Myocardial Protection In Hypoxic Immature Hearts[1]

 

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Current myocardial protection techniques in cyanotic immature hearts are not optimal. Despite successful surgical correction of congenital cardiac defects causing hypoxemia, myocardial dysfunction remains the leading cause of postoperative mortality. New studies indicate that the intraoperative reintroduction of molecular oxygen on cardiopulmonary bypass causes a reoxygenation injury leading to postoperative cardiac dysfunction. Biochemical and functional changes of reoxygenation injury can be avoided by several methods aimed at reducing oxygen free radical production and nitric oxide release. The present investigation provides an overview of our current understanding of pathogenesis, implication, and treatment of myocardial reoxygenation injury. New surgical concepts of myocardial protection including normoxic CPB and controlled reoxygenation are introduced.

1 Based on the paper awarded the Ernst-Derra Prize 1997 by the German Society for Thoracic and Cardiovascular Surgery

References

• 1 Ihnken K, Morita K, Buckberg G D, Matheis G, Sherman M P, Allen B S, Young H H. Studies of hypoxemic/reoxygenation injury: Without aortic clamping. II. Evidence for reoxygenation damage.  J Thorac Cardiovasc Surg.. 1995;  110 1171-81
  PubMedGoogle Scholar
• 2 Del Nido P J, Mickle D AG, Wilson G J, Benson L N, Coles J G, Trusler G A, Williams W G. Evidence of myocardial free radical injury during elective repair of tetralogy of Fallot.  Circulation.. 1987;  76 (suppl V) V174-9
  PubMedGoogle Scholar
• 3 Del Nido R J, Mickle D AG, Wilson G J, Benson L N, Weisel R D, Coles J G, Trusler G A, Williams W G. Inadequate myocardial protection with cold cardioplegic arrest during repair of tetralogy of Fallot.  J Thoracic Cardiovasc Surg.. 1988;  95 223-9
  PubMedGoogle Scholar
• 4 Fujiwara T, Kurtts T, Anderson W, Heinle J, Mayer J E. Myocardial protection in cyanotic neonatal lambs.  J Thorac Cardiovasc Surg.. 1988;  96 700-10
  PubMedGoogle Scholar
• 5 Silverman N A, Kohler J, Levitsky S, Pavel D G, Fang R B, Feinberg H. Chronic hypoxemia depresses global ventricular function and predisposes to the depletion of high-energy phosphates during cardioplegic arrest: Implications for surgical repair of cyanotic congenital heart defects.  Ann Thorac Surg.. 1984;  37 304-8
  PubMedGoogle Scholar
• 6 Teoh K H, Mickle D AG, Weisel R D, Li R, Tumiati L C, Coles J G, Williams W G. Effect of oxygen tension and cardiovascular operations on the myocardial antioxidant enzyme activities in patients with tetralogy of Fallot and aorta-coronary bypass.  J Thoracic Cardiovasc Surg.. 1992;  104 159-64
  PubMedGoogle Scholar
• 7 Ihnken K, Morita K, Buckberg G D, Sherman M P, Ignarro L J, Young H H. Studies of hypoxemic/reoxygenation injury: With aortic clamping. XIII. Interaction between oxygen tension and cardioplegic composition in limiting nitric oxide production and oxidant damage.  J Thorac Cardiovasc Surg.. 1995;  110 1274-86
  PubMedGoogle Scholar
• 8 Bull C, Cooper J, Stark J. Cardioplegic protection of the child's heart.  J Thorac Cardiovasc Surg.. 1984;  88 287-93
  CrossrefPubMedGoogle Scholar
• 9 Kofsky E, Julia P, Buckberg G D, Young H H, Tixier D. Studies of myocardial protection in the immature heart V safety of prolonged aortic clamping wich hypocalcemic glutamate/aspartate Blood cardioplcgia.  J Thorac Cardiovasc Surg.. 1991;  101 33-43
  PubMedGoogle Scholar
