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Perinatal changes in mitochondrial respiration of the rabbit heart
Insights
Rabbit heart mitochondria show increased oxidative metabolism and citrate synthase activity after birth, indicating a shift towards fatty acid utilization. Fetal hearts have a lower capacity for long-chain fatty acyl CoA oxidation.
Area of Science:
- Cardiovascular Physiology
- Mitochondrial Biology
- Perinatal Metabolism
Background:
- Mitochondrial function and substrate utilization in the heart undergo significant changes during the perinatal period.
- Understanding these metabolic shifts is crucial for comprehending neonatal cardiac adaptation.
Purpose of the Study:
- To investigate oxidative metabolism and citrate synthase activity in rabbit heart mitochondria during late gestation and early postpartum.
- To compare mitochondrial function in fetal and neonatal rabbit hearts with adult hearts.
Main Methods:
- Isolated rabbit heart mitochondria were used to measure oxygen consumption (state 3 and state 4 respiration) with various substrates.
- Citrate synthase activity was assessed as an indicator of mitochondrial mass.
- Measurements were taken at 27 days' gestation (27 dpc), 1 day postpartum (1 dpp), and 10 days postpartum (10 dpp), and compared to adult ventricles.
Main Results:
- State 3 oxygen consumption rates using tricarboxylic acid cycle intermediates and palmitylcarnitine were higher in 1 dpp and 10 dpp rabbits compared to adult ventricles.
- Respiratory activity in fetal (27 dpc) mitochondria was similar to adult left ventricles for these substrates.
- Palmityl CoA oxidation was lower in fetal mitochondria, suggesting reduced capacity for long-chain fatty acyl CoA transport into mitochondria.
Conclusions:
- Neonatal rabbit hearts exhibit enhanced oxidative metabolism compared to adult hearts, particularly utilizing fatty acids.
- Fetal rabbit hearts show a developmental immaturity in long-chain fatty acid oxidation capacity.
- Increased citrate synthase activity postnatally correlates with increased mitochondrial mass, supporting metabolic adaptation.
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, alpha-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.