Pathophysiology of microcirculatory dysfunction and the pathogenesis of septic shock

References

• 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; http://dx.doi.org/10.1164/rccm.200109-016OC; PMID: 12091178
   PubMed Web of Science ®Google Scholar
• Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med 2004; 32:1825 - 31; http://dx.doi.org/10.1097/01.CCM.0000138558.16257.3F; PMID: 15343008
   PubMed Web of Science ®Google Scholar
• De Backer D, Donadello K, Sakr Y, Ospina-Tascon G, Salgado D, Scolletta S, Vincent JL. Microcirculatory alterations in patients with severe sepsis: impact of time of assessment and relationship with outcome. Crit Care Med 2013; 41:791 - 9; http://dx.doi.org/10.1097/CCM.0b013e3182742e8b; PMID: 23318492
   PubMed Web of Science ®Google Scholar
• Ospina-Tascon G, Neves AP, Occhipinti G, Donadello K, Büchele G, Simion D, Chierego ML, Silva TO, Fonseca A, Vincent JL, et al. Effects of fluids on microvascular perfusion in patients with severe sepsis. Intensive Care Med 2010; 36:949 - 55; http://dx.doi.org/10.1007/s00134-010-1843-3; PMID: 20221744
   PubMed Web of Science ®Google Scholar
• De Backer D, Creteur J, Dubois MJ, Sakr Y, Koch M, Verdant C, Vincent JL. The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit Care Med 2006; 34:403 - 8; http://dx.doi.org/10.1097/01.CCM.0000198107.61493.5A; PMID: 16424721
   PubMed Web of Science ®Google Scholar
• Morelli A, Donati A, Ertmer C, Rehberg S, Lange M, Orecchioni A, Cecchini V, Landoni G, Pelaia P, Pietropaoli P, et al. Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study. Crit Care 2010; 14:R232; http://dx.doi.org/10.1186/cc9387; PMID: 21182783
   PubMed Web of Science ®Google Scholar
• Croner RS, Hoerer E, Kulu Y, Hackert T, Gebhard MM, Herfarth C, Klar E. Hepatic platelet and leukocyte adherence during endotoxemia. Crit Care 2006; 10:R15; http://dx.doi.org/10.1186/cc3968; PMID: 16420661
   PubMed Web of Science ®Google Scholar
• Secor D, Li F, Ellis CG, Sharpe MD, Gross PL, Wilson JX, Tyml K. Impaired microvascular perfusion in sepsis requires activated coagulation and P-selectin-mediated platelet adhesion in capillaries. Intensive Care Med 2010; 36:1928 - 34; http://dx.doi.org/10.1007/s00134-010-1969-3; PMID: 20689935
   PubMed Web of Science ®Google Scholar
• Verdant CL, De Backer D, Bruhn A, Clausi CM, Su F, Wang Z, Rodriguez H, Pries AR, Vincent JL. Evaluation of sublingual and gut mucosal microcirculation in sepsis: a quantitative analysis. Crit Care Med 2009; 37:2875 - 81; http://dx.doi.org/10.1097/CCM.0b013e3181b029c1; PMID: 19770750
   PubMed Web of Science ®Google Scholar
• 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 - 6; http://dx.doi.org/10.1006/jsre.1996.0103; PMID: 8769965
   PubMed Web of Science ®Google Scholar
• Taccone FS, Su F, Pierrakos C, He X, James S, Dewitte O, Vincent JL, De Backer D. Cerebral microcirculation is impaired during sepsis: an experimental study. Crit Care 2010; 14:R140; http://dx.doi.org/10.1186/cc9205; PMID: 20667108
   PubMedGoogle Scholar
• Hollenberg SM, Broussard M, Osman J, Parrillo JE. Increased microvascular reactivity and improved mortality in septic mice lacking inducible nitric oxide synthase. Circ Res 2000; 86:774 - 8; http://dx.doi.org/10.1161/01.RES.86.7.774; PMID: 10764411
   PubMed Web of Science ®Google Scholar
• McKinnon RL, Lidington D, Tyml K. Ascorbate inhibits reduced arteriolar conducted vasoconstriction in septic mouse cremaster muscle. Microcirculation 2007; 14:697 - 707; http://dx.doi.org/10.1080/10739680701410389; PMID: 17885995
   PubMed Web of Science ®Google Scholar
