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Thrombosis Research (2004) 113, 129–136

Regular Article

The effects of arm cranking exercise andtraining on platelet aggregation in male spinalcord individuals

Mahmoud S. El-Sayeda,*, Ali Younesiana, Khalid Rahmanb, Fyaz M. Ismailc,Zeinab El-Sayed Alic

aSchool of Sport and Exercise Science, Liverpool John Moores University, Liverpool, UKbSchool of Biomolecular Sciences, Liverpool John Moores University, Liverpool, UKcSchool of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, UK

Received 19 October 2003; received in revised form 12 February 2004; accepted 12 February 2004

0049-3848/$ - see front matter D 200doi:10.1016/j.thromres.2004.02.014

* Corresponding author. Faculty ofStreet, Liverpool L3 2ET, England, UK.

E-mail address: m.s.elsayed@livjm

KEYWORDSPlatelet aggregation;Spinal cord injury;Arm cranking

exercise;Exercise conditioning

ABSTRACT

Platelet aggregation at rest and in responses to exercise and training were comparedbetween spinal cord injured (SCI) individuals (N¼ 5) and able-bodied subjects(N¼ 7). All participants performed arm cranking exercise at 60–65% VO2peak for 30min. Venous blood samples were obtained before and after sub-maximal exerciseand measured for platelet aggregation using ADP and collagen. To assess the effectsof arm cranking training, platelet aggregation was re-measured in all subjects at restand in response to the sub-maximal arm cranking exercise after 12 weeks ofindividually supervised training programme. Before training, the resting mean valuesof platelet aggregation induced by ADP and collagen were not different ( P>0.05)between SCI and able-bodied. However the SCI individuals, but not the able-bodiedsubjects, exhibited a significantly ( P< 0.05) higher maximal platelet aggregationinduced by ADP and collagen following sub-maximal arm cranking exercise. AlthoughVO2peak after training was significantly increased ( P< 0.05) in both groups, theresting mean values of platelet aggregation induced with ADP and collagen were notsignificantly different ( P>0.05) from those observed before training and were notdifferent ( P>0.05) between SCI and able-bodied. Post-training, the SCI individuals,but not able-bodied individuals, exhibited a significant decrease ( P< 0.05) inplatelet aggregation following sub-maximal arm cranking exercise and this occurredwith both ADP and collagen. These results suggest that SCI individuals, but notnormal subjects increase their platelet aggregation following sub-maximal armcranking exercise. Furthermore, arm cranking training in SCI individuals, appears todiminish the percentage of platelet aggregation ex vivo.D 2004 Published by Elsevier Ltd.

Science, School of Sport and Exercise Science, Liverpool John Moores University, 15-21 Webster

4 Published by Elsevier Ltd.

Tel.: +44-151-231-4289; fax: +44-151-231-4353..ac.uk (M.S. El-Sayed).

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Introduction

Individuals with lower limb paralysis due to spinalcord injury (SCI) naturally use their arms for wheel-chair locomotion and other activities of daily living,as well as for exercise training and sports activities[1]. The relatively small muscle mass under volun-tary control, impaired cardiovascular reflexresponses, and the inactivity of the skeletal musclepump of the legs all lead to a diminished armmuscles ability to exercise. Furthermore, theweakness of the skeletal muscle results in prema-ture onset of fatigue. This dampens an activelifestyle and daily life activities become morephysically demanding to perform due to low levelof muscular strength and cardiovascular fitness.Sedentary lifestyles worsen this condition leadinga debilitative series of physical and cardiovascularcomplications that can be difficult to stop. Indeed,spinal cord injured (SCI) individuals suffer from ahost of cardiovascular complications including cor-onary heart disease [2].

