Skip to main content
Erschienen in: Critical Care 6/2002

01.12.2002 | Review

Bench-to-bedside review: Cytopathic hypoxia

verfasst von: Mitchell P Fink

Erschienen in: Critical Care | Ausgabe 6/2002

Einloggen, um Zugang zu erhalten

Abstract

The rate of oxygen consumption by certain tissues is impaired when mice or rats are injected with lipopolysaccharide. A similar change in the rate of oxygen consumption is observed when Caco-2 human enterocyte-like cells are incubated in vitro with cytomix, a cocktail of cytokines containing tumor necrosis factor, IL-1β, and IFN-γ. The decrease in the rate of oxygen consumption is not due to a change in oxygen delivery (e.g. on the basis of diminished microvascular perfusion), but rather to an acquired intrinsic defect in cellular respiration, a phenomenon that we have termed 'cytopathic hypoxia'. A number of different biochemical mechanisms have been postulated to account for cytopathic hypoxia in sepsis, including reversible inhibition of cytochrome a,a3 by nitric oxide, and irreversible inhibition of one or more mitochondrial respiratory complexes by peroxynitrite. Recently, however, our laboratory has obtained data to suggest that the most important mechanism underlying the development of cytopathic hypoxia is depletion of cellular stores of nicotinamide adenine dinucleotide (NAD+/NADH) as a result of activation of the enzyme, poly(ADP-ribose) polymerase-1. If cytopathic hypoxia is important in the pathophysiology of established sepsis and multiorgan dysfunction syndrome, then efforts in the future will need to focus on pharmacological interventions designed to preserve normal mitochondrial function and energy production in sepsis.
Literatur
1.
Zurück zum Zitat Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345: 1368-1377. 10.1056/NEJMoa010307CrossRefPubMed Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345: 1368-1377. 10.1056/NEJMoa010307CrossRefPubMed
2.
Zurück zum Zitat Tuchschmidt J, Fried J, Astiz M, Rackow E: Elevation of cardiac output and oxygen improves outcome in septic shock. Chest 1992, 102: 216-220.CrossRefPubMed Tuchschmidt J, Fried J, Astiz M, Rackow E: Elevation of cardiac output and oxygen improves outcome in septic shock. Chest 1992, 102: 216-220.CrossRefPubMed
3.
Zurück zum Zitat Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, Fumagalli R: A trial of goal-oriented hemodynamic therapy in critically ill patients. N Engl J Med 1995, 333: 1025-1032. 10.1056/NEJM199510193331601CrossRefPubMed Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, Fumagalli R: A trial of goal-oriented hemodynamic therapy in critically ill patients. N Engl J Med 1995, 333: 1025-1032. 10.1056/NEJM199510193331601CrossRefPubMed
4.
Zurück zum Zitat Hayes MA, Timmins AC, Yau EHS, Palazzo M, Hinds CJ, Watson D: Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994, 330: 1717-1722. 10.1056/NEJM199406163302404CrossRefPubMed Hayes MA, Timmins AC, Yau EHS, Palazzo M, Hinds CJ, Watson D: Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994, 330: 1717-1722. 10.1056/NEJM199406163302404CrossRefPubMed
5.
Zurück zum Zitat Hotchkiss RS, Karl IE: Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis. JAMA 1992, 267: 1503-1509. 10.1001/jama.267.11.1503CrossRefPubMed Hotchkiss RS, Karl IE: Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis. JAMA 1992, 267: 1503-1509. 10.1001/jama.267.11.1503CrossRefPubMed
6.
Zurück zum Zitat Fink MP: Cytopathic hypoxia in sepsis. Acta Anaesthesiol Scand 1997,41(suppl 100):87-95.CrossRef Fink MP: Cytopathic hypoxia in sepsis. Acta Anaesthesiol Scand 1997,41(suppl 100):87-95.CrossRef
7.
Zurück zum Zitat Fink MP: Cytopathic hypoxia: mitochondrial dysfunction as a mechanism contributing to organ dysfunction in sepsis. Crit Care Clin North Am 2001, 17: 219-237.CrossRef Fink MP: Cytopathic hypoxia: mitochondrial dysfunction as a mechanism contributing to organ dysfunction in sepsis. Crit Care Clin North Am 2001, 17: 219-237.CrossRef
8.
Zurück zum Zitat Barcroft J: On anoxaemia. Lancet 1920, ii: 485. Barcroft J: On anoxaemia. Lancet 1920, ii: 485.
9.
