Increases in factor VIII complex and fibrinolytic activity are dependent on exercise intensity

1986 ◽  
Vol 60 (6) ◽  
pp. 1917-1922 ◽  
Author(s):  
M. Andrew ◽  
C. Carter ◽  
H. O'Brodovich ◽  
G. Heigenhauser
Keyword(s):  
Steady State ◽  
Factor Viii ◽  
Exercise Test ◽  
Blood Clot ◽  
Venous Blood ◽  
Lactate Concentration ◽  
Cycle Ergometer ◽  
Fibrinolytic System ◽  
Clot Lysis ◽  
Base Line

Components of the factor VIII complex increase and activation of the fibrinolytic system occur during exercise. The relation between the duration and intensity of exercise and the relative changes in the VIII complex and fibrinolytic system have not been previously examined. Five healthy male subjects were exercised with three protocols: a graded progressive exercise test to exhaustion on a cycle ergometer with 50-W increments every 4 min, steady-state exercise, 15 min at 5 and 125 W each, and an acute 30-s maximal exercise test on a cycle ergometer. Venous blood samples were drawn at base line, during the last 30 s of each power output in the graded exercise, at 5-min intervals for the steady-state exercise, and for up to 1 h after completion of exercise in all three protocols. At the maximum exercise intensities, increases in plasma lactate concentration ([La]), O2 uptake, and [H+] were observed. Components of the VIII complex [VIII procoagulant, VIII procoagulant antigen, VIII-related antigen (VIIIR:Ag), VIII ristocetin cofactor activity] abruptly rose at only the highest work intensities, whereas the whole blood clot lysis time began to gradually shorten much earlier at low work intensities. There were no qualitative changes in the factor VIIIR:Ag on crossed immunoelectrophoresis nor was there evidence of thrombin generation as determined by fibrinopeptide A generation. We conclude that during exercise the changes observed in the coagulation and fibrinolytic systems are related to the intensity of the exercise, which is reflected by increases in plasma [La] and [H+], and that the fibrinolytic system is activated before the changes in the VIII complex are observed.

Effect of pH on Muscle Glycolysis during Exercise

1981 ◽  
Vol 61 (3) ◽  
pp. 331-338 ◽  
Author(s):  
J. R. Sutton ◽  
N. L. Jones ◽  
C. J. Toews
Keyword(s):  
Venous Blood ◽  
Lactate Concentration ◽  
Cycle Ergometer ◽  
Plasma Lactate ◽  
Glycogen Depletion ◽  
Vo2 Max ◽  
Muscle Lactate ◽  
Blood Ph ◽  
Plasma Lactate Concentration ◽  
Control Study

1. Five males were studied on three occasions, after oral administration of CaCO3 (control), NH4Cl (acidosis) and NaHCO3 (alkalosis), in a dose of 0.3 g/kg, taken over a 3 h period at rest. The subjects then exercised on a cycle ergometer for 20 min at 33% maximal oxygen uptake (Vo2 max.), followed by 20 min at 66% and at 95% Vo2 max. until exhaustion. 2. Endurance at 95% Vo2 max. was longest with alkalosis (5.44 ± 1.05 min), shortest with acidosis (3.13 ± 0.97 min) and intermediate in the control study (4.56 ± 1.31 min); venous blood pH at exhaustion was 7.33 ± 0.02 (mean ±1 sem), 7.13 ± 0.02 and 7.26 ± 0.02 respectively. 3. Concentrations of plasma lactate at exhaustion were 7.10 ± 0.8 mmol/l 4.0 ± 0.5 and 7.9 ± 0.9 mmol/l in the control, acidosis and alkalosis studies respectively. 4. Muscle lactate increased most from rest to exhaustion with alkalosis to 17.1 ± 2.5 μmol/g and least with acidosis to 12.2 ± 1.4 μmol/g. Muscle glycogen depletion was comparable in control and alkalosis studies. 5. The lower plasma lactate concentration during exercise in acidosis compared with control and alkalosis appears to be due to an inhibition of muscle glycolysis combined with a reduction in lactate efflux from muscle.

