hemostasis. Fibrinolysis.
Plasminogen and antiplasmin were analysed by chromogenic substrate assays. t-PA, PAI-1, D-dimers, and TAT were determinedusing enzyme immunoassays.
The influence of acute exercise on hemostasis and fibrinolysis is subject of numerous studies which have recently been reviewed’. Alterations of hemostasisand fibrinolysis following chronic, severephysical exercise lasting for several days or weeks have not been studied extensively. We examined35 long-distancerunnerswho took part in a 1000&n race.
RESULTS Factor VII and fibrinogen levels are presentedin Figure 1. Factor VII significantly droppedby about 20% on day 1 and remained decreaseduntil day 19. There was a significant increaseof fibrinogen on day 3 and a further increaseuntil day 19. t-PA antigen rose to about 3-fold the initial value reaching a peak on day 1. The t-PA levels returned to their initial values on days 6 and 8 and increasedagain on days 11 and 19 (Fig. 2). Plasminogen dropped significantly on day 3 and reached the baseline values again on days 11 and 19. Antiplasmin was not influenced (Fig. 3). There were large interindividual variations of D-dimer and TAT levels (Fig. 4). D-dimers rose continuously and significantly reachingthe maximum on day 19. A significant increase of TAT levels was only observedon day 19.
MATERIALS AND METHODS Thirty-five experiencedlong-distancerunners(8 females and 27 males) participated in a 1000~kmrace from the north to the south of West Germany lasting for 20 days and divided into daily portions of approximately50 km. Group I (19 people) consumeda conventional Western diet. Group II consumed only wholesome lacto-ovovegetarianfood. Runners were only offered the diet of their respective group without restriction of caloric intake. All participants were nonsmokers,and no alcohol was allowed. Blood was always collected in the early afternoonon the day before the race (day 0) and on days 1,3, 6,8, 11 and 19 immediately after finishing the race. Factor VII was measured by a one-stageclotting assay,fibrinogen was assayedusing the Clauss’method.
DISCUSSION AND CONCLUSIONS
P. Hellstern, K. Obereank, Institut fik Transfusionsmedizin und Immonh&natologie, Klinikum Ludwigshafen, D-6700 Ludwigshaven D. Seiler, D. Nagel, Institot fiir Klinische Chemie, Klinkum Ludwigshafen, D-6700 Ludwigshaven M. Heiden, M. KShler, Abt. fiir Klinische H’dmostaseologie und Transfusionmedizin, Universitiskinken des Saarlandes, Homburg-Saar S. Golf, Institot ti KIinische Chemie, UniversitUiniken Giessen, F.R.G.
Chronic severephysical exercise leads to a marked and rapid increase and to a second, delayed and more moderaterise of t-PA levels. This is very similar to the course of C-reactive protein levels following exercise, expressingan acutephasereaction (data not shown).The same holds true for fibrinogen levels showing a more 99
100
L.ong-Distance Rumhg
& Hemostasis/Fibrinolysis
Factor
VII
FIBRINOGEN
UllOOml
140
4
120
100
9
80
2.6
60
2
40
1.6
20
0 1’
9.
6..
8.
Il.
1
19.
01
*’
a-
6..
II..
-
mean - SD
la..
day
day
-I- nl.M
-man
l
SD
-niun-SD
+
/
Ill..”
-8
in..”
SD
l
Fig. 1 Factor VII (* P
t-PA
PAI-
no/ml
1 20
60
nglml
17,6 60 16 12.6
7.6 6 2.6 ol........‘.....‘..‘lo 0 9. a.
a
8
13..
0
1D..
01
8
9
a
-
III..”
- SD
+
II
1g
day
day ns*n
-E-
mean
l
SD
-
III..”
- SD
-
m.m
-
tn..”
l
SD
Fig. 2 t-PA (* P
PLASMINOGEN 120
ANTIPLASMIN
UllWml 120
SO
QO
80
a0
70
70
a0
0 1
a..
e.
a.