• 10 Cosgrove D M, Loop F D, Lytle B W, Baillot R, Gill C C, Golding L AR, Taylor P C, Goormastic M. Primary myocardial revascularization trends in surgical mortality.  J Thorac Cardiovasc Surg.. 1984;  88 673-84
  PubMedGoogle Scholar
• 11 Rudolph W. Myocardial metabolism in cyanotic congenital heart discase.  Cardiology.. 1972;  56 209-15
  PubMedGoogle Scholar
• 12 Ascuitto R J, Ross-Ascuitto N T, Ramage D, McDonought K H. Mechanical function and fatty acid oxidation in the neonatal pig heart with ischemia and reperfusion.  J Develop Physiol.. 1990;  14 249-57
  PubMedGoogle Scholar
• 13 Jarmakani J M, Nagatomo T, Nakazawa M, Langer G A. Effect of hypoxia on myocardial high-energy phosphates in the neonatal mammalian heart.  Am J Physiol.. 1978;  235 H475-81
  PubMedGoogle Scholar
• 14 Julia P L, Kofsky E R, Buckberg G D, Young H H, Bugyi H I. Studies of myocardial protection in the immature heart. I. Enhanced tolerance of immature versus adult myocardium to global ischemia with reference to metabolic differences.  J Thorac Cardiovasc Surg.. 1990;  100 879-87
  PubMedGoogle Scholar
• 15 Ihnken K, Morita K, Buckberg G D, Sherman M P, Young H H. Studies of hypoxemic/reoxygenation injury: Without aortic clamping. III. Comparison of the magnitude of damage by hypoxemia/reoxygenation versus ischemia/reperfusion.  J Thorac Cardiovasc Surg.. 1995;  110 1182-9
  PubMedGoogle Scholar
• 16 Julia P L, Kofsky E R, Buckberg G D, Young H H, Bugyi H I. Studies of myocardial protection in the immature heart. III. Models of ischemic and hypoxic/ischemic injury in the immature puppy heart.  J Thorac Cardiovasc Surg.. 1991;  101 14-22
  PubMedGoogle Scholar
• 17 Julia P L, Young H H, Buckberg G D, Kofsky E R, Bugyi H I. Studies of myocardial protection in the immature heart. IV. Improved tolerance of immature myocardium to hypoxia and ischemia by intravenous metabolic support.  J Thorac Cardiovasc Surg.. 1991;  101 23-32
  PubMedGoogle Scholar
• 18 Dhaliwal H, Kirshenbaum L A, Randhawa A K, Singal P K. Correlation between antioxidant changes during hypoxia and recovery on reoxygenation.  Am J Physiol.. 1991;  261 H632-8
  PubMedGoogle Scholar
• 19 Kirklin J K, Blackstone E H, Kirklin J W, McKay R, Pacifico A D, Bargeron L J Jr. Intracardiac surgery in infants under age 3 months: Incremental risk factors for hospital mortality.  Am J Cardiol. . 1981;  48 500-6
  CrossrefPubMedGoogle Scholar
• 20 Hirschl R B, Heiss K F, Bartlett R H. Severe myocardial dysfunction during extracorporeal membrane oxygenation.  J Pediatric Surgery.. 1992;  27 48-53
  CrossrefPubMedGoogle Scholar
• 21 Martin G R, Short B L, Abbott C, O'Brien A N. Cardiac stun in infants undergoing extracorporeal membrane oxygenation.  J Thorac Cardiovasc Surg.. 1991;  101 607-11
  PubMedGoogle Scholar
• 22 Halliwell B. Oxidants and human discase: Some new concepts.  Fed Am Soc Exp Biol.. 1987;  1 358-64
  PubMedGoogle Scholar
• 23 Hearse D J, Hymphrey S M, Chain E B. Abrupt reoxygenation of the anoxic potassium-arrested perfused rat heart: A study of myocardial enzyme release.  J Mol Cell Cardiol.. 1973;  5 395-407
  CrossrefPubMedGoogle Scholar
• 24 Allen B S, Rahman S, Ilbawi M N, Kronon M, Bolling K S, Halldorsson A O, Feinberg H. Detrimental effects of cardiopulmonary bypass in cyanotic infants: preventing the reoxygenation injury.  Ann Thorac Surg.. 1997;  64 1381-8
  CrossrefPubMedGoogle Scholar
• 25 Freeman B A, Topolosky M K, Crapo J D. Hyperoxia increases oxygen radical production in rat lung homogenates.  Arch Biochem Biophy.. 1982;  216 477-84
