(Stroke. 2000;31:1269.)
© 2000 American Heart Association, Inc.
Original Contributions |
The Effect of Acute Ingestion of a Large Dose of Alcohol on the Hemostatic System and Its Circadian Variation
From the Department of Neurology, Oulu University Hospital (H.N., M.H.), Oulu, Finland; and the Department of Clinical Chemistry, Helsinki University Hospital (M.S.), Department of Clinical Physiology, Karolinska Institutet at Huddinge University Hospital (G.B.). and Department of Neurology, Helsinki University Hospital (M.K.), Helsinki, Finland.
Correspondence to Prof Matti Hillbom, MD, Department of Neurology, Oulu University Hospital, FIN-90220, Oulu, Finland. E-mail matti.hillbom{at}oulu.fi
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Background and Purpose—Heavy binge drinking may trigger the onset of embolic stroke and acute myocardial infarction, but the underlying mechanisms are unclear. The effects of binge drinking on the hemostatic system and its circadian variation have not been investigated. We investigated the effects of an acute intake of a large dose of alcohol (1.5 g/kg).
Methods—Twelve healthy, nonsmoking men participated in sessions where they were served ethanol in fruit juice or served fruit juice alone and, lying in a supine position, were followed up for 12 to 24 hours. The treatments were randomized and separated from each other by a 1-week washout period. Blood and urine were collected for hemostatic measurements.
Results—The urinary excretion of the platelet
thromboxane A2 metabolite
2,3-dinor-thromboxane B2 was significantly
(P<0.05) greater during the night after an evening
intake of alcohol than during the control night. A smaller increase was
observed during the daytime after an intake of alcohol in the morning.
The effects on the endothelial prostacyclin metabolite
2,3-dinor-6-ketoprostaglandin F1
excretion
were negligible. A 7-fold increase in plasminogen
activator inhibitor 1 activity was observed
after both morning (P<0.05) and evening
(P<0.01) intakes of alcohol.
Conclusions—This is the first study to suggest that acute ingestion of a relatively large but tolerable dose of alcohol transiently enhances thromboxane-mediated platelet activation. The observations also demonstrate alcohol-induced changes in the normal circadian periodicity of the hemostatic system in subjects not accustomed to consumption of alcohol.
Key Words: alcohol • circadian rhythm • hemostasis • prostaglandins • thrombolysis
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Many studies indicate that regular light-to-moderate alcohol drinking protects against coronary heart disease.1 Some studies also suggest that alcohol protects against ischemic stroke of atherothrombotic origin2 and peripheral arterial disease.3 These effects have been ascribed to the antiatherogenic and antithrombotic actions of ethanol or some other components of alcoholic beverages. However, some investigations also suggest that heavy alcohol consumption promotes the development of carotid arterial atherosclerosis and that heavy binge drinking may precipitate fatal myocardial infarction and embolic stroke.4 5 6
Atherogenesis and thrombogenesis may both be influenced by drinking patterns. Acute heavy drinking may exert different effects compared with those of moderate regular drinking. The favorable effects of alcohol consumption on the lipid profile were recently observed to be independent of the drinking pattern in moderate-to-heavy drinkers.7 However, the effects on thrombogenesis were not reported and have yet to be investigated.
