Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Critical Care
Erschienen in: Critical Care 5/2003

01.10.2003 | Review

Bench-to-bedside review: Microvascular dysfunction in sepsis –hemodynamics, oxygen transport, and nitric oxide

verfasst von: Ryon M Bateman, Michael D Sharpe, Christopher G Ellis

Erschienen in: Critical Care | Ausgabe 5/2003

Einloggen, um Zugang zu erhalten

Abstract

The microcirculation is a complex and integrated system that supplies and distributes oxygen throughout the tissues. The red blood cell (RBC) facilitates convective oxygen transport via co-operative binding with hemoglobin. In the microcirculation oxygen diffuses from the RBC into neighboring tissues, where it is consumed by mitochondria. Evidence suggests that the RBC acts as deliverer of oxygen and 'sensor' of local oxygen gradients. Within vascular beds RBCs are distributed actively by arteriolar tone and passively by rheologic factors, including vessel geometry and RBC deformability. Microvascular oxygen transport is determined by microvascular geometry, hemodynamics, and RBC hemoglobin oxygen saturation. Sepsis causes abnormal microvascular oxygen transport as significant numbers of capillaries stop flowing and the microcirculation fails to compensate for decreased functional capillary density. The resulting maldistribution of RBC flow results in a mismatch of oxygen delivery with oxygen demand that affects both critical oxygen delivery and oxygen extraction ratio. Nitric oxide (NO) maintains microvascular homeostasis by regulating arteriolar tone, RBC deformability, leukocyte and platelet adhesion to endothelial cells, and blood volume. NO also regulates mitochondrial respiration. During sepsis, NO over-production mediates systemic hypotension and microvascular reactivity, and is seemingly protective of microvascular blood flow.
Literatur
1.
Gilbert RP: Mechanisms of the hemodynamic effects of endotoxin. Physiol Rev 1960, 40: 245-278.
2.
Carroll GC, Snyder JV: Hyperdynamic severe intravascular sepsis depends on fluid administration in cynomolgus monkey. Am J Physiol 1982, 243: R131-R141.
3.
Krishnagopalan S, Kumar A, Parrillo JE, Kumar A: Myocardial dysfunction in the patient with sepsis. Curr Opin Crit Care 2002, 8: 376-388. 10.1097/00075198-200210000-00003
4.
Zhang H, Rogiers P, Smail N, Cabral A, Preiser JC, Peny MO, Vincent JL: Effects of nitric oxide on blood flow distribution and O 2 extraction capabilities during endotoxic shock. J Appl Physiol 1997, 83: 1164-1173.
5.
Yang S, Cioffi WG, Bland KI, Chaudry IH, Wang P: Differential alterations in systemic and regional oxygen delivery and consumption during the early and late stages of sepsis. J Trauma 1999, 47: 706-712.
6.
Samsel RW, Nelson DP, Sanders WM, Wood LD, Schumacker PT: Effect of endotoxin on systemic and skeletal muscle O 2 extraction. J Appl Physiol 1988, 65: 1377-1382.
7.
Nelson DP, Samsel RW, Wood LD, Schumacker PT: Pathological supply dependence of systemic and intestinal O 2 uptake during endotoxemia. J Appl Physiol 1988, 64: 2410-2419.
8.
Shoemaker WC, Appel PL, Kram HB: Tissue oxygen debt as a determinant of lethal and nonlethal postoperative organ failure. Crit Care Med 1988, 16: 1117-1120.
9.
Walley KR: Heterogeneity of oxygen delivery impairs oxygen extraction by peripheral tissues: theory. J Appl Physiol 1996, 81: 885-894.
10.
Humer MF, Phang PT, Friesen BP, Allard MF, Goddard CM, Walley KR: Heterogeneity of gut capillary transit times and impaired gut oxygen extraction in endotoxemic pigs. J Appl Physiol 1996, 81: 895-904.
11.
Bredle DL, Samsel RW, Schumacker PT, Cain SM: Critical O 2 delivery to skeletal muscle at high and low PO 2 in endotoxemic dogs. J Appl Physiol 1989, 66: 2553-2558.
12.
