There is an established link between congenital heart disease and acquired brain injury, which relates to the dependence of the nervous system on a consistent and responsive supply of oxygen and glucose. The advances in the field of infant cardiac surgery have presented new and different challenges to the arena of child neurology This review provides an overview of the mechanisms of neurologic injury and cerebral hemodynamics and metabolism during cardiac surgery. This review discusses current and future strategies for the management of children with congenital heart disease. (J Child Neurol 1997;12:285-300).
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References
1.
Benson D.: Changing profile of congenital heart disease. Pediatrics1989;83:790-791.
2.
Castaneda A. , Mayer J., Jonas R., et al: The neonate with critical congenital heart disease: Repair—a surgical challenge . J Thorac Cardiovasc Surg1989;98:869-875.
3.
Ferry P.: Neurologic sequelae of cardiac surgery in children. Am J Dis Child1987;141:309-312.
4.
Ferry P.: Neurologic sequelae of open-heart surgery in children: An irritating question . Am J Dis Child1990;144:369-373.
5.
Michenfelder J ,Theye R.: Hypothermia: Effect on canine brain and whole body metabolism. Anesthesiology1968;29:1107-1111.
6.
Newburger J. , Jonas R., Wernovsky G., et al: A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery. N Engl J Med1993;329:1057-1064.
7.
Kontos H., Wei E., Navari R., et al: Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol1978;3:H371-H383.
8.
Kontos H.: Validity of cerebral blood flow calculations from velocity measurements . Stroke1989;20:1-3.
9.
van der Linden J., Priddy R., Eckroth R., et al: Cerebral perfusion and metabolism during profound hypothermia in children: A study of middle cerebral artery ultrasonic variables and cerebral extraction of oxygen. J Thorac Cardiovasc Surg1991;102:103-114.
10.
Markus H.: Transcranial Doppler detection of circulating emboli: A review. Stroke1993;24:1246-1250.
11.
Greeley W., Ungerleider R., Smith L., Reves J.: The effects of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral blood flow in infants and children. J Thorac Cardiovasc Surg1989;97:737-745.
12.
Greeley W., Ungerleider R., Kern F., et al: Effects of cardiopulmonary bypass on cerebral blood flow in neonates, infants, and children. Circulation1989;80 (Suppl 1):209-215.
13.
Spahn D., Quill T., Hu W., et al: Validation of 133Xe clearance as a cerebral blood flow measurement during cardiopulmonary bypass. J Cereb Blood Flow Metab1992;12:155-161.
14.
Dexter F., Hindman B.: Theoretical analysis of cerebral venous blood hemoglobin oxygen saturation as an index of cerebral oxygenation during hypothermic cardiopulmonary bypass . Anesthesiology1995;83:405-412.
15.
Schell R., Kern F., Reves F.: The role of continuous jugular venous saturation monitoring during cardiac surgery with cardiopulmonary bypass. Anesth Analg1992;74:627-629.
16.
Nakajima T. , Kuro M., Hayashi Y., et al: Clinical evaluation of cerebral oxygen balance during cardiopulmonary bypass: On-line continuous monitoring of jugular venous oxyhemoglobin saturation. Anesth Analg1992;74:630-635.
17.
Croughwell N., Newman M., Blumenthal J., et al: Jugular bulb saturation and cognitive dysfunction after cardiopulmonary bypass. Ann Thorac Surg1994;58:1702-1708.
18.
Wyatt J., Delpy D., Cope M., Wray S., Reynolds E.: Quantification of cerebral oxygenation and hemodynamics in sick newborn infants by near infrared spectroscopy. Lancet1986 ;ii:1063-1066.
19.
Edwards A., Richardson C., Cope M., et al: Cotside measurement of cerebral blood flow in ill newborn infants by near infrared spectroscopy. Lancet1988 ;ii:770-771.
20.
du Plessis A.: Near-infrared spectroscopy for the in vivo study of cerebral hemodynamics and oxygenation. Curr Opin Pediatr1995;7:632-639.
21.
du Plessis A., Newburger J., Jonas R., et al: Cerebral oxygen supply and utilization during infant cardiac surgery. Ann Neurol1995;37:488-497.
22.
Greeley W., Bracey V., Ungerleider R., et al: Recovery of cerebral metabolism and mitochondrial oxidation state is delayed after hypothermic circulatory arrest. Circulation1991;84(Suppl III):III-400-III-406.
23.
Kurth C., Steven J., Nicolson S.: Cerebral oxygenation during pediatric cardiac surgery using deep hypothermic circulatory arrest. Anesthesiology1995;82:74-82.
24.
Fallon P., Roberts I., Kirkham F., et al: Cerebral hemodynamics during cardiopulmonary bypass in children using near-infrared spectroscopy. Ann Thorac Surg1993;56:1473-1477.