Zurück zum Zitat Astiz M, Rackow EC, Weil MH, Schumer W: Early impairment of oxidative metabolism and energy production in severe sepsis. Circ Shock 1988, 26: 311-320.PubMed Astiz M, Rackow EC, Weil MH, Schumer W: Early impairment of oxidative metabolism and energy production in severe sepsis. Circ Shock 1988, 26: 311-320.PubMed
10.
Zurück zum Zitat Hotchkiss RS, Rust RS, Dence CS, Wasserman TH, Song S-K, Hwang D-R, Karl IE, Welch MJ: Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [ 18 F]fluoroisonidazole. Am J Physiol 1991, 261: R965-R972.PubMed Hotchkiss RS, Rust RS, Dence CS, Wasserman TH, Song S-K, Hwang D-R, Karl IE, Welch MJ: Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [ 18 F]fluoroisonidazole. Am J Physiol 1991, 261: R965-R972.PubMed
11.
Zurück zum Zitat VanderMeer TJ, Wang H, Fink MP: Endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia in a normodynamic porcine model of septic shock. Crit Care Med 1995, 23: 1217-1226. 10.1097/00003246-199507000-00011CrossRefPubMed VanderMeer TJ, Wang H, Fink MP: Endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia in a normodynamic porcine model of septic shock. Crit Care Med 1995, 23: 1217-1226. 10.1097/00003246-199507000-00011CrossRefPubMed
12.
Zurück zum Zitat Rosser DM, Stidwill RP, Jacobson D, Singer M: Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis. J Appl Physiol 1995, 79: 1878-1882.PubMed Rosser DM, Stidwill RP, Jacobson D, Singer M: Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis. J Appl Physiol 1995, 79: 1878-1882.PubMed
13.
Zurück zum Zitat Boekstegers P, Weidenhofer S, Pilz G, Werdan K: Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: comparison to limited infection and cardiogenic shock. Infection 1991, 19: 317-323.CrossRefPubMed Boekstegers P, Weidenhofer S, Pilz G, Werdan K: Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: comparison to limited infection and cardiogenic shock. Infection 1991, 19: 317-323.CrossRefPubMed
14.
Zurück zum Zitat Sair M, Etherington PJ, Winlove CP, Evans TW: Tissue oxygenation and perfusion in patients with systemic sepsis. Crit Care Med 2001, 29: 1343-1349. 10.1097/00003246-200107000-00008CrossRefPubMed Sair M, Etherington PJ, Winlove CP, Evans TW: Tissue oxygenation and perfusion in patients with systemic sepsis. Crit Care Med 2001, 29: 1343-1349. 10.1097/00003246-200107000-00008CrossRefPubMed
15.
Zurück zum Zitat Simonson SG, Welty-Wolf K, Huang Y-CT, Griebel JA, Caplan MS, Fracica PJ, Piantadosi CA: Altered mitochondrial redox responses in Gram negative septic shock in primates. Circ Shock 1994, 43: 34-43.PubMed Simonson SG, Welty-Wolf K, Huang Y-CT, Griebel JA, Caplan MS, Fracica PJ, Piantadosi CA: Altered mitochondrial redox responses in Gram negative septic shock in primates. Circ Shock 1994, 43: 34-43.PubMed
16.
Zurück zum Zitat Vallet B, Lund N, Curtis SE, Kelly D, Cain SM: Gut and muscle tissue PO 2 in endotoxemic dogs during shock and resuscitation. J Appl Physiol 1994, 76: 793-800.PubMed Vallet B, Lund N, Curtis SE, Kelly D, Cain SM: Gut and muscle tissue PO 2 in endotoxemic dogs during shock and resuscitation. J Appl Physiol 1994, 76: 793-800.PubMed
17.
Zurück zum Zitat Hasibeder W, Germann R, Wolf HJ, Haisjackl M, Hausdorfer H, Riedmann B, Bonatti J, Gruber E, Schwarz B, Waldenberger P, Friesenecker B, Furtner B: Effects of short-term endotoxemia and dopamine on mucosal oxygenation in porcine jejunum. Am J Physiol 1996, 270: G667-G675.PubMed Hasibeder W, Germann R, Wolf HJ, Haisjackl M, Hausdorfer H, Riedmann B, Bonatti J, Gruber E, Schwarz B, Waldenberger P, Friesenecker B, Furtner B: Effects of short-term endotoxemia and dopamine on mucosal oxygenation in porcine jejunum. Am J Physiol 1996, 270: G667-G675.PubMed
18.
Zurück zum Zitat Sair M, Etherington PJ, Curzen NP, Winlove CP, Evans TW: Tissue oxygenation and perfusion in endotoxemia. Am J Physiol 1996, 271: H1620-H1625.PubMed Sair M, Etherington PJ, Curzen NP, Winlove CP, Evans TW: Tissue oxygenation and perfusion in endotoxemia. Am J Physiol 1996, 271: H1620-H1625.PubMed
19.