Schumacker PT, Samsel RW: Oxygen delivery and uptake by peripheral tissues: physiology and pathophysiology. Crit Care Clin 1989, 5: 255-269.
13.
Kirschenbaum LA, Astiz ME, Rackow EC: Interpretation of blood lactate concentrations in patients with sepsis. Lancet 1998, 352: 921-922.
14.
Vary TC, Hazen S: Sepsis alters pyruvate dehydrogenase kinase activity in skeletal muscle. Mol Cell Biochem 1999, 198: 113-118. 10.1023/A:1006993910781
15.
Vary TC: Sepsis-induced alterations in pyruvate dehydrogenase complex activity in rat skeletal muscle: effects on plasma lactate. Shock 1996, 6: 89-94.
16.
James JH, Luchette FA, McCarter FD, Fischer JE: Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 1999, 354: 505-508. 10.1016/S0140-6736(98)91132-1
17.
L'Her E, Sebert P: A global approach to energy metabolism in an experimental model of sepsis. Am J Respir Crit Care Med 2001, 164: 1444-1447.
18.
Cohen ES, Hollenberg SM: Tissue oxygenation and sepsis. Crit Care Med 2001, 29: 1479-1480. 10.1097/00003246-200107000-00032
19.
Lam C, Tyml K, Martin C, Sibbald W: Microvascular perfusion is impaired in a rat model of normotensive sepsis. J Clin Invest 1994, 94: 2077-2083.
20.
Neviere R, Mathieu D, Chagnon JL, Lebleu N, Millien JP, Wattel F: Skeletal muscle microvascular blood flow and oxygen transport in patients with severe sepsis. Am J Respir Crit Care Med 1996, 153: 191-195.
21.
Tyml K, Yu J, McCormack DG: Capillary and arteriolar responses to local vasodilators are impaired in a rat model of sepsis. J Appl Physiol 1998, 84: 837-844.
22.
Zhao H, Spain DA, Matheson PJ, Vaughn C, Harris PD, Garrison RN: Sustained infection induces 2 distinct microvascular mechanisms in the splanchnic circulation. Surgery 2000, 128: 513-519. 10.1067/msy.2000.108114
23.
Whitworth PW, Cryer HM, Garrison RN, Baumgarten TE, Harris PD: Hypoperfusion of the intestinal microcirculation without decreased cardiac output during live Escherichia coli sepsis in rats. Circ Shock 1989, 27: 111-122.
24.
Cryer HM, Garrison RN, Kaebnick HW, Harris PD, Flint LM: Skeletal microcirculatory responses to hyperdynamic Escherichia coli sepsis in unanesthetized rats. Arch Surg 1987, 122: 86-92.
25.
Piper RD, Pitt-Hyde M, Li F, Sibbald WJ, Potter RF: Microcirculatory changes in rat skeletal muscle in sepsis. Am J Respir Crit Care Med 1996, 154: 931-937.
26.
Bateman RM, Jagger JE, Sharpe MD, Ellsworth ML, Mehta S, Ellis CG: Erythrocyte deformability is a nitric oxide-mediated factor in decreased capillary density during sepsis. Am J Physiol Heart Circ Physiol 2001, 280: H2848-H2856.
27.
Drazenovic R, Samsel RW, Wylam ME, Doerschuk CM, Schumacker PT: Regulation of perfused capillary density in canine intestinal mucosa during endotoxemia. J Appl Physiol 1992, 72: 259-265. 10.1063/1.352124
28.
Farquhar I, Martin CM, Lam C, Potter R, Ellis CG, Sibbald WJ: Decreased capillary density in vivo in bowel mucosa of rats with normotensive sepsis. J Surg Res 1996, 61: 190-196. 10.1006/jsre.1996.0103
29.
Madorin WS, Martin CM, Sibbald WJ: Dopexamine attenuates flow motion in ileal mucosal arterioles in normotensive sepsis. Crit Care Med 1999, 27: 394-400. 10.1097/00003246-199902000-00048
30.
Ellis CG, Bateman RM, Sharpe MD, Sibbald WJ, Gill R: Effect of a maldistribution of microvascular blood flow on capillary O 2 extraction in sepsis. Am J Physiol Heart Circ Physiol 2002, 282: H156-H164.
31.
Nakajima Y, Baudry N, Duranteau J, Vicaut E: Microcirculation in intestinal villi: a comparison between hemorrhagic and endotoxin shock. Am J Respir Crit Care Med 2001, 164: 1526-1530.
32.
Weinberg JR, Boyle P, Thomas K, Murphy K, Tooke JE, Guz A: Capillary blood cell velocity is reduced in fever without hypotension. Int J Microcirc Clin Exp 1991, 10: 13-19.
33.
Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF: Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet 2002, 360: 1395-1396. 10.1016/S0140-6736(02)11393-6