In recent years the involvement of plateletsdysfunction in atherogenesis and the clinical com-plications from arteriosclerosis has become morerecognised. Systemic platelet-related thrombo-genic factors have been implicated in the initiationand subsequent development of atherogenesis andplaque formation [3,4]. Platelet aggregation is acomplex process that is affected by a multitude ofinternal and external factors. Over the last twodecades, interest has been heightened regardingthe effects of exercise and training on plateletaggregation and function, not only in normalhealthy subjects, but also in patients with differentailments particularly those with cardiovascularcomplications [5]. Although regular exercise hasbeen shown to protect against coronary heart dis-ease, the mechanism(s) through which it exerts thiseffect is not fully understood. Therefore the rec-ognition of the effects of exercise on platelets isdecidedly pertinent with respect to primary andsecondary prevention of cardiovascular complica-tions. Earlier reports on the effects of exercise onplatelets aggregation and functions in normalhealthy subjects have produced conflicting results[6]. However for patients with cardiovascular com-plications, particularly coronary heart disease, thebalance of evidence available would suggest thatplatelet aggregation and activation are increasedwith exercise [2–5]. The exact effects of vigorousarm exercise and conditioning in SCI on plateletaggregation is not known.

Therefore studying the influence of exercise onplatelet aggregation in spinal cord injured individ-uals may have clinical as well as scientific signifi-

cance because these individuals usually adoptphysically inactive lifestyle and cardiovascular dis-eases are the most frequent cause of death in thispopulation [7]. Therefore the present study wasdesigned to examine the effects of arm-crankingexercise and conditioning of high intensity on plate-let aggregation in spinal cord injured individuals incomparison with normal healthy subjects.

Material and methods

Subjects

Seven normal healthy subjects and five spinalcord injured individuals volunteered to participatein the study. All normal subjects and SCI individ-uals were untrained and followed a sedentarylifestyle. The subjects in the SCI group had alesion level below T10. Of the five SCI, only onesubject was a regular drug user who was also acigarette smoker. The Ethics Committee of theinstitution approved the study protocol and test-ing procedures and all subjects signed an in-formed consent prior to the commencement ofthe investigation. All subjects took part in twosessions of habituation in order to familiarisethemselves with the arm-cranking exercise proto-col, testing procedures, and laboratory environ-ment. Subjects age (meanF S.D.) was 32F 1.6years for normal subjects and 31F 2.9 years forspinal cord injury individuals.

Measurement of peak oxygen consumption(VO2peak)

All subjects performed a continuous progressiveworkload arm cranking exercise test on arm crank-ing ergometer until volitional fatigue for the de-termination of VO2peak. All subjects performed theVO2peak test trial twice, 1 week before and 1 weekafter the completion of the conditioningprogramme. When subjects reported to the labo-ratory for testing, they were fasted for 12 h andhad had no alcohol for the preceding 24 h. Alltests and blood sampling commenced at the sametime of day. Following a warm up period for 5 minat exercise intensity 30 W, the work rate wasincreased every 2 min by 30 W until exhaustion.During the test, a cranking frequency of 60–65was maintained by using metronome. Minute ven-tilation, oxygen uptake, and carbon dioxide pro-duction were continuously sampled and analysedby an open-circuit system (Metamax, Cortex, Ger-many). Calibration of the system was carried out

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according to the manufacturer instructions. Heartrate was measured at rest and continuously duringexercise by short-range radio telemetry (Polar, P.E.3000, Kempele, Finland). The physiological dataobtained from the peak oxygen consumption(VO2peak) test were utilised, using regression anal-ysis, for the calculation of the exercise intensitycorresponding to 60–65% VO2peak for each subject.The indication for termination of exercise wassubjective maximal exercise as indicated by theparticipants’ own symptom of fatigue or breath-lessness. Other indication for stopping the exer-cise was the occurrence and progression of anysymptoms to the point of unwillingness of thesubject to proceed further or that continuationof the test might be detrimental to the subjects’welfare. The attainment of VO2peak was judgedwhen the following criteria were met (1) a plateauin VO2 with increasing the workload, (2) inabilityof the subject to maintain the designated pedal-ling frequency, (3) a respiratory exchange ratio of1.1 or above. If a subject did not complete asatisfactory maximal test, the testing procedureswere repeated after 7 days.

Sub-maximal arm cranking exercise testprotocol before conditioning

Approximately 1 week after the measurement ofVO2peak each subject performed a sub-maximalexercise protocol. The exercise protocol con-sisted of a warm-up period for 5 min at 30 W,thereafter the external work load was increasedto elicit a physiological response corresponding to60–65% VO2peak and arm cranking exercise con-tinued at this intensity for 30 min. A crankingfrequency of 60–65 per minute was maintainedand heart rate was monitored continuously by atelemetry heart rate monitor (Polar, P.E.3000,Kempele, Finland).

