The effect of androgenic anabolic steroids on the susceptibility of the rat heart to ischaemia and reperfusion injury

[摘要] ENGLISH ABSTRACT:Background: Athletes use androgenic anabolic steroids (AAS) to enhancetheir physical performance. The abuse of AAS is however associated with ahost of side effects including sudden death due to cardiac arrest. The use ofAAS leads to myocardial hypertrophy, which possibly makes the heart moreprone to ischaemia/reperfusion injury, since it often develops in the absenceof proper vasculature development.Chronic AAS use also disrupts myocardial p-adrenoreceptor function andpossibly cAMP, signalling in the heart. Drugs increasing cAMP anddecreasing cGMP levels in the ischaemic myocardium exacerbate myocardialischaemia/reperfusion injury.We also know that AAS causes coronary artery disease secondary to thedeleterious alteration of lipid profiles by increasing the LOL cholesterol anddecreasing the HOLcholesterol levels.AAS treatment may increase systemic TNFa levels by stimulating lymphocyteTNFa secretion that has been implicated in the depression of myocardialfunction, myocardial hypertrophy and the worsening of ischaemia/reperfsuioninjury.Aims: To determine whether chronic AAS treatment in trained and untrainedrats influences: 1) heart function and susceptibility to ischaemia/reperfusioninjury, 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 4groups: sedentary vehicle (placebo) treated group, sedentary AAS treatedgroup, exercise vehicle (placebo) treated group, and exercise AAS treatedgroup. Steroid treated animals received an intramuscular injection ofnandrolone laureate (0.375 mg/kg) once a week, for six weeks.Training consisted of swim sessions 6 days a week for 6 weeks. Swim timewas incrementally increased up to a maximum of 50 minutes a day. Forbiometric parameters heart weight and body weight were documented. Heartswere mounted on a l.anqendorff perfusion apparatus and left ventriculardeveloped pressure (LVDP), heart rate (HR) and coronary flow (CF) wasmonitored. The hearts were subjected to a period of 20 minutes of globalischaemia, followed by 30 minutes of reperfusion. Functional parameters wasagain monitored and documented. For biochemical analysis, blood wascollected for the determination of serum lipid levels and myocardial tissuesamples were collected before, during and after ischaemia for thedetermination of myocardial TNFa, cGMP and cAMP levels and p38 activity.Conclusions: Results obtained would suggest that AAS exacerbate exerciseinduced myocardial hypertrophy. It also prevents the exercise-inducedimprovement in cardiac function. AAS use reduces reperfusion function intreated hearts, which may suggest that AAS exacerbates ischaemie andreperfusion injury. Furthermore it was seen that AAS elevates basal (preischaemie)cyclic nucleotide levels and basal (pre-ischaemic) as well asreperfusion TNFa levels. This may also contribute to the exacerbation ofischaemic and reperfusion injury.

[发布机构] Stellenbosch University