  PubMedGoogle Scholar
• 26 Ganote C E, Kaltenbach J P. Oxygen-induced enzyme release: Early events and proposed mechanism.  J Cel Moll Cardiol.. 1979;  11 389-406
  PubMedGoogle Scholar
• 27 Morita K, Ihnken K, Buckberg G D, Sherman M P, Ignarro I J. Pulmonary vasoconstriction due to impaired nitric oxide production after cardiopulmonary bypass.  Ann Thorac Surg.. 1996;  61 1775-80
  CrossrefPubMedGoogle Scholar
• 28 Ihnken K, Winkler A, Schlensak C, Sarai K, Neidhart G, Unkelbach U, Mülsch A, Sewell A. Normoxic cardiopulmonary bypass reduces oxidative myocardial damage and nitric oxide during cardiac operations in the adult.  J Thorac Cardiovasc Surg.. 1998;  116 327-34
  PubMedGoogle Scholar
• 29 Frank L, Massaro D. Oxygen toxicity.  Am J Med.. 1980;  69 117-26
  CrossrefPubMedGoogle Scholar
• 30 Littauer A, De Groot H. Release of reactive oxygen by hepatocytes on reoxygenation: three phases and role of mitochondria.  Am J Physiol.. 1992;  262 G1015-20
  PubMedGoogle Scholar
• 31 Sher P K, Hu S. Neuroprotective effect of graded reoxygenation following chronic hypoxia in neuronal cell cultures.  Neuroscience.. 1992;  47 979-984
  CrossrefPubMedGoogle Scholar
• 32 Deneke S M, Fanburg B L. Normobaric oxygen toxicity of the lung.  New Engl J Med.. 1980;  303 76-86
  PubMedGoogle Scholar
• 33 Lum H, Barr D A, Shaffer J R, Gordon R J, Ezrin A M, Malik A B. Reoxygenation of endothelial cells increases permiability by oxidant-dependent mechanisms.  Circ Res.. 1992;  70 991-8
  PubMedGoogle Scholar
• 34 Piper H M, Siegmund B, Schlüter K D. Prevention of the oxygen paradox in the isolated cardiomyocyte and the whole heart.  A J Cardiovasc Pathol.. 1992;  4 115-22
  PubMedGoogle Scholar
• 35 Guarnieri C, Flamigni F, Caldarera C M. Role of oxygen in the cellular damage induced by re-oxygenation of hypoxic heart.  J Mol Cell Cardiol.. 1980;  12 797-808
  CrossrefPubMedGoogle Scholar
• 36 Fujiwara T, Kurtts T, Anderson W, Heinle J, Mayer J E. Myocardial protection in cyanotic neonatal lambs.  J Thorac Cardiovasc Surg.. 1988;  96 700-10
  PubMedGoogle Scholar
• 37 Lupinetti F M, Wareing T H, Huddleston C B, Collins J C, Boucek R J, Bender H W Jr, Hammon J W Jr. Pathophysiology of chronic cyanosis in a canine model.  J Thorac Cardiovasc Surg.. 1985;  90 291-6
  PubMedGoogle Scholar
• 38 Li R K, Mickle D AG, Weisel R D, Tumiati L C, Jackowski G, Wu T W, Williams W G. Effect of oxygen tension on the anti-oxidant enzyme activities of tetralogy of Fallot ventricular myocytes.  J Mol Cell Cardiol.. 1989;  21 567-75
  CrossrefPubMedGoogle Scholar
• 39 Sagawa K, Manghan W L, Suga H, Sunagawa K. Cardiac contraction and pressure-volumr relationship. New York; Oxford University Press 1988: 56-61 & 110 - 119
  Google Scholar
• 40 Lesnefsky E J, Fennessey P M, Van Benthuysen K M, McMurtry I F, Travis V L, Horwitz L D. Superoxide dismutase decreases early reperfusion release of conjugated dienes following regional canine ischemia.  Basic Res Cardiol.. 1989;  84 191-96
  PubMedGoogle Scholar
• 41 Godin D V, Ko K M, Garnett M E. Altered antioxidant status in the ischemic/reperfused rabbit myocardium: Effects of allopurinol.  Can J Cardiol.. 1989;  5 365-71
  PubMedGoogle Scholar
• 42 Bush P A, Gonzales N E, Griscavage J M, Ignarro L J. Nitric oxide synthase from cerebellum catalyzes the formation of equimolar quantities of nitric oxide and citrulline from L-arginine.  Biochem Biophys Res Com.. 1992;  85 960-6
  PubMedGoogle Scholar