25.
Nollert G., Mohnle P., Tassani-Prell P., Reichart B.: Determinants of cerebral oxygenation during cardiac surgery. Circulation1995;92(Suppl II):327-333.
26.
Tamura M.: Non-invasive monitoring of brain oxygen metabolism during cardiopulmonary bypass by near-infrared spectrophotometry. Jpn Circ J1991;55:330-335.
27.
Roberts I., Fallon P., Kirkham F., et al: Estimation of cerebral blood flow with near infrared spectroscopy and indocyanine green. Lancet1993;342(ii):1425.
28.
Bozoky B., Bara D., Kertesz E.: Autopsy study of cerebral complications of congenital heart disease and cardiac surgery. J Neurol1984;3:153-161.
29.
Terplan K.: Brain changes in newborns, infants and children with congenital heart disease in association with cardiac surgery. Additional observations. J Neurosurg1976;212:225.
30.
Terplan K.: Patterns of brain damage in infants and children with congenital heart disease: Association with catheterization and surgical procedures. Am J Dis Child1973;125:175-185.
31.
Mujsce D., Towfighi J., Yager J., Vannucci R.: Neuropathologic aspects of hypothermic circulatory arrest in newborn dogs . Acta Neuropathol1993;85:190-198.
32.
Redmond J., Gillinov A., Zehr K., et al: Glutamate excitotoxicity: A mechanism of neurologic injury associated with hypothermic circulatory arrest. J Thorac Cardiovasc Surg1994;107:776-786.
33.
Johnston M., Redmond J., Gillinov A., et al: Neuroprotective strategies in a model of selective neuronal necrosis from hypothermic circulatory arrest, in Moskowitz M, Caplan L (eds): Cerebrovascular Diseases. Boston, Butterworth-Heinemann, 1995, pp 165-174.
34.
Kupsky W., Drozd M., Barlow C.: Selective injury of the globus pallidus in children with post-cardiac surgery choreic syndrome. Dev Med Child Neurol1995 ;37:135-144.
35.
Volpe J.: Hypoxic-ischemic encephalopathy: Neuropathology and pathogenesis, in Neurology of the Newborn, 3rd ed. Philadelphia, WB Saunders, 1994, pp 279-313.
36.
Dietrich W., Busto R., Alonso O., Globus M-T., Ginsberg M.: Intraischemic but not postischemic brain hypothermia protects chronically following global forebrain ischemia in rats. J Cereb Blood Flow Metab1993;13:541-549.
Wong P., Barlow C., Hickey P., et al: Factors associated with choreoathetosis after cardiopulmonary bypass in children with congenital heart disease. Circulation1992;86(Suppl II):II-118-II-126.
39.
Solis R., Kennedy P., Beall A., Noon G., DeBakey M.: Cardiopulmonary bypass: Microembolization and platelet aggregation . Circulation1975;52:103-108.
40.
Blauth C., Arnold J., Schulenberg W., et al: Cerebral microembolism during cardiopulmonary bypass. J Thorac Cardiovasc Surg1988; 95:668-676.
41.
Moody D., Bell M., Challa V., Johnston W., Prough D.: Brain microemboli during cardiac surgery or aortography. Ann Neurol1990;28:477-486.
42.
Boyajian R. , Sobel D., DeLaria G., et al: Embolic stroke as a sequela of cardiopulmonary bypass. J Neuroimag1993;3:1-5.
43.
Kirklin J., Westaby S., Blackstone E., et al: Complement and the damaging effects of cardiopulmonary bypass . J Thorac Cardiovasc Surg1983;86:845-857.
44.
Casey L.: Role of cytokines in the pathogenesis of cardiopulmonary-induced multisystem organ failure. Ann Thorac Surg1993;56(Suppl 5):S92-S96.
45.
Steinberg J. , Kapelanski D., Olson J., et al: Cytokine and complement levels in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg1993;106:1008-1016.
46.
Padayachee T., Parsons S., Theobold R., et al: The detection of microemboli in the middle cerebral artery during cardiopulmonary bypass: A transcranial Doppler ultrasound investigation using membrane and bubble oxygenators. Ann Thorac Surg1987; 44:298-302.
47.
Nussmeier N. , McDermott J.: Macroembolization: Prevention and outcome modification, in Hilberman M (ed): Brain Injury and Protection During Cardiac Surgery. Boston , Martinus Nijhoff, 1988, pp 85-108.
48.
Fish K.: Microembolization: Etiology and prevention, in Hilberman M (ed): Brain Injury and Protection During Cardiac Surgery. Boston, Martinus Nijhoff , 1988, pp 67-84.