The activities of some parameters of the hemostatic system show significant circadian variation. The onsets of myocardial infarction and ischemic stroke also show circadian variation, with a peak at the time when people wake up and become active.8 9 10 11 12 This phenomenon has been speculated to result from the circadian periodicity of the hemostatic system.8 9 10 11 12 13 14 15 16 In fact, increased platelet aggregability9 and decreased fibrinolytic activity13 14 15 occur in the morning. The former has been observed in healthy volunteers after getting out of bed but not during steady bed rest, which suggests that the act of getting out of bed is responsible for the effect,9 16 whereas the morning decrease in fibrinolytic activity has been observed to be attenuated by keeping the volunteers in upright posture.17 The effects of acute alcohol ingestion on platelet aggregability and fibrinolytic activity in relation to the circadian periodicity of the hemostatic system have not yet been investigated.18
To find out whether acute ingestion of a large dose of alcohol influences the hemostatic system and its circadian pattern, 12 healthy human volunteers were randomly assigned to ingest a large dose of ethanol in fruit juice or fruit juice alone either in the morning or in the evening and were then followed up in a supine position for 12 hours. We measured plasminogen activator inhibitor 1 (PAI-1) activity, excretion in urine of platelet thromboxane and endothelial prostacyclin 2,3-dinor-metabolites, serum thromboxane B2 which reflects the capacity of platelets to form thromboxane in vitro and platelet aggregability ex vivo.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Subjects and Study Design
Twelve healthy, nonsmoking men aged 20 to 39 years volunteered for the trial. They were all nonobese (body mass index 23.8±1.6 [mean±SD]), infrequent light drinkers (1 to 5 drinks during weekends or less frequently), and they had abstained from alcoholic beverages and drugs for 1 week before the trial. None had arterial hypertension, heart disease, hematological disorders, hyperlipemia, diabetes, or any other serious disease in their history, and none were on regular medication. After a full explanation of the purpose, nature, and risks of the study, written informed consent was obtained from each. The study protocol was approved by the Ethical Committee of the Helsinki University Central Hospital. The investigation conforms with the principles outlined in the Declaration of Helsinki.
Each subject participated in 3 sessions, 2 ethanol sessions and 1 control session. The order of the sessions for each individual was randomized, and there was a 1-week washout period between the sessions. The 3 arrangements of treatment and control were equally distributed. The subjects were not allowed to eat for 6 hours before the start of the session, and they served as their own controls. The alcohol sessions started either at 7:00 PM or at 8:00 AM and lasted for 12 hours. If the session started in the morning, the subjects had to arrive in the hospital on the preceding evening and spend the night sleeping in hospital beds. The control session always started in the evening and lasted for 24 hours, including both the control night and the control day. During every session the subjects were awakened at 7 AM. During the daytime they lay in bed, reading books or watching TV. They were allowed to go to the toilet but not move otherwise.
All the sessions were started by taking baseline blood samples and by voiding the urinary bladder. From 7:30 until 10:00 PM or from 8:30 until 11:00 AM, the subjects received half-hourly drinks containing either fruit juice (not including grapefruit) or, during the ethanol session, an equal volume of a mixture of the same fruit juice and ethanol (2 mol/L solution). The time schedule of drinking and the total amount of ethanol (1.5 g/kg of body weight) were chosen to provoke a tolerable but moderately severe intoxication. During the control session, the subjects were given carbohydrate-rich snacks together with the fruit juice to balance their calorie intake, but no meals were served. Accordingly, during both the alcohol and the control sessions the total energy intake was kept constant (14.8 kcal/kg per 12 hours).
Blood and Urine Sampling
Blood samples were taken at 3-hour intervals, starting either at
7 PM or at 8 AM After voiding the bladder,
urine was collected for 12 hours. After preparation, the plasma and
urine samples were frozen at -70°C for subsequent testing.
Platelet Aggregation
Platelet aggregation was measured by Born’s
method.19 Blood was collected with minimal stasis via a
plastic cannula into tubes containing 3.8% sodium citrate. To obtain
platelet-rich plasma (PRP) and platelet-poor plasma (PPP), the
blood samples were centrifuged at 330g for 10
minutes and at 1500g for 10 minutes. PPP was used to adjust
the platelet count of PRP to 250x109/L.
Platelet aggregations were measured with a dual-channel
aggregometer (Chrono-Log, Coulter Electronics Ltd), starting 45 minutes
after the blood sampling. Arachidonic acid (AA; 1
mmol/L, Sigma Chemical Co) and collagen (5 µg/mL, Hormon Chemie GmbH)
were used to stimulate platelets in PRP. The reaction was stopped
by 1 mmol/L HCl after 5 minutes. The aggregation results were
expressed as the maximum percentage change in light transmittance
during the 5-minute period.