34.
De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL: Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 2002, 166: 98-104. 10.1164/rccm.200109-016OC
35.
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.
36.
Anning PB, Sair M, Winlove CP, Evans TW: Abnormal tissue oxygenation and cardiovascular changes in endotoxemia. Am J Respir Crit Care Med 1999, 159: 1710-1715.
37.
Boekstegers P, Weidenhofer S, Kapsner T, Werdan K: Skeletal muscle partial pressure of oxygen in patients with sepsis. Crit Care Med 1994, 22: 640-650.
38.
Ince C, Sinaasappel M: Microcirculatory oxygenation and shunting in sepsis and shock. Crit Care Med 1999, 27: 1369-1377. 10.1097/00003246-199907000-00031
39.
Hotchkiss RS, Rust RS, Dence CS, Wasserman TH, Song SK, Hwang DR, Karl IE, Welch MJ: Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F]fluoromisonidazole. Am J Physiol 1991, 261: R965-R972.
40.
Boczkowski J, Vicaut E, Aubier M: In vivo effects of Escherichia coli endotoxemia on diaphragmatic microcirculation in rats. J Appl Physiol 1992, 72: 2219-2224.
41.
Cryer HM, Garrison RN, Harris PD: Role of muscle microvasculature during hyperdynamic and hypodynamic phases of endotoxin shock in decerebrate rats. J Trauma 1988, 28: 312-318.
42.
Hollenberg SM, Piotrowski MJ, Parrillo JE: Nitric oxide synthase inhibition reverses arteriolar hyporesponsiveness to endothelin-1 in septic rats. Am J Physiol 1997, 272: R969-R974.
43.
Hollenberg SM, Cunnion RE, Zimmerberg J: Nitric oxide synthase inhibition reverses arteriolar hyporesponsiveness to catecholamines in septic rats. Am J Physiol 1993, 264: H660-H663.
44.
Sato Y, Walley KR, Klut ME, English D, D'yachkova Y, Hogg JC, van Eeden SF: Nitric oxide reduces the sequestration of polymorphonuclear leukocytes in lung by changing deformability and CD18 expression. Am J Respir Crit Care Med 1999, 159: 1469-1476.
45.
Tugtekin IF, Radermacher P, Theisen M, Matejovic M, Stehr A, Ploner F, Matura K, Ince C, Georgieff M, Trager K: Increased ileal-mucosal-arterial PCO 2 gap is associated with impaired villus microcirculation in endotoxic pigs. Intensive Care Med 2001, 27: 757-766. 10.1007/s001340100871
46.
Unger LS, Cryer HM, Garrison RN: Differential response of the microvasculature in the liver during bacteremia. Circ Shock 1989, 29: 335-344.
47.
Gundersen Y, Corso CO, Leiderer R, Dorger M, Lilleaasen P, Aasen AO, Messmer K: The nitric oxide donor sodium nitroprusside protects against hepatic microcirculatory dysfunction in early endotoxaemia. Intensive Care Med 1998, 24: 1257-1263. 10.1007/s001340050759
48.
Corso CO, Gundersen Y, Dorger M, Lilleaasen P, Aasen AO, Messmer K: Effects of the nitric oxide synthase inhibitors N G -nitro-L-arginine methyl ester and aminoethyl-isothiourea on the liver microcirculation. J Hepatol 1998, 28: 61-69. 10.1016/S0168-8278(98)80203-1
49.
Nishida J, McCuskey RS, McDonnell D, Fox ES: Protective role of NO in hepatic microcirculatory dysfunction during endotoxemia. Am J Physiol 1994, 267: G1135-G1141.
50.
Piper RD, Pitt-Hyde ML, Anderson LA, Sibbald WJ, Potter RF: Leukocyte activation and flow behavior in rat skeletal muscle in sepsis. Am J Respir Crit Care Med 1998, 157: 129-134.
51.
Groom AC, Ellis CG, Wrigley SJ, Potter RF: Capillary network morphology and capillary flow. Int J Microcirc Clin Exp 1995, 15: 223-230.
52.
Griffith TM: Endothelial control of vascular tone by nitric oxide and gap junctions: a haemodynamic perspective. Biorheology 2002, 39: 307-318.
53.
Fisher AB, Chien S, Barakat AI, Nerem RM: Endothelial cellular response to altered shear stress. Am J Physiol 2001, 281: L529-L533.
54.
Furchgott RF, Zawadzki JV: The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980, 288: 373-376.
55.
