Hennie Knoester

Perinatal changes in myocardial metabolism in lambs

BACKGROUND Lactate accounts for a third of myocardial oxygen consumption before and in the first 2 weeks after birth. It is unknown how the remainder of myocardial oxygen is consumed. Glucose is thought to be important before birth, whereas long-chain fatty acids (LC-FA) are the prime substrate for the adult. However, the ability of the myocardium of the newborn to use LC-FA has been doubted. METHODS AND RESULTS We measured the myocardial metabolism of glucose and LC-FA with [U-(13)C]glucose and [1-(13)C]palmitate in chronically instrumented fetal and newborn lambs. In fetal lambs, myocardial oxidation of glucose was high and that of LC-FA was low. Glucose and LC-FA accounted for 48+/-4% and 2+/-2% of myocardial oxygen consumption, respectively. In newborn lambs, oxidation of glucose decreased, whereas oxidation of LC-FA increased. Glucose and LC-FA accounted for 12+/-3% and 83+/-19% of myocardial oxygen consumption. To test whether near-term fetal lambs could use LC-FA, we increased the supply of LC-FA with a fat infusion. In fetal lambs during fat infusion, the oxidation of LC-FA increased 15-fold. Although the oxidation of LC-FA was still lower than in newborn lambs, the contribution to myocardial oxygen consumption (70+/-13%) was the same as in newborn lambs. CONCLUSIONS These data show that glucose and lactate account for the majority of myocardial oxygen consumption in fetal lambs, whereas in newborn lambs, LC-FA and lactate account for the majority of myocardial oxygen consumption. Moreover, we showed that the fetal myocardium can use LC-FA as an energy substrate.

Follow‐up after paediatric intensive care treatment: parental posttraumatic stress

Aim: To study the prevalence of posttraumatic stress in parents after an acute admission to a paediatric intensive care unit (PICU) and to determine risk factors for the development of posttraumatic stress.

Course and Predictors of Posttraumatic Stress Disorder in Parents after Pediatric Intensive Care Treatment of their Child

OBJECTIVE To study posttraumatic stress disorder (PTSD) in parents after unexpected pediatric intensive care unit (PICU) treatment of their child and to identify risk factors for its development. METHOD Parents completed PTSD questionnaires 3 and 9 months (N = 190) after PICU treatment. Risk factors included pretrauma data, medical data, social demographics and posttraumatic stress responses at 3 months. RESULTS In total, 30.3% of parents met criteria for subclinical PTSD and 12.6% for clinical PTSD at 3 months. Clinical PTSD prevalence rates did not change over time. At 9 months, 10.5% of parents still met criteria for PTSD. Number of earlier stressful life events, earlier psychosocial care and posttraumatic stress responses at 3 months predicted persistent subclinical and clinical PTSD. CONCLUSIONS PICU admission is a stressful event associated with persistent parental PTSD. Assessment of risk factors can facilitate detection of persistent PTSD for early intervention.

Myocardial Lactate Metabolism in Fetal and Newborn Lambs

BACKGROUND Around birth, myocardial substrate supply changes from carbohydrates before birth to primarily fatty acids after birth. Parallel to these changes, the myocardium is expected to switch from the use of primarily lactate before birth to fatty acids thereafter. However, myocardial lactate uptake and oxidation around birth has not been measured in vivo. METHODS AND RESULTS We measured myocardial lactate uptake, oxidation, and release with infusion of [1-13C]lactate and myocardial flux of fatty acids and glucose in chronically instrumented fetal and newborn (1 to 15 days) lambs. Myocardial lactate oxidation was the same in newborn (81.7+/-14.7 micromol. min-1. 100 g-1, n=11) as in fetal lambs (60.7+/-26.7 micromol. min-1. 100 g-1, n=7). Lactate uptake was also the same in newborn as in fetal lambs. Lactate uptake was higher than lactate flux, indicating lactate release simultaneously with uptake. In the newborn lambs, lactate uptake declined with age. Lactate uptake was strongly related to lactate supply, whereas lactate oxidation was not. The supply of fatty acids or glucose did not interfere with lactate uptake, but the flux of fatty acids was inversely related to lactate oxidation. CONCLUSIONS We show that lactate is an important energy source for the myocardium before birth as well as in the first 2 weeks after birth in lambs. We also show that there is release of lactate by the myocardium simultaneously with uptake of lactate. Furthermore, we show that lactate oxidation may be attenuated by fatty acids but not by glucose, probably at the level of pyruvate dehydrogenase.

Perinatal changes in myocardial supply and flux of fatty acids, carbohydrates, and ketone bodies in lambs

No information is available on perinatal changes in myocardial metabolism in vivo. We measured myocardial supply and flux of fatty acids, carbohydrates, and ketone bodies in chronically instrumented fetal, newborn (1-4 days), and juvenile (7 wk) lambs, by measuring aorta-coronary sinus concentration differences and blood flow. In the fetal lambs, myocardial supply and flux of fatty acids were zero. In the newborn lambs, the supply of fatty acids increased tenfold, but there was no flux of fatty acids. Carbohydrates were the major energy source in fetal and newborn lambs, accounting for 89 and 69% of myocardial oxygen consumption, respectively. In the juvenile lambs, the flux of fatty acids was increased threefold. The supply and flux of carbohydrates were decreased (by 31 and 82%, respectively). The supply and flux of ketone bodies gradually increased with age. We show that the myocardium of the lamb in vivo does not switch immediately after birth from carbohydrates to fatty acids. The mechanisms involved in the development of myocardial fatty acid oxidation remain to be elucidated.

Single nucleotide polymorphisms in genes of circulatory homeostasis in surviving pediatric intensive care patients with meningococcal infection

Objective: In the course of a meningococcal infection, invasive and severe disease occurs in a restricted number of individuals. The predominant mechanism of death in case of meningococcal septic shock is circulatory failure. Inotropic requirements between patients vary widely. We investigated whether polymorphisms in genes regulating the hemodynamic response influence the amount of inotropics required or the susceptibility to severe meningococcal disease. Design: Retrospective case control study. Setting: Single-center pediatric intensive care unit (PICU). Patients: Fifty-six cases (all consecutive patients admitted to the PICU between 1993 and 2001 with a proven meningococcal infection) and 136 controls. Patients were divided into two groups according to their inotropic requirements. Intervention: DNA analysis was performed to determine the polymorphisms of the beta-adrenergic receptor gene-1, beta-adrenergic receptor gene-2, alpha-adducin, angiotensin converting enzyme, and angiotensin II type-1 receptor-1 genes. Results: For the alpha-adducin gene a significant difference of the genotype distribution was found between the cases and controls. The odds ratio for admission to the PICU with meningococcal sepsis with or without meningitis, for carriers of the variant allele (Gly460Trp or Trp460Trp) was 2.1 (95% confidence interval 1.11–4.04; p < 0.02). Cases, homozygote for the wild-type allele of the beta-1 adrenergic receptor at locus 389, were more likely to have a low pediatric risk of mortality score on admission (odds ratio 3.6, 95% confidence interval 1.11–11.76). No difference was found in the distribution of the beta-adrenergic receptor gene-1, beta-adrenergic receptor gene-2, angiotensin converting enzyme, and angiotensin II type-1 receptor-1 polymorphisms between the two groups of patients or between cases and controls. Conclusions: Among patients admitted to the PICU with a meningococcal infection, the variant allele of the alpha-adducin gene was more prevalent compared with controls. Patients with the variant allele of the beta-adrenergic receptor gene-1 at locus 389 were more likely to have a high pediatric risk of mortality score on admission. The mechanism and clinical relevance of these findings is unclear.