Determination of Plasminogen Activator
Inhibitor Activity
Citrated plasma was used to analyze PAI-1 activity
(units per milliliter). The blood samples were immediately put into
crushed ice and centrifuged for 20 minutes at 4°C and
at 1500g. PAI-1 was measured as duplicate determinations
with a colorimetric assay (Stachrom PAI,
Diagnostica Stago) in the kinetic mode using an automatic
coagulometer (Thrombolyzer, Behnk Elektronic GmbH & Co) equipped with a
chromogenic channel.
Determination of Prostanoids and Other Laboratory
Parameters
Urine was collected for the determination of
2,3-dinor-6-ketoprostaglandin F1
(2,3-dinor-PGF1) and 2,3-dinor-
thromboxane B2
(2,3-dinor-TXB2). The samples were
analyzed by a stable isotope dilution assay with a mass
spectrometer (Finnigan MAT 4500) coupled to a gas
chromatographer (Varian Vista 6000), as previously
described.20 21 The urinary excretion of prostanoids was
related to the amount of creatinine excreted.
The capacity of platelets to form thromboxane was measured as serum thromboxane B2 (TXB2). For the measurement of serum TXB2, 2 mL of blood was drawn into a glass tube and incubated at 37°C for 60 minutes to allow clotting. The amount of TXB2 was measured from the serum by ELISA (Cayman Co).
Creatinine in urine and blood ethanol were determined by routine liquid chromatographic and gas-liquid chromatographic techniques, respectively. The ingestion of 1.5 g/kg ethanol in fruit juice within 2.5 hours resulted in peak blood concentrations of 32.3±4.4 mmol/L (95% CI 29.3 to 35.2) and 31.0±9.3 mmol/L (95% CI 28.7 to 33.4) in the evening and in the morning, respectively. These values correspond to blood levels that cause a moderately severe but tolerable acute alcoholic intoxication (1.5/1000) in a subject who has not developed central nervous system tolerance to alcohol. The time needed to eliminate the dose of alcohol from the body was more than 12 hours.
Statistical Methods
The results were expressed as mean±SEM, SD, or 95% CI. The
time-dependent changes, including the testing of trend during each
session, were compared by repeated-measures ANOVA, either as a 1-way
analysis for a single session or as a 2-way analysis
between the sessions. A paired t test was also used to test
the differences in urinary excretion of prostanoids and the
Wilcoxon signed rank test to test the differences in plasma
PAI-1 values between the control and alcohol sessions. The associations
between the different parameters were calculated by simple
regression. All the analyses were made with Statview II or
SuperAnova (Abacus Concepts).
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Alcohol drinking in the evening produced a significant increase in urinary excretion of 2,3-dinor-TXB2 (Figure 1
). The mean difference was 13.0
pg/µmol creatinine (95% CI 6.2 to 19.8,
P<0.01) between the values of the night (from 7
PM to 7 AM) following
alcohol ingestion and those of the night following fruit juice
ingestion (control night). Alcohol drinking during the daytime also
caused an increase. In contrast, the urinary excretion of
2,3-dinor-PGF1 was similar during the day
(from 8 AM to 8 PM) and the
night, irrespective of whether alcohol was consumed or not. The urinary
excretion of 2,3-dinor-TXB2 decreased during the
control night compared with the control day (mean difference 3.3
pg/µmol creatinine, 95% CI 1.0 to 5.7,
P<0.01). The urinary excretion of
2,3-dinor-TXB2 correlated positively with the
serum TXB2 values
(r2=0.18, slope 0.20, 95% CI 0.01 to
0.40, P<0.05). The correlation was not significantly
influenced by alcohol.
|
Because alcohol ingestion could have influenced the urinary excretion
of creatinine, we also calculated urinary excretion of the
prostaglandin metabolites per total volume urine excreted
to avoid bias due to a possible effect of alcohol on
creatinine excretion
(Table). A significant effect of
alcohol drinking was confirmed. During the evening drinking session the
mean difference in urinary excretion of TXB2 was
78.6 ng/12 h (95% CI 21.1 to 136.0, P<0.05). The urinary
excretion of 2,3-dinor-TXB2 expressed in this way
also correlated positively with the serum TXB2
values (r2=0.20, slope 0.22, 95% CI
0.1 to 0.35, P<0.01).
