Relationship Between Cerebral Oxygenation and Phosphorylation Potential During Secondary Energy Failure in Hypoxic-Ischemic Newborn Piglets

Abstract

ABSTRACT:The aim of this study was to evaluate the hypothesis that cerebral hemoglobin (Hb) oxygenation is related to phosphorylation potential during primary and secondary cerebral energy failure in newborn infants who have experienced birth asphyxia. We subjected newborn piglets to severe transient cerebral hypoxic-ischemia followed by resuscitation and examined cerebral energy metabolism by 31 P-magnetic resonance spectroscopy and evaluated changes in cerebral Hb oxygen saturation (ScO 2 ) using full-spectrum nearinfrared spectroscopy before, during, and up to 54 h after the hypoxic-ischemic insult. ScO 2 was significantly decreased during the hypoxic-ischemic insult compared with baseline values. During secondary energy failure, piglets were separated based on the relationship between the ratio of phosphocreatine to inorganic phosphate and ScO 2 ; those with a negative correlation were less injured than those with a positive correlation. These results indicate that changes in ScO 2 as measured by near-infrared spectroscopy are related to phosphorylation potential during secondary energy failure in asphyxiated infants. (Pediatr Res 65: 317-322, 2009) H ypoxic-ischemic encephalopathy remains a major cause of permanent neurodevelopmental disability and infant mortality. Phosphorus nuclear magnetic resonance spectroscopy ( 31 P-MRS) has shown that on the first day of life there are no differences in the high-energy phosphate metabolites found in the brains of infants who have experienced birth asphyxia and normal infants (1,2). However, over the next several days, inverse changes in the concentrations of phosphocreatine (PCr) and inorganic phosphate (Pi) cause a significant reduction in the ͓PCr͔/͓Pi͔ ratio of asphyxiated infants, despite optimal medical management. Low values of ͓PCr͔/͓Pi͔ were found to be associated with very poor prognoses for survival and early neurodevelopmental outcome (1,2). The late metabolic deterioration that is characteristic of asphyxiated infants indicates the existence of metabolic stress and implies that there may be a therapeutic window during which appropriate therapy could improve outcomes.Near-infrared spectroscopy (NIRS), which uses light in the near-infrared range, can detect changes in the oxygenation state of hemoglobin (Hb) and water in biologic tissues. Several studies have shown the usefulness of NIRS as a noninvasive means of measuring hemodynamic changes in infants (3-10), particularly for quantifying cerebral blood volume (CBV) during small-induced changes in arterial oxygen saturation (4,7), for quantifying cerebral blood flow with rapid changes in oxyHb (or indocyanine green as an intravascular tracer) (5,8,9), and for quantifying cerebrovenous oxygen saturation during downward tilting of the head or jugular venous occlusion (10).Cerebral vascular Hb oxygen saturation (ScO 2 ) is another parameter that can be measured in absolute terms using NIRS without manipulating inspired oxygen concentration or impeding venous outflow. The output value is the weighted average ...

Simultaneous measurement of cerebral hemoglobin oxygen saturation and blood volume in asphyxiated neonates by near-infrared time-resolved spectroscopy

“…It is possible that this neonate, who later exhibited symptoms of cerebral palsy, developed rapid brain edema, inducing further ischemia during secondary energy failure [21]. Alternatively, CBV may have been affected by changes in Hb concentration, as this particular neonate had anemia at 6 h after birth and received a blood transfusion during HT ([Hb] changed from 11.0 g/dl at 6 h to 17.0 g/dl at 24 h).…”

Brain Temperature Is Increased During the First Days of Life in Asphyxiated Newborns: Developing Brain Injury Despite Hypothermia Treatment

“…[31][32][33] The increased brain temperatures in the neonates who developed brain injury may also correspond to the often-described phenomenon of luxury perfusion during which brain perfusion exceeds the metabolic demands, which leads to an increase of cerebral oxygen delivery. [34][35][36][37] Thus, the current hypothermia guidelines did not seem to prevent the development of brain injury when increased brain temperatures were found during the first days of life. These neonates with increased brain temperatures may be candidates for adjustments in their hypothermia therapy or for adjunctive therapies.…”

Does Near-Infrared Spectroscopy Identify Asphyxiated Newborns at Risk of Developing Brain Injury During Hypothermia Treatment?

“…This phenomenon may be associated with a more severe injury to the neurons, which results in neuronal apoptosis and consequently a decrease in the utilization of oxygen by dead tissues, or to the phenomenon of luxury perfusion during which brain perfusion exceeds the metabolic demands, which leads to an increase of cerebral oxygen delivery. 1,7,10,17,31,34 It also is thought to reflect the described secondary energy failure with its associated delayed neuronal death and the lack of recovery of a normal brain metabolism because of severe brain damages. 1,7,9,17,31,34 The degree of secondary energy failure has been reported to correlate with the severity of neurodevelopmental delay in asphyxiated newborns at 1 to 4 years of age.…”

“…1,7,10,17,31,34 It also is thought to reflect the described secondary energy failure with its associated delayed neuronal death and the lack of recovery of a normal brain metabolism because of severe brain damages. 1,7,9,17,31,34 The degree of secondary energy failure has been reported to correlate with the severity of neurodevelopmental delay in asphyxiated newborns at 1 to 4 years of age. 35 Similarly, an increase in rSO 2 has been reported previously in asphyxiated newborns not treated with hypothermia and also has been linked to poor outcome, although the rSO 2 increase typically started 24 hours after the initial event and evolved over the next 24 hours.…”