O2 uptake kinetics after acetazolamide administration during moderate- and heavy-intensity exercise

1998 ◽  
Vol 85 (4) ◽  
pp. 1384-1393 ◽  
Author(s):  
Barry W. Scheuermann ◽  
John M. Kowalchuk ◽  
Donald H. Paterson ◽  
David A. Cunningham
Keyword(s):  
Energy Demand ◽  
Ventilatory Threshold ◽  
Venous Blood ◽  
Lactate Concentration ◽  
Exponential Model ◽  
Constant Load ◽  
Cycle Ergometer ◽  
Work Rate ◽  
Ergometer Exercise ◽  
Single Response

Inhibition of carbonic anhydrase (CA) is associated with a lower plasma lactate concentration ([La−]pl) during fatiguing exercise. We hypothesized that a lower [La−]plmay be associated with faster O2uptake (V˙o 2) kinetics during constant-load exercise. Seven men performed cycle ergometer exercise during control (Con) and acute CA inhibition with acetazolamide (Acz, 10 mg/kg body wt iv). On 6 separate days, each subject performed 6-min step transitions in work rate from 0 to 100 W (below ventilatory threshold, <V˙eT) or to a V˙o 2 corresponding to ∼50% of the difference between the work rate atV˙eT and peakV˙o 2(>V˙eT). Gas exchange was measured breath by breath. Trials were interpolated at 1-s intervals and ensemble averaged to yield a single response. The mean response time (MRT, i.e., time to 63% of total exponential increase) for on- and off-transients was determined using a two- (<V˙eT) or a three-component exponential model (>V˙eT). Arterialized venous blood was sampled from a dorsal hand vein and analyzed for [La−]pl. MRT was similar during Con (31.2 ± 2.6 and 32.7 ± 1.2 s for on and off, respectively) and Acz (30.9 ± 3.0 and 31.4 ± 1.5 s for on and off, respectively) for work rates <V˙eT. At work rates >V˙eT, MRT was similar between Con (69.1 ± 6.1 and 50.4 ± 3.5 s for on and off, respectively) and Acz (69.7 ± 5.9 and 53.8 ± 3.8 s for on and off, respectively). On- and off-MRTs were slower for >V˙eT than for <V˙eT exercise. [La−]plincreased above 0-W cycling values during <V˙eT and >V˙eT exercise but was lower at the end of the transition during Acz (1.4 ± 0.2 and 7.1 ± 0.5 mmol/l for <V˙eT and >V˙eT, respectively) than during Con (2.0 ± 0.2 and 9.8 ± 0.9 mmol/l for <V˙eT and >V˙eT, respectively). CA inhibition does not affect O2 utilization at the onset of <V˙eT or >V˙eT exercise, suggesting that the contribution of oxidative phosphorylation to the energy demand is not affected by acute CA inhibition with Acz.

scholarly journals Plasma clearance rates of coagulation factors VIII and IX in factor- deficient individuals

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 969-972
Author(s):  
DA Noe ◽  
WR Bell ◽  
PM Ness ◽  
J Levin
Keyword(s):  
Steady State ◽  
Factor Viii ◽  
Clearance Rate ◽  
Plasma Clearance ◽  
Factor Ix ◽  
Base Line ◽  
Clearance Rates ◽  
Plasma Factor ◽  
The Mean ◽  
State Plasma

The plasma clearance rates of factors IX and VIII were determined in patients with hemophilia A and B who had received factor replacement by prolonged, continuous infusion of factor concentrates. The clearance rates were calculated by dividing the factor infusion rates by the steady-state plasma factor activities corrected for base-line factor activities. The mean factor IX clearance rate in eight factor IX- deficient patients was 233 mL/h (range 159 to 340 mL/h). The mean normalized clearance rate was 3.4 mL/h/kg. The mean factor VIII clearance rate in eight factor VIII-deficient patients was 294 mL/h (range 229 to 361 mL/h) and the mean normalized rate was 5.0 mL/h/kg. Both factors show linear relationships between the factor infusion rates and the steady-state plasma factor activities achieved.

Use of arterialized venous blood sampling during incremental exercise tests

1992 ◽  
Vol 73 (3) ◽  
pp. 937-940 ◽  
Author(s):  
P. McLoughlin ◽  
P. Popham ◽  
R. A. Linton ◽  
R. C. Bruce ◽  
D. M. Band
Keyword(s):  
Exercise Test ◽  
Venous Blood ◽  
Normal Subjects ◽  
Work Load ◽  
Cycle Ergometer ◽  
Incremental Exercise ◽  
Exercise Tests ◽  
Incremental Exercise Test ◽  
Arterial Ph ◽  
Incremental Testing

Close agreement between arterialized venous and arterial pH, PCO2, and lactate has previously been demonstrated during steady-state exercise. The purpose of the present study was to compare arterialized venous and arterial pH, PCO2, K+, lactate, pyruvate, and epinephrine during the constantly changing circumstances of an incremental exercise test. Eight normal subjects undertook an incremental exercise test (increasing by 20 W/min) to exhaustion on a cycle ergometer during which simultaneous arterial and arterialized venous samples were drawn over the last 20 s of each work load. Linear regression of arterialized venous on arterial values showed that r varied from 0.97 to 0.99 for the variables examined and, therefore, showed that accurate estimates of arterial values could be made from the arterialized venous results during incremental testing. For many purposes it could be assumed that arterialized venous values equaled arterial values without serious error.