49.
Jorens P., De Jongh R., De Backer W., et al: Interleukin-8 production in patients undergoing cardiopulmonary bypass. The influence of pretreatment with methylprednisolone. Am Rev Respir Dis1993;148:890-895.
50.
Millar A., Armstrong L., van der Linden J., et al: Cytokine production and hemodilution in children undergoing cardiopulmonary bypass. 1993;56:1499-1502.
51.
Seghaye M., Duchateau J., Grabitz R., et al: Complement activation during cardiopulmonary bypass in infants and children. Relation to postoperative multiple system organ failure. J Thorac Cardiovasc Surg1993; 106:978∼987.
52.
Palmer C.: Hypoxic-ischemic encephalopathy: Therapeutic approaches against microvascular injury, and role of neutrophils, PAF, and free radicals. Clin Perinatol1995;22:481-517.
53.
Hickey P., Buckley M., Philbin D.: Pulsatile and nonpulsatile cardiopulmonary bypass: Review of a counterproductive controversy. Ann Thorac Surg1983;36:720-737.
54.
Yada I.: Is nonpulsatile blood flow detrimental to patients?Artif Organs1993;17:291-292.
55.
Hindman B., Dexter F., Smith T., Cutkomp J.: Pulsatile versus nonpulsatile flow: No difference in cerebral blood flow or metabolism during normothermic cardiopulmonary bypass in rabbits. Anesthesiology1995;82:241-250.
56.
Sorensen H. , Husum B., Waaben J., et al: Brain microvascular function during cardiopulmonary bypass. J Thorac Cardiovasc Surg1987;94:727-732.
57.
Murkin J., Farrar K., Tweed A., et al: The influence of non-pulsatile normothermic perfusion on cerebral blood flow and metabolism, abstracted. Anesth Analg1987;66:S125.
58.
Andersen K. , Waaben J., Husum B., et al: Nonpulsatile cardiopulmonary bypass disrupts the flow-metabolism couple in the brain. J Thorac Cardiovasc Surg1985;90:570-579.
59.
Kono M., Orita H., Shimanuki T., et al: A clinical study of cerebral perfusion during pulsatile and nonpulsatile cardiopulmonary bypass. J Jpn Surg Soc1990;29:1021-1022.
60.
Sadahiro M. , Haneda K., Mohri H.: Experimental study of cerebral autoregulation during cardiopulmonary bypass with or without pulsatile perfusion. J Thorac Cardiovasc Surg1994;108(3):446-454.
61.
Lundar T., Lindegaard K., Froysaker T., et al: Dissociation between cerebral autoregulation and carbon dioxide reactivity during nonpulsatile cardiopulmonary bypass. Ann Thorac Surg1985;40: 582-587.
62.
Dernevik L. , Ardvidsson S., William-Olsson G.: Cerebral perfusion in dogs during pulsatile and nonpulsatile extracorporeal perfusion. J Cardiovasc Surg1985;26:32-35.
63.
Greeley W., Kern F., Ungerleider R., et al: The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants and children. J Thorac Cardiovasc Surg1991;101:783-794.
64.
Murkin J., Farrar J., Tweed W., et al: Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: The influence of PaCO2. Anesth Analg1987;66:825-832.
65.
Prough D., Rogers A., Stump D., et al: Cerebral blood flow decreases with time whereas cerebral oxygen consumption remains stable during hypothermic cardiopulmonary bypass in humans . Anesth Analg1991;72:161-168.
66.
Govier A., Reves J., McKay R., et al: Factors and their influence on regional cerebral blood flow during nonpulsatile cardiopulmonary bypass. Ann Thorac Surg1984;38:592-600.
67.
Schwartz A. , Michler R., Young W.: Cerebral blood flow during low flow hypothermic cardiopulmonary bypass in baboons, abstracted . Anesth Analg1992;74:S267.
68.
Dapper F., Neppl H., Wozniak G., et al: Effects of pulsatile and nonpulsatile perfusion mode during extracorporeal circulation—a comparative clinical study. Thorac Cardiovasc Surg1992;40: 345-351.
69.
Masumoto T. , Wolferth C., Perlman M.: Effect of pulsatile and nonpulsatile perfusion upon cerebral and conjunctival microcirculation in dogs. Arch Surg1966;93:730-740.
70.
Mori A., Sono J., Nakashima M., Okada Y.: Application of pulsatile cardiopulmonary bypass for profound hypothermia in cardiac surgery. Jpn Circ J1981;45:315-320.
71.
Taylor K., Devlin B., Mittra S., et al: Assessment of cerebral damage during open-heart surgery: A new experimental model. Scand J Thorac Cardiovasc Surg1980;14:197-203.
72.
