Ductus Closure in Preterm Infants <i>Effects on Cerebral Hemodynamics</i>

Lundell, Bo; Sonesson, Sven‐Erik; Cotton, Robert B.

doi:10.1111/j.1651-2227.1986.tb10401.x

Cited by 30 publications

(11 citation statements)

References 27 publications

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“…As confirmed by previous literature [1,15,24,25] , we found significantly increased rSO 2 values after PDA ligation (72 8 7% by 24 h). This change likely reflects a low baseline rSO 2 and subsequent normalization of cerebral oxygenation, with post-ligation levels comparable to the mean rSO 2 in control infants without a hsPDA (69 8 4%).…”

Section: Discussionsupporting

confidence: 81%

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Cerebral Oxygenation during Different Treatment Strategies for a Patent Ductus Arteriosus

2011

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Background: Preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA) are at risk for fluctuations in cerebral blood flow, but it is unclear how different hsPDA treatment strategies may affect cerebral oxygenation. Objective: To compare regional cerebral oxygen saturation (rSO₂) as measured by near-infrared spectroscopy (NIRS) in very low birth weight (VLBW) infants with a hsPDA treated with conservative management, indomethacin, or surgical ligation. Methods: This prospective observational study enrolled 33 VLBW infants with a hsPDA diagnosed by echocardiogram and 12 control VLBW infants without a hsPDA. Infants had NIRS cerebral monitoring applied prior to conservative treatment, indomethacin, or surgical ligation. Cranial ultrasound and magnetic resonance imaging data were also collected. Results: Infants undergoing surgical ligation had a greater time period with >20% change in rSO₂ from baseline (30%) compared to those receiving indomethacin (7.4%, p = 0.001) or control infants without a hsPDA (2.6%, p = 0.0004). NIRS measures were not associated with abnormal neuroimaging in this small cohort. Conclusion:These findings suggest that infants requiring surgical ligation for a hsPDA are at high risk for significant changes in cerebral oxygenation, whereas those receiving either indomethacin or conservative management maintain relatively stable cerebral oxygenation levels. Additional research is necessary to determine if NIRS monitoring identifies infants with a hsPDA at highest risk for brain injury.

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Section: Discussionsupporting

confidence: 81%

“…However, consequences of this rapid change in cerebral oxygenation are unclear. A sustained increase in rSO 2 after PDA ligation implies increased cerebral blood flow, as transcranial Doppler ultrasound studies have demonstrated [24,26] . In contrast to our findings, two studies found unchanged or decreased rSO 2 after PDA ligation [14,27] .…”

Section: Discussionmentioning

confidence: 99%

Cerebral Oxygenation during Different Treatment Strategies for a Patent Ductus Arteriosus

2011

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“…These data suggest an age-dependent shift in the primary endothelial-dependent dilator mechanism of the human vertebral artery from prostanoid to NO. Numerous studies in premature human infants suggest a high sensitivity of the cerebral circulation, particularly hypercapnia responsiveness, to the COX inhibitor indomethacin (21)(22)(23)26). Data from human infant cerebral arteries in vitro suggest that generation of NO in response to calcium ionophore is markedly reduced in the human infant compared with newborn lambs (27).…”

Section: Discussionmentioning

confidence: 99%

COX-1 and COX-2 Contributions to Basal and IL-1β-Stimulated Prostanoid Synthesis in Human Neonatal Cerebral Microvascular Endothelial Cells