11
a0 19
100
0
UIl00ml
01
9
a
6
day
+ I..” - aD + In.*” -8 m.an. SD
11
IQ
day -mean
- SD
-
i7le.n
Fig. 3 Plasminogen (** P
*mean*SD
Fibrinolysis
101
D- Dimer rig/ml 3Or
-01
a
3
B
11
IS.
day -
mean
- SD
+
mean
-moan
- SD
-mean
- SD
+
mean
-mean
+ BD
Fig. 4 D-dimer (* P
delayed increase due to its much longer generation and half-life time. The early decreaseof plasminogen as well as the continuous increase of D-dimer levels indicate that plasmin is formed and that fibrinolysis does occur. However, it remains to be established whether fibrin split products mainly stem from a “physiological” intravital fibrin pool or from fibrin that has been formed by activation of hemostasis during exercise. It is known that severe physical exercise may lead to cell damage and that hemostasismay be activated by releaseof tissue factor from damaged cells. Activation of hemostasis is also supported by elevated TAT levels at the end of the competition. Since there is also a decrease of other proteins synthesized in the liver (like albumin or cholinesterase; data not shown) the drop of factor VII activity may be
rather due to diminished synthesis than to consumption. It was demonstrated by others that an acute phase reaction caused by interleukind leads to diminished synthesis of albumin and other proteins. Surprisingly, runners on vegetarian diet had significantly greater factor VII levels than runners on Western diet. This is in contrast to previous findings and may be due to the fact that runners on vegetarian diet consumedthe same amount of calories and that their diet had the sameratio of lipids, proteins and carbohydrates. REFERENCES 1. Bourney R E, Santoro S A 1988 Interactions of exercise, coagulation, and fibrinolysis - a brief review. Med Sci Sport Exert 201439-446
0268-9499/90/0004-0099/$10.00
Q LongmanGmup UK Ltd 1990
Effects of Long-Distance Running on Hemostasis and Fibrinolysis
P. Hellstem, D. Seiler, M. Heiden, S. Golf, D. Nagel, K. Oberfrank, M. Kilhler SUMMARY. The effect of chronic physical exercise on hemostasisand thrombosis was studied in 35 long-distance runners who took part in an 1.000~kmrace lasting for 20 days and divided into daily portions of about 50 km. The following parameters were measured on the day before the race (day 0) and on days 1,3,6,8,11, and 19: factor VII activity, fibrinogen, t-PA, PAI-1, plasminogen, antiplasmin, D-dhners, and thrombinantithrombin-III complexes (TAT). During the race there was a rapid drop of factor VII and a continuous increase of fibrinogen. t-PA rapidly increased on day 1 and returned to baseline values on days 6 and 8. PAIand antiplasmin were not influenced. Plasminogen decreasedsignificantly on day 3 and returned to initial levels on days 11 and 19. D-Dimers continuously increased reaching the maximum levels on day 19. TAT levels were only significantly increased on day 19. KEYWORDS. Long-distance running. Physical exercise. Hemostasis. Fibrinolysis.
Plasminogen and antiplasmin were analysed by chromogenic substrate assays. t-PA, PAI-1, D-dimers, and TAT were determinedusing enzyme immunoassays.
The influence of acute exercise on hemostasis and fibrinolysis is subject of numerous studies which have recently been reviewed’. Alterations of hemostasisand fibrinolysis following chronic, severephysical exercise lasting for several days or weeks have not been studied extensively. We examined35 long-distancerunnerswho took part in a 1000&n race.
RESULTS Factor VII and fibrinogen levels are presentedin Figure 1. Factor VII significantly droppedby about 20% on day 1 and remained decreaseduntil day 19. There was a significant increaseof fibrinogen on day 3 and a further increaseuntil day 19. t-PA antigen rose to about 3-fold the initial value reaching a peak on day 1. The t-PA levels returned to their initial values on days 6 and 8 and increasedagain on days 11 and 19 (Fig. 2). Plasminogen dropped significantly on day 3 and reached the baseline values again on days 11 and 19. Antiplasmin was not influenced (Fig. 3). There were large interindividual variations of D-dimer and TAT levels (Fig. 4). D-dimers rose continuously and significantly reachingthe maximum on day 19. A significant increase of TAT levels was only observedon day 19.