Zurück zum Zitat Bankey PE, Hill S, Geldon D: Sequential insult enhances liver macrophage-signaled hepatocyte dysfunction. J Surg Res 1994, 57: 185-191. 10.1006/jsre.1994.1129CrossRefPubMed Bankey PE, Hill S, Geldon D: Sequential insult enhances liver macrophage-signaled hepatocyte dysfunction. J Surg Res 1994, 57: 185-191. 10.1006/jsre.1994.1129CrossRefPubMed
20.
Zurück zum Zitat Zingarelli B, Day BJ, Crapo JD, Salzman AL, Szabó C: The potential role of peroxynitrite in the vascular contractile and cellular energetic failure in endotoxic shock. Br J Pharmacol 1997, 120: 259-267.PubMedCentralCrossRefPubMed Zingarelli B, Day BJ, Crapo JD, Salzman AL, Szabó C: The potential role of peroxynitrite in the vascular contractile and cellular energetic failure in endotoxic shock. Br J Pharmacol 1997, 120: 259-267.PubMedCentralCrossRefPubMed
21.
Zurück zum Zitat Unno N, Wang H, Menconi MJ, Tytgat SHAJ, Larkin V, Smith M, Morin MJ, Chavez A, Hodin RA, Fink MP: Inhibition of inducible nitric oxide synthase ameliorates lipopolysaccharide-induced gut mucosal barrier dysfunction in rats. Gastroenterology 1997, 113: 1246-1257.CrossRefPubMed Unno N, Wang H, Menconi MJ, Tytgat SHAJ, Larkin V, Smith M, Morin MJ, Chavez A, Hodin RA, Fink MP: Inhibition of inducible nitric oxide synthase ameliorates lipopolysaccharide-induced gut mucosal barrier dysfunction in rats. Gastroenterology 1997, 113: 1246-1257.CrossRefPubMed
22.
Zurück zum Zitat Gross SS, Levi R: Tetrahydrobiopterin synthesis. An absolute requirement for cytokine-induced nitric oxide generation by vascular smooth muscle. J Biol Chem 1992, 267: 25722-25729.PubMed Gross SS, Levi R: Tetrahydrobiopterin synthesis. An absolute requirement for cytokine-induced nitric oxide generation by vascular smooth muscle. J Biol Chem 1992, 267: 25722-25729.PubMed
23.
Zurück zum Zitat Kantrow SP, Taylor DE, Carraway MS, Piantadosi CA: Oxidative metabolism in rat hepatocytes and mitochondria during sepsis. Arch Biochem Biophys 1997, 345: 278-288. 10.1006/abbi.1997.0264CrossRefPubMed Kantrow SP, Taylor DE, Carraway MS, Piantadosi CA: Oxidative metabolism in rat hepatocytes and mitochondria during sepsis. Arch Biochem Biophys 1997, 345: 278-288. 10.1006/abbi.1997.0264CrossRefPubMed
24.
Zurück zum Zitat King CJ, Tytgat S, Delude RL, Fink MP: Ileal mucosal oxygen consumption is decreased in endotoxemic rats but is restored toward normal by treatment with aminoguanidine. Crit Care Med 1999, 27: 2518-2524. 10.1097/00003246-199911000-00032CrossRefPubMed King CJ, Tytgat S, Delude RL, Fink MP: Ileal mucosal oxygen consumption is decreased in endotoxemic rats but is restored toward normal by treatment with aminoguanidine. Crit Care Med 1999, 27: 2518-2524. 10.1097/00003246-199911000-00032CrossRefPubMed
25.
Zurück zum Zitat Vary TC, Siegel JH, Nakatani T, Sato T, Aoyama H: Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. Am J Physiol 1986, 250: E634-E640.PubMed Vary TC, Siegel JH, Nakatani T, Sato T, Aoyama H: Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. Am J Physiol 1986, 250: E634-E640.PubMed
26.
Zurück zum Zitat Vary TC: Sepsis-induced alterations in pyruvate dehydrogenase complex activity in rat skeletal muscle: effects on plasma lactate. Shock 1996, 6: 89-94.CrossRefPubMed Vary TC: Sepsis-induced alterations in pyruvate dehydrogenase complex activity in rat skeletal muscle: effects on plasma lactate. Shock 1996, 6: 89-94.CrossRefPubMed
27.