|
The platelet aggregability observed during the daytime (control
session) showed significant variation over time when tested with both
AA (P<0.05) and collagen (P<0.001). During the
control session, platelet aggregability decreased from morning to
afternoon, as was expected (Figure 2). It
decreased from 8 AM until 2
PM, after which it increased again. A comparison
between the values obtained during the control night and the control
day also showed significant heterogeneity in
collagen-induced aggregation (P<0.05) but not in AA-induced
aggregation (P>0.05). The differences in the curves for the
alcohol and control periods were not statistically significant,
although drinking of alcohol tended to inhibit the daytime decrease in
platelet aggregability.
|
) and control (•)
sessions. Aggregations were induced by AA (1 mmol/L) and collagen
(5 µg/mL).
PAI-1 activity was significantly increased by the intake of alcohol
(Figure 3). An increase was observed
irrespective of whether the alcohol was ingested in the morning
(P<0.05) or in the evening (P<0.01). The
alcohol-induced increase was transient and peaked at about 3 hours
after the discontinuation of drinking. Thereafter, PAI-1 started to
decrease, and it decreased rapidly until the end of the session.
Unfortunately, we have no data to show the levels shortly after the end
of each session. We did not follow the PAI-1 value after alcohol had
been eliminated from the blood. PAI-1 showed circadian variation during
the control session, as was expected. The PAI-1 levels were lowest in
the evening and remained higher from 1 AM until 5
PM.
|
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The main finding of our experiment was the significant increase in urinary excretion of 2,3-dinor-TXB2 in the absence of a simultaneous change in urinary excretion of 2,3-dinor-PGF1
after acute ingestion of a
large dose of alcohol. Another interesting finding was a significant
alcohol-induced increase in plasma PAI-1 activity. The increased urinary excretion of 2,3-dinor-TXB2 reflects increased platelet activation in vivo.22 23 Platelets are activated in the arterial circulation, particularly at sites that are stenosed or ulcerated by atherosclerosis, but also at sites of bifurcation and sharp bends in the absence of atherosclerosis. The extent of activation could be influenced by hemodynamic factors, such as the velocity of blood flow and vasospasm.
The absence of a simultaneous change in urinary excretion
of 2,3-dinor-PGF1 suggests that factors
capable of influencing endothelial prostacyclin were
not significantly stimulated in subjects who were kept in a supine
position. Unfortunately, we did not measure markers of
endothelial activation, such as von
Willebrand’s factor or thrombomodulin. However, other
investigators have found these 2 markers to be uninfluenced or
negatively associated with alcohol intake.24 25 26 The
subjects were kept supine during the day and were asleep during the
night. In fact, it has been shown that the endothelial
formation of prostacyclin is low at rest but increases during physical
activity.27 28
Acute drinking of a large dose of alcohol produces tachycardia and increases blood flow. The effect is transient and dose dependent, and may lead to platelet activation because of increased shear. The increased urinary excretion of 2,3-dinor-TXB2 in our experiment was possibly due to acute platelet activation caused by a change in turbulence and shear associated with an alcohol-induced rapid increase in blood flow.
Alcohol drinking increases urinary excretion of 2,3-dinor-TXB2 dose dependently. In this study, a rather large dose of alcohol was ingested. We have recently shown that acute drinking of a moderate dose of alcohol does not increase urinary excretion of 2,3-dinor-TXB2.28A Our findings seem to be reliable because the levels of prostanoids did not markedly deviate from those reported in physiological conditions.29
The rapid increase in PAI-1 activity after an acute ingestion of a large dose of alcohol suggests decreased fibrinolytic activity. Unfortunately, we did not measure plasminogen activator (tPA) activity, which is the most important parameter reflecting fibrinolytic activity. However, Hendriks et al30 have shown that an acute intake of even a moderate dose of beer, spirits, or wine, if ingested with an evening meal, causes a significant decrease of tPA activity. Our observations indicate that the alcohol-induced increase of PAI-1 activity occurs to the same extent during the night and the day, and that an acute intake of a relatively large dose of alcohol disturbs the normal circadian pattern of PAI-1 activity. Accordingly, it is likely that the decrease of fibrinolytic activity observed by Hendriks et al30 also occurs irrespective of whether alcohol is ingested in the evening or in the morning.