Sanderson J. , Wright G., Sims F.: Brain damage in dogs immediately following pulsatile and non-pulsatile blood flows in extracorporeal circulation. Thorax1972;27:275-286.
73.
Henze T., Stephan H., Sonntag H.: Cerebral dysfunction following extracorporeal circulation for aortocoronary bypass surgery: No differences in neuropsychological outcome after pulsatile versus nonpulsatile flow. J Thorac Cardiovasc Surg1990;38:65-68.
74.
Kern F., Jonas R., Mayer J., et al: Temperature monitoring during infant CPB: Does it predict efficient brain cooling?Ann Thorac Surg1992;54:749-754.
75.
Bellinger D. , Wernovsky G., Rappaport L., et al: Cognitive development of children following early repair of transposition of the great arteries using deep hypothermic circulatory arrest . Pediatrics1991;87:701-707.
76.
Steen P., Newberg L., Milde J., Michenfelder J.: Hypothermia and barbiturates: Individual and combined effects on canine cerebral oxygen metabolism. Anesthesiology1983;58:527-532.
77.
Reeves R.: The effect of temperature on the oxygen equilibrium curve of human blood. Respir Physiol1980;42:317-328.
78.
Coetzee A., Swanepoel C.: The oxyhemoglobin dissociation curve before, during and after cardiac surgery . Scand J Clin Lab Invest Suppl1990 ;203:149-153.
79.
Hillier S., Burrows F., Bissonnette B., Taylor R.: Cerebral hemodynamics in neonates and infants undergoing cardiopulmonary bypass and profound hypothermic circulatory arrest: Assessment by transcranial Doppler sonography. Anesth Analg1991;72: 723-728.
80.
Kern F., Ungerleider R., Reves J., et al: The effect of altering pump flow on cerebral blood flow and metabolism in infants and children. Ann Thorac Surg1993;56:1366-1372.
81.
Speziali G. , Russo P., Davis D., Wagerle L.: Hypothermia enhances contractility in cerebral arteries of newborn lambs. J Surg Res1994 ;57:80-84.
82.
Prough D., Stump D., Roy R., et al: Response of cerebral blood flow to changes in carbon dioxide tension during hypothermic cardiopulmonary bypass. Anesthesiology1986;64:576-581.
83.
Kern F., Ungerleider R., Quill T., et al: Cerebral blood flow response to changes in arterial carbon dioxide tension during hypothermic cardiopulmonary bypass in children. J Thorac Cardiovasc Surg1991;101:618-622.
84.
Venn G., Sherry K., Klinger L., et al: Cerebral blood flow during cardiopulmonary bypass. Eur J Cardiothorac Surg1988;2:360-363.
85.
Koster J., Van de Vanter S., Bean J., Collins J., Cohn L.: Effect of hemodilution and profound hypothermic circulatory arrest on blood flow and oxygen consumption of the brain. Surg Forum1976;27:235-237.
86.
Hall T.: The pathophysiology of cardiopulmonary bypass: The risks and benefits of hemodilution . Chest1995;107:1125-1133.
87.
Lacour-Gayet F., Nicolas F., Coll J., et al: Continuous perfusion without hemodilution in neonates: The experience at the Marie Lannelongue Hospital. Cardiol Young1993;3:340-346.
88.
Hiramatsu T. , Miura T., Forbess J., et al: pH strategies and cerebral energetics before and after circulatory arrest. J Thorac Cardiovasc Surg1995;109:948-958.
89.
Rossi R., Ekroth R., Lincoln C., et al: Detection of cerebral injury after total circulatory arrest and profound hypothermia by estimation of specific creatinine kinase isoenzyme levels using monoclonal antibody techniques. Am J Cardiol1986;58:1236-1241.
90.
Fox L., Blackstone E., Kirklin J., et al: Relationship of brain blood flow and oxygen consumption to perfusion flow rate during profoundly hypothermic cardiopulmonary bypass. J Thorac Cardiovasc Surg1984;87:658-664.
91.
Swain J., McDonald T., Griffith P., et al: Low-flow hypothermic cardiopulmonary bypass protects the brain . J Thorac Cardiovasc Surg1991;102:76-83.
92.
Lundar T., Lindegaard K., Froysaker T., et al: Cerebral perfusion during nonpulsatile cardiopulmonary bypass . Ann Thorac Surg1985; 40:144-150.
93.
Astudillo R. , van der Linden J., Ekroth R., et al: Absent diastolic cerebral blood flow velocity after circulatory arrest but not after low flow in infants. Ann Thorac Surg1993;56:515-519.
94.
Jonassen A. , Quaegebeur J., Young W.: Cerebral blood flow velocity in pediatric patients is reduced after cardiopulmonary bypass with profound hypothermia . J Thorac Cardiovasc Surg1995;110: 934-943.