Zurück zum Zitat Vary TC, Hazen S: Sepsis alters pyruvate dehydrogenase kinase activity in skeletal muscle. Mol Cell Biochem 1999, 198: 113-118. 10.1023/A:1006993910781CrossRefPubMed Vary TC, Hazen S: Sepsis alters pyruvate dehydrogenase kinase activity in skeletal muscle. Mol Cell Biochem 1999, 198: 113-118. 10.1023/A:1006993910781CrossRefPubMed
28.
Zurück zum Zitat Vary TC: Increased pyruvate dehydrogenase kinase activity in response to sepsis. Am J Physiol 1991, 250: E669-E674. Vary TC: Increased pyruvate dehydrogenase kinase activity in response to sepsis. Am J Physiol 1991, 250: E669-E674.
29.
Zurück zum Zitat Borutaité V, Brown GC: Rapid reduction of nitric oxide by mitochondria, and reversible inhibition of mitochondrial respiration by nitric oxide. Biochem J 1996, 315: 295-299.PubMedCentralCrossRefPubMed Borutaité V, Brown GC: Rapid reduction of nitric oxide by mitochondria, and reversible inhibition of mitochondrial respiration by nitric oxide. Biochem J 1996, 315: 295-299.PubMedCentralCrossRefPubMed
30.
Zurück zum Zitat Cassina A, Radi R: Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 1996, 328: 309-316. 10.1006/abbi.1996.0178CrossRefPubMed Cassina A, Radi R: Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 1996, 328: 309-316. 10.1006/abbi.1996.0178CrossRefPubMed
31.
Zurück zum Zitat Takehara Y, Kanno T, Yoshioka T, Inoue M, Utsumi K: Oxygen-dependent regulation of mitochondrial energy metabolism by nitric oxide. Arch Biochem Biophys 1995, 323: 27-32. 10.1006/abbi.1995.0005CrossRefPubMed Takehara Y, Kanno T, Yoshioka T, Inoue M, Utsumi K: Oxygen-dependent regulation of mitochondrial energy metabolism by nitric oxide. Arch Biochem Biophys 1995, 323: 27-32. 10.1006/abbi.1995.0005CrossRefPubMed
32.
Zurück zum Zitat Nishikawa M, Sato EF, Kuroki T, Inoue M: Role of glutathione and nitric oxide in the energy metabolism of rat liver mitochondria. Febs Lett 1997, 415: 341-345. 10.1016/S0014-5793(97)01156-3CrossRefPubMed Nishikawa M, Sato EF, Kuroki T, Inoue M: Role of glutathione and nitric oxide in the energy metabolism of rat liver mitochondria. Febs Lett 1997, 415: 341-345. 10.1016/S0014-5793(97)01156-3CrossRefPubMed
33.
Zurück zum Zitat Torres J, Darley-Usmer V, Wilson MT: Inhibition of cytochrome c oxidase in turnover by nitric oxide: mechanism and implications for control of respiration. Biochem J 1995, 312: 169-173.PubMedCentralCrossRefPubMed Torres J, Darley-Usmer V, Wilson MT: Inhibition of cytochrome c oxidase in turnover by nitric oxide: mechanism and implications for control of respiration. Biochem J 1995, 312: 169-173.PubMedCentralCrossRefPubMed
34.
Zurück zum Zitat Giuffre A, Sarti P, D'Itri E, Buse G, Soulimane T, Brunori M: On the mechanism of inhibition of cytochrome c oxidase by nitric oxide. J Biol Chem 2000, 271: 33404-33408.CrossRef Giuffre A, Sarti P, D'Itri E, Buse G, Soulimane T, Brunori M: On the mechanism of inhibition of cytochrome c oxidase by nitric oxide. J Biol Chem 2000, 271: 33404-33408.CrossRef
35.
Zurück zum Zitat Brown GC, Bolanos JP, Heales SJ, Clark JB: Nitric oxide produced by activated astrocytes rapidly and reversibly inhibits cellular respiration. Neurosci Lett 1995, 193: 201-204. 10.1016/0304-3940(95)11703-YCrossRefPubMed Brown GC, Bolanos JP, Heales SJ, Clark JB: Nitric oxide produced by activated astrocytes rapidly and reversibly inhibits cellular respiration. Neurosci Lett 1995, 193: 201-204. 10.1016/0304-3940(95)11703-YCrossRefPubMed
36.
Zurück zum Zitat Wink DA, Mitchell JB: Chemical biology of nitric oxide: insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med 1998, 25: 434-456. 10.1016/S0891-5849(98)00092-6CrossRefPubMed Wink DA, Mitchell JB: Chemical biology of nitric oxide: insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med 1998, 25: 434-456. 10.1016/S0891-5849(98)00092-6CrossRefPubMed
37.