A high shear and a sudden increase in shear could cause the activation of circulating platelets.31 This may not be a harmful effect if the vessels are nonatheromatous. However, a rapid increase in shear-induced platelet activation may aggravate the imbalance between thromboxane and prostacyclin at sites of severe atherosclerosis, because it has been shown that prostacyclin synthesis is deficient in atherosclerotic carotid plaques.32 Such an imbalance could rapidly develop during heavy alcoholic intoxication and lead to local thrombus formation if not simultaneously compensated for by enhanced prostacyclin formation. Because fairly heavy physical activity is needed to stimulate prostacyclin formation,27 bed rest and severe alcoholic intoxication could be a harmful combination for individuals with atherosclerotic arteries. In addition, sleep apneas are aggravated by alcohol and may precipitate atrial fibrillation.33 Acute intake of large doses of alcohol by those who snore and experience sleep apnea may therefore be detrimental. Drinking of alcohol may promote thrombogenesis, and atrial fibrillation may detach emboli from intracardiac thrombi. Palomäki and Kaste34 have already observed increased morning production of platelet thromboxane B2 in subjects suffering from the obstructive sleep apnea syndrome.
The sharp increase of PAI-1 activity caused by acute alcohol intake could result in a transient decrease of fibrinolysis. PAI-1 is released into the vasculature by platelets and endothelial cells. It has recently been shown that the thrombolysis resistance of platelet-rich thrombi is largely due to the presence of PAI-1.35 Accordingly, the increase of PAI-1 activity in vivo by moderate-to-heavy acute alcohol intake suggests that alcohol ingestion could transiently enhance thrombolysis resistance and thereby retard lysis of the already-formed thrombi. However, the effect seems to be rapidly compensated for,30 and regular alcohol intake results in enhanced fibrinolytic activity.36 37 In vitro experiments indicate enhancement of fibrinolysis by alcohol,38 39 but the significance of such findings with regard to alcohol intake in humans is unclear.
The present study is the first to show effects of acute heavy alcohol ingestion on urinary excretion of prostanoids. The increase in the urinary excretion of 2,3-dinor-TXB2 by alcohol intake, a parameter of platelet function in vivo, was modest compared with the effects observed in clinical cardiovascular disease causing signs and symptoms.40 41 None of our healthy volunteers showed signs or symptoms of any cardiovascular disease, nor did they report any adverse events after drinking the relatively large dose of alcohol. Heavy drinkers who suffer a stroke after binge drinking certainly have other factors that predispose to stroke, such as underlying atherosclerotic lesions and cardiac abnormalities. Our findings could be among those which contribute, but alcohol drinking may cause also other effects that are still more important and need to be identified.
Taken together, the present results indicate that acute ingestion of a relatively large but tolerable dose of alcohol results in a marked elevation of plasma PAI-1 activity and a modest increase of urinary excretion of 2,3-dinor-TXB2. The effects seem to be independent of the circadian variation of the hemostatic system and may favor thrombogenesis. The circadian variation in hemostatic factors that maintains resistance to thrombosis in healthy men during sleep seems to be disturbed by acute heavy drinking of alcohol. Therefore, heavy drinking in the evening before going to bed could be more hazardous than heavy drinking during the daytime.
|
Acknowledgments |
|---|
This study was supported by the Oulu Medical Research Foundation (Drs Numminen and Hillbom). We wish to thank Mrs Saija Eirola for technical assistance.
Received November 2, 1999; revision received March 17, 2000; accepted March 17, 2000.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
1. Rimm EB, Klatsky A, Grobbee D, Stampfer MJ. Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits? BMJ. 1996;312:731–736.
2. Camargo CA Jr. Case-control and cohort studies of moderate alcohol consumption and stroke. Clin Chem Acta. 1996;246:107–119.[Medline] [Order article via Infotrieve]
3.
