There is substantial evidence that there are dramatic sex-related differences in the incidence of cardiovascular disease, apparently related to the presence of steroid hormones. This is supported by the discovery of steroid hormone receptors in the heart and vasculature. More controversial is the area of sex-related differences in cardiac metabolism and function. A number of human and animal studies have demonstrated that estrogen and testosterone have cardiac metabolic effects. Additionally, research shows females have higher heart rates and various indices of function, including cardiac output and stroke volume, compared with males. However, some controversy exists, as other studies report that function in isolated muscle preparations is lower in females versus males. The reasons for these differences may reflect effects of sex hormones that are dependent on the conditions being studied. Cardiac function is reduced in postmenopausal females, suggesting that female sex hormones, specifically estrogen and progesterone, influence cardiac function. Apart from its well-documented vasodilatory effects, estrogen has also been shown to have negative inotropic effects and to reduce Ca(2+) transients in cardiomyocytes. Similar results have been found for progesterone. Several studies show that testosterone administration appears to increase cardiac performance, while others show that it increases the stiffness of the ventricle due to increased collagen synthesis, thereby reducing diastolic performance. This review will discuss current evidence suggesting sex-related differences in cardiac metabolism and its energetics and function and will present the potential role of the principal sex steroid hormones.

ABSTRACT:In children with congenital heart disease, female sex has been linked to greater in-hospital mortality associated with low cardiac output, yet the reasons for this are unclear. Therefore, we examined whether newborn sex differences in the heart's metabolic response to ischemia exist. Left ventricular (LV) in vivo and ischemic biopsies of newborn male and female piglets were compared. Tissue ATP, creatine phosphate (CP), glycogen, anaerobic end-products lactate and hydrogen ion (H ϩ ), and key regulatory enzymes were measured. Compared with males, newborn females displayed 14% lower ATP, 22% lower CP, and 32% lower glycogen reserves (p Ͻ 0.05) at baseline. During ischemia, newborn females accumulated 17% greater lactate and 40% greater H ϩ accumulation (p Ͻ 0.02), which was associated with earlier cessation of glycolysis and lower ischemic ATP levels (p Ͻ 0.02) compared with males. Newborn females demonstrated a greater ability to use their glycogen reserves, resulting in significantly lower (p Ͻ 0.003) glycogen levels throughout the ischemic period. Thus, newborn females are at a metabolic disadvantage because they exhibited lower energy levels and greater tissue lactic acidosis, both linked to an increase susceptibility to ischemic injury and impair myocardial function on reperfusion. (Pediatr Res 70: 148-152, 2011)

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Despite significant advances in the management and treatment of heart disease in children, there continue to be patients who have worse outcomes than might be expected. A number of risk factors that could be responsible have been identified. Evidence-based findings will be reviewed, including whether young age and (or) reduced body weight exacerbate these responses. For example, newborn children undergoing congenital cardiac surgery are known to have worse outcomes than older children. Evidence exists that newborn hearts do not tolerate ischemia as well as adult hearts, developing irreversible injury sooner and exhibiting at-risk metabolic profiles. As well, in response to the administration of heparin, elevations in free fatty acids occur during congenital heart surgery in children, which can have detrimental effects on the heart. Furthermore, myocardial energetic state has also been suggested to impact outcomes. Unfavourable energetic profiles were correlated to lower body weights in the same age healthy newborn piglet model. Newborn children suffering from congenital heart disease, with lower body weights, also had lower myocardial energetic state and this correlated with longer postoperative ventilatory support as well as a trend to longer intensive care unit stay. These findings imply that unfavourable myocardial metabolic profiles could contribute to postoperative complications.