Zurück zum Zitat Pryor WA, Squadrito GL: The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol 1995, 268: L699-L722.PubMed Pryor WA, Squadrito GL: The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol 1995, 268: L699-L722.PubMed
38.
Zurück zum Zitat Squadrito GL, Pryor WA: Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite, and carbon dioxide. Free Radic Biol Med 2001, 25: 392-403. 10.1016/S0891-5849(98)00095-1CrossRef Squadrito GL, Pryor WA: Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite, and carbon dioxide. Free Radic Biol Med 2001, 25: 392-403. 10.1016/S0891-5849(98)00095-1CrossRef
39.
Zurück zum Zitat Radi R, Peluffo G, Alvarez MN, Naviliat M, Cayota A: Unraveling peroxynitrite formation in biological systems. Free Radic Biol Med 2001, 30: 463-488. 10.1016/S0891-5849(00)00373-7CrossRefPubMed Radi R, Peluffo G, Alvarez MN, Naviliat M, Cayota A: Unraveling peroxynitrite formation in biological systems. Free Radic Biol Med 2001, 30: 463-488. 10.1016/S0891-5849(00)00373-7CrossRefPubMed
40.
Zurück zum Zitat Du G, Mouithys-Mickalad A, Sluse FE: Generation of superoxide anion by mitochondria and impairment of their functions during anoxia and reoxygenation in vitro. Free Radic Biol Med 1988, 25: 1066-1074. 10.1016/S0891-5849(98)00148-8CrossRef Du G, Mouithys-Mickalad A, Sluse FE: Generation of superoxide anion by mitochondria and impairment of their functions during anoxia and reoxygenation in vitro. Free Radic Biol Med 1988, 25: 1066-1074. 10.1016/S0891-5849(98)00148-8CrossRef
41.
Zurück zum Zitat Poderoso JJ, Carreras MC, Lisdero C, Riobo N, Schopfer F, Boveris A: Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys 1996, 328: 85-92. 10.1006/abbi.1996.0146CrossRefPubMed Poderoso JJ, Carreras MC, Lisdero C, Riobo N, Schopfer F, Boveris A: Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys 1996, 328: 85-92. 10.1006/abbi.1996.0146CrossRefPubMed
42.
Zurück zum Zitat Ghafourifar P, Richter C: Nitric oxide synthase activity in mitochondria. FEBS Lett 1997, 418: 291-296. 10.1016/S0014-5793(97)01397-5CrossRefPubMed Ghafourifar P, Richter C: Nitric oxide synthase activity in mitochondria. FEBS Lett 1997, 418: 291-296. 10.1016/S0014-5793(97)01397-5CrossRefPubMed
43.
Zurück zum Zitat Kanai AJ, Pearce LL, Clemens PR, Birder LA, VanBibber MM, Choi SY, de Groat WC, Peterson J: Identification of a neuronal nitric oxide synthase in isolated cardiac mitochondria using electrochemical detection. Proc Natl Acad Sci USA 2001, 98: 14126-14131. 10.1073/pnas.241380298PubMedCentralCrossRefPubMed Kanai AJ, Pearce LL, Clemens PR, Birder LA, VanBibber MM, Choi SY, de Groat WC, Peterson J: Identification of a neuronal nitric oxide synthase in isolated cardiac mitochondria using electrochemical detection. Proc Natl Acad Sci USA 2001, 98: 14126-14131. 10.1073/pnas.241380298PubMedCentralCrossRefPubMed
44.
Zurück zum Zitat Ghafourifar P, Schenk U, Klein SD, Richter C: Mitochondrial nitric-oxide synthase stimulation causes cytochrome c release from isolated mitochondria. Evidence for intramitochondrial peroxynitrite formation. J Biol Chem 1999, 27: 31185-31188. 10.1074/jbc.274.44.31185CrossRef Ghafourifar P, Schenk U, Klein SD, Richter C: Mitochondrial nitric-oxide synthase stimulation causes cytochrome c release from isolated mitochondria. Evidence for intramitochondrial peroxynitrite formation. J Biol Chem 1999, 27: 31185-31188. 10.1074/jbc.274.44.31185CrossRef
45.