• 43 Ihnken K, Morita K, Buckberg G D. Studies of hypoxemic/reoxygenation injury: With aortic clamping. XI. Cardiac advantages of normoxemic versus hyperoxemic management during cardiopulmonary bypass.  J Thorac Cardiovasc Surg.. 1995;  110 1255-64
  PubMedGoogle Scholar
• 44 Ihnken K, Morita K, Buckberg G D, Beyersdorf F. Reduction of reoxygenation injury and nitric oxide production in the cyanotic immature heart by controlling pO₂.  Eur J Candio-thorac Surg.. 1995;  9 410-8
  PubMedGoogle Scholar
• 45 Ihnken K, Morita K, Buckberg G D, Winkelmann B, Beyersdorf F, Sherman M P. Reduced oxygen tension during cardiopulmonary bypass limits myocardial damage in acute hypoxic immature piglet hearts.  Eur J Cardio-thorac Surg.. 1996;  10 1127-35
  CrossrefPubMedGoogle Scholar
• 46 Ihnken K, Morita K, Buckberg G D, Ihnken O, Winkelmann B, Sherman M P. Prevention of reoxygenation injury in hypoxaemic immature hearts by priming the extracorporeal circuit with antioxidants.  Cardiovasc Surg.. 1997;  5 608-19
  PubMedGoogle Scholar
• 47 Morita K, Ihnken K, Buckberg G D, Sherman M P, Young H H. Studies of hypoxemic/reoxygenation injury: Without aortic clamping. IV. Role of the iron-catalyzed pathway: Deferoxamine.  J Thorac Cardiovasc Surg.. 1995;  110 1190-9
  PubMedGoogle Scholar
• 48 Ihnken K, Morita K, Buckberg G D, Sherman M P, Young H H. Studies of hypoxemic/reoxygenation injury: Without aortic clamping. VI. Counteraction of oxidant damage by exogenous antioxidants: N-(2-mercaptopropionyl)- glycine and catalase.  J Thorac Cardiovasc Surg.. 1995;  110 1212-20
  PubMedGoogle Scholar
• 49 Morita K, Ihnken K, Buckberg G D, Sherman M P, Young H H. Studies of hypoxemic/reoxygenation injury: Without aortic clamping. VII. Countcraction of oxidant damage by exogenous antioxidants: Coenzyme Q₁₀.  J Thorac Cardiovasc Surg.. 1995;  110 1221-27
  PubMedGoogle Scholar
• 50 Morita K, Ihnken K, Buckberg G D, Matheis G, Sherman M P, Young H H. Studies of hypoxemic/reoxygenation injury: With aortic clamping. X. Exogenous antioxidants to avoid nullification of the cardioprotective effects of blood cardioplegia.  J Thorac Cardiovasc Surg.. 1995;  110 1245-54
  PubMedGoogle Scholar
• 51 Ihnken K, Morita K, Buckberg G D, Winkelmann G D, Schmitt M, Ignarro L J, Sherman M P. Nitric Oxide induced reoxygenation injury in the cyanotic immature heart is prevented by controlling oxygen content during initial reoxygenation.  Angiology.. 1997;  48 189-202
  PubMedGoogle Scholar
• 52 Morita K, Matheis G, Buckberg G D, Ihnken K, Sherman M P, Young H H, Ignarro L J. Studies of hypoxemic/reoxygenation injury: Without aortic clamping. V. Role of the L-arginine-nitric oxide pathway: The nitric oxide paradox.  J Thorac Cardiovasc Surg.. 1995;  110 1200-11
  PubMedGoogle Scholar
• 53 Morita K, Ihnken K, Buckberg G D, Sherman M P, Young H H, Ignarro L J. Role of controlled cardiac reoxygenation in reducing nitric oxide production and cardiac oxidant damage in cyanotic infantile hearts.  J Clin Invest.. 1994;  93 2658-66
  PubMedGoogle Scholar
• 54 Ihnken K, Morita K, Buckberg G D. Delayed cardioplegic reoxygenation reduces reoxygenation injury in cyanotic immature hearts.  Ann Thorac Surg.. 1998;  66 177-82
  CrossrefPubMedGoogle Scholar
• 55 Morita K, Ihnken K, Buckberg G D, Sherman M P, Young H H. Studies of hypoxemic/reoxygenation injury: Without aortic clamping. IX. Importance of avoiding perioperative hyperoxemia in the setting of previous cyanosis.  J Thorac Cardiovasc Surg.. 1995;  110 1235-44
  PubMedGoogle Scholar
