Myocardial Lactate Metabolism in Children with Non-Cyanotic Congenital Heart Disease

Abstract

It is well recognized that main energy source for myocardium is fatty acids (Wisneski et al.,1987, Lopaschuk et al.,2010). However, in failing heart or in hypertrophied heart, fatty acid oxidation ability was reported to be impaired and, on the contrary, carbohydrates were preferred to use for provision of energy demand (Stanle et al.,2005,Lopaschuk et al.,1992). The fetal heart is exposed to relatively high lactate concentrations. Immediately after birth, plasma lactate concentrations decrease. In the immature heart, lactate dehydrogenase (LDH) is predominated by the M type isozyme, as higher activity, resulting in greater lactate production from pyruvate (Brooks et al., 1985). This requires greater NADH levels than seen in the adult heart. The dominance of glycolytic flux in immature hearts leads to accumulation of lactate to a greater extent than is seen in adult hearts during profoundly hypoxic states (Brooks et al., 1985). It has been shown that, in the isolated perfused rat heart, lactate significantly contributes to acetyl-CoA formation more than glucose. When fatty acid oxidation is activated, pyruvate dehydrogenase (PDH) activity is suppressed by increase of the NADH/NAD+ ratio followed by an enhancement of lactate production from accumulated pyruvate. As a result, lactate is released from myocardium even under aerobic status (Brooks et al., 1985). Immediately after birth, fatty acids are not the major energy substrate in newborn hearts, although the capacity of the heart for oxidization of fatty acids rapidly increases. Of interest, lactate is also important ATP provider in newborn heart (Lopaschuk et al. 1991). Patho-physiology of congenital heart defects (CHD) is very wide ranging from the right ventricular (RV) volume overload and/or pressure overload to the left ventricular (LV) volume overload and/or pressure overload. CHD with left-to-right shunt is basically a noncyanotic status. However, the myocardial cells may be in the milieu of relatively low oxygen because of relative decreased of coronary circulation from hypertrophy. Despite the evidence that lactate may be an important fuel for myocardial energy metabolism, there is remarkably little information on the lactate utilization in immature hearts especially in CHD. Lactate plays the other important role as a regulator of cellular redox state. The redox state described in this chapter is defined as the balance of NADH/NAD+ in the myocardium. The cytosolic NADH/NAD+ ratio in most tissues is enhanced by activation of glycolysis. If lactate dehydrogenase (LDH) activity is high such as in heart, the lactate/pyruvate (L/P)