Translate this page to:
Dutch
In JoVE (1)
Other Publications (7)
Automatic Translation
This translation into Dutch was automatically generated.
English Version | Other Languages
Articles by Danilyn M. Angeles in JoVE
JoVE Clinical and Translational Medicine
Biochemische Meting van Neonatale Hypoxie
1Division of Biochemistry, Department of Basic Sciences, Loma Linda University, 2Division of Physiology, Department of Basic Sciences, Loma Linda University
Een methode wordt beschreven om biochemische markers van neonatale hypoxie-ischemie te meten. De aanpak maakt gebruik van hoge druk vloeistofchromatografie (HPLC) en gaschromatografie-massaspectrometrie (GC / MS).
Other articles by Danilyn M. Angeles on PubMed
Use of Opioids in Asphyxiated Term Neonates: Effects on Neuroimaging and Clinical Outcome
Perinatal asphyxia is a common cause of neurologic morbidity in neonates who are born at term. Asphyxiated neonates are frequently treated with analgesic medications, including opioids, for pain and discomfort associated with their care. On the basis of previous laboratory studies suggesting that opioids may have neuroprotective effects, we conducted a retrospective review of medical records of 52 neonates who were admitted to our neonatal intensive care unit between 1995 and 2002 and had undergone magnetic resonance imaging (MRI) of the brain. Our review revealed that 33% of neonates received morphine or fentanyl. The neonates who received opioids also had experienced hypoxic/ischemic insults of greater magnitude as suggested by higher plasma lactate levels and lower 5-min Apgar scores. It is interesting that the MRI studies of neonates who were treated with opioids during the first week of life demonstrated significantly less brain injury in all regions studied. More important, follow-up studies of a subgroup of opioid-treated neonates whose MRI scans were obtained in the second postnatal week had better long-term neurologic outcomes. Our results suggest that the use of opioids in the first week of life after perinatal asphyxia have no significant long-term detrimental effects and may increase the brain's resistance to hypoxic-ischemic insults.
Dexamethasone Alters Vascular Reactivity by Enhancing COX-related Vasodilatation in Fetal Ovine Carotids
Based on preliminary studies that contractile efficacy was altered in vertebral and basilar arteries from neonatal donors treated with postnatal glucocorticoids, we examined the hypothesis that postnatal dexamethasone (DEX), a glucocorticoid used for respiratory disease in neonates, can alter vascular reactivity. Using near-term fetal lamb carotids, we measured 5-hydroxytryptamine (5-HT) dose-response relationship in DEX-treated and untreated arteries. We found that DEX incubation for 1 h had no effect on 5-HT sensitivity and agonist affinity but significantly reduced 5-HT contractile efficacy, a response that became even more pronounced after 4 h of DEX treatment. Coincubation of DEX-treated arteries with INDO for 4 h reversed this DEX-induced attenuation in 5-HT contractile efficacy, although DEX had no significant effects on cyclooxygenase (COX)-1 and COX-2 protein abundance. This data suggests that DEX alters vascular reactivity through a COX-related mechanism, with possible repercussions to neurological injury.
Effect of Dopamine on Vascular Reactivity in Near-term Lamb Carotids: Role of the Endothelium
Many neonates are diagnosed with hypotension in the first 24 hr of life. Those with severe hypotension are often given high doses of dopamine at 10 to 20 microg/kg/min. This study examined the hypothesis that dopamine, a vasoactive drug commonly used in the neonatal intensive care unit, alters vascular reactivity. Vascular reactivity was measured by comparing 5HT dose-response characteristics in untreated near-term lamb common carotid arteries and arteries treated with 15 microg/kg/min of dopamine. The authors found that dopamine pretreatment for 60 min significantly potentiated 5HT-induced contractile tone by approximately 100% ( p < .05). This observed increase in tone was accompanied by a significant decrease in the affinity of 5HT to its receptor ( p < .05), suggesting an activation of a separate contractile pathway, or a mechanism downstream from agonist-receptor binding. Interestingly, an increase in contractility was observed only in endothelium-intact arteries. In arteries with denuded endothelium, dopamine pretreatment resulted in a small but significant decrease in tone compared to control arteries ( p < .05), suggesting a vasodilatory mechanism unmasked by endothelium removal. Although multiple mechanisms can increase vascular resistance, these data described the in vitro effects of high doses of dopamine on vascular tone as well as the role of the endothelium in dopaminemediated vasoconstriction.