• 56 Morita K, Ihnken K, Buckberg G D. Studies of hypoxemic/reoxygenation injury: With aortic clamping. XII. Delay of cardiac reoxygenation damage in the presence of cyanosis: A new concept of controlled cardiac reoxygenation.  J Thorac Cardiovasc Surg.. 1995;  110 1265-73
  PubMedGoogle Scholar
• 57 Ihnken K, Matheis G, Winkelmann B, Beyersdorf F. Die Bedeutung der Myokardprotektion in der Herzchirurgie.  Zeitschrift für Allgemeinmedizin.. 1995;  71 99-106
  PubMedGoogle Scholar
• 58 Buckberg G D. Studies of controlled reperfusion after ischemia: A series of experimental and clinical observations from the Division of Thoracic Surgery, UCLA School of Medicine, Los Angeles, California.  J Thorac Cardiovasc Surg.. 1986;  92 483-648
  PubMedGoogle Scholar
• 59 Kraemer R, Mullane K M. Neutrophils delay functional recovery of the post-hypoxic heart of the rabbit.  J Pharmacol Exp Therap.. 1989;  251 620-6
  PubMedGoogle Scholar
• 60 Hearse D J, Humphrey S M, Nayler W G, Slade A, Border D. Ultrastructural damage associated wich reoxygenation of the anoxic myocardium.  J Mol Cell Cardiol.. 1975;  7 315-24
  CrossrefPubMedGoogle Scholar
• 61 Bolli R, Jeroudi M O, Patel B S. et al . Direct evidence that oxygen-derived free radicals contribute to postischemic myocardial dysfunction in the intact dog.  Proc Natl Acad Sci USA.. 1989;  86 4695-9
  PubMedGoogle Scholar
• 62 Gauduel Y, Duvelleroy A. Role of oxygen radicals in cardiac injury due to reoxygenation.  J Moll Cardiol.. 1984;  16 459-70
  PubMedGoogle Scholar
• 63 Davies M J. Applications of electron spin resonance spectroscopy to the identification of radicals produced during lipid peroxidation.  Chemistry and Physics of Lipids.. 1987;  44 149-73
  CrossrefPubMedGoogle Scholar
• 64 Schlüter K D, Schwartz P, Siegmund B, Piper H M. Prevention of the oxygen paradox in hypoxic-reoxygenated hearts.  Am J Physiol.. 1991;  261 H416-23
  PubMedGoogle Scholar
• 65 Beckman J S, Beckman T W, Chen J, Marshall P A, Freeman B A. Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide.  Proc Natl Acad Sci.. 1990;  87 1620-4
  PubMedGoogle Scholar
• 66 Brady A JB, Poole-Wilson P, Harding S E, Warren J B. Nitric oxide production within cardiac myocytes reduces their contractility in endotoxemia.  Am J Physiol.. 1992;  263 H1963-6
  PubMedGoogle Scholar
• 67 Radi R, Beckman J S, Bush K M, Freeman B A. Peroxynitrite oxidation of sulfhydrils. The cytotoxic potential of superoxide and nitric oxide.  J Biol Chem.. 1991;  266 4244-50
  PubMedGoogle Scholar
• 68 Rengasamy A, Johns R A. Characterization of endothelium-derived relaxing factor/nitric oxide synthase from bovine cerebellum and mechanism of modulation by high and low oxygen tensions.  J Pharmacol Exp Therapeutics.. 1991;  259 310-6
  PubMedGoogle Scholar
• 69 Kinsella J P, Neish S R, Shaffer E, Abman S H. Low-dose inhalational nitric oxide in persitent pulmonary hypertension of the newborn.  Lancet.. 1992;  340 819-20
  CrossrefPubMedGoogle Scholar
• 70 Moncada S, Palmer R MJ, Higgs E A. Nitric Oxide: Physiology, pathophysiology, and pharmacology.  Pharmacol Rev.. 1991;  43 109-34
  PubMedGoogle Scholar
• 71 Ignarro L J. Biosynthesis and metabolism of endothelium-derived nitric oxide.  Annu Rev Phamacol Toxicol.. 1990;  30 535-60
  PubMedGoogle Scholar
• 72 Kanter K R, Glower D D, Schaff H V, Gardner T J. Mechanism of defective oxygen extraction following global ischemia.  J Surg Res.. 1981;  30 482-8
  CrossrefPubMedGoogle Scholar