Camargo CA Jr, Stampfer MJ, Glynn RJ, Gaziano JM,
Manson JE, Goldhaber SZ, Hennekens CH. Prospective study of moderate
alcohol consumption and risk of peripheral
arterial disease in US male physicians.
Circulation. 1997;95:577–580.
4.
Kiechl S, Willeit J, Rungger G, Egger G, Oberhollenzer
F, Bonora E, for the Bruneck Study Group. Alcohol consumption and
atherosclerosis: what is the relation? Prospective
results from the Bruneck Study. Stroke. 1998;29:900–907.
5.
Kauhanen J, Kaplan GA, Goldberg DE, Salonen JT. Beer
binging and mortality: results from the Kuopio ischaemic heart disease
risk factor study, a prospective population based study.
BMJ. 1997;315:846–851.
6.
Hillbom M, Numminen H, Juvela S. Recent heavy drinking
of alcohol and embolic stroke. Stroke. 1999;30:2307–2312.
7. Rakic V, Puddey IB, Dimmitt SB, Burke V, Beilin LJ. A controlled trial of the effects of pattern of alcohol intake on serum lipid levels in regular drinkers. Atherosclerosis. 1998;137:243–252.[Medline] [Order article via Infotrieve]
8. Muller JE, Stone PH, Turi ZG, Rutherford JD, Czeisler CA, Parker C, Poole WK, Passamani E, Roberts R, Robertson T, Sobell BE, Willerson JT, Branwald E, and the MILIS Study Group. Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med. 1985;313:1315–1322.[Abstract]
9. Tofler GH, Brezinski D, Schafer AI, Czeisler CA, Rutherford JD, Willich SN, Gleason RE, Williams GH, Muller JE. Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death. N Engl J Med. 1987;316:1514–1518.[Abstract]
10.
Marler JR, Price TR, Clark GL, Muller JE, Robertson T,
Mohr JP, Hier DB, Wolf PA, Caplan LR, Foulkes MA. Morning increase in
onset of ischemic stroke. Stroke. 1989;20:473–476.
11. Haapaniemi H, Hillbom M, Numminen H, Juvela S, Palomäki H, Kaste M. Early-morning increase in the onset of ischemic stroke. Cerebrovasc Dis. 1992;2:282–286.
12. Torun S, Özdemir G. Very early morning increase in onset of ischemic stroke. Ann Saudi Med. 1995;14:201–203.
13. Andreotti F, Davies GJ, Hackett DR, Khan MI, De Bart ACW, Aber VR, Maseri A, Kluft C. Major circadian fluctuations in fibrinolytic factors and possible relevance to time onset of myocardial infarction, sudden cardiac death and stroke. Am J Cardiol. 1988;62:635–637.[Medline] [Order article via Infotrieve]
14. Kluft C, Jie AF, Rijken DC, Verheijen JH. Daytime fluctuations in blood of tissue-type plasminogen activator (t-PA) and its fast-acting inhibitor (PAI-1). Thromb Haemost. 1988;59:329–332.[Medline] [Order article via Infotrieve]
15.
Angleton P, Chandler WL, Schmer G. Diurnal variation of
tissue-type plasminogen activator and its rapid
inhibitor (PAI-1). Circulation. 1989;79:101–106.
16. Rosenfeld BA, Faraday N, Campbell D, Sakima N, Bell W. The effects of bedrest on circadian changes in hemostasis. Thromb Haemost. 1994;72:281–284.[Medline] [Order article via Infotrieve]
17. Kofoed KF, Gleerup G, Hedman C, Winther K. The circadian variation in fibrinolytic activity is not related to posture. Thromb Res. 1994;73:447–450.[Medline] [Order article via Infotrieve]
18. Renaud SC, Ruf J-C. Effects of alcohol on platelet functions. Clin Chim Acta. 1996;246:77–89.[Medline] [Order article via Infotrieve]
19. Born GVR. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature. 1962;194:927–929.[Medline] [Order article via Infotrieve]
20. Falardeau P, Oates JA, Brash AR. Quantitative analysis of two dinor urinary metabolites of prostaglandin I2. Anal Biochem. 1981;115:359–367.[Medline] [Order article via Infotrieve]
21. Lawson JA, Brash AR, Doran J, FitzGerald GA. Measurement of urinary 2,3-dinor thromboxane B2 and thromboxane B2 using bonded-phase phenylboronic acid columns and capillary gas chromatography–negative-ion chemical ionization mass spectrometry. Anal Biochem. 1985;150:463–470.[Medline] [Order article via Infotrieve]
22. Patrono C, Ciabattoni G, Pugliese F, Pierucci A, Blair IA, FitzGerald GA. Estimated rate of thromboxane secretion into the circulation of normal humans. J Clin Invest. 1986;77:590–594.