Collins DM, McCullough WT, Ellsworth ML: Conducted vascular responses: communication across the capillary bed. Microvasc Res 1998, 56: 43-53. 10.1006/mvre.1998.2076
56.
Tyml K, Wang X, Lidington D, Ouellette Y: Lipopolysaccharide reduces intercellular coupling in vitro and arteriolar conducted response in vivo. Am J Physiol Heart Circ Physiol 2001, 281: H1397-H1406.
57.
Vallet B: Endothelial cell dysfunction and abnormal tissue perfusion. Crit Care Med 2002, 30: S229-S234. 10.1097/00003246-200205001-00010
58.
Krogh A: The number and the distribution of capillaries in muscle with the calculation of the oxygen pressure necessary for supplying tissue. J Physiol (Lond) 1919, 52: 409-515.
59.
Ellsworth ML, Pittman RN: Arterioles supply oxygen to capillaries by diffusion as well as by convection. Am J Physiol 1990, 258: H1240-H1243.
60.
Kon K, Maeda N, Shiga T: Effect of nitric oxide on the oxygen transport of human erythrocytes. J Toxicol Environ Health 1977, 2: 1109-1113.
61.
Kosaka H, Seiyama A: Physiological role of nitric oxide as an enhancer of oxygen transfer from erythrocytes to tissues. Biochem Biophys Res Commun 1996, 218: 749-752. 10.1006/bbrc.1996.0133
62.
Patel RP, Hogg N, Spencer NY, Kalyanaraman B, Matalon S, Darley-Usmar VM: Biochemical characterization of human S-nitrosohemoglobin. Effects on oxygen binding and transnitrosation. J Biol Chem 1999, 274: 15487-15492. 10.1074/jbc.274.22.15487
63.
Ellsworth ML, Forrester T, Ellis CG, Dietrich HH: The erythrocyte as a regulator of vascular tone. Am J Physiol 1995, 269: H2155-H2161.
64.
Jagger JE, Bateman RM, Ellsworth ML, Ellis CG: Role of erythrocyte in regulating local O2 delivery mediated by hemoglobin oxygenation. Am J Physiol Heart Circ Physiol 2001, 280: H2833-H2839.
65.
Stamler JS, Jia L, Eu JP, McMahon TJ, Demchenko IT, Bonaventura J, Gernert K, Piantadosi CA: Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science 1997, 276: 2034-2037. 10.1126/science.276.5321.2034
66.
Ellsworth ML: The red blood cell as an oxygen sensor: what is the evidence? Acta Physiol Scand 2000, 168: 551-559. 10.1046/j.1365-201x.2000.00708.x
67.
Sprague RS, Ellsworth ML, Stephenson AH, Kleinhenz ME, Lonigro AJ: Deformation-induced ATP release from red blood cells requires CFTR activity. Am J Physiol 1998, 275: H1726-H1732.
68.
Powell RJ, Machiedo GW, Rush BF Jr, Dikdan G: Oxygen free radicals: effect on red cell deformability in sepsis. Crit Care Med 1991, 19: 732-735.
69.
Baskurt OK, Gelmont D, Meiselman HJ: Red blood cell deformability in sepsis. Am J Respir Crit Care Med 1998, 157: 421-427.
70.
Condon MR, Kim JE, Deitch EA, Machiedo GW, Spolarics Z: Appearance of an erythrocyte population with decreased deformability and hemoglobin content following sepsis. Am J Physiol Heart Circ Physiol 2003, 284: H2177-H2184.
71.
Hinshaw LB: Sepsis/septic shock: participation of the microcirculation: an abbreviated review. Crit Care Med 1996, 24: 1072-1078. 10.1097/00003246-199606000-00031
72.
Baskurt OK, Temiz A, Meiselman HJ: Red blood cell aggregation in experimental sepsis. J Lab Clin Med 1997, 130: 183-190.
73.
Eichelbronner O, Sielenkamper A, Cepinskas G, Sibbald WJ, Chin-Yee IH: Endotoxin promotes adhesion of human erythrocytes to human vascular endothelial cells under conditions of flow. Crit Care Med 2000, 28: 1865-1870. 10.1097/00003246-200006000-00030
74.
Diaz NL, Finol HJ, Torres SH, Zambrano CI, Adjounian H: Histochemical and ultrastructural study of skeletal muscle in patients with sepsis and multiple organ failure syndrome (MOFS). Histol Histopathol 1998, 13: 121-128.
75.
Hwang TL, Han ML: The changes of hepatic sinusoidal microcirculation and effects of nitric oxide synthase inhibitor during sepsis. Hepatogastroenterology 2003, 50: 213-216.
76.
