Perinatal Changes in Mitochondrial Respiration of the Rabbit Heart

Abstract

Oxidative metabolism and citrate synthase activity during the perinatal period were assessed in isolated rabbit heart mitochondria at 27 days’ gestation (27 dpc), 1 day postpartum (1 dpp) and 10 dpp. Oxygen consumption was measured during state 3 and state 4 respiration using the following substrates: glutamate, α-ketoglutarate, pyruvate/malate, succinate/rotenone, acetate, palmitylcarnitine, and palmityl CoA/carnitine. Results obtained from fetal and neonatal animals were compared to values obtained from adult left and right ventricles. Rates of state 3 oxygen consumption per milligram mitochondrial protein using tricarboxylic acid cycle intermediates or palmitylcarnitine were higher in both 1 and 10 dpp animals than in either left or right ventricles. Respiratory activity per milligram mitochondrial protein using these substrates was similar in 27 dpc fetuses and adult left ventricles. The rate of oxidation of palmityl CoA was lower in fetal mitochondria than in adult left ventricle, indicating that the capacity for conversion of long-chain fatty acyl CoA to acylcarnitine necessary for transport of fatty substrates into the mitochondria is decreased in fetal hearts. Increases in myocardial citrate synthase corresponded to increases in mitochondrial mass reported by other investigators.

Fatty acid oxidation and ketogenesis during development

“…As newborn rats have a low ability to synthesize carnitine during the first postnatal week (Hahn, 1981) ln vitro studies using tissue homogenates (Warshaw, 1972 ;Glatz and Veerkamp, 1982 ;Wolfe, Maxwell and Nelson, 1978), isolated mitochondria (Warshaw and Terry, 1970 ;Werner et al, 1982) or isolated perfused organ (Werner et al, 1983b) have shown that the heart of fetal rats, rabbits, pigs and calves has a very low capacity for long-chain fatty acid oxidation, even in the presence of carnitine. Similarly, compared to adults, the rate of palmitate oxidation is reduced in skeletal muscle homogenates (Glatz and Veerkamp, 1982 ;Carroll et al, 1983 ;Wolfe, Maxwell and Nelson, 1978 ;Mac Larty et al, 1984) and in kidney slices (Wolfe, Maxwell and Nelson, 1978 ;Freund, Sedraoui and Geloso, 1984), lung (Warshaw, Terry and Ranis, 1980) and small intestine (Warshaw, 1974) of fetal rats and pigs.…”

“…The capacity of heart (Wittels and Bressler, 1965 ;Warshaw and Terry, 1970 ;Warshaw, 1972 ;Mersmann and Phinney, 1973 ;Aprille, 1976 ;Wolfe, Maxwell and Nelson, 1978 ;Werner et al, 1982Werner et al, , 1983a, skeletal muscle (Wolfe, Maxwell and Nelson, 1978 ;Glatz and Veerkamp, 1982 ;Carroll et al, 1983) and kidney (Wolfe, Maxwell and Nelson, 1978 ;Freund, Sedraoui and Geloso, 1984) to oxidize NEFA increases shortly after birth in rats, rabbits, pigs and calves. In contrast, it has been reported that substantial fatty acid oxidation occurs only 2 weeks after birth in dog heart (Breuer et al, 1968).…”

“…After weaning, this capacity remains elevated in heart (Warshaw, 1972 ;Glatz and Veerkamp, 1982 ;Werner et al, 1982), kidney (Novakova et al, 1980 ;Freund, Sedraoui and Geloso, 1984) and, to a lesser extent, in skeletal muscles (Glatz and Veerkamp, 1982 ;Carroll et al, 19831. This is not surprising since it is well known that NEFA are the preferred fuel of adult heart, kidney and resting muscles (see review by Owen and Reichard, 1974 (Callikan et al, 1979 ;Duée et al, 1983).…”

Force and Oxygen Consumption in the Immature Rabbit Heart

“…For example, glucose is the only metabolic substrate provided in our model. Because adult myocardium relies more on fatty acid oxidation than does neonate myocardium (15,16), our model may place the adult heart at a relative disadvantage. Werner et al (1 6 ) did note that 10-d-old rabbit hearts have an increased ability to oxidize palmitylCoA compared with the fetal heart.…”

Integration of carbohydrate and lipid metabolism in skeletal muscle during postnatal development

“…1 ) In mammals, during the suckling period, 50-70 % of the caloric intake is in the form of lipids (Ferré et al, 1986). In rats (Page, Krebs and Williamson, 1971 ;Foster and Bailey, 1976 ;Robles-Valdes, McGarry and Foster, 1976) as well as in humans (Bougneres et al, 1982(Bougneres et al, , 1986 (Wittels and Bressler ;Warshaw, 1972;Mersmann and Phinney, 1973 ;Aprille, 1976 ;Wolfe, Maxwell and Nelson, 1978 ;Werner et al, 1982Werner et al, , 1983 and skeletal muscle (Wolfe, Maxwell and Nelson, 1978 ;Glatz and Veerkamp, 1982 ;Caroll et al, 1983) (Newsholme, 1976 al., 1978, 1983) and thus increases lactate production from glucose. A similar mechanism has been postulated in the human newborn oxidizing ketone bodies (Bougnères et a/., 1983).…”