et al. 2002

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Mechanisms of endothelium-dependent regulation of cerebral circulation in human neonates are poorly understood owing to the lack of experimental data. Prostanoids, the products of the cyclooxygenase (COX) pathway, appear to be important regulators of blood flow in neonates. COX activity in cultured endothelial cells from small (60 -300 m) and large (Ͼ300 m) microvessels from the autopsy specimens of neonatal human cerebral cortex and cerebellum (22-26 wk gestational age) was detected as production of vasodilator prostanoids, prostacyclin [as 6-keto-prostaglandin (PG) F 1␣ ] and PGE 2 from arachidonic acid. Treatment of neonatal human cerebral microvascular endothelial cells (hCMVEC) with IL-1␤ (50 ng/mL, 17 h) stimulated COX activity 5-to 20-fold. Basal and IL-1␤-stimulated COX activities were inhibited by NS-398, indicating substantial COX-2 contribution to endothelial prostanoid synthesis in neonatal human brain cortex and cerebellum at rest and when mimicking the inflammatory conditions. Increased COX-2-linked activity in response to IL-1␤ was observed in hCMVEC from both cerebrum and cerebellum (5-to 20-fold), while under the same conditions elevated COX-1-linked activity was detected only in hCMVEC from cerebellum (5-to 10-fold). In IL-1␤-treated hCMVEC, a shift toward PGE 2 as the major vasodilator product of the COX pathway was observed. Acute treatment with the protein tyrosine kinase inhibitor, tyrphostin 25, inhibited basal and IL-1␤-induced COX activities, suggesting the importance of posttranslational modifications in endothelial COX-2 activation in human brain. Altogether, these data indicate that both COX-1 and COX-2 contribute to endothelial prostanoid synthesis in the neonatal human brain under basal conditions and in response to proinflammatory cytokine IL-1␤. Cerebral circulatory disorders produce serious complications in human neonates, such as cerebral hemorrhages and hypoxicischemic injuries, that can result in life-long neurologic dysfunction in survivors including cerebral palsy, epilepsy, and mental retardation. Mechanisms of the regulation of cerebral circulation in neonates are understood incompletely, and experimental data are very limited. Vascular endothelium-derived dilator prostanoids, NO, and carbon monoxide are vasorelaxant factors essential in the regulation of cerebral blood flow. There are speciesspecific and age-dependent differences in physiologically relevant endothelial vasorelaxants in the cerebral circulation (1). In human newborns, prostanoids appear to be major factors that contribute to regulation of cerebral blood flow in response to hypercapnia, asphyxia, ischemia, and cerebral hemorrhage (1-3), and indomethacin is widely used in neonatal practice (2,4,5). Similarly, in newborn pigs, prostanoids contribute to the regulation of cerebral blood flow under basal conditions and in response to physiologically important stimuli, such as CO 2 , oxygen, and changes in blood pressure (1). Prostanoids are also important in the pathogenesis of inflammation because they alter in...

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“…The decision to administer indomethacin should be carefully considered in terms of riskbenefit ratio, given its potential adverse effects on cerebral 42,43 and/or mesenteric blood flow. 44 As renal perfusion, glomerular filtration rate and diuresis in early neonatal life strongly depend on the vasodilator effects of prostaglandins on the afferent glomerular arterioles, indomethacin and ibuprofen, as other cyclo-oxygenase inhibitors may not be exempt from some renal undesirable effects.…”

Section: Ductal Steal and Nonsteroidal Anti-inflammatory Agentsmentioning

confidence: 99%

Spectral Doppler waveforms in systemic arteries and physiological significance of a patent ductus arteriosus

et al. 2010

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Patent ductus arteriosus in extremely premature babies is associated with major neonatal morbidities, such as necrotizing enterocolitis and intraventricular hemorrhage. This may be attributable, at least in part, to systemic hypoperfusion secondary to ductal steal. A hemodynamically significant ductus arteriosus (HSDA) is known to be associated with altered systemic blood flow and end-organ hypoperfusion. Although descending aorta blood flow profiles may show abnormal diastolic retrograde flow, Doppler studies of blood flow in the systemic arteries may help improve our understanding of the relationship of a HSDA with these morbidities. In this article, we discuss aspects of diastolic blood flow reversal in the systemic arteries in premature infants with a hemodynamically significant duct. Whether these hemodynamic effects are significant enough to form the basis for initiating treatment is still unclear; these should form the basis for prospective studies.

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Ductus Closure in Preterm Infants Effects on Cerebral Hemodynamics

Cited by 30 publications

References 27 publications

Cerebral Oxygenation during Different Treatment Strategies for a Patent Ductus Arteriosus

Cerebral Oxygenation during Different Treatment Strategies for a Patent Ductus Arteriosus

COX-1 and COX-2 Contributions to Basal and IL-1β-Stimulated Prostanoid Synthesis in Human Neonatal Cerebral Microvascular Endothelial Cells

Spectral Doppler waveforms in systemic arteries and physiological significance of a patent ductus arteriosus

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