Reduction of Cytochrome aa3 Measured by Near-Infrared Spectroscopy Predicts Cerebral Energy Loss in Hypoxic Piglets

Abstract

Near-infrared spectroscopy is a noninvasive monitoring technique that allows quantitative measurement of changes in cerebral oxygenated Hb (HbO,), deoxygenated Hb (Hb), total Hb, and oxidized cytochrome aa, (CytO,). Changes in cerebral Hb oxygenation and CytO, have been measured in human neonates and infants under a variety of conditions. However, the association of these measurements with cerebral high-energy phosphate loss is not known. We studied simultaneous changes in cerebral HbO,, Hb, total Hb, and CytO, by near-infrared spectroscopy and changes in nucleoside triphosphate (NTP, mostly ATP) and phosphocreatine (PC) concentrations and intracellular pH by in vivo "P-labeled magnetic resonance spectroscopy. Four-wk-old piglets (n = 8) underwent sequential hypoxic episodes of increasing severity (inspired 0, concentration, 12, 8, 6, 4, and 0%). Animals were anesthetized and mechanically ventilated. At all levels of hypoxia, cerebral HbO, decreased, and Hb increased. Loss of PC or NTP was not observed until inspired 0, concentration was decreased to less than 12%. With such severe hypoxia, hypotension, intracellular acidosis, and increasingly severe PC and NTP depletions occurred. Decreases in PC and NTP correlated closely with decreased CytO, and arterial blood pressure ( p < 0.0001) but not with changes in HbO, and Hb. In conclusion, cerebral hypoxemia is readily detected by nearinfrared spectroscopy as a decrease in HbO, and an increase in Hb. However, relative changes in cerebral HbO, and Hb have low predictive value for cerebral energy failure. Reduction of CytO, is highly correlated with decreased brain energy state and may indicate impending cellular injury. (Pediatr Res 37: 253- 259, 1995)Abbreviations NIRS, near-infrared spectroscopy HbO,, oxygenated Hb Hb, deoxygenated Hb HbT, total Hb CytO,, oxidized cytochrome aa, PC, phosphocreatine NTP, nucleoside triphosphate Pi, inorganic phosphate pHi, intracellular pH MR, magnetic resonance NMR, nuclear magnetic resonance ABG, arterial blood gas dpf, differential path-length factor Pao,, arterial Po, MAP, mean arterial pressure Episodic or sustained hypoxemia and cerebral ischemia are frequent events in critically ill neonates and infants (1, 2).These conditions may contribute to brain injury through mechanisms that include a probable initial cellular energy failure neonatal cerebral monitoring has focused on noninvasive techniques to detect the presence of cerebral hypoxemia and ischemia.NIRS is a light-based technique, which allows in vivo measurement of changes in cerebral HbO,, Hb, HbT (the sum of HbO, and Hb), and the level of CytO,. Cytochrome aa, is the terminal enzyme of the mitochondria1 electron transport chain, the site of electron transfer to molecular 0,. Because the NIRS technique is noninvasive and portable, it may provide a means to monitor cerebral oxygenation in human newborns and infants. Several investigators have demonstrated changes in NIRS measures of cerebral oxygenation in human neonates and infants during events such as apnea and bra...

Changes in Cerebral Hemodynamics and Oxygenation during Hypothermic Cardiopulmonary Bypass in Neonates and Infants

“…There is concern that ACytaa3 does not properly reflect changes in brain cell oxygenation, be cause of the use of the wrong algorithms for calculation of its changes [26,34]. Moreover, the normally low-energy requirement of the newborn brain may mask fluctuations in the oxidation-reduction level of the enzyme and effect the reliability of ACytaa3 as a marker of actual changes in oxidation of the enzyme Cytaa3 [35], In this respect, however, it is important to mention the results of a recent study in hypoxic newborn pigs which showed that reduction of Cytaa3, measured by NIRS, predicted indeed cerebral energy loss in these animals [36], Although the value of ACytaa3 as a marker of brain cell oxygenation remains uncertain so far, our results suggest a role for ACytaa3 as a relative measure for cerebral oxi dation. Yager et al [7] showed in newborn dogs major perturbations in the energy status of the brain early after the start of hypother mic circulatory arrest: ATP was preserved only during the first 10 min after the start of circulatory arrest in the parietal cortex, sug gesting alterations in oxidative and energy metabolism thereafter.…”

Impaired cerebral autoregulation and brain injury in newborns with hypoxic-ischemic encephalopathy treated with hypothermia

“…These mediators lead to dysregulation of cerebral vascular tone (Lassen 1964;Meek et al 1999). The association between cerebrovascular dysfunction and cerebral injury has been supported by studies linking CBF abnormalities with proton magnetic resonance spectroscopy markers of cerebral energy failure (Tsuji et al 1995;Winter et al 2009) and adverse neurological outcomes (Meek et al 1999;Pryds et al 1990;Toet et al 2006;Zaramella et al 2007).…”

“…More recently, NIRS has emerged as an alternative method to interrogate CBF continuously and noninvasively at the bedside (Edwards et al 1988;Skov et al 1991). While prior studies have linked NIRS measures with outcomes in HIE (Ancora et al 2013;Lemmers et al 2013;Meek et al 1999;Toet et al 2006;van Bel et al 1993;Zaramella et al 2007), few studies have focused on evaluating the relationship between MAP and NIRS as a method to interrogate autoregulation (Howlett et al 2013;Tekes et al 2015). Signs of impaired cerebral pressure autoregulation may precede the presence of unregulated CBF, giving this approach the potential advantage of directing intervention before irreversible injury has occurred.…”

Measurement of cytochrome oxidase and mitochondrial energetics by near–infrared spectroscopy

“…Correlations have previously been shown with cortical impedance , [ATP] (Tsuji et al 1996) and EEG & Tamura 1993). We therefore used our neonatal piglet model ) to perform simultaneous NIRS and magnetic resonance spec-tochrome oxidase IRS C. E. Cooper and R. Springett .…”