23. Catella F, FitzGerald GA. Paired analysis of urinary thromboxane B2 metabolites in humans. Thromb Res. 1987;47:647–656.[Medline] [Order article via Infotrieve]
24. Conlan MG, Folsom AR, Finch A, Davis CE, Sorlie P, Marcucci G, Wu KK. Associations of factor VIII and von Willebrand factor with age, race, sex, and risk factors for atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study. Thromb Haemost. 1993;70:380–385.[Medline] [Order article via Infotrieve]
25. Pellegrini N, Pareti FI, Stabile F, Brusamolino A, Simonetti P. Effect of moderate consumption of red wine on platelet aggregation and haemostatic variables in healthy volunteers. Eur J Clin Nutr. 1996;50:209–213.[Medline] [Order article via Infotrieve]
26. Mihara H, Murai A, Handa K, Saku K, Shirai K, Tanaka K, Arakawa K. Thrombomodulin levels in patients with coronary artery disease. Artery. 1997;22:293–308.[Medline] [Order article via Infotrieve]
27.
Wennmalm Å, FitzGerald GA. Excretion of prostacyclin
and thromboxane A2 metabolites during
leg exercise in man. Am J Physiol. 1988;255:H15–H18.
28. Chen M-F, Hsu H-C, Lee Y-T. Effects of acute exercise on the changes of lipid profiles and peroxides, prostanoids, and platelet activation in hypercholesterolemic patients before and after treatment. Prostaglandins. 1994;48:157–174.[Medline] [Order article via Infotrieve]
28. Numminen H, Kobayashi M, Uchiyama S, Iwata M, Ikeda Y, Riutta A, Syrjälä M, Kekomäki R, Hillborn M. Effects of alcohol and the evening meal on shear-induced platelet aggregation and urinary excretion of prostanoids. Alcohol Alcohol. In press.
29. Wennmalm Å, Benthin G, Granström EF, Persson L, Winell S. 2,3-dinor metabolites of thromboxane A2 and prostacyclin in urine from healthy human subjects: diurnal variation and relation to 24h excretion. Clin Sci. 1992;83:461–465.[Medline] [Order article via Infotrieve]
30.
Hendriks HFJ, Veenstra J, Velthuis-te Wierik EJM,
Schaafsma G, Kluft C. Effect of moderate dose of alcohol with evening
meal on fibrinolytic factors. BMJ. 1994;308:1003–1006.
31.
Holme PA, Ørvim U, Hamers MJAG, Solum NO,
Brosstad FR, Barstad RM, Sakariassen KS. Shear-induced platelet
activation and platelet microparticle formation at blood flow
conditions as in arteries with a severe stenosis.
Arterioscler Thromb Vasc Biol. 1997;17:646–653.
32.
Rush DS, Kerstein MD, Bellan JA, Knoop SM, Mayeux PR,
Hyman AL, Kadowitz PJ, McNamara DB. Prostacyclin. Thromboxane
A2, and prostaglandin
E2 formation in atherosclerotic human carotid
artery. Arteriosclerosis. 1988;8:73–78.
33. Miller WP. Cardiac arrhythmias and conduction disturbances in the sleep apnea syndrome. Am J Med. 1982;73:317–321.[Medline] [Order article via Infotrieve]
34. Palomäki H, Kaste M. Association of thromboxane B2 production to hypoxemic periods during sleep in male stroke patients. J Stroke Cerebrovasc Dis. 1993;3:145–149.