A Unique Recombinant Plasmin Molecule Lacking Kringles 2-5 Possesses Equivalent Hemostatic Safety as Full-Length Human Plasmin.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2028-2028
Author(s):  
Victor J. Marder ◽  
Valery Novokhatny ◽  
Steve Manyak ◽  
Theresa Gruber ◽  
Jennifer Hunt ◽  
...  
Keyword(s):  
Animal Model ◽  
Factor Viii ◽  
Blood Clot ◽  
Plasma Concentrations ◽  
Full Length ◽  
Bleeding Complications ◽  
Clot Lysis ◽  
Serine Protease Domain ◽  
Pre Treatment

Abstract Background: All thrombolytic agents in current clinical use are plasminogen activators (PA). While effective, PA have a downside because of unavoidable and potentially lifethreatening bleeding complications in vulnerable patients. We previously demonstrated a striking margin of hemostatic safety for the “direct-acting” thrombolytic enzyme, plasmin. Now, a novel recombinant derivative of plasmin has been synthesized which lacks kringles 2-5, consisting only of kringle 1 linked to the serine protease domain. Methods: We evaluated escalating dosages of recombinant D (K2-K5) plasmin in a randomized and blinded manner in comparison with molar equivalent dosages of full-length plasmin in an animal model of fibrinolytic hemorrhage. Hemostatic safety was measured by primary bleeding time (PBT) and plasma concentrations of a-2 antiplasmin, factor VIII and fibrinogen. Results: A dose-related nadir in a-2 antiplasmin, factor VIII and fibrinogen followed administration of 4, 6, 8 and 10 mg/kg of D (K2-K5) plasmin, with residual fibrinogen of 65%, 40%, 30% and 0% of initial pre-treatment concentrations. Hemostasis was undisturbed with 4 mg/kg of D (K2-K5) plasmin (mean PBT 2.2 +/- 0.7 min), minimally so at the 6 or 8 mg/kg dosages (5 +/- 2.9 and 4.4 +/- 2.2 min). Hemostasis was markedly abnormal at the purposefully toxic 10 mg/kg dose (12.8 +/- 18.8 min), in association with complete depletion of plasma fibrinogen. Comparison of agents at 10 mg/kg showed no difference, but at 4 mg/kg (2-4-fold more than needed for efficacy), D (K2-K5) plasmin showed slightly less prolongation of PBT (2.2 +/- 0.7 vs 3.3 +/- 2.1 min). Both agents were equally potent for in vitro whole blood clot lysis, indicating that the safety advantage of D (K2-K5) plasmin was not due to decreased fibrinolytic activity. Conclusions: Recombinant D (K2-K5) plasmin has equivalent hemostatic safety as full-length plasmin in an animal model of fibrinolytic hemorrhage and warrants evaluation in clinical thrombotic disease.

Factors influencing hydrogen ion concentration in muscle after intense exercise

1988 ◽  
Vol 65 (5) ◽  
pp. 2080-2089 ◽  
Author(s):  
J. M. Kowalchuk ◽  
G. J. Heigenhauser ◽  
M. I. Lindinger ◽  
J. R. Sutton ◽  
N. L. Jones
Keyword(s):  
Venous Blood ◽  
Lactate Concentration ◽  
Quadriceps Muscle ◽  
Cycle Ergometer ◽  
Ion Concentration ◽  
Strong Ion Difference ◽  
Hydrogen Ion Concentration ◽  
Factors Influencing ◽  
Venous Pco2 ◽  
Muscle Biopsies