Zurück zum Zitat Lacza Z, Puskar M, Figueroa JP, Zhang J, Rajapakse N, Busija DW: Mitochondrial nitric oxide synthase is constitutively active and is functionally upregulated in hypoxia. Free Radic Biol Med 2001, 31: 1609-1615. 10.1016/S0891-5849(01)00754-7CrossRefPubMed Lacza Z, Puskar M, Figueroa JP, Zhang J, Rajapakse N, Busija DW: Mitochondrial nitric oxide synthase is constitutively active and is functionally upregulated in hypoxia. Free Radic Biol Med 2001, 31: 1609-1615. 10.1016/S0891-5849(01)00754-7CrossRefPubMed
46.
Zurück zum Zitat Packer MA, Porteous CM, Murphy MP: Superoxide production by mitochondria in the presence of nitric oxide forms peroxynitrite. Biochem Mol Biol Int 1996, 40: 527-534.PubMed Packer MA, Porteous CM, Murphy MP: Superoxide production by mitochondria in the presence of nitric oxide forms peroxynitrite. Biochem Mol Biol Int 1996, 40: 527-534.PubMed
47.
Zurück zum Zitat Radi R, Rodriguez M, Castro L, Telleri R: Inhibition of mitochondrial electron transport by peroxynitrite. Arch Bioch Biophys 1994, 308: 96-102. 10.1006/abbi.1994.1014CrossRef Radi R, Rodriguez M, Castro L, Telleri R: Inhibition of mitochondrial electron transport by peroxynitrite. Arch Bioch Biophys 1994, 308: 96-102. 10.1006/abbi.1994.1014CrossRef
48.
Zurück zum Zitat Brealey D, Brand M, Hargreaves I, Heales S, Land S, Smolenski R, Davies NA, Cooper CE, Singer M: Association between mitochondiral dysfunction and severity and outcome of septic shock. Lancet 2002, 360: 219-223. 10.1016/S0140-6736(02)09459-XCrossRefPubMed Brealey D, Brand M, Hargreaves I, Heales S, Land S, Smolenski R, Davies NA, Cooper CE, Singer M: Association between mitochondiral dysfunction and severity and outcome of septic shock. Lancet 2002, 360: 219-223. 10.1016/S0140-6736(02)09459-XCrossRefPubMed
49.
Zurück zum Zitat Castro L, Rodriguez M, Radi R: Aconitase is readily inactivated by peroxynitrite, but not its precursor, nitric oxide. J Biol Chem 1994, 269: 29409-29415.PubMed Castro L, Rodriguez M, Radi R: Aconitase is readily inactivated by peroxynitrite, but not its precursor, nitric oxide. J Biol Chem 1994, 269: 29409-29415.PubMed
50.
Zurück zum Zitat Boczkowski J, Lisdero C, Lanone S, Samb A, Carreras MC, Boveris A, Aubier M, Poderoso JJ: Endogenous peroxynitrite mediates mitochondrial dysfunction in rat diaphragm during endotoxemia. FASEB J 1999, 13: 1637-1646.PubMed Boczkowski J, Lisdero C, Lanone S, Samb A, Carreras MC, Boveris A, Aubier M, Poderoso JJ: Endogenous peroxynitrite mediates mitochondrial dysfunction in rat diaphragm during endotoxemia. FASEB J 1999, 13: 1637-1646.PubMed
51.
Zurück zum Zitat Durkacz BW, Omidiji O, Gray DA, Shall S: (ADP-ribose)n participates in DNA excision repair. Nature 1980, 283: 593-596.CrossRefPubMed Durkacz BW, Omidiji O, Gray DA, Shall S: (ADP-ribose)n participates in DNA excision repair. Nature 1980, 283: 593-596.CrossRefPubMed
52.
Zurück zum Zitat Saitoh MS, Poirier GG, Lindahl T: Dual function for poly(ADP-ribose) synthesis in response to DNA strand breakage. Biochemistry 1994, 33: 7099-7106.CrossRef Saitoh MS, Poirier GG, Lindahl T: Dual function for poly(ADP-ribose) synthesis in response to DNA strand breakage. Biochemistry 1994, 33: 7099-7106.CrossRef
53.
Zurück zum Zitat Simbulan-Rosenthal CM, Rosenthal DS, Iyer S, Boulares H, Smulson ME: Involvement of PARP and poly(ADP-ribosyl)ation in the early stages of apoptosis and DNA replication. Mol Cell Biochem 1999, 193: 137-148. 10.1023/A:1006988832729CrossRefPubMed Simbulan-Rosenthal CM, Rosenthal DS, Iyer S, Boulares H, Smulson ME: Involvement of PARP and poly(ADP-ribosyl)ation in the early stages of apoptosis and DNA replication. Mol Cell Biochem 1999, 193: 137-148. 10.1023/A:1006988832729CrossRefPubMed
54.
