Effect of ischemia on fatty acid metabolism in fetal lung

The effects of ischemia on in vivo fatty acid metabolism in fetal lung were studied using rabbit fetuses of 25 to 28 gestational age. Ischemia was produced by inflating the aortic balloon thereby reducing the uterine blood flow. Ischemic insult resulted significant increase in lactate/pyruvate and NADH/NAD ratios and decrease in ATP/ADP ratio in fetal lung. Levels of CoA, acetyl CoA, carnitine and acetyl carnitine decreased while those of long chain acyl CoA and long chain acyl carnitine enhanced. Tissue content of these metabolites returned to normal after 2 hr stabilization following 20 min of ischemic insult. Ischemia also caused small increase in lipogenesis and neutral lipid content of fetal lungs. Our results thus suggest that beta-oxidation in fetal lung is inhibited and becomes rate-limiting for fatty acid oxidation during ischemia. Sudden occurrence of hypoxia or ischemia in the fetus is a typical challenge for the obstetricians. The patients occasionally suffer from neurological injury following cerebral hypoxemia. The hypoxic insult may also affect the respiratory activity significantly. For example, acute alveolar hypoxia causes pulmonary vasoconstriction by damaging pulmonary vascular smooth muscle (1) and results in reduction of fatty acid oxidation by limiting the ATP supply required for metabolic processes (2). Hypoxia has also been shown to decrease the rate of palmitate incorporation into phospholipids (3), inhibit rate of fatty acid synthesis (3) and depress rate of incorporation of fatty acid and phosphatidic acid into lipids (4). Despite the fact that fatty acids represent a major substrate for energy metabolism in lung, no work has been done on the fatty acid metabolism in fetal lung. The present study was designed to determine the fate of fatty acid oxidation in fetal lung during ischemic challenge. The levels of acyl CoA and acylcarnitine intermediates were also measured in order to determine the rate-controlling steps of fatty acid metabolism in the fetal lung.