95.
Nathan H., Lavallee G.: The management of temperature during hypothermic cardiopulmonary bypass : 1. Canadian survey. Can J Anaesth1995;42:669-671.
96.
Dietrich D. , Busto R., Halley M., Valdes I.: The importance of brain temperature in alterations of the blood-brain barrier following cerebral ischemia. J Neuropathol Exp Neurol1990;49:486-497.
97.
Mitani A., Kataoka K.: Critical levels of extracellular glutamate mediating gerbil hippocampal delayed neuronal death during hypothermia: Brain microdialysis study. Neuroscience1991;42: 661-670.
98.
Mezrow C., Midulla P., Sadeghi A., et al: Evaluation of cerebral metabolism and quantitative electroencephalography after hypothermic circulatory arrest and low-flow cardiopulmonary bypass at different temperatures. J Thorac Cardiovasc Surg1994;107:1006-1019.
99.
Ohare B., Bissonnette B., Bohn D., Cox P., Williams W.: Persistent low cerebral blood flow velocity following profound hypothermic circulatory arrest in infants. Can J Anaesth1995;42:964-971.
100.
van der Linden J., Astudillo R., Ekroth R., Scallan M., Lincoln C.: Cerebral lactate release after circulatory arrest but not after low flow in pediatric heart operations. Ann Thorac Surg1993;56:1485-1489.
101.
McNeill B. , Murkin J., Farrar J.: Autoregulation and the CO2 responsiveness of cerebral blood flow after cardiopulmonary bypass . Can JAnaesth1990;37:313-317.
102.
du Plessis A., Newburger J., Jonas R., et al: Cerebral CO2 vasoreactivity is impaired in the early postoperative period following hypothermic infant cardiac surgery, abstracted. Eur J Neurol1995;2(Suppl 2):68A.
103.
Wyatt J., Edwards A., Cope M., et al: Response of cerebral blood volume to changes in arterial carbon dioxide tension in preterm and term infants. Pediatr Res1991;29:553-557.
104.
Astrup J., Sorensen P., Rahbek Sorensen H: Inhibition of cerebral oxygen and glucose consumption in the dog by hypothermia, pentobarbital, and lidocaine. Anesthesiology1981;55:256-262.
105.
Swain J., McDonald T., Balaban R., Robbins R.: Metabolism of the heart and brain during hypothermic cardiopulmonary bypass . Ann Thorac Surg1991;51:105-109.
106.
Aoki M., Nomura F., Stromski M., et al: Effects of pH on brain energetics after hypothermic circulatory arrest. Ann Thorac Surg1993;55:1093-1103.
107.
Buchan A., Pulsinelli W.: Hypothermia but not the N-methyl-D-aspartate antagonist, MK801, attenuates neuronal damage in gerbils subjected to transient global ischemia. J Neurosci1990;10: 311-316.
108.
Busto R., Dietrich W., Globus M-T., et al: Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cereb Blood Flow Metab1987;7: 729-738.
109.
Busto R., Globus M., Dietrich W., et al: Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain. Stroke1989;20:904-910.
110.
Busto R., Dietrich W., Globus M., et al: Post-ischemic moderate hypothermia inhibits CA1 hippocampal ischemic neuronal injury. Neurosci Lett1989 ;101:299-304.
111.
Rokkas CK, Cronin CS, Nitta T., et al: Profound systemic hypothermia inhibits the release of neurotransmitter amino acids in spinal cord ischemia. J Thorac Cardiovasc Surg1995;110:27-35.
112.
Penrice J. , Thoresen M., Lorek A., et al: Mild hypothermia following severe hypoxia-ischemia ameliorates delayed cerebral energy failure in the newborn piglet, abstracted. Early Hum Dev1994;39: 146A.
113.
Laptook A., Corbett R., Burns D., Sterett R.: Neonatal ischemic neuroprotection by modest hypothermia is associated with attenuated brain acidosis. Stroke1995 ;26:1240-1246.
114.
Edwards A., Yue X., Squier M., et al: Specific inhibition of apoptosis after cerebral hypoxia-ischaemia by moderate post-insult hypothermia. Biochem Biophys Res Commun1995;217:1193-1199.
115.
Ledeist F., Menasche P., Kucharski C., et al: Hypothermia during cardiopulmonary bypass delays but does not prevent neutrophilendothelial cell adhesion. A clinical study. Circulation1995;92(Suppl II):II-354-II-358.
116.
Williams G. , Palmer C., Heitjan D., et al: Allopurinol preserves cerebral energy metabolism during perinatal hypoxia-ischemia: A 31P NMR study in unanesthetized immature rats. Neurosci Lett1992; 144:103-106.