Zurück zum Zitat Lautier D, Lageux J, Thibodeau J, Ménard L, Poirier GG: Molecular and biochemical features of poly (ADP-ribose) metabolism. Mol Cell Biochem 1993, 122: 171-193.CrossRefPubMed Lautier D, Lageux J, Thibodeau J, Ménard L, Poirier GG: Molecular and biochemical features of poly (ADP-ribose) metabolism. Mol Cell Biochem 1993, 122: 171-193.CrossRefPubMed
55.
Zurück zum Zitat D'Amours D, Desnoyers S, D'Silva I, Poirier GG: Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J 1999, 342: 249-268. 10.1042/0264-6021:3420249PubMedCentralCrossRefPubMed D'Amours D, Desnoyers S, D'Silva I, Poirier GG: Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J 1999, 342: 249-268. 10.1042/0264-6021:3420249PubMedCentralCrossRefPubMed
56.
Zurück zum Zitat Ame JC, Jacobson EL, Jacobson MK: Molecular heterogeneity and regulation of poly(ADP-ribose) glycohydrolase. Mol Cell Biochem 1999, 193: 75-81. 10.1023/A:1006912210439CrossRefPubMed Ame JC, Jacobson EL, Jacobson MK: Molecular heterogeneity and regulation of poly(ADP-ribose) glycohydrolase. Mol Cell Biochem 1999, 193: 75-81. 10.1023/A:1006912210439CrossRefPubMed
57.
Zurück zum Zitat Schraufstatter IU, Hinshaw DB, Hyslop PA, Spragg RG, Cochrane CG: Oxidant injury of cells. DNA strand-breaks activate polyadenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide. J Clin Invest 1986, 77: 1312-1320.PubMedCentralCrossRefPubMed Schraufstatter IU, Hinshaw DB, Hyslop PA, Spragg RG, Cochrane CG: Oxidant injury of cells. DNA strand-breaks activate polyadenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide. J Clin Invest 1986, 77: 1312-1320.PubMedCentralCrossRefPubMed
58.
Zurück zum Zitat Szabó C, Zingarelli B, O'Connor M, Salzman AL: DNA strand breakage, activation of poly-ADP ribosyl synthetase, and cellular energy depletion are involved in the cytotoxicity in macrophages and smooth muscle cells exposed to peroxynitrite. Proc Natl Acad Sci USA 1996, 93: 1753-1758. 10.1073/pnas.93.5.1753PubMedCentralCrossRefPubMed Szabó C, Zingarelli B, O'Connor M, Salzman AL: DNA strand breakage, activation of poly-ADP ribosyl synthetase, and cellular energy depletion are involved in the cytotoxicity in macrophages and smooth muscle cells exposed to peroxynitrite. Proc Natl Acad Sci USA 1996, 93: 1753-1758. 10.1073/pnas.93.5.1753PubMedCentralCrossRefPubMed
59.
Zurück zum Zitat Zingarelli B, O'Connor M, Wong H, Salzman AL, Szabó C: Peroxynitrite-mediated DNA strand breakage activates poly-ADP ribosyl synthetase and causes cellular energy depletion in macrophages stimulated with bacterial lipopolysaccharide. J Immunol 1996, 156: 350-358.PubMed Zingarelli B, O'Connor M, Wong H, Salzman AL, Szabó C: Peroxynitrite-mediated DNA strand breakage activates poly-ADP ribosyl synthetase and causes cellular energy depletion in macrophages stimulated with bacterial lipopolysaccharide. J Immunol 1996, 156: 350-358.PubMed
60.
Zurück zum Zitat Szabó C, Zingarelli B, Salzman AL: Role of poly-ADP ribosyltransferase activation in the vascular contractile and energetic failure elicited by exogenous and endogenous nitric oxide and peroxynitrite. Circ Res 1996, 78: 1051-1063.CrossRefPubMed Szabó C, Zingarelli B, Salzman AL: Role of poly-ADP ribosyltransferase activation in the vascular contractile and energetic failure elicited by exogenous and endogenous nitric oxide and peroxynitrite. Circ Res 1996, 78: 1051-1063.CrossRefPubMed
61.
Zurück zum Zitat Khan AU, Delude RL, Han YH, Sappington PL, Han X, Carcillo JA, Fink MP: Liposomal NAD + prevents diminished O 2 consumption by immunostimulated Caco-2 cells. Am J Physiol 2002, 282: L1082-L1091. Khan AU, Delude RL, Han YH, Sappington PL, Han X, Carcillo JA, Fink MP: Liposomal NAD + prevents diminished O 2 consumption by immunostimulated Caco-2 cells. Am J Physiol 2002, 282: L1082-L1091.