Exercise conditioning programme

The conditioning programme was individually su-pervised for each subject in both the SCI andcontrol groups. All exercise sessions were per-formed using arm-cranking ergometer and eachtraining session started out with a 5-min warm-upat a light workload. Thereafter, the workload wasincreased to elicit a heart rate corresponding to60–65 VO2peak for each subject. The externalresistance to arm cranking during each trainingsession was continuously adjusted to maintain thepre-assigned intensity and all subjects exercisedat this intensity for 30 min. The exercise sessions

were continuous, and supervised and monitoredregularly. Each subject’s training heart rate wasadjusted as sub-maximal heart rate was de-creased training. All exercise trials and trainingsessions were performed in a temperature-con-trolled environment (22F 2 jC). All subjects ex-ercised for 30-min on three non-consecutivedays/week for 12 weeks. No dietary changeswere recommended, but subjects were instructedto consume their normal diet and maintain theirnormal activity and lifestyle patterns throughoutthe study. The attendance rate was 100% in boththe SCI and able-bodied groups. During the con-ditioning programme, all subjects were instructedto follow their normal routine and refrain fromstrenuous exercise.

Sub-maximal arm cranking exercise testprotocol after conditioning

The same sub-maximal arm cranking exercise, asdescribed above, was used after conditioning todetermine the effects of exercise and training onplatelet aggregation at rest and in response toacute exercise. Although the subjects’ cardiorespi-ratory fitness was improved due to conditioning,the acute arm cranking following conditioning wasperformed at the same relative exercise intensityin relation to VO2peak (60–65% VO2peak).

Blood sampling and analysis

Blood sampling occurred at the same time of dayin an ambient temperature of 20F 2 jC andrelative humidity of 55F 5%. All subjects weregiven well in advance explicit instructions to re-frain from food, caffeine or strenuous physicalactivity during the 12 h preceding the bloodsampling. After reporting to the laboratory, sub-jects were requested to remain in the sittingposition for 15 min, after which a resting 10 mlof venous blood sample was obtained with nostasis. The resting blood sample was taken beforeany warm-up exercise and was kept in crushed iceuntil the completion of the sub-maximal exercisebefore and after conditioning. A second 10-mlblood sample was removed immediately after thesub-maximal arm cranking exercise test (60% ofVO2peak). Blood was transferred in to tubes con-taining 3.8%trisodium citrate dihydrate (4.5 mlblood to 0.5 volume of citrate). Tubes were mixedgently and thoroughly and platelet rich plasma(PRP) and platelet poor plasma (PPP) were pre-pared by centrifugation. Citrated blood wascentrifuged for 5 min at 400� g to obtain PRP,

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then the blood sample centrifuged again at2000� g for 20 min to acquire PPP. AutologousPPP was used to adjust the platelet count of PRPto 200� 10� 9/l before measurement of plateletaggregation was made. Approximately 30 min af-ter blood sampling, platelet aggregation was mea-sured with a four-channel aggregometer (PAP-4,BioData, UK). Aggregation of PRP was induced byADP and collagen (with final concentrations of2� 10� 5M for ADP and collagen) at 37 jC withcontinuous stirring by a magnetic stirrer. Bothresting and post exercise blood samples from eachsubject were analysed together. Over the durationof the study, blood samples were coded an ana-lysed using the same batch of ADP and collagen.The aggregating agents ADP and collagen wereused as agonists because of differences in themode of platelet response. Collagen being a po-tent agonist inducing platelet release from thethree granuli populations, while ADP is a weakerplatelet agonist that stimulates a release onlyfrom the dense and alpha granule but not fromthe lysosomes. The initial light transmission of PRPwas set at 0%, while that of PPP was set at 100%.Maximum aggregation (percent of maximal lighttransmittance after the addition of the aggregat-ing agent) was determined.

