**3.3 Myocardial substrate uptake**

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

Myocardial Lactate Metabolism in Children with Non-Cyanotic Congenital Heart Disease 323

under heprinized state because of two reasons; 1) for preservation of veins and arteries from obstruction in younger children and 2) for our aim of studying myocardial metabolism in patients under critical states as in pediatric intensive care unit or in surgical intervention

In spite of these limitation, this method we applied here is still useful for clinical study on myocardial metabolism (Vánky et al. 2006) because data obtained are supposed not far from animal model study (Lopaschuk et al., 1992), computer simulation study and isotopical

It is very important to know the myocardial energy substrate use *during the management of heart failure* or cardiac surgery of children with CHD. However, myocardial metabolism even in the normal immature heart has not been fully elucidated. Although data we can refer on myocardial energy substrate use in normal children are limited, myocardial fatty acids uptake of KD group *resembles the results that Rudolph demonstrated* (Rudorph et al., 1971). For this reason, we considered that results from KD group represented normal myocardial substrate use in children. Table 4 shows the comparison among some previous reports on the substrates use in hearts in young including cyanotic CHD. Myocardial FFA uptake in children shows very similar levels among the reports. The very variable glucose uptake shown in other reports including adults suggested that glucose may not play an important role for myocardial energy supply for children at rest. (Vánky et al. 2006,Lopaschuk et al.,

It has been demonstrated that adult hypertrophied hearts prefer to oxidize glucose. Increase of glucose oxidation may be beneficial for hypertrophied heart on production of ATP with less myocardial oxygen consumption than fatty acid oxidation. Allard *et al* reported that the steady-state palmitate oxidation rates were decreased in the hypertrophied hearts compared with control hearts (Allard et al., 1994). Although the uptake of glucose of CHD hearts, in our study, was quite variable, both hearts with the volume overloaded RV (ASD group) and with the pressure overloaded RV (PH group) showed tendency of increase of glucose uptake. (Figure 1, Table 4). These suggest that a myocardial potential of glucose use in children with CHD may not be an inferior level in comparison with adult hearts against overload. However, *one should note in our results that* FFA use was high levels even in PH group and that lactate was dominant energy supplier more than glucose in ASD group. Gertz *et al* have reported that in subjects with high blood free fatty acids, myocardial lactate extraction may be low (Gertz et al., 1980). However, this is not the case at least in children with CHD (Table 4). The lactate use including of cyanotic CHD is relatively high even under the high levels of fatty acid use. From another point of view, it is speculated that fatty acid use in children with CHD *have reached to* near maximum levels and, as a result, lactate regulated the energy supply against additional loads on the heart. Some studies have clarified that fatty acids oxidation increased with elevation of ventricular workload in immature hearts (Itoi et al., 1993a,Ascuitto et al., 1999). The lactate oxidation rates of the immature hearts were also increased by the addition of preload to the RV without significant change of glucose oxidation (Itoi et al., 1993b). The ASD group in our study showed the very same result of this experimental model on change of the lactate oxidation (Figure 1). Recently, Vánky *et al* revealed that no significant uptake of glucose was detected before or after surgery for aortic stenosis but the uptake of lactate was significant before

**4.2 Myocardial use of lactate and other substrates in non-cyanotic CHD** 

where many patients were heparinized.

study in human.

1992).

surgery (Vánky et al. 2006).

infusion of low dose lactate and glucose did not influence the concentrations of both lactate and glucose since blood levels of those substrates were within the normal values.

We calculated myocardial OER of each substrate since, in this study, coronary sinus blood flow could not be measured. Figure 1 shows OER of each substrate in each group. Glucose OER in each patient was quite variable so that there was no significant difference on the mean value; 2.0±13.0% for KD group, 8.4±11.0% for ASD group, and 15.5±20.4% for PH group. Mean arterio-venous difference of lactate in PH group was negative resulting in - 5.3±11.2% of calculated lactate OER. This value was significantly lower than both of KD group (7.8±9.2 %, p=0.013) and of ASD group (19.7±9.5, p=0.004). On the other hand, the lactate OER of ASD group showed higher trend than both KD group and PH group. There were no significant difference on FFA OER in each group; 62.8±28.2% for KD group, 63.6±9.8% for ASD group, and 62.8±28.0% for PH group. Sum of each glucose, lactate, and FFA OER was calculated as a total OER of heart.