62.
Zurück zum Zitat Kim H, Jacobson EL, Jacobson MK: Synthesis and degredation of cyclic ADP-ribose by NAD glycohydrolases. Science 1993, 261: 1330-1333.CrossRefPubMed Kim H, Jacobson EL, Jacobson MK: Synthesis and degredation of cyclic ADP-ribose by NAD glycohydrolases. Science 1993, 261: 1330-1333.CrossRefPubMed
63.
Zurück zum Zitat Pulido EJ, Shames BD, Selzman CH, Barton HA, Banerjee A, Bensard DD, McIntyre RC Jr: Inhibition of PARS attenuates endotoxin-induced dysfunction of pulmonary vasorelaxation. Am J Physiol 1999, 277: L769-L776.PubMed Pulido EJ, Shames BD, Selzman CH, Barton HA, Banerjee A, Bensard DD, McIntyre RC Jr: Inhibition of PARS attenuates endotoxin-induced dysfunction of pulmonary vasorelaxation. Am J Physiol 1999, 277: L769-L776.PubMed
64.
Zurück zum Zitat Szabó A, Salzman AL, Szabó C: Poly (ADP-ribose) synthetase activation mediates pulmonary microvascular and intestinal mucosal dysfunction in endotoxin shock. Life Sci 1998, 63: 2133-2139. 10.1016/S0024-3205(99)80010-1CrossRefPubMed Szabó A, Salzman AL, Szabó C: Poly (ADP-ribose) synthetase activation mediates pulmonary microvascular and intestinal mucosal dysfunction in endotoxin shock. Life Sci 1998, 63: 2133-2139. 10.1016/S0024-3205(99)80010-1CrossRefPubMed
65.
Zurück zum Zitat Kuhnle S, Nicotera P, Wendel A, Leist M: Prevention of endotoxin-induced lethality, but not of liver apoptosis in poly(ADP-ribose) polymerase-deficient mice. Biochem Biophys Res Commun 1999, 263: 433-438. 10.1006/bbrc.1999.1393CrossRefPubMed Kuhnle S, Nicotera P, Wendel A, Leist M: Prevention of endotoxin-induced lethality, but not of liver apoptosis in poly(ADP-ribose) polymerase-deficient mice. Biochem Biophys Res Commun 1999, 263: 433-438. 10.1006/bbrc.1999.1393CrossRefPubMed
66.
Zurück zum Zitat Oliver FJ, Menissier-de Murcia J, Nacci C, Decker P, Andriantsitohaina R, Muller S, de la Rubia G, Stoclet J-C, de Murcia G: Resistance to endotoxic shock as a consequence of defective NF-kappaB activation in poly (ADP-ribose) polymerase-1 deficient mice. EMBO J 1999, 18: 4446-4454. 10.1093/emboj/18.16.4446PubMedCentralCrossRefPubMed Oliver FJ, Menissier-de Murcia J, Nacci C, Decker P, Andriantsitohaina R, Muller S, de la Rubia G, Stoclet J-C, de Murcia G: Resistance to endotoxic shock as a consequence of defective NF-kappaB activation in poly (ADP-ribose) polymerase-1 deficient mice. EMBO J 1999, 18: 4446-4454. 10.1093/emboj/18.16.4446PubMedCentralCrossRefPubMed
67.
Zurück zum Zitat Goldfarb RD, Marton A, Szabó E, Virag L, Salzman AL, Glock D, Akhter I, McCarthy R, Parrillo JE, Szabó C: Protective effect of a novel, potent inhibitor of poly(adenosine 5'-diphosphate-ribose) synthetase in a porcine model of severe bacterial sepsis. Crit Care Med 2002, 30: 974-980. 10.1097/00003246-200205000-00004CrossRefPubMed Goldfarb RD, Marton A, Szabó E, Virag L, Salzman AL, Glock D, Akhter I, McCarthy R, Parrillo JE, Szabó C: Protective effect of a novel, potent inhibitor of poly(adenosine 5'-diphosphate-ribose) synthetase in a porcine model of severe bacterial sepsis. Crit Care Med 2002, 30: 974-980. 10.1097/00003246-200205000-00004CrossRefPubMed
Metadaten
Titel
Bench-to-bedside review: Cytopathic hypoxia
verfasst von
Mitchell P Fink
Publikationsdatum
01.12.2002
Verlag
BioMed Central
Erschienen in
Critical Care / Ausgabe 6/2002
Elektronische ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc1824

Weitere Artikel der Ausgabe 6/2002

Critical Care 6/2002 Zur Ausgabe

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.