• 73 Gauduel Y, Menasche P, Duvelleroy M. Enzyme release and mitochondrial activity in reoxygenated cardiac muscle: Relationship with oxygen-induced lipid peroxidation.  General Physiological Biophysics.. 1989;  8 327-40
  PubMedGoogle Scholar
• 74 Follette D M, Fey K, Buckberg G D, Helly J J, Steed D L, Foglia R P, Maloney J M Jr. Reducing postischemic damage by temporary modification of reperfusate calcium, potassium, pH, and osmolarity.  J Thorac Cardiovasc Surg.. 1981;  82 221-38
  PubMedGoogle Scholar
• 75 Rosenkranz E R, Okamoto F, Buckberg G D, Vinten-Johansen J, Robertson J M, Bugyi H. Safety of prolonged aortic clamping wich blood cardioplegia II Glutamate enrichment in energy-depleted hearts.  J Thorac Cardiovasc Surg.. 1984;  88 402-10
  PubMedGoogle Scholar
• 76 Grinwald P M, Brosnahan C. Sodium imbalance as a cause of calcium overload in post-hypoxic reoxygenation injury.  J Mol Cell Cardiol.. 1987;  19 487-95
  PubMedGoogle Scholar
• 77 Peng C F, Kane J J, Murphy M L, Straub K D. Abnormal mitochondrial oxidative phosphorylation of ischemic myocardium reversed by Ca chelating agent.  J Mol Cell Cardiol.. 1977;  9 897-908
  PubMedGoogle Scholar
• 78 Kukreja R C, Kontos H A, Hess M L, Ellis E F. PGH synthase and lipoxygenase generate superoxide in the presence of NADH or NADPH.  Circ Res.. 1986;  59 612-9
  CrossrefPubMedGoogle Scholar
• 79 Taegtmeyer H. Metabolic responses to cardiac hypoxia. Increased production of succinate by rabbit papillary muscle.  Circ Res.. 1978;  43 808-15
  PubMedGoogle Scholar
• 80 Rosenkranz E R, Okamoto F, Buckberg G D, Vinten-Johansen J, Robertson J M, Bugyi H. Safety ol prolonged aortic clamping with blood cardioplegia II Glutamate enrichment in energy-depleted hearts.  J Thorac Cardiovasc Surg.. 1984;  88 402-10
  PubMedGoogle Scholar
• 81 Lazar H L, Buckberg G D, Manganaro A M, Becker H. Myocardial energy replenishment and reversal of ischemic damage by substrate enhancement of secondary blood cardioplegia with amino acids during reperfusion.  J Thorac Cardiovasc Surg.. 1980;  80 350-9
  PubMedGoogle Scholar
• 82 Morita K, Ihnken K, Buckberg G D, Matheis G, Sherman M P, Young H H. Studies of hypoxemic/reoxygenation injury: Without aortic clamping. VIII. Counteraction of oxidant damage by exogenous glutamate and aspartate.  J Thorac Cardiovasc Surg.. 1995;  110 1228-34
  PubMedGoogle Scholar
• 83 Bogie R G, Coade S B, Moncada S, Pearson J D, Mann G E. Bradykinin and ATP stimulate L-arginine uptake and nitric oxide release in vascular endothelial cells.  Biochem Biophys Res Comms.. 1991;  180 926-32
  PubMedGoogle Scholar
• 84 Sweiry J H, Munoz M, Mann G E. Cis-inhibition and trans-stimulation of cationic amino acid transport in the perfused rat pancreas.  Am J Physiol.. 1991;  261 C506-14
  PubMedGoogle Scholar
• 85 Tribble D L, Jones D P. Oxygen dependence of oxidative stress. Rate of NADPH supply for maintaining the GSH pool during hypoxia.  Biochem Pharmacol.. 1990;  39 729-36
  CrossrefPubMedGoogle Scholar
• 86 Cavarocchi N C, England M D, Schaff H V, Russo P, Orszulak T A, Schnell W A Jr, O'Brien J F, Pluth J R. Oxygen free radical generation during cardiopulmonary bypass: correlation with complement activation.  Circulation.. 1986;  74 (suppl. III) 130-3
  PubMedGoogle Scholar

1 Based on the paper awarded the Ernst-Derra Prize 1997 by the German Society for Thoracic and Cardiovascular Surgery

Dr. Kai Ihnken

Stanford University Hospital

Department of Surgery

Room H3680

300 Pasteur Drive

Stanford, CA 94305

USA



Phone: 650-725-2181

Fax: 650-725-0791