Thesis (MSc)--University of Stellenbosch, 2002. / ENGLISH ABSTRACT: Background: Athletes use androgenic anabolic steroids (AAS) to enhance
their physical performance. The abuse of AAS is however associated with a
host of side effects including sudden death due to cardiac arrest. The use of
AAS leads to myocardial hypertrophy, which possibly makes the heart more
prone to ischaemia/reperfusion injury, since it often develops in the absence
of proper vasculature development.
Chronic AAS use also disrupts myocardial p-adrenoreceptor function and
possibly cAMP, signalling in the heart. Drugs increasing cAMP and
decreasing cGMP levels in the ischaemic myocardium exacerbate myocardial
ischaemia/reperfusion injury.
We also know that AAS causes coronary artery disease secondary to the
deleterious alteration of lipid profiles by increasing the LOL cholesterol and
decreasing the HOLcholesterol levels.
AAS treatment may increase systemic TNFa levels by stimulating lymphocyte
TNFa secretion that has been implicated in the depression of myocardial
function, myocardial hypertrophy and the worsening of ischaemia/reperfsuion
injury.
Aims: To determine whether chronic AAS treatment in trained and untrained
rats influences: 1) heart function and susceptibility to ischaemia/reperfusion
injury, 2) myocardial cyclic nucleotide levels (cAMP and cGMP) and 3)
myocardial TNFa levels. Material and methods: Male Sprague-Dawley rats (n=100) were divided into 4
groups: sedentary vehicle (placebo) treated group, sedentary AAS treated
group, exercise vehicle (placebo) treated group, and exercise AAS treated
group. Steroid treated animals received an intramuscular injection of
nandrolone laureate (0.375 mg/kg) once a week, for six weeks.
Training consisted of swim sessions 6 days a week for 6 weeks. Swim time
was incrementally increased up to a maximum of 50 minutes a day. For
biometric parameters heart weight and body weight were documented. Hearts
were mounted on a l.anqendorff perfusion apparatus and left ventricular
developed pressure (LVDP), heart rate (HR) and coronary flow (CF) was
monitored. The hearts were subjected to a period of 20 minutes of global
ischaemia, followed by 30 minutes of reperfusion. Functional parameters was
again monitored and documented. For biochemical analysis, blood was
collected for the determination of serum lipid levels and myocardial tissue
samples were collected before, during and after ischaemia for the
determination of myocardial TNFa, cGMP and cAMP levels and p38 activity.
Conclusions: Results obtained would suggest that AAS exacerbate exercise
induced myocardial hypertrophy. It also prevents the exercise-induced
improvement in cardiac function. AAS use reduces reperfusion function in
treated hearts, which may suggest that AAS exacerbates ischaemie and
reperfusion injury. Furthermore it was seen that AAS elevates basal (preischaemie)
cyclic nucleotide levels and basal (pre-ischaemic) as well as
reperfusion TNFa levels. This may also contribute to the exacerbation of
ischaemic and reperfusion injury. / AFRIKAANSE OPSOMMING: Agtergrond: Androgeniese anaboliese steroïede (AAS) word dikwels deur
atlete gebruik om sportprestasie te verbeter. Die misbruik van AAS het egter
talle newe effekte, insluitende skielike dood wat gewoonlik toegeskryf word
aan hartaanvalle. Die gebruik van AAS lei onder andere tot miokardiale
hipertrofie wat opsigself, as gevolg van ontoereikende vaskulêre ontwikkeling
tydens die ontwikkeling van hipertrofie, die hart nog meer vatbaar vir
isgemie/herperfusie skade maak.
Kroniese AAS toediening versteur miokardiale beta-adtenoresepter funksie en
moontlik die tweede boodskapper, sAMP, seintransduksie in die hart. Ons
weet ook dat AAS koronêre hartvatsiektes veroorsaak. Laasgenoemde is
sekondêr tot die nadelige lipiedprofiel verandering, wat 'n verhoging in LDL-C
en 'n verlaging in HDL-C insluit. Middels wat miokardiale sAMP vlakke
verhoog en sGMP vlakke in die isgemiese miokardium verlaag, vererger
miokardiale isgemie/herperfusie skade.
AAS behandeling kan moontlik ook sistemiese TNFa vlakke verhoog deur
limfosiet TNFa sekresie te stimuleer. Die verhoogde TNFa vlakke word
verbind aan die onderdrukking van miokardiale funksie, miokardiale hipertrofie
en die verergering van isgemie/herperfusie skade.
Doelwitte: Die doelwitte van die studie was om te bepaal of kroniese AAS
toediening in geoefende en ongeoefende rotte 1) hartfunksie en die hart se
vatbaarheid vir isgemie/herperfusie skade beïnvloed, 2) miokardiale sikliese nukleotiedvlakke (sAMP en sGMP) beïnvloed en 3) miokardiale TNFa-vlakke
beïnvloed.
Materiale en metodes: Manlike Sprague-Dawley rotte (n=100) is gebruik en in
4 groepe verdeel: 'n ongeoefende placebo groep (kontrole); 'n ongeoefende
steroïedbehandelde groep; 'n geoefende placebo groep (kontrole) en 'n
geoefende steroïedbehandelde groep. Steroïed behandelde diere het 'n
intramuskulêre nandroloon lauraat inspuiting (0.375 mg/kg) een keer per
week vir ses weke ontvang. Die oefenprogram het bestaan uit ses
swemsessies 'n week vir ses weke. Die swemtyd is geleidelik weekliks
verhoog tot by 'n maksimum tyd 50 min. Die waterbadtemperatuur is tussen
30 - 32 oe gehandhaaf. Vir biometriese parameters is hartgewig en
liggaamsgewig genoteer. Harte is op 'n Langendorff perfusie apparaat
gemonteer en linker ventrikulêre ontwikkelde druk (LVOD), koronêre vloei
(KV) en harttempo (HT) is genoteer. Die harte is vervolgens blootgestel aan
20 minute van globale isgemie gevolg deur 'n 30 minute herperfusieperiode.
LVOD, KV en HT is weer eens noteer. Vir biochemiese doeleindes is bloed
voor perfusie versamelom serum lipied vlakke te bepaal. Miokardiale weefsel
is versamel voor, tydens en na isgemie vir die bepaling van TNFa, cGMP en
AMP vlakke asook p38 aktiwiteit.
Gevolgtrekkings: Na aanleiding van resultate verkry wil dit voorkom asof die
gebruik van steroïde oefeningsgeïnduseerde miokardiale hipertrofie vererger.
Dit verhoed ook oefeningsgeïnduseerde verbetering in miokardiale funksie.
AAS lei tot 'n verlaagde herperfusiefunksie in behandelde harte, wat dalk mag dui op MS verergering van isgemie en herperfusie skade. Verder was daar
ook waargeneem dat MS basale (pre-isgemiese) sikliese nukleotiedvlakke
en basale TNFa-vlakke sowel as herperfusie TNFa vlakke verhoog. Die
verhoging in TNF-a vlakke mag dus moontlik ook bydra tot die verergering
van isgemie- en herperfusieskade.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/53105 |
| Date | 12 1900 |
| Creators | Rossouw, Ellen |
| Contributors | Du Toit, E. F., Van Rooyen, J., Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | Unknown |
| Type | Thesis |
| Format | 130 p. : ill. |
| Rights | Stellenbosch University |
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