117.
McDonald J. , Silverstein F., Johnston M.: MK-801 pretreatment enhances N-methyl-D-aspartate-mediated brain injury and increases brain N-methyl-D-aspartate recognition site binding in rats. Neuroscience1990;38:103-113.
118.
Nathan HJ, Polls T.: The management of temperature during hypothermic cardiopulmonary bypass: 2. Effect of prolonged hypothermia. Can J Anaesth1995;42:672-676.
119.
Ginsberg M. , Sternau L., Globus M-T., Dietrich W., Busto R.: Therapeutic modulation of brain temperature: relevance to ischemic brain injury. Cerebrovasc Brain Metab Rev1992;4:189-225.
120.
Rodriguez R., Austin E., Audenaert S.: Postbypass effects of delayed rewarming on cerebral blood flow velocities in infants after total circulatory arrest. J Thorac Cardiovasc Surg1995;110:1686-1691.
121.
Sirimanne E., Blumberg R., Bossano D., et al: The effect of prolonged modification of cerebral temperature on outcome after hypoxic-ischemic brain injury in the infant rat. Pediatr Res1996;39:591-597.
122.
Kramer R., Sanders A., Lesage A., Woodhall B., Sealy W.: The effect of profound hypothermia on preservation of cerebral ATP content during circulatory arrest. J Thorac Cardiovasc Surg1968;56: 699-709.
123.
Fisk G., Wright G., Turner B., et al: Cerebral effects of circulatory arrest at 20°C in the infant pig. Anaesth Intensive Care1974;2: 33-42.
124.
Fisk G., Wright J., Hicks R., et al: The influence of duration of circulatory arrest at 20 degrees C on cerebral changes. Anaesth Intensive Care1976;4:126-134.
125.
Treasure T. , Naftel D., Conger K., et al: The effect of hypothermic arrest time on cerebral function, morphology, and biochemistry: An experimental study . J Thorac Cardiovasc Surg1983;86:761-770.
126.
Coles J., Taylor M., Pearce J.: Cerebral monitoring of somatosensory evoked potentials during profoundly hypothermic circulatory arrest. Circulation1984;70:96-102.
127.
Weiss M., Weiss C., Nicolas F., Binet J.: A study of the electroencephalogram during surgery with deep hypothermia and circulatory arrest. J Thorac Cardiovasc Surg1975;70:316-329.
128.
Bellinger D., Jonas R., Rappaport L., et al: Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl JMed1995;332:549-555.
129.
Bailes J., Leavitt M., Teeple E., et al: Ultraprofound hypothermia with complete blood substitution in a canine model. J Neurosurg1991;74:781-788.
130.
Robbins R. , Balaban R., Swain J.: Intermittent hypothermic asanguinous cerebral perfusion (cerebroplegia) protects the brain during prolonged circulatory arrest. J Thorac Cardiovasc Surg1990;99:878-884.
131.
Aoki M., Jonas R., Nomura F., et al: Effects of cerebroplegic solutions during hypothermic circulatory arrest and short-term recovery. J Thorac Cardiovasc Surg1994;108:291-301.
132.
Taylor M., Bailes J., Elrifai A., et al: A new solution for life without blood. Asanguinous low-flow perfusion of a whole-body perfusate during 3 hours of cardiac arrest and profound hypothermia. Circulation1995;91:431-434.
133.
Mault J., Whitaker E., Heinle J., et al: Intermittent perfusion during hypothermic circulatory arrest: A new and effective technique for cerebral protection. Surg Forum1992;44:314-316.
134.
Mault J., Whitaker E., Heinle J., et al: Cerebral metabolic effects of sequential periods of hypothermic circulatory arrest. Ann Thorac Surg1994;57:96-101.
135.
Filgueiras C., Winsborrow B., Ye J., et al: A 31P-magnetic resonance study of antegrade and retrograde cerebral perfusion during aortic arch surgery in pigs. J Thorac Cardiovasc Surg1995;110:55-62.
136.
Oohara K., Usui A., Murase M., Tanaka M., Abe T.: Regional cerebral tissue blood flow measured by the colored microsphere method during retrograde cerebral perfusion. J Thorac Cardiovasc Surg1995;109:772-779.
137.
Safi H., Brien H., Winter J., et al: Brain protection via cerebral retrograde perfusion during aortic arch aneurysm repair. Ann Thorac Surg1993 ;56:270-276.
138.
Usui A., Hotta T., Hiroura M., et al: Retrograde cerebral perfusion through a superior vena caval cannula protects the brain. Ann Thorac Surg1992;53:47-53.
139.