Statistical analysis

All statistical analyses were performed using thesoftware statistical package SPSS version 11 (SPSS,Chicago, USA). A two-way analysis of variance(ANOVA) with repeated measurements was used todetect differences in mean values. When ANOVAindicated the presence of overall significant differ-ence, Tukey’s post hoc tests were employed toascertain which mean values were statistically sig-nificant. The alpha level of P< 0.05 was the min-imum level required to reject the null hypothesis.

Table 1 Physiological responses to maximal arm cranking eand able-bodied subjects (N = 7)

SCI individuals

BT AT

VO2peak (1 min� 1) 1.81F 0.10 1.94VO2peak (1 kg min� 1) 24.12F 2.60 26.2HRpeak (beat/min) 173F 8.2 173.2VEpeak (1 min� 1) 75.3F 9.1 83.56WLpeak (W) 168F 37.6 185

VO2peak =maximum amount of oxygen consumed at the endheart rate achieved at the end of the incremental arm crankincremental arm cranking test. WLpeak =maximum workloadtest. BT = before training and AT= after training. *Significan

Values in the text are meanF S.D. unless otherwisestated.

Results

Physiological results

Spinal cord individuals and normal subjects wereof similar age with no differences in resting lipidprofiles (unpublished data). Table 1 presents phys-iological and performance-related data beforeand after the conditioning programme in SCIindividuals and able-bodied subjects. Before theconditioning programme, VO2peak and maximalexercise duration and exercise intensity achievedwere similar for the two groups. All SCI and able-bodied subjects exhibited a significant increase inVO2peak and in maximum exercise duration andintensity following training. Thus indicating thatthe physical conditioning programme had inducedfavourable cardiovascular improvements with aresultant significant increase in the maximal aer-obic capacity.

Platelet aggregation at rest and followingacute sub-maximal arm cranking exercisebefore conditioning

The resting and post sub-maximal arm crankingexercise mean results of platelet aggregation stud-ies with ADP are shown in Fig. 1. The resting meanvalues of platelet aggregation induced by ADP werenot different (P>0.05) between SCI individuals andnormal healthy subjects. Compared to rest, the SCIgroup exhibited a significantly (P< 0.05) highermaximal platelet aggregation induced by ADP fol-lowing strenuous arm cranking exercise. In con-trast, strenuous arm cranking exercise had no

xercise before and after training in SCI individuals (N = 5)

Normal subjects

BT AT

F 0.05* 1.82F 0.11 2.1F 0.1*F 1.36* 26.79F 1.85 29.1F 1.05*F 10.8* 169F 5.9 169.8F 7.3*F 10.2* 68.4F 5.4 80.3F 7.7*F 24.1* 160F 16.5 204F 11.2*

of the incremental arm cranking test. HRpeak =maximuming test. VEpeak =maximum ventilation at the end of theachieved at the end of the incremental arm cranking

t difference ( P < 0.05) compared to before training.

Fig. 2 Mean (F SE) values of platelet aggregation (%)with ADP at rest (open bars) and after arm crankingexercise (solid bars). SCI¼ spinal cord injured; N¼ normalsubjects. A represent before training and B representafter training. *Statistically significant difference.

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significant effect (P>0.05) on platelet aggregationinduced by ADP in normal subjects.

The resting and post sub-maximal arm crankingexercise results of platelet aggregation studies withcollagen are illustrated in Fig. 2. Resting meanvalues of maximal platelet aggregation induced bycollagen were not significantly different betweenSCI individuals and normal subjects. Followingstrenuous arm cranking exercise; maximal plateletaggregation induced by collagen increased signifi-cantly in SCI individuals. In contrast, maximalplatelet aggregation with collagen in response toexercise was not altered by exercise in normalsubjects.

Platelet aggregation at rest and followingacute sub-maximal arm cranking exerciseafter conditioning

The resting mean values of platelet aggregationinduced by ADP before training were not different(P>0.05) from those observed after training andwere similar between SCI individuals and normalhealthy subjects. In contrast to the resultsobtained before training, individuals in the SCIgroup exhibited a significantly ( P< 0.05) lowermaximal platelet aggregation induced by ADP fol-lowing strenuous arm cranking exercise. In normalsubjects, the mean value of maximum plateletaggregation following strenuous arm cranking ex-

Fig. 1 Mean (F SE) values of platelet aggregation (%)with collagen at rest (open bars) and after arm crankingexercise (solid bars). SCI = spinal cord injured; N = normalsubjects. A represent before training and B representafter training. *Statistically significant difference.

ercise after training was not significantly different(P>0.05) from that found before exercise and wasnot affected by training (Fig. 1A and B).