35.
Stringer HAR, van Swieten P, Heijnen HFG, Sixma JJ,
Pannekock H. Plasminogen activator
inhibitor-1 released from activated platelets
plays a key role in thrombolysis resistance: studies
with thrombi generated in the Chandler loop. Arterioscler
Thromb. 1994;14:1452–1458.
36.
Ridker PM, Vaughan DE, Stampfer MJ, Glynn RJ, Hennekens
CH. Association of moderate alcohol consumption and plasma
concentration of endogenous tissue-type
plasminogen activator. JAMA. 1994;272:929–933.
37. Gorinstein S, Zemser M, Lichman I, Berebi A, Kleipfish A, Libman I, Trakhtenberg S, Caspi A. Moderate beer consumption and the blood coagulation in patients with coronary artery disease. J Intern Med. 1997;241:47–51.[Medline] [Order article via Infotrieve]
38.
Laug WE. Ethyl alcohol enhances plasminogen
activator secretion by endothelial cells.
JAMA. 1983;250:772–776.
39. Aikens ML, Grenett HE, Benza RL, Tabengwa EM, Davis GC, Booyse FM. Alcohol-induced upregulation of plasminogen activators and fibrinolytic activity in cultured human endothelial cells. Alcohol Clin Exp Res. 1998;22:375–381.[Medline] [Order article via Infotrieve]
40. FitzGerald DJ, Roy L, Catella F, FitzGerald GA. Platelet activation in unstable coronary disease. N Engl J Med. 1986;315:983–989.[Abstract]
41. Reilly IAG, Roy L, Fitzgerald GA. Biosynthesis of thromboxane in patients with systemic sclerosis and Raynaud’s phenomenon. BMJ. 1986;292:1037–1039.
This article has been cited by other articles:
 |
|
 |
|
  K. J. Mukamal, M. Maclure, J. E. Muller, and M. A. Mittleman Binge Drinking and Mortality After Acute Myocardial Infarction Circulation, December 20, 2005; 112(25): 3839 - 3845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. W. Lee and G. Y. H. Lip Effects of Lifestyle on Hemostasis, Fibrinolysis, and Platelet Reactivity: A Systematic Review Arch Intern Med, October 27, 2003; 163(19): 2368 - 2392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Gill REPORTED LEVELS OF ALCOHOL CONSUMPTION AND BINGE DRINKING WITHIN THE UK UNDERGRADUATE STUDENT POPULATION OVER THE LAST 25 YEARS Alcohol Alcohol., March 1, 2002; 37(2): 109 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bleich, K. Bleich, S. Kropp, H.-J. Bittermann, D. Degner, W. Sperling, E. Ruther, and J. Kornhuber Moderate alcohol consumption in social drinkers raises plasma homocysteine levels: a contradiction to the 'French Paradox'? Alcohol Alcohol., May 1, 2001; 36(3): 189 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-w. Yang, J. Wang, T. Zheng, B. T. Altura, B. M. Altura, and P. D. Hurn Ethanol-Induced Contractions in Cerebral Arteries : Role of Tyrosine and Mitogen-Activated Protein Kinases Editorial Comment: Role of Tyrosine and Mitogen-Activated Protein Kinases Stroke, January 1, 2001; 32(1): 249 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Heavy Nocturnal Drinking and Stroke Journal Watch Psychiatry, November 14, 2000; 2000(1114): 10 - 10. [Full Text]
|
|
|
|
|
|
H. Numminen, M. Kobayashi, S. Uchiyama, M. Iwata, Y. Ikeda, A. Riutta, M. Syrjala, R. Kekomaki, and M. Hillbom EFFECTS OF ALCOHOL AND THE EVENING MEAL ON SHEAR-INDUCED PLATELET AGGREGATION AND URINARY EXCRETION OF PROSTANOIDS Alcohol Alcohol., November 1, 2000; 35(6): 594 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Heavy Nocturnal Drinking and Stroke Journal Watch Neurology, September 20, 2000; 2000(920): 4 - 4. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||