Kazui T., Inoue N., Yamada O., Komatsu S.: Selective cerebral perfusion during operation for aneurysms of the aortic arch. Ann Thorac Surg1992;53:109-114.
140.
Lundstrom K., Pryds O., Greisen G.: Oxygen at birth and prolonged cerebral vasoconstriction in preterm infants. Arch Dis Child1995;73:F81-F86.
141.
Journois D. , Pouard P., Greeley W., et al: Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery. Anesthesiology1994;81:1181-1189.
142.
Elliott M. : Ultrafiltration and modified ultrafiltration in pediatric open heart operations. Ann Thorac Surg1993;56:1518-1522.
143.
Aoki M., Jonas R., Nomura F., Kawata H., Hickey P.: Anti-CD 18 attenuates deleterious effects of cardiopulmonary bypass and hypothermic circulatory arrest in piglets. J Cardiac Surg1995;10:407-417.
144.
Kirschbom P., Skaryak L., DiBernardo L., et al: Effects of aortopulmonary collaterals on cerebral cooling and cerebral metabolic recovery after circulatory arrest . Circulation1995;92(Suppl II):II-490-II-494.
145.
Watanabe T. , Orita H., Kobayashi M., et al: Brain tissue pH, oxygen tension and carbon dioxide in profoundly hypothermic cardiopulmonary bypass. J Thorac Cardiovasc Surg1989;97:396-401.
146.
Watanabe T. , Miura M., Orita H., et al: Brain tissue pH, oxygen tension, and carbon dioxide tension in profoundly hypothermic cardiopulmonary bypass. Pulsatile assistance for circulatory arrest, low-flow perfusion and moderate-flow perfusion . J Thorac Cardiovasc Surg1990;100:274-280.
147.
Swain J., McDonald T., Robbins R., Balaban R.: Relationship of cerebral and myocardial intracellular pH to blood pH during hypothermia. Am J Physiol1991;260:H1640-H1644.
148.
Skaryak L. , Chai P., Kern F., Greeley W., Ungerleider R.: Blood gas management and degree of cooling: Effects on cerebral metabolism before and after circulatory arrest. J Thorac Cardiovasc Surg1995;110:1649-1657.
149.
Bashein G. , Townes B., Nessly M., et al: A randomized study of carbon dioxide management during hypothermic cardiopulmonary bypass . Anesthesiology1990;72:3-6.
150.
Stephan H. , Weyland A., Kazmaier S., et al: Acid-base management during hypothermic cardiopulmonary bypass does not affect cerebral metabolism but does affect blood flow and neurological outcome. Br J Anaesth1992;69:51-57.
151.
Murkin JM, Martzke JS, Buchan AM, Bentley C., Wong C.: A randomized study of the influence of perfusion technique and pH management strategy in 316 patients undergoing coronary artery bypass surgery. II. Neurologic and cognitive outcomes. J Thorac Cardiovasc Surg1995;110:349-362.
152.
Jonas R., Bellinger D., Rappaport L., et al: Relation of pH strategy and developmental outcome after hypothermic circulatory arrest. J Thorac Cardiovasc Surg1993;106:362-368.
153.
Morad M., Dichter M., Tang C.: The NMDA activated current in hippocampal neurons is highly sensitive to [H+], abstracted. Soc Neurosci Abst1989 ;14:791.
154.
Takadera T., Shimada Y., Mohri T.: Extracellular pH modulates N-methyl-D-aspartate receptor mediated neurotoxicity and calcium accumulation in rat cortical cultures. Brain Res1992;572:126-131.
155.
Kaku D., Giffard R., Choi D.: Neuroprotective effects of glutamate antagonists and extracellular acidity . Science1993;260:1516-1518.
156.
Tombaugh G. , Sapolsky R.: Evolving concepts about the role of acidosis in ischemic neuropathology. J Neurochem1993 ;61:793-803.
157.
Hindman B. , Dexter F., Cutkomp J., Smith T.: pH stat management reduces the cerebral metabolic rate for oxygen during profound hypothermia (17°C). Anesthesiology1995;82:983-995.
158.
Vannucci R. , Towfighi J., Heitjan D., Brucklacher R.: Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: An experimental study in the immature rat. Pediatrics1995 ;95: 868-874.
159.
Cohen P.: Effect of anesthetics on mitochondrial function. Anesthesiology1973;39:153-164.
160.
Verhaegen M., Iaizzo PA, Todd MM: A comparison of the effects of hypothermia, pentobarbital, and isoflurane on cerebral energy stores at the time of ischemic depolarization. Anesthesiology1995;82:1209-1215.
161.
Siegman M. , Anderson R., Balaban R., et al: Barbiturates impair cerebral metabolism during hypothermic circulatory arrest. Ann Thorac Surg1992;54:1131-1136.