Similar to ADP, the resting mean values of plate-let aggregation induced by collagen before trainingwere not different (P>0.05) from those observedafter training and were similar between SCI individ-uals and normal healthy subjects. In contrast to theresults obtained before training, individuals in theSCI group exhibited a significantly (P< 0.05) lowermaximal platelet aggregation induced by collagenfollowing strenuous arm cranking exercise. In nor-mal subjects, the mean value of maximum plateletaggregation following strenuous arm cranking exer-cise after training was not significantly different(P>0.05) from that found before exercise and wasnot affected by training (Fig. 2A and B).

Discussion

Numerous studies have been conducted on theeffects of exercise and training on blood haemo-stasis [1–5], but few studies were carried out toascertain such effects in SCI individuals; particu-larly those related to platelet aggregation andactivation [8]. The results of the present study

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suggests that (a) platelet aggregation at restappears to be similar between SCI and able bodiedindividuals and is not affected by training, (b)strenuous bout of arm cranking exercise is associ-ated with a significant increase in platelet aggre-gation in SCI individuals, but not in able bodiedsubjects and (c) arm cranking training in SCI indi-viduals appears to significantly suppress plateletaggregability following acute bout of arm crankingexercise. These results clearly demonstrate thatarm cranking exercise training is associated withfavourable effects on acute exercise-inducedchanges in platelets aggregation in SCI individuals.

Platelet aggregation is a complex process that isaffected by a multitude of internal and externalfactors [3–5,9]. The majority of previous clinicaland pathological studies have indicated that pla-telets play a fundamental role in the pathogenesesof thrombosis and atherosclerosis [9]. Data showedthat platelet aggregation induced by ADP andcollagen at rest in SCI subjects did not differsignificantly from those of able-bodied individuals.However acute bout of arm cranking exercise wasfollowed by a significant increase in platelet ag-gregation only in the SCI individuals. The enhancedplatelet aggregation in response to an acute boutof arm cranking exercise in the SCI group mayaccelerate the thrombogenic process in the coro-nary microcirculation. It may also contribute tothe pathogenesis of thrombosis; particularly asincreased platelet aggregation may also enhanceblood coagulation [3]. It is therefore possible that,as a result of exercise intolerance in the SCI group,the sub-maximal exercise intensity and durationemployed in the study herein was sufficientlystressful to trigger direct increase in plateletaggregation.

Although physical exercise is widely recognisedas being beneficial to health, attempts to relatethe effects of exercise to changes in plateletaggregation have produced conflicting results[3,5,9–11]. The present work describes arm-crank-ing exercise and training related responses ofplatelet aggregation in SCI individuals and normalsubjects, but it does not offer additional informa-tion on the possible mechanism(s) responsible forthese responses. Although the exact mechanism(s)responsible for this phenomenon is not clear, itmight be related to catecholamines particularlyepinephrine. Earlier reports indicated that strenu-ous exercise is associated with epinephrine release[11] in those individuals with SCI below T10, as it isthe case in the present study exhibit a highersympathoadrenal activity than the normal non-injured individuals. Therefore it is reasonable tosuggest that enhanced platelet aggregation by an

acute bout of intense arm cranking exercise mighthave been caused by endogenous release of epi-nephrine in SCI group but not in the control. Invivo experiments indicated that SCI individualsexhibit greater P-selectin than normal subjects.It could also be argued that the arm crankingexercise bout employed in the present study wasassociated with higher level of P-selectin andconsequently higher platelet aggregation and ac-tivation. Although P-selectin was not measured inthe present study, previous studies indicated thatP-selectin is increased in response to arm crankingexercise in SCI individuals but not in able-bodiedsubjects [8]. It is generally accepted that plateletsactivity and aggregation is highly variable evenwithin the normal population, and it is importantto take into account that platelet activation in theSCI individuals may be secondary to areas ofischemia developing in leg microcirculation. Addi-tionally, influences of metabolic or hormonal adap-tations are also significant variables in theregulation and behaviour of platelet aggregationand activation in SCI individuals.