To assess the importance of factors influencing the resolution of exercise-associated acidosis, measurements of acid-base variables were made in nine healthy subjects after 30 s of maximal exercise on an isokinetic cycle ergometer. Quadriceps muscle biopsies (n = 6) were taken at rest, immediately after exercise, and at 3.5 and 9.5 min of recovery; arterial and femoral venous blood were sampled (n = 3) over the same time. Intracellular and plasma inorganic strong ions were measured by neutron activation and ion-selective electrodes, respectively; lactate concentration ([La-]) was measured enzymatically, and plasma PCO2 and pH were measured by electrodes. Immediately after exercise, intracellular [La-] increased to 47 meq/l, almost fully accounting for a reduction in intracellular strong ion difference ([SID]) from 154 to 106 meq/l. At the same time, femoral venous PCO2 increased to 100 Torr and plasma [La-] to 9.7 meq/l; however, plasma [SID] did not change because of a concomitant increase in inorganic [SID] secondary to increases in [K+], [Na+], and [Ca2+]. During recovery, muscle [La-] fell to 26 meq/l by 9.5 min; [SID] remained low (101 and 114 meq/l at 3.5 and 9.5 min, respectively) due almost equally to the elevated [La-] (30 and 26 meq/l) and reductions in [K+] (from 142 meq/l at rest to 123 and 128 meq/l). Femoral venous PCO2 rose to 106 Torr at 0.5 min postexercise and fell to resting values at 9.5 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of erythrocytes to the control of the electrolyte changes of exercise

1991 ◽  
Vol 69 (7) ◽  
pp. 984-993 ◽  
Author(s):  
R. S. McKelvie ◽  
M. I. Lindinger ◽  
G. J.F. Heigenhauser ◽  
N. L. Jones
Keyword(s):  
Venous Blood ◽  
Lactate Concentration ◽  
Exercise Bout ◽  
Cycle Ergometer ◽  
Hydrogen Ion ◽  
Concentration Difference ◽  
Arterial Blood ◽  
Ion Movement ◽  
Net Flux ◽  
Healthy Males

Five healthy males performed four 30-s bouts of maximal isokinetic cycling with 4 min rest between each bout. Arterial and femoral venous blood was sampled during and for 90 min following exercise. During exercise, arterial erythrocyte [K+] increased from 117.0 ± 6.6 mequiv./L at rest to 124.2 ± 5.9 mequiv./L after the second exercise bout. Arterial erythrocyte [K+] returned to the resting values during the first 5 min of recovery. No significant change was observed in femoral venous erythrocyte [K+]. Arterial erythrocyte lactate concentration ([Lac−]) increased during exercise from 0.2 ± 0.1 mequiv./L peaking at 9.5 ± 1.5 mequiv./L at 5 min of recovery, after which the values returned to control. Femoral venous erythrocyte [Lac−] changed in a similar fashion. Arterial erythrocyte [Cl−] rose during exercise to 76 ± 3 mequiv./L and returned to resting values (70 ± 2 mequiv./L) by 25 min recovery. During exercise there was a net flux of Cl− into the erythrocyte. We conclude that erythrocytes are a sink for K+ ions leaving working muscles. Furthermore, erythrocytes function to transport Lac− from working muscle and reduce plasma acidosis by uptake of Cl−. The erythrocyte uptake of K+, Lac−, and Cl− helps to maintain a concentration difference between plasma and muscle, facilitating diffusion of Lac− and K+ from the interstitial space into femoral venous plasma.Key words: isokinetic cycle ergometer, ion movement, hydrogen ion, cell volume, arterial blood.

THE EFFECT OF PHYSICAL EXERCISE ON MONOCYTE FUNCTION, COAGULATION FACTORS, FIBRINOLYSIS AND PLATELETS

1987 ◽  
Author(s):  
B Ûsterud ◽  
J B Hansen ◽  
J O Olsen ◽  
L Wilsgård
Keyword(s):  
Blood Cell ◽  
Whole Blood ◽  
Cell Activation ◽  
Specific Activity ◽  
Blood Clot ◽  
Fibrinolytic System ◽  
Clot Lysis ◽  
Long Distance ◽  
National Team

Over a 2 years period, the Norwegian national team of cross country skiers, have been tested after strenous championships as well as before and after regular training.Finishing a 50 km race generated a rise of white cells from 5.4 ± 1.0 to 19.3 ± 3.7 × 109 /I (n=14). The mobilization of new and more sensitive white cells may explain the resultant rise in monocyte response to stimuli in vitro after the race. Thus, monocytes from blood incubated with 2 ng/ml blood, drawn from the athletes just after finishing the 50 km race, possessed 6-7 fold higher specific activity of thromboplastin than monocytes from blood drawn and stimulated in a rest-period. There was a positive correlation between the inverse level of F. VII in plasma of the skiers after the race and the monocyte response to stimuli in vitro as expressed by the level of thromboplastin. Activated monocytes with exposed thromboplastin are probably pulling out F. VII from the circulation just as seen in patients with gram negative septicaemia.A group of long distance runners were also tested after strenous jogging. High monocyte response to stimuli in vitro was associated with extremely active platelets that aggregated spontaneously after drawing the blood into heparin and tested it in a whole blood aggregometer. Those individuals with very active monocytes and platelets had also an extremely activation of their fibrinolytic system as judged by whole blood clot lysis. In contrast, everyone with low cell activation had hardly any change in their fibrinolytic activity after strenous running.The clear trend in this study was that almost everyone of our top athletes had a very depressed blood-cell activation system as compared to non athletes. Low blood cell activation in vivo was also associated with a low induction of the fibrinolytic system.