162.
Hoff J., Smith A., Hankinson H., Nielsen S.: Barbiturate protection from cerebral infarction in primates. Stroke1975;6:28-33.
163.
Michenfelder J., Milde J., Sundt T.: Cerebral protection by barbiturate anesthesia: Use of middle cerebral artery occlusion in Java monkeys. Arch Neurol1976;33:345-350.
164.
Shapiro H. : Barbiturates in brain ischemia. Br J Anaesth1985;57: 82-95.
165.
Zaidan J., Klochany A., Martin W., et al: Effect of thiopental on neurologic outcome following coronary artery bypass grafting. Anesthesiology1991 ;74:406-411.
166.
Nussmeier N., Arlund C., Slogoff S.: Neuropsychiatric complications after cardiopulmonary bypass: Cerebral protection by a barbiturate. Anesthesia1986;64:165-170.
167.
Waxman S.: Molecular and cellular organization of the central nervous system: Implications for new therapies, in Waxman S (ed): Molecular and Cellular Approaches to the Treatment of Neurological Disease. New York, Raven Press, 1993, pp 1-21.
168.
Siesjo B., Bengtsson F.: Calcium fluxes, calcium antagonists, and calcium-related pathology in brain ischemia, hypoglycemia, and spreading depression: A unifying hypothesis . J Cereb Blood Flow Metab1989;9:127-140.
169.
Buchan A.: Advances in cerebral ischemia: Experimental approaches. Neurol Clin1992;10:49-61.
Gelmers H. , Gorter K., De Weerdt C., Wiezer H.: A controlled trial of nimodipine in acute ischemic stroke. N Engl J Med1988;318:203-207.
172.
Buchan A., Gertler S., Li H., et al: A selective N-type Ca2+ channel blocker prevents CA1 injury 24 h following severe forebrain ischemia and reduces infarction following focal ischemia. J Cereb Blood Flow Metab1994 ;14:903-910.
173.
Valentino K., Newcomb R., Gadbois T., et al: A selective N-type calcium channel antagonist protects against neuronal cell loss after global cerebral ischemia . Proc Natl Acad Sci U S A1993;90: 7894-7897.
174.
Forsman M. , Tubylewicz Olsnes B, Semb G., Steen P.: Effects of nimodipine on cerebral blood flow and neuropsychological outcome after cardiac surgery . Br J Anaesth1990;65:514-520.
175.
Aoki M., Nomura F., Stromski M., et al: Effects of MK-801 and NBQX on acute recovery of cerebral metabolism after hypothermic circulatory arrest. J Cereb Blood Flow Metab1994;14:156-165.
176.
Redmond J. , Gillinov A., Blue M., et al: The monosialoganglioside, GM1, reduces neurologic injury associated with hypothermic circulatory arrest . Surgery1993;114:324-333.
177.
Redmond J. , Zehr K., Blue M., et al: AMPA glutamate receptor antagonism reduces neurologic injury after hypothermic circulatory arrest . Ann Thorac Surg1995;59:579-584.
178.
Xue D. , Huang Z., Barnes K., et al: Delayed treatment with AMPA, but not NMDAm, antagonists reduces neocortical infarction. J Cereb Blood Flow Metab1994;14:251-261.
179.
Buchan A., Lesiuk H., Barnes K., et al: AMPA antagonists: Do they hold more promise for clinical stroke trials than NMDA antagonists?Stroke1993;24:148-152.
180.
Olney J.: Neurotoxicity of NMDA receptor antagonists: An overview. Psychopharmacol Bull1994;30:533-540.
181.
McDonald J. , Johnston M.: Physiological and pathophysiological roles of excitatory amino acids during central nervous system development . Brain Res Rev1990;15:41-70.
182.
Palmer C., Vannucci R., Towfighi J.: Reduction of hypoxic-ischemic brain damage with allopurinol. Pediatr Res1990;27:332-336.
183.
Palmer C., Roberts R.: Reduction of perinatal brain damage with oxipurinol treatment after hypoxic-ischemic injury. Pediatr Res1991;29:362A.
184.
Hall E., Braughler J., Yonker P., et al: A potent inhibitor of lipid per-oxidation with activity in experimental injury and ischemia. J Pharmacol Exp Ther1991;258:688-694.
185.
Mohaved A. , Nair K., Ashavaid T., Kumad P.: Free radical generation and the role of allopurinol as a cardioprotective agent during coronary artery bypass grafting surgery, abstracted. Can J Cardiol1995;12:138-144.
186.
McGaurn S. , Davis L., Krawczeniuk M., et al: The pharmacokinetics of injectable allopurinol in newborns with the hypoplastic left heart syndrome . Pediatrics1994;94:820-823.