It is probable that acute arm cranking exercise inSCI individuals, but not in normal subjects, resultedin the mobilisation of recently produced and met-abolically more active platelets from the pulmo-nary vessels. These platelets exhibit raised activityof monoamine oxidase and elevated aggregationpotential [3,5]. Lactic acidosis has also been impli-cated in exercise-associated increase in plateletaggregation as high correlation between the in-crease in hydrogen ion concentration and plateletaggregates was reported [3]. The exact role oflactic acidosis in exercise-induced alterations inplatelet aggregation cannot be deduced from thedata of the present study and further investigationsare needed. Additional hypotheses have been sug-gested to elucidate the mechanisms through whichexercise induced alteration in platelet aggregation.For example, Sakita et al. [12] suggested that theenhanced platelet aggregation might be linked witha decrease of platelet sensitivity to endothelial-derived nitric oxide, probably due to a reduction inits availability. However, this clarification appearsimplausible in light of the evidence reported byTozzi-Ciancarelli et al. [13], who demonstrated anincrease in nitric oxide availability after strenuousexercise with concurrent increase in plateletaggregability. Thus, it appears that SCI individuals,but not normal subjects, increase their plateletaggregation following sub-maximal arm crankingexercise.

In contrast to reports on the acute effects ofexercise, only few data are available on the influ-ence of regular exercise training on platelet aggre-

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gation and function. The training programme of thepresent study was associated with a marked im-provement in the cardiorespiratory system asreflected by a significant increase in the peakamount of oxygen consumed at the end of maximalexercise. There was also proof of improvement inperformance as indicated by an evident increase inthe maximal exercise duration and the workloadaccomplished at the end of the maximal test (Table1). These improvements in cardiorespiratory fitnessand performance related indices occurred in paral-lel with a significant reduction in platelet aggrega-tion in response to arm cranking exercise in SCIindividual. In the past only few experimental trialswere conducted to determine the effects of phys-ical training on platelets in able-bodied men andwomen [14,15]. The data generated from thesestudies suggested that exercise training of moder-ate intensity in young able-bodied males andfemales is associated with diminished platelet ad-hesiveness and aggregation at rest and in responseto an acute bout of vigorous exercise. Interestingly,men exhibited augmented platelet aggregation be-fore training in response to acute exercise, but thisresponse was attenuated following training [14].The beneficial effects of training on platelet ag-gregation at rest and in response to exercise wereno longer apparent with detraining both in men[14] and in women [15].

In partial agreement with the above studies, armcranking exercise training in SCI individuals,appears to suppress platelet aggregability followingacute bout of arm cranking exercise (Figs. 1 and 2).The acute platelet aggregability response to armcranking exercise and the beneficial effects oftraining were consistent and occurred in all SCIindividuals. An earlier study in overweight, mildlyhypertensive middle-age men also showed thatphysical training of moderate intensity was associ-ated with desensitisation of platelets [16]. Like-wise, the known unfavourable adverse effects ofageing on platelets appear to be attenuated withphysical training [17]. Although the precise mech-anism(s) by which physical training desensitiseplatelet is not completely understood, this couldbe attributed to an increase in prostacyclin and/ornitric oxide; both of which are known to be potentinhibitors of platelet aggregation. This may havebeen associated with, and contributed to, physicaltraining induced desensitisation of platelet in re-sponse to exercise [14,15,18].

In conclusion, the results of the present studydemonstrate that SCI individuals, but not normalsubjects increase their platelet aggregation follow-ing sub-maximal arm cranking exercise. Further-more, arm cranking training in SCI individuals,

appears to suppress platelet aggregability followingacute bout of arm cranking exercise.