James PE, Madhani M, Roebuck W, Jackson SK, Swartz HM: Endotoxin-induced liver hypoxia: defective oxygen delivery versus oxygen consumption. Nitric Oxide 2002, 6: 18-28. 10.1006/niox.2001.0383
77.
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.
78.
Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, Davies NA, Cooper CE, Singer M: Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 2002, 360: 219-223. 10.1016/S0140-6736(02)09459-X
79.
Fink MP: Bench-to-bedside review: Cytopathic hypoxia. Crit Care 2002, 6: 491-499. 10.1186/cc1824
80.
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, EarlyGoal-Directed Therapy Collaborative Group: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345: 1368-1377. 10.1056/NEJMoa010307
81.
Macedo MP, Lautt WW: Shear-induced modulation by nitric oxide of sympathetic nerves in the superior mesenteric artery. Can J Physiol Pharmacol 1996, 74: 692-700. 10.1139/cjpp-74-6-692
82.
Boegehold MA: Shear-dependent release of venular nitric oxide: effect on arteriolar tone in rat striated muscle. Am J Physiol 1996, 271: H387-H395.
83.
Bor-Kucukatay M, Wenby RB, Meiselman HJ, Baskurt OK: Effects of nitric oxide on red blood cell deformability. Am J Physiol Heart Circ Physiol 2003, 284: H1577-H1584.
84.
Kubes P, Suzuki M, Granger DN: Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 1991, 88: 4651-4655.
85.
Mitchell DJ, Yu J, Tyml K: Local L-NAME decreases blood flow and increases leukocyte adhesion via CD18. Am J Physiol 1998, 274: H1264-H1268.
86.
Radomski MW, Vallance P, Whitley G, Foxwell N, Moncada S: Platelet adhesion to human vascular endothelium is modulated by constitutive and cytokine induced nitric oxide. Cardiovasc Res 1993, 27: 1380-1382.
87.
Cerwinka WH, Cooper D, Krieglstein CF, Feelisch M, Granger DN: Nitric oxide modulates endotoxin-induced platelet-endothelial cell adhesion in intestinal venules. Am J Physiol Heart Circ Physiol 2002, 282: H1111-H1117.
88.
Laszlo F, Whittle BJ, Evans SM, Moncada S: Association of microvascular leakage with induction of nitric oxide synthase: effects of nitric oxide synthase inhibitors in various organs. Eur J Pharmacol 1995, 283: 47-53. 10.1016/0014-2999(95)00281-O
89.
Laszlo F, Whittle BJ, Moncada S: Time-dependent enhancement or inhibition of endotoxin-induced vascular injury in rat intestine by nitric oxide synthase inhibitors. Br J Pharmacol 1994, 111: 1309-1315.
90.
Jia L, Bonaventura C, Bonaventura J, Stamler JS: S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature 1996, 380: 221-226. 10.1038/380221a0
91.
Lauer T, Kleinbongard P, Kelm M: Indexes of NO bioavailability in human blood. News Physiol Sci 2002, 17: 251-255.
92.
Feelisch M, Rassaf T, Mnaimneh S, Singh N, Bryan NS, Jourd'Heuil D, Kelm M: Concomitant S-, N-, and hemenitros(yl)ation in biological tissues and fluids: implications for the fate of NO in vivo. FASEB J 2002, 16: 1775-1785. 10.1096/fj.02-0363com
93.
Gladwin MT, Ognibene FP, Pannell LK, Nichols JS, Pease-Fye ME, Shelhamer JH, Schechter AN: Relative role of heme nitrosylation and beta-cysteine 93 nitrosation in the transport and metabolism of nitric oxide by hemoglobin in the human circulation. Proc Natl Acad Sci USA 2000, 97: 9943-9948. 10.1073/pnas.180155397
94.
Cannon RO 3rd, Schechter AN, Panza JA, Ognibene FP, Pease-Fye ME, Waclawiw MA, Shelhamer JH, Gladwin MT: Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxide delivery. J Clin Invest 2001, 108: 279-287. 10.1172/JCI200112761
95.
Ignarro LJ, Fukuto JM, Griscavage JM, Rogers NE, Byrns RE: Oxidation of nitric oxide in aqueous solution to nitrite but not nitrate: comparison with enzymatically formed nitric oxide from L-arginine. Proc Natl Acad Sci USA 1993, 90: 8103-8107.
96.