scholarly journals Plasma clearance rates of coagulation factors VIII and IX in factor- deficient individuals

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 969-972 ◽  
Author(s):  
DA Noe ◽  
WR Bell ◽  
PM Ness ◽  
J Levin
Keyword(s):  
Steady State ◽  
Factor Viii ◽  
Clearance Rate ◽  
Plasma Clearance ◽  
Factor Ix ◽  
Base Line ◽  
Clearance Rates ◽  
Plasma Factor ◽  
The Mean ◽  
State Plasma

Abstract The plasma clearance rates of factors IX and VIII were determined in patients with hemophilia A and B who had received factor replacement by prolonged, continuous infusion of factor concentrates. The clearance rates were calculated by dividing the factor infusion rates by the steady-state plasma factor activities corrected for base-line factor activities. The mean factor IX clearance rate in eight factor IX- deficient patients was 233 mL/h (range 159 to 340 mL/h). The mean normalized clearance rate was 3.4 mL/h/kg. The mean factor VIII clearance rate in eight factor VIII-deficient patients was 294 mL/h (range 229 to 361 mL/h) and the mean normalized rate was 5.0 mL/h/kg. Both factors show linear relationships between the factor infusion rates and the steady-state plasma factor activities achieved.

Differential Role of Components of the Fibrinolytic System in the Formation and Removal of Thrombus Induced by Endothelial Injury

1999 ◽  
Vol 81 (04) ◽  
pp. 601-604 ◽  
Author(s):  
Hiroyuki Matsuno ◽  
Osamu Kozawa ◽  
Masayuki Niwa ◽  
Shigeru Ueshima ◽  
Osamu Matsuo ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Thrombus Formation ◽  
Endothelial Injury ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Clot Lysis ◽  
Wild Type ◽  
Type Plasminogen Activator ◽  
Pai 1

SummaryThe role of fibrinolytic system components in thrombus formation and removal in vivo was investigated in groups of six mice deficient in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), or plasminogen activator inhibitor-1 (PAI-1) (u-PA-/-, t-PA-/- or PAI-1-/-, respectively) or of their wild type controls (u-PA+/+, t-PA+/+ or PAI-1+/+). Thrombus was induced in the murine carotid artery by endothelial injury using the photochemical reaction between rose bengal and green light (540 nm). Blood flow was continuously monitored for 90 min on day 0 and for 20 min on days 1, 2 and 3. The times to occlusion after the initiation of endothelial injury in u-PA+/+, t-PA+/+ or PAI-1+/+ mice were 9.4 ± 1.3, 9.8 ± 1.1 or 9.7 ± 1.6 min, respectively. u-PA-/- and t-PA-/- mice were indistinguishable from controls, whereas that of PAI-1-/- mice were significantly prolonged (18.4 ± 3.7 min). Occlusion persisted for the initial 90 min observation period in 10 of 18 wild type mice and was followed by cyclic reflow and reocclusion in the remaining 8 mice. At day 1, persistent occlusion was observed in 1 wild type mouse, 8 mice had cyclic reflow and reocclusion and 9 mice had persistent reflow. At day 2, all injured arteries had persistent reflow. Persistent occlusion for 90 min on day 0 was observed in 3 u-PA-/-, in all t-PA-/- mice at day 1 and in 2 of the t-PA-/-mice at day 2 (p <0.01 versus wild type mice). Persistent patency was observed in all PAI-1-/- mice at day 1 and in 5 of the 6 u-PA-/- mice at day 2 (both p <0.05 versus wild type mice). In conclusion, t-PA increases the rate of clot lysis after endothelial injury, PAI-1 reduces the time to occlusion and delays clot lysis, whereas u-PA has little effect on thrombus formation and spontaneous lysis.

Sign in / Sign up

Export Citation Format

Share Document