Coronary heart disease is frequently associated with obstructive sleep apnea syndrome and treating obstructive sleep apnea appears to significantly improve the outcome in coronary heart disease. We have previously shown in the rat that chronic intermittent hypoxia increases heart sensitivity to infarction. In this study, deleterious mechanisms potentially involved in this IH-induced infarction aggravation were explored using the antiischemic drug trimetazidine (TMZ), and a free radical scavenger Tempol, investigating the role of oxidative stress, and myocardial vascularization.
Wistar male rats were divided in two experimental groups subjected to chronic IH (IH group) or normoxia (N group). IH consisted of repetitive cycles of 1min (40s with inspired O2 fraction 5 % followed by 20s normoxia) and was applied for 8h during daytime, for 14 or 35 days. Normoxic cycles were applied in the same conditions, inspired O2 fraction remaining constant at 21 %. After the 14-day exposure, mean arterial blood pressure (MABP) was measured. Isolated hearts were then submitted to an ischemia-reperfusion protocol at the end of which infarct size were measured.
MABP was significantly increased in IH group compared to N group. Infarct sizes (expressed in percent of ventricle’s area) were significantly higher in IH group (34.0±2.8 %) compared with N group (21.8±3.1 %). Tempol (1mM administered in water during the 14-day exposure) prevented this deleterious effect since infarction was comparable between IH (24.8±2.8 %) and N (27.9±4.0 %) groups. Moreover, Tempol also prevented the IH-induced increase in MABP after the 14-day exposure. Trimetazidine (10mg/day administered in food during the 14-day exposure) did not prevent the IH-induced infarction aggravation (40.1±3.6 % in IH+TMZ group significantly higher than 29.1±2.9 % in N+TMZ group) and has no effect on IH-induced increase in MABP. After a 35-day exposure, IH significantly increased ventricular vascular density and VEGF expression.
In conclusion, reduction of IH effects with Tempol suggest that IH induced cardiac infarction aggravation involves free radical pathway rather than metabolic or angiogenic modifications.Le texte complet de cet article est disponible en PDF.