It is recognised that the small number of SCIindividuals participated in the study limits theresults obtained. This was mainly due to difficultiesof recruiting SCI individuals who were capable ofperforming arm cranking exercise for the duration ofthe study. It is important to repeat this type of studywith a larger number of subjects, and at differentenvironmental conditions (hot and cold), with addi-tional measurements including catecholamines andobjective markers of in vivo platelet activation suchas beta thromboglobulin and platelet factor 4. Thefailure to construct a dose– response curve forplatelet agonists may be a limitation as there isabsence of specific intervention designed to eluci-date potential mechanism(s) involved. Further stud-ies should also focus on the potential mechanism ofthe interaction between platelet aggregation andexercise and training in this population. The resultsof these studies would further our understanding ofthe effects of exercise and training on plateletaggregation and function in SCI individuals. It isequally important, given the complexity of thehaemostatic system, that future studies should ex-amine arm cranking exercise and training effects onblood coagulation and fibrinolysis in parallel withplatelet aggregation and function.

References

[1] Glaser RM. Exercise and locomotion for the spinal cord in-jured. In: Terjung RL, editor. Exercise and Sports Science Re-views, vol. 13. New York: Macmillan; 1985;105. p. 263–303.

[2] Hoffman MD. Cardiorespiratory fitness and training in quad-riplegics and paraplegics. Sport Med 1986;3:312–30.

[3] El-Sayed MS. Exercise and training effects on platelets inhealth and disease. Platelets 2002;13:261–6.

[4] Puri RN, Colman RW. ADP-induced platelet activation. CritRev Biochem Mol Biol 1997;3:437–502.

[5] El-Sayed MS, El-Sayed AZ, Ahmadizad S. Exercise and trai-ning effects on blood haemostasis in health and disease.Sports Med 2004;34:181–200.

[6] El-Sayed MS. Effects of exercise on blood coagulation, fib-rinolysis and platelet aggregation. Sport Med 1996;22:282–98.

[7] Whiteneck G. Learning from empirical investigations. In:Menter R, Whiteneck G, editors. Perspective on Agingwith Spinal Cord Injury: Demos Publications, USA; 1992.p. 23–37.

[8] Wang J-S, Yang CF, Wong M-K. Effect of strenuous armcranking exercise on platelet function in patient with spi-nal cord injury. Arch Phys Med Rehabil 2002;83:210–6.

[9] El-Sayed MS, Sale S, Jones P, Chester M. Blood haemostasisin exercise and training. Med Sci Sports Exer 2000;32:918–25.

[10] El-Sayed MS. Effect of alcohol ingestion post-exercise onplatelet aggregation. Thromb Res 2002;105:147–51.

[11] Wang J-S, Cheng LJ. The effects of strenuous acute

M.S. El-Sayed et al. / Thrombosis Research 113 (2004) 129–136136

exercise on alpha2 adrenergic agonist-potentiated plate-let activation. Arterioscler Thromb Vasc Biol 1999;19:1559–965.

[12] Sakita S, Kishi Y, Numano F. Acute vigorous exercise attenu-ates sensitivity of platelets to nitric acid. Thromb Res 1997;87:461–71.

[13] Tozzi-Ciancarelli MG, Penco M, Massimo D. Influence ofacute exercise on human platelet responsiveness: possibleinvolvement of exercise induced oxidative stress. Eur JAppl Physiol 2002;86:266–72.

[14] Wang JS, Jen CJ, Chen HI. Effects of exercise training anddecoditioning on platelet function in men. ArteriosclerThromb Vasc Biol 1995;15:1668–74.

[15] Wang JS, Jen CJ, Chen HI. Effects of chronic exercise and

deconditioning on platelet function in women. J Appl Phy-siol 1997;83:2080–5.

[16] Rauramaa R, Salonen JT, Seppanen K. Inhibition of plateletaggregability by moderate intensity physical exercise: arandomised clinical trial in overweight men. Circulation1986;74:939–44.

[17] Gonzales F, Manas M, Seiquer I, et al. Blood platelet func-tion in healthy individuals of different ages. Effects ofexercise and exercise deconditioning. J Sports Med PhysFitness 1996;36:112–6.

[18] Wang JS, Yang CF, Wong MK, Chow SE, Chen JK. Effect ofstrenuous arm exercise on oxidised-LDL potentiated plate-let activation in individuals with spinal cord injury. ThrombHaemost 2000;84:118–23.