0012: Cardiac effects of a treatment with prolyl-hydroxylase inhibitors (PHI), used to improve exercise performance, in sedentary and trained rats

Abstract

Stabilization of the Hypoxia Inducible Factor (HIF) using prolyl-hydroxylase inhibitors (PHI) leads to an EPO synthesis which is suspected to be used as a doping practice. Such a treatment is suspected to improve endurance performance by increasing oxygen transport. However the effects of a PHI treatment on heart morphology and function has never been investigated. Therefore the aim of this study was to evaluate whether potential effects of PHI on cardiac function could contribute to explain its beneficial effect on aerobic performance. We tested the effects of a 1 week treatment with a PHI (DMOG, 150 mg.kg –1 , I.P.) or a placebo (NaCl) on both sedentary (Sed) and trained rats (Ex; trained during 5 weeks before treatment started; 40min at 25 m.min –1 per day; 5days/week). Our first result was that PHI increased running performance (+12%, p<0,05) in both Sed and Ex groups. This increased performance was associated with a major increase in total hemoglobin in PHI-treated animals (+13% p<0,05). However, regarding cardiac function and cardiac remodeling no beneficial effect of PHI was observed. Indeed, in hearts of sedentary as well as exercised rats no significal change in any morphological parameters (LVEDs, LVEDd, AWTd, PWTd and RWT) was found. Moreover, no change in systolic function likely to explain enhanced exercise performance was observed in PHI-treated hearts, when evaluated by intraventricular pressure probe (Millar®). Finally it is interesting to note that in sedentary rat hearts an impairment of diastolic function characterized by an altered E/A and dp/dt min ratios was found when they were challenged with isoproterenol (0,5 mg.kg -1 ). These last results obtained in sedentary hearts could suggest that a more prolonged treatment with such PHI could have deleterious consequences on heart health and point out the danger of such a doping strategy; however, this point remains to be more precisely investigated.