PubMed · 6754750
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J E Cremer. 1982. Substrate utilization and brain development.. https://doi.org/10.1038/jcbfm.1982.45
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Increased oxidation of fat is an important host response to sepsis, and carnitine is essential for long-chain fatty acid oxidation. Because neonates have low levels of carnitine, their ability to respond to a septic insult may be impaired. The purpose of this study was to compare fatty acid and carnitine metabolism in septic weanling (60 to 85 g) and septic adult (285 to 310 g) rats. Sepsis was induced in weanling and adult male Sprague-Dawley rats by cecal ligation and puncture (CLP). The rats were killed 16 hours after CLP or sham operation, and serum glucose, lactate, beta-hydroxybutyrate, fatty acid, carnitine, liver fatty acid, and tissue carnitine levels were measured. The data suggest that during sepsis weanling rats may be more dependent on fatty acid oxidation than adult rats are, as evidenced by their elevated serum fatty acid and acylcarnitine levels, and relative hypoglycemia and hyperketonemia. In addition, although total serum carnitine levels were increased in both adult and weanling septic rats, tissue carnitine levels of weanling rats became significantly depleted during sepsis, unlike in adult rats. This study supports further investigation regarding the role of exogenous carnitine in newborn sepsis.
We have made serial measurements of the plasma adrenocorticotrophic hormone (ACTH), cortisol, glucose, lactate, glycerol, nonesterified fatty acid (NEFA), and beta-hydroxybutyrate concentrations in 14 recently injured patients. We took 6 to 9 blood samples at about 20-minute intervals from each patient within the first 3 hours after accidental injury of moderate severity (Injury Severity Score of 9 to 13). Plasma ACTH varied greatly both with time and between patients; in the majority, it fell throughout the sampling period and in the others, the pattern varied. The changes in plasma cortisol were mostly appropriate to those in ACTH. Plasma glucose and glycerol did not change systematically with time. In contrast, plasma lactate fell, and plasma NEFA, beta-hydroxybutyrate, and the NEFA:glycerol ratio rose, throughout the sampling period. Analysis of variance for these data showed that time after injury made a contribution that was highly significant, although smaller than that arising from differences between patients.
A method for determining regional cerebral utilization of ketone bodies in humans is described. After a bolus injection of R-beta-[1-11C]hydroxybutyrate, the time course of the tracer in the brain was measured with positron emission tomography in five healthy volunteers. The regional cerebral blood flow was measured separately. The tracer uptake in the brain could be well described by a single rate constant, indicating that the concentration of unmetabolized ketone bodies in the brain is very low and that transport across the blood-brain barrier is the rate-limiting step. At an average plasma concentration of beta-hydroxybutyrate of 0.043 mumol/ml, the utilization rate was estimated to be 0.48 nmol.ml-1.min-1. In accordance with previous animal studies, the utilization rate was found to increase almost linearly with increasing plasma concentration of beta-hydroxybutyrate. Furthermore, the utilization was higher in gray than in white matter. Finally, the ratio between the utilization in the basal ganglia and the brain as a whole was lower for ketone bodies than for glucose.