Rassaf T, Kleinbongard P, Preik M, Dejam A, Gharini P, Lauer T, Erckenbrecht J, Duschin A, Schulz R, Heusch G, Feelisch M, Kelm M: Plasma nitrosothiols contribute to the systemic vasodilator effects of intravenously applied NO: experimental and clinical study on the fate of NO in human blood. Circ Res 2002, 91: 470-477. 10.1161/01.RES.0000035038.41739.CB
97.
Rassaf T, Preik M, Kleinbongard P, Lauer T, Heiss C, Strauer BE, Feelisch M, Kelm M: Evidence for in vivo transport of bioactive nitric oxide in human plasma. J Clin Invest 2002, 109: 1241-1248. 10.1172/JCI200214995
98.
Baveja R, Kresge N, Ashburn JH, Keller S, Yokoyama Y, Sonin N, Zhang JX, Huynh T, Clemens MG: Potentiated hepatic microcirculatory response to endothelin-1 during polymicrobial sepsis. Shock 2002, 18: 415-422. 10.1097/00024382-200211000-00005
99.
Avontuur JA, Boomsma F, van den Meiracker AH, de Jong FH, Bruining HA: Endothelin-1 and blood pressure after inhibition of nitric oxide synthesis in human septic shock. Circulation 1999, 99: 271-275.
100.
Beasley D, Eldridge M: Interleukin-1 beta and tumor necrosis factor-alpha synergistically induce NO synthase in rat vascular smooth muscle cells. Am J Physiol 1994, 266: R1197-R1203.
101.
Cunha FQ, Assreuy J, Moss DW, Rees D, Leal LM, Moncada S, Carrier M, O'Donnell CA, Liew FY: Differential induction of nitric oxide synthase in various organs of the mouse during endotoxaemia: role of TNF-alpha and IL-1. Immunology 1994, 81: 211-215.
102.
Gocan NC, Scott JA, Tyml K: Nitric oxide produced via neuronal NOS may impair vasodilatation in septic rat skeletal muscle. Am J Physiol Heart Circ Physiol 2000, 278: H1480-H1489.
103.
Sade K, Schwartz D, Wolman Y, Schwartz I, Chernichovski T, Blum M, Brazowski E, Keynan S, Raz I, Blantz RC, Iaina A: Time course of lipopolysaccharide-induced nitric oxide synthase mRNA expression in rat glomeruli. J Lab Clin Med 1999, 134: 471-477.
104.
Harada S, Imaki T, Chikada N, Naruse M, Demura H: Distinct distribution and time-course changes in neuronal nitric oxide synthase and inducible NOS in the paraventricular nucleus following lipopolysaccharide injection. Brain Res 1999, 821: 322-332. 10.1016/S0006-8993(99)01124-5
105.
Chen K, Inoue M, Okada A: Expression of inducible nitric oxide synthase mRNA in rat digestive tissues after endotoxin and its role in intestinal mucosal. Biochem Biophys Res Commun 1996, 224: 703-708. 10.1006/bbrc.1996.1087
106.
Preiser JC, Zhang H, Vray B, Hrabak A, Vincent JL: Time course of inducible nitric oxide synthase activity following endotoxin administration in dogs. Nitric Oxide 2001, 5: 208-211. 10.1006/niox.2001.0342
107.
Kengatharan KM, De Kimpe SJ, Thiemermann C: Role of nitric oxide in the circulatory failure and organ injury in a rodent model of gram-positive shock. Br J Pharmacol 1996, 119: 1411-1421.
108.
Shieh P, Zhou M, Ornan DA, Chaudry IH, Wang P: Upregulation of inducible nitric oxide synthase and nitric oxide occurs later than the onset of the hyperdynamic response during sepsis. Shock 2000, 13: 325-329.
109.
Scott JA, Mehta S, Duggan M, Bihari A, McCormack DG: Functional inhibition of constitutive nitric oxide synthase in a rat model of sepsis. Am J Respir Crit Care Med 2002, 165: 1426-1432. 10.1164/rccm.2011144
110.
Lu JL, Schmiege LM 3rd, Kuo L, Liao JC: Downregulation of endothelial constitutive nitric oxide synthase expression by lipopolysaccharide. Biochem Biophys Res Commun 1996, 225: 1-5. 10.1006/bbrc.1996.1121
111.
Evans T, Carpenter A, Kinderman H, Cohen J: Evidence of increased nitric oxide production in patients with the sepsis syndrome. Circ Shock 1993, 41: 77-81.
112.
Strand OA, Leone A, Giercksky KE, Kirkeboen KA: Nitric oxide indices in human septic shock. Crit Care Med 2000, 28: 2779-2785. 10.1097/00003246-200008000-00017
113.
Ochoa JB, Udekwu AO, Billiar TR, Curran RD, Cerra FB, Simmons RL, Peitzman AB: Nitrogen oxide levels in patients after trauma and during sepsis. Ann Surg 1991, 214: 621-626.