MATERIALS AND METHODS Thirty-five experiencedlong-distancerunners(8 females and 27 males) participated in a 1000~kmrace from the north to the south of West Germany lasting for 20 days and divided into daily portions of approximately50 km. Group I (19 people) consumeda conventional Western diet. Group II consumed only wholesome lacto-ovovegetarianfood. Runners were only offered the diet of their respective group without restriction of caloric intake. All participants were nonsmokers,and no alcohol was allowed. Blood was always collected in the early afternoonon the day before the race (day 0) and on days 1,3, 6,8, 11 and 19 immediately after finishing the race. Factor VII was measured by a one-stageclotting assay,fibrinogen was assayedusing the Clauss’method.
DISCUSSION AND CONCLUSIONS
P. Hellstern, K. Obereank, Institut fik Transfusionsmedizin und Immonh&natologie, Klinikum Ludwigshafen, D-6700 Ludwigshaven D. Seiler, D. Nagel, Institot fiir Klinische Chemie, Klinkum Ludwigshafen, D-6700 Ludwigshaven M. Heiden, M. KShler, Abt. fiir Klinische H’dmostaseologie und Transfusionmedizin, Universitiskinken des Saarlandes, Homburg-Saar S. Golf, Institot ti KIinische Chemie, UniversitUiniken Giessen, F.R.G.
Chronic severephysical exercise leads to a marked and rapid increase and to a second, delayed and more moderaterise of t-PA levels. This is very similar to the course of C-reactive protein levels following exercise, expressingan acutephasereaction (data not shown).The same holds true for fibrinogen levels showing a more 99
100
L.ong-Distance Rumhg
& Hemostasis/Fibrinolysis
Factor
VII
FIBRINOGEN
UllOOml
140
4
120
100
9
80
2.6
60
2
40
1.6
20
0 1’
9.
6..
8.
Il.
1
19.
01
*’
a-
6..
II..
-
mean - SD
la..
day
day
-I- nl.M
-man
l
SD
-niun-SD
+
/
Ill..”
-8
in..”
SD
l
Fig. 1 Factor VII (* P
t-PA
PAI-
no/ml
1 20
60
nglml
17,6 60 16 12.6
7.6 6 2.6 ol........‘.....‘..‘lo 0 9. a.
a
8
13..
0
1D..
01
8
9
a
-
III..”
- SD
+
II
1g
day
day ns*n
-E-
mean
l
SD
-
III..”
- SD
-
m.m
-
tn..”
l
SD
Fig. 2 t-PA (* P
PLASMINOGEN 120
ANTIPLASMIN
UllWml 120
SO
QO
80
a0
70
70
a0
0 1
a..
e.
a.
11
a0 19
100
0
UIl00ml
01
9
a
6
day
+ I..” - aD + In.*” -8 m.an. SD
11
IQ
day -mean
- SD
-
i7le.n
Fig. 3 Plasminogen (** P
*mean*SD
Fibrinolysis
101
D- Dimer rig/ml 3Or
-01
a
3
B
11
IS.
day -
mean
- SD
+
mean
-moan
- SD
-mean
- SD
+
mean
-mean
+ BD
Fig. 4 D-dimer (* P
delayed increase due to its much longer generation and half-life time. The early decreaseof plasminogen as well as the continuous increase of D-dimer levels indicate that plasmin is formed and that fibrinolysis does occur. However, it remains to be established whether fibrin split products mainly stem from a “physiological” intravital fibrin pool or from fibrin that has been formed by activation of hemostasis during exercise. It is known that severe physical exercise may lead to cell damage and that hemostasismay be activated by releaseof tissue factor from damaged cells. Activation of hemostasis is also supported by elevated TAT levels at the end of the competition. Since there is also a decrease of other proteins synthesized in the liver (like albumin or cholinesterase; data not shown) the drop of factor VII activity may be
rather due to diminished synthesis than to consumption. It was demonstrated by others that an acute phase reaction caused by interleukind leads to diminished synthesis of albumin and other proteins. Surprisingly, runners on vegetarian diet had significantly greater factor VII levels than runners on Western diet. This is in contrast to previous findings and may be due to the fact that runners on vegetarian diet consumedthe same amount of calories and that their diet had the sameratio of lipids, proteins and carbohydrates. REFERENCES 1. Bourney R E, Santoro S A 1988 Interactions of exercise, coagulation, and fibrinolysis - a brief review. Med Sci Sport Exert 201439-446