**1. Introduction**

318 Congenital Heart Disease – Selected Aspects

Zhang, G. M., M; Holtby, H; Cai,S; Van Arsdell,G; Li,J (2008). "Blood Glucose Negatively

913.

Correlates with Systemic Hemodynamics and Oxygen Transport and Cerebral Oxygenation in Neonates after the Norwood Procedure." Circulation 118(Suppl.):

> 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)

Myocardial Lactate Metabolism in Children with Non-Cyanotic Congenital Heart Disease 321

concentration, oxygen saturation, and an oxygen-binding capacity of 1.34 ml/g. The oxygen

The substrate factor for glucose or lactate is 0.75 and 5.7 for free fatty acids (FFA). FFA concentration of whole blood was calculated by multiplying plasma concentration with

Values are expressed as mean ± standard deviation. All statistical tests were performed using JMP (ver.6, SAS Institute Japan, Co). We used Kruskal-Wallis one way analysis of variance on ranks to compare overall differences among three groups. We compared median value of all groups using two tailed Mann-Whitney U tests. Because three pairwise planed comparisons were made we considered P<0.016 as significant. In case of comparison of paired samples, Wilcoxon signed-rank test was applied and P<0.05 was considered as

There was no significant difference among the groups on age. Heart rates (HR) and left ventricular systolic pressure (LVSP) were similar among groups, so the double products (LVSP x HR) of the left ventricle in PH group was same to those in ASD group. The ratio of the right ventricular systolic pressure (RVSP) to the LVSP was higher in PH group than in ASD group (0.35 ± 0.13 mmHg vs 0.79 ± 0.17 mmHg ) . Qp/Qs of 1.7 ± 0.5 in PH group was

The arterial-coronary vein oxygen concentration differences were similar among three groups; 11.1 ± 0.7 Vol% for KD, 11.1 ± 2.3 Vol% for ASD group, and 10.9 ± 0.9 for PH group. However, this does not mean that the myocardial oxygen consumption of each group was similar, because we could not measure coronary flow in each group. Among three groups, however, the similar LV double products value may suggest the same levels of the LV oxygen consumption. On the other hand, the RV double products of the PH group were the highest level. These results suggested that the myocardial oxygen consumption in PH group

The concentrations of glucose, lactate, and FFA in the artery were same levels among the groups (Table 2). Plasma FFA concentrations were thought to be higher levels in all groups than normal values due to heparinization, although blood FFA was not measured before heparin injection. Concerning substrate concentrations in the coronary vein, lactate levels of PH group was significantly higher than other groups. Pyruvate concentrations of PH group showed no significant difference in comparison with values of other groups. Continuous

also the same level in comparison with that of 1.8 ± 0.2 in ASD group.

Redox potential (Eh) = -204+30.7x log([pyruvate]/[lactate]) (Gudbjarnason & Bing, 1962). ΔEh = Ehcv – Ehao (Ehcv and Ehao represent Eh of coronary venous blood and of aortic blood,

extraction rate (OER) for each substrate was calculated using the following formula:



(100-hematocrit)/100.

respectivelty) *Statistical analysis* 

significant.

**3. Results** 

**3.2 Oxygen uptake** 

**3.1 Patients profiles (Table 1)** 

may be the highest level among the groups.

**3.3 Myocardial substrate uptake** 

ratio of a given cell is regarded to reflect the cytosolic NADH/NAD+ ratio. The lactate and pyruvate are thought to provide for a redox coupling between organs through blood since plasma level of these metabolites equilibrate with cytosolic concentrations of cells. In view of "lactate shuttle theory" by Brooks (Brooks, 2002), lactate released into the coronary venous circulation and taken up by distal tissue that is to say myocardium via coronary artery circulation may affect redox state in the myocardial cells .

The energy substrates use in CHD had been focused on cyanotic disease (Scheuer et al.,1970, 1972, Rudolph et al.,1971, Fridli et al.,1977). As such, the studies of myocardial metabolism have long history but are very limited (Scheuer et al.,1970, 1972, Fridli et al.,1977, Åmark et al., 2007). In recent years, advancement of intensive care before and after surgical treatment, and carrying out of the long-term care of the circulation are getting to require precise *understanding* of myocardial metabolism in CHD.

In this article, we focused on myocardial use of energy substrates, especially lactate, in young patients with RV volume overload (*represented in the atrial septal defect, ASD*) or with both RV pressrure load and LV volume load (represented in the ventricular septal defect, VSD). The author will also consider the myocardial redox state of non-cyanotic CHD in young patients with reviewing of myocardial substrate use.