114.
Gomez-Jimenez J, Salgado A, Mourelle M, Martin MC, Segura RM, Peracaula R, Moncada S: L-arginine: nitric oxide pathway in endotoxemia and human septic shock. Crit Care Med 1995, 23: 253-258. 10.1097/00003246-199502000-00009
115.
Wu F, Cepinskas G, Wilson JX, Tyml K: Nitric oxide attenuates but superoxode enhances iNOS expression in endotoxin- and IFN gamma-stimulated skeletal muscle endothelial cells. Microcirculation 2001, 8: 415-425. 10.1038/sj/mn/7800113
116.
Gunnett CA, Chu Y, Heistad DD, Loihl A, Faraci FM: Vascular effects of LPS in mice deficient in expression of the gene for inducible nitric oxide synthase. Am J Physiol 1998, 275: H416-H421.
117.
Kilbourn RG, Gross SS, Jubran A, Adams J, Griffith OW, Levi R, Lodato RF: NG-methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide. Proc Natl Acad Sci USA 1990, 87: 3629-3632.
118.
Broccard A, Hurni JM, Eckert P, Liaudet L, Schaller MD, Lazor R, Perret C, Feihl F: Tissue oxygenation and hemodynamic response to NO synthase inhibition in septic shock. Shock 2000, 14: 35-40.
119.
Lorente JA, Landin L, De Pablo R, Renes E, Liste D: L-arginine pathway in the sepsis syndrome. Crit Care Med 1993, 21: 1287-1295.
120.
Avontuur JA, Tutein Nolthenius RP, van Bodegom JW, Bruining HA: Prolonged inhibition of nitric oxide synthesis in severe septic shock: a clinical study. Crit Care Med 1998, 26: 660-667. 10.1097/00003246-199804000-00012
121.
Petros A, Lamb G, Leone A, Moncada S, Bennett D, Vallance P: Effects of a nitric oxide synthase inhibitor in humans with septic shock. Cardiovasc Res 1994, 28: 34-39.
122.
Petros A, Bennett D, Vallance P: Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet 1991, 338: 1557-1558. 10.1016/0140-6736(91)92376-D
123.
Nava E, Palmer RM, Moncada S: Inhibition of nitric oxide synthesis in septic shock: how much is beneficial? Lancet 1991, 338: 1555-1557. 10.1016/0140-6736(91)92375-C
124.
Booke M, Hinder F, McGuire R, Traber LD, Traber DL: Selective inhibition of inducible nitric oxide synthase: effects on hemodynamics and regional blood flow in healthy and septic sheep. Crit Care Med 1999, 27: 162-167. 10.1097/00003246-199901000-00045
125.
Booke M, Hinder F, McGuire R, Traber LD, Traber DL: Nitric oxide synthase inhibition versus norepinephrine for the treatment of hyperdynamic sepsis in sheep. Crit Care Med 1996, 24: 835-844. 10.1097/00003246-199605000-00018
126.
Meyer J, Hinder F, Stothert J Jr, Traber LD, Herndon DN, Flynn JT, Traber DL: Increased organ blood flow in chronic endotoxemia is reversed by nitric oxide synthase inhibition. J Appl Physiol 1994, 76: 2785-2793.
127.
Grover R, Lopez A, Lorente J, Steingrub J, Bakker J, Willatts S, McLuckie A, Takala J: Multi-center, randomized, placebo-controlled, double blind study of nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock [abstract]. Crit Care Med 1999, 27: A33. 10.1097/00003246-199901001-00021
128.
Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD: Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001, 344: 699-709. 10.1056/NEJM200103083441001
129.
Isobe H, Okajima K, Uchiba M, Mizutani A, Harada N, Nagasaki A, Okabe K: Activated protein C prevents endotoxin-induced hypotension in rats by inhibiting excessive production of nitric oxide. Circulation 2001, 104: 1171-1175.
130.
Spain DA, Wilson MA, Bar-Natan MF, Garrison RN: Nitric oxide synthase inhibition aggravates intestinal microvascular vasoconstriction and hypoperfusion of bacteremia. J Trauma 1994, 36: 720-725.
131.
Walker TA, Curtis SE, King-VanVlack CE, Chapler CK, Vallet B, Cain SM: Effects of nitric oxide synthase inhibition on regional hemodynamics and oxygen transport in endotoxic dogs. Shock 1995, 4: 415-420.
132.