Relationship Between Opioid Therapy, Tissue-damaging Procedures, and Brain Metabolites As Measured by Proton MRS in Asphyxiated Term Neonates
To examine the effects of opioid and tissue-damaging procedures (TDPs) [i.e. procedures performed in the neonatal intensive care unit (NICU) known to result in pain, stress, and tissue damage] on brain metabolites, we reviewed the medical records of 28 asphyxiated term neonates (eight opioid-treated, 20 non-opioid treated) who had undergone magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) within the first month of life as well as eight newborns with no clinical findings of asphyxial injury. We found that lower creatine (Cr), myoinositol (Ins), and N-acetylaspartate (NAA)/choline (Cho) (p < or = 0.03) and higher Cho/Cr and glutamate/glutamine (Glx) Cr (p < or = 0.02) correlated with increased TDP incidence in the first 2 d of life (DOL). We also found that occipital gray matter (OGM) NAA/Cr was decreased (p = 0.03) and lactate (Lac) was present in a significantly higher amount (40%; p = 0.03) in non-opioid-treated neonates compared with opioid-treated neonates. Compared with controls, untreated neonates showed larger changes in more metabolites in basal ganglia (BG), thalami (TH), and OGM with greater significance than treated neonates. Our data suggest that TDPs affect spectral metabolites and that opioids do not cause harm in asphyxiated term neonates exposed to repetitive TDPs in the first 2-4 DOL and may provide a degree of neuroprotection.
Necrotizing Enterocolitis is Associated with Neonatal Intestinal Injury
We hypothesized that a subset of premature newborns has subclinical, intestinal mucosal compromise that predisposes to the development of necrotizing enterocolitis (NEC) days or weeks later.
An Animal Model for Measuring the Effect of Common NICU Procedures on ATP Metabolism
Neonates exposed to common neonatal intensive care unit (NICU) procedures show alterations in heart rate, blood pressure, and oxygen saturation. However, it is unclear if these physiologic changes increase adenosine triphosphate (ATP) utilization, thus potentially increasing the risk for tissue hypoxia in medically fragile neonates. Plasma uric acid is a commonly used marker of increased ATP utilization because uric acid levels increase when ATP consumption is enhanced. To examine the effect of a common NICU procedure on plasma uric acid concentration, we developed a model that allows for acute monitoring of this biochemical marker in plasma in 7- to 9-day-old rabbits. In our pilot study, we exposed neonatal rabbits to a single heel lance 2.5 hr after catheter placement. We measured uric acid concentration before and 30 min after the heel lance and compared findings to levels in control animals not exposed to the heel lance. Our pilot data shows a significant difference in uric acid concentration over time between the control and heel lance groups (46.2 ± 7.1 μM vs. 54.7 ± 5.8 μM, respectively, p = .027). Calculation of percentage change from baseline showed uric acid concentration increasing in rabbits exposed to heel lance and decreasing in control rabbits (1.5 ± 4.7% vs. -16.1 ± 4.2%, respectively, p = .03). These data suggest that this animal model can be successfully used to examine the biochemical effect of common NICU procedures, such as heel lance, on markers of ATP breakdown and purine metabolism.
The Role of Morphine in a Rat Model of Hypoxic-ischemic Injury
We investigated whether morphine plays a neuroprotective role in a neonatal rat pup model of bilateral carotid artery occlusion with hypoxia. At postnatal day 10, rats received either morphine (n = 7), naloxone (n = 7), or saline placebo (n = 15) after hypoxic-ischemic injury. Survival (days), weight gain and animal testing (negative geotaxis, surface righting, and rotarod) were compared between treatment groups. Lesion volume was delineated with magnetic resonance imaging at days 7 and 28-57 after injury. Survival in rats treated with morphine, naloxone, or saline was, respectively, 14, 29, and 73%. Median number of days of survival after bilateral carotid artery occlusion with hypoxia treated with morphine was 4 (95% confidence interval 4 to 22), with naloxone was 3 (95% confidence interval -1.4 to 21), and with placebo was 28 (95% confidence interval 18 to 28). There were no statistically significant differences in magnetic resonance imaging-derived ischemic lesion volumes, weight gain, or behavioral testing measures between the groups. Morphine was ineffective as a neuroprotectant in rat pups with severe hypoxic-ischemic injury and may have contributed to their decreased survival.
