Postnatal overfeeding induces higher cardiac sensitivity to in vivo ischemia-reperfusion injury at all ages in males, but only in young females

Abstract

Nutritional disturbances during the postnatal period may be responsible for a predisposition in adulthood to increased cardio-metabolic risk and a greater myocardial vulnerability to ischemia. However, these data have mainly been obtained in young male mice, but less is known for females and for old animals. Evaluate the impact of postnatal overfeeding on cardiac sensitivity after in vivo ischemia reperfusion (I-R) on both sexes and in young (4 months: mths), adult (6 mths) and mature (12 mths) mice. PNOF was induced by reduction of litter size of C57/BL6 mice immediately after birth: normally-fed group (NF) litters were composed of 9 pups/mother and overfed group litters (OF) of 3 pups/mother. The in vivo ischemia was induced by a 45 min ligation of the left anterior interventricular artery, followed by 24 hours of reperfusion, in hearts from 4-, 6- and 12-months aged male and female mice. The area at risk (AAR) was determined by Evans blue coloration and the infarct size by TTC staining. PNOF induced an early and permanent increase in body weight in OF group, for males (4 mths: +13%; 6 mths: +23%; 12 mths: +23%) and female mice (4 mths: +23%; 6 mths: +27%; 12 mths: +15%). A significant increase of infarct size was observed in hearts of overfed male mice aged at all ages (4 mths: +37%, 6 mths: +32% and 12 mths: +38% of AAR), but for females, infarct size was significant increased at 4 mths (+34%), but not at 6 and 12 mths. However, in all female groups (NF and OF) we observed a higher post-surgical mortality and a greater data variability as compared to males. Nutritional programming through short-term PNOF induced a higher susceptibility to myocardial I-R injury in vivo at all ages in male mice, but only in young females. The mechanism of this sexual dimorphism in our model is not well understood, but could involve distinct levels of cardioprotective pathways expression, related to hormonal status.