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 (HbO2), deoxygenated Hb (Hb), total Hb, and oxidized cytochrome aa3 (CytO2). Changes in cerebral Hb oxygenation and CytO2 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 HbO2, Hb, total Hb, and CytO2 by near-infrared spectroscopy and changes in nucleoside triphosphate (NTP, mostly ATP) and phosphocreatine (PC) concentrations and intracellular pH by in vivo 31P-labeled magnetic resonance spectroscopy. Four-wk-old piglets (n = 8) underwent sequential hypoxic episodes of increasing severity (inspired O2 concentration, 12, 8, 6, 4, and 0%). Animals were anesthetized and mechanically ventilated. At all levels of hypoxia, cerebral HbO2 decreased, and Hb increased. Loss of PC or NTP was not observed until inspired O2 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 CytO2 and arterial blood pressure (p < 0.0001) but not with changes in HbO2 and Hb. In conclusion, cerebral hypoxemia is readily detected by near-infrared spectroscopy as a decrease in HbO2 and an increase in Hb. However, relative changes in cerebral HbO2 and Hb have low predictive value for cerebral energy failure. Reduction of CytO2 is highly correlated with decreased brain energy state and may indicate impending cellular injury.

[1]  M. Delivoria-Papadopoulos,et al.  Fluctuations in cerebral oxygenation and blood volume during endotracheal suctioning in premature infants. , 1992, The Journal of pediatrics.

[2]  B. Siesjö,et al.  Mechanisms of ischemic brain damage , 1988, Critical care medicine.

[3]  W. Dalton Dietrich,et al.  Small Differences in Intraischemic Brain Temperature Critically Determine the Extent of Ischemic Neuronal Injury , 1987, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[4]  D. Delpy,et al.  Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation. , 1988, Biochimica et biophysica acta.

[5]  R. Vannucci.  Experimental Biology of Cerebral Hypoxia-Ischemia: Relation to Perinatal Brain Damage , 1990, Pediatric Research.

[6]  Susan Wray,et al.  QUANTIFICATION OF CEREBRAL OXYGENATION AND HAEMODYNAMICS IN SICK NEWBORN INFANTS BY NEAR INFRARED SPECTROPHOTOMETRY , 1986, The Lancet.

[7]  D. Delpy,et al.  Effects of indomethacin on cerebral haemodynamics in very preterm infants , 1990, The Lancet.

[8]  S R Arridge,et al.  Quantitation of pathlength in optical spectroscopy. , 1989, Advances in experimental medicine and biology.

[9]  D. Delpy,et al.  Brain Metabolism and Intracellular pH During Ischaemia and Hypoxia: An In Vivo 31P and 1H Nuclear Magnetic Resonance Study in the Lamb , 1987, Journal of neurochemistry.

[10]  M. Reilly,et al.  Cerebral Energy Metabolism and Oxygen State during Hypoxia in Neonate and Adult Dogs , 1990, Pediatric Research.

[11]  R. Duckrow,et al.  Disparate Recovery of Resting and Stimulated Oxidative Metabolism Following Transient Ischemia , 1981, Stroke.

[12]  D. Delpy,et al.  Methods of quantitating cerebral near infrared spectroscopy data. , 1988, Advances in experimental medicine and biology.

[13]  Frank D. Gray,et al.  Hypoxia , 1964, The Yale Journal of Biology and Medicine.

[14]  W. Oh,et al.  The effects of different rates of plasmanate infusions upon brain blood flow after asphyxia and hypotension in newborn piglets. , 1982, The Journal of pediatrics.

[15]  M. Schnall,et al.  Simultaneous 31P- and 1H-Nuclear Magnetic Resonance Studies of Hypoxia and Ischemia in the Cat Brain , 1987, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[16]  S R Arridge,et al.  The effect of optode positioning on optical pathlength in near infrared spectroscopy of brain. , 1990, Advances in experimental medicine and biology.

[17]  M. Cope,et al.  New non-invasive methods for assessing brain oxygenation and haemodynamics. , 1988, British medical bulletin.

[18]  N. Hansen,et al.  The Effects of Variations in Paco2 on Brain Blood Flow and Cardiac Output in the Newborn Piglet , 1984, Pediatric Research.

[19]  J. LaManna,et al.  Effects of respiratory gases on cytochrome a in intact cerebral cortex: Is there a critical Po2? , 1976, Brain Research.

[20]  D. Hirtz.  Report of the National Institute of Neurological Disorders and Stroke workshop on near infrared spectroscopy. , 1993, Pediatrics.

[21]  I. Silver,et al.  Oxygen in mammalian tissue: methods of measurement and affinities of various reactions. , 1991, The American journal of physiology.

[22]  C. Piantadosi,et al.  Recovery of cerebral metabolism and mitochondrial oxidation state is delayed after hypothermic circulatory arrest. , 1991, Circulation.

[23]  M. Raichle.  The pathophysiology of brain ischemia , 1983, Annals of neurology.

[24]  J. Dobbing,et al.  Prenatal and postnatal growth and development of the central nervous system of the pig , 1967, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[25]  J. Brazy,et al.  Changes in cerebral blood volume and cytochrome aa3 during hypertensive peaks in preterm infants. , 1986, The Journal of pediatrics.

[26]  F. Samson,et al.  THE HIGH‐ENERGY PHOSPHATES IN DEVELOPING BRAIN * , 1961, Journal of neurochemistry.

[27]  Current Concepts of Brain Injury in the Premature Infant , 1989 .

[28]  S A Spencer,et al.  Effects of hypoxaemia and bradycardia on neonatal cerebral haemodynamics. , 1991, Archives of disease in childhood.

[29]  R. Auer,et al.  Biological differences between ischemia, hypoglycemia, and epilepsy , 1988, Annals of neurology.

[30]  B. Chance,et al.  Oxidative phosphorylation system during steady-state hypoxia in the dog brain. , 1990, Journal of applied physiology.

[31]  R G Shulman,et al.  Cerebral intracellular pH by 31P nuclear magnetic resonance spectroscopy , 1985, Neurology.

[32]  M. Bendall.  Theory and Technique of Surface Coils in In Vivo Spectroscopy , 1990 .

[33]  David K. Stevenson,et al.  Noninvasive Methods for Estimating In Vivo Oxygenation , 1992, Clinical pediatrics.

[34]  D T Delpy,et al.  Quantification of concentration changes in neonatal human cerebral oxidized cytochrome oxidase. , 1991, Journal of applied physiology.

[35]  L. Skov,et al.  Carbon Dioxide-Related Changes in Cerebral Blood Volume and Cerebral Blood Flow in Mechanically Ventilated Preterm Neonates: Comparison of Near Infrared Spectrophotometry and 133Xenon Clearance , 1990, Pediatric Research.

[36]  M. Tsuji,et al.  Profound, reversible energy loss in the hypoxic immature rat brain. , 1993, Brain research. Developmental brain research.

[37]  M. Phelps,et al.  Maturational changes in cerebral function in infants determined by 18FDG positron emission tomography. , 1986, Science.

[38]  T N Raju,et al.  Some animal models for the study of perinatal asphyxia. , 1992, Biology of the neonate.

[39]  M. Tamura,et al.  The simultaneous measurements of tissue oxygen concentration and energy state by near-infrared and nuclear magnetic resonance spectroscopy. , 1988, Advances in experimental medicine and biology.