Avontuur JA, Bruining HA, Ince C: Inhibition of nitric oxide synthesis causes myocardial ischemia in endotoxemic rats. Circ Res 1995, 76: 418-425.
133.
Huang TP, Nishida T, Kamike W, Kosaka H, Seiyama A, Morimoto Y, Tanaka S, Obunai S, Takei Y, Shiga T, Matsuda H: Role of nitric oxide in oxygen transport in rat liver sinusoids during endotoxemia. Hepatology 1997, 26: 336-342. 10.1016/S0168-8278(97)80050-5
134.
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. 10.1097/00003246-199911000-00032
135.
Pittner A, Nalos M, Asfar P, Yang Y, Ince C, Georgieff M, Bruckner UB, Radermacher P, Froba G: Mechanisms of inducible nitric oxide synthase (iNOS) inhibition-related improvement of gut mucosal acidosis during hyperdynamic porcine endotoxemia. Intensive Care Med 2003, 29: 312-316.
136.
Saetre T, Gundersen Y, Thiemermann C, Lilleaasen P, Aasen AO: Aminoethyl-isothiourea, a selective inhibitor of inducible nitric oxide synthase activity, improves liver circulation and oxygen metabolism in a porcine model of endotoxemia. Shock 1998, 9: 109-115.
137.
Wang Y, Lawson JA, Jaeschke H: Differential effect of 2-aminoethyl-isothiourea, an inhibitor of the inducible nitric oxide synthase, on microvascular blood flow and organ injury in models of hepatic ischemia-reperfusion and endotoxemia. Shock 1998, 10: 20-25.
138.
Tadros T, Traber DL, Herndon DN: Hepatic blood flow and oxygen consumption after burn and sepsis. J Trauma 2000, 49: 101-108.
139.
Lizasoain I, Moro MA, Knowles RG, Darley-Usmar V, Moncada S: Nitric oxide and peroxynitrite exert distinct effects on mitochondrial respiration which are differentially blocked by glutathione or glucose. Biochem J 1996, 314: 877-880.
140.
Torres J, Darley-Usmar 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.
141.
Brown GC, Cooper CE: Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett 1994, 356: 295-298. 10.1016/0014-5793(94)01290-3
142.
Cleeter MW, Cooper JM, Darley-Usmar VM, Moncada S, Schapira AH: Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases. FEBS Lett 1994, 345: 50-54. 10.1016/0014-5793(94)00424-2
143.
Borutaite V, Matthias A, Harris H, Moncada S, Brown GC: Reversible inhibition of cellular respiration by nitric oxide in vascular inflammation. Am J Physiol Heart Circ Physiol 2001, 281: H2256-H2260.
144.
Simonson SG, Welty-Wolf K, Huang YT, 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.
Metadaten
Titel
Bench-to-bedside review: Microvascular dysfunction in sepsis –hemodynamics, oxygen transport, and nitric oxide
verfasst von
Ryon M Bateman
Michael D Sharpe
Christopher G Ellis
Publikationsdatum
01.10.2003
Verlag
BioMed Central
Erschienen in
Critical Care / Ausgabe 5/2003
Elektronische ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc2353

Weitere Artikel der Ausgabe 5/2003

Critical Care 5/2003 Zur Ausgabe

Commentary

Recent progress in sepsis epidemiology – have we learned enough?

Research

The limited utility of electrocardiography variables used to predict arrhythmia in psychotropic drug overdose

Research

Diagnostic ability of hand-held echocardiography in ventilated critically ill patients

Web report

Critical Care Medicine Tutorials

Commentary

Recently published papers: Curing, caring and follow-up

Research

Estimation of energy requirements for mechanically ventilated, critically ill patients using nutritional status

Neu im Fachgebiet AINS

23.04.2024 | Appendizitis | Nachrichten

Hinter dieser Appendizitis steckte ein Erreger

23.04.2024 | Leitsymptom Rückenschmerzen | Nachrichten

Ärztliche Empathie hilft gegen Rückenschmerzen

23.04.2024 | Operationsvorbereitung | Nachrichten

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

23.04.2024 | Pankreaskarzinom | Nachrichten

S3-Leitlinie zu Pankreaskrebs aktualisiert
weitere anzeigen

Update AINS

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

hier abonnieren