• Wester T, Häggblad E, Awan ZA, Barratt-Due A, Kvernebo M, Halvorsen PS, Mollnes TE, Kvernebo K. Assessments of skin and tongue microcirculation reveals major changes in porcine sepsis. Clin Physiol Funct Imaging 2011; 31:151 - 8; http://dx.doi.org/10.1186/cc9271; PMID: 21087397
   PubMed Web of Science ®Google Scholar
• Pranskunas A, Pilvinis V, Dambrauskas Z, Rasimaviciute R, Planciuniene R, Dobozinskas P, Veikutis V, Vaitkaitis D, Boerma EC. Early course of microcirculatory perfusion in eye and digestive tract during hypodynamic sepsis. Crit Care 2012; 16:R83; http://dx.doi.org/10.1186/cc11341; PMID: 22587828
   PubMedGoogle Scholar
• Bateman RM, Tokunaga C, Kareco T, Dorscheid DR, Walley KR. Myocardial hypoxia-inducible HIF-1alpha, VEGF, and GLUT1 gene expression is associated with microvascular and ICAM-1 heterogeneity during endotoxemia. Am J Physiol Heart Circ Physiol 2007; 293:H448 - 56; http://dx.doi.org/10.1152/ajpheart.00035.2007; PMID: 17369472
   PubMed Web of Science ®Google Scholar
• Groner W, Winkelman JW, Harris AG, Ince C, Bouma GJ, Messmer K, Nadeau RG. Orthogonal polarization spectral imaging: a new method for study of the microcirculation. Nat Med 1999; 5:1209 - 12; http://dx.doi.org/10.1038/13529; PMID: 10502828
   PubMed Web of Science ®Google Scholar
• Goedhart PT, Khalilzada M, Bezemer R, Merza J, Ince C. Sidestream Dark Field (SDF) imaging: a novel stroboscopic LED ring-based imaging modality for clinical assessment of the microcirculation. Opt Express 2007; 15:15101 - 14; http://dx.doi.org/10.1364/OE.15.015101; PMID: 19550794
   PubMed Web of Science ®Google Scholar
• Edul VS, Enrico C, Laviolle B, Vazquez AR, Ince C, Dubin A. Quantitative assessment of the microcirculation in healthy volunteers and in patients with septic shock. Crit Care Med 2012; 40:1443 - 8; http://dx.doi.org/10.1097/CCM.0b013e31823dae59; PMID: 22430243
   PubMed Web of Science ®Google Scholar
• Walley KR. Heterogeneity of oxygen delivery impairs oxygen extraction by peripheral tissues: theory. J Appl Physiol 1996; 81:885 - 94; PMID: 8872660
   PubMed Web of Science ®Google Scholar
• Goldman D, Bateman RM, Ellis CG. Effect of decreased O2 supply on skeletal muscle oxygenation and O2 consumption during sepsis: role of heterogeneous capillary spacing and blood flow. Am J Physiol Heart Circ Physiol 2006; 290:H2277 - 85; http://dx.doi.org/10.1152/ajpheart.00547.2005; PMID: 16399873
   PubMed Web of Science ®Google Scholar
• Legrand M, Bezemer R, Kandil A, Demirci C, Payen D, Ince C. The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats. Intensive Care Med 2011; 37:1534 - 42; http://dx.doi.org/10.1007/s00134-011-2267-4; PMID: 21695476
   PubMed Web of Science ®Google Scholar
• 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 - 64; PMID: 11748059
   PubMedGoogle Scholar
• 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; PMID: 8872661
   PubMed Web of Science ®Google Scholar
• Eipel C, Bordel R, Nickels RM, Menger MD, Vollmar B. Impact of leukocytes and platelets in mediating hepatocyte apoptosis in a rat model of systemic endotoxemia. Am J Physiol Gastrointest Liver Physiol 2004; 286:G769 - 76; http://dx.doi.org/10.1152/ajpgi.00275.2003; PMID: 14715524
   PubMedGoogle Scholar
• Kao R, Xenocostas A, Rui T, Yu P, Huang W, Rose J, Martin CM. Erythropoietin improves skeletal muscle microcirculation and tissue bioenergetics in a mouse sepsis model. Crit Care 2007; 11:R58; http://dx.doi.org/10.1186/cc5920; PMID: 17509156
   PubMedGoogle Scholar
• Doerschug KC, Delsing AS, Schmidt GA, Haynes WG. Impairments in microvascular reactivity are related to organ failure in human sepsis. Am J Physiol Heart Circ Physiol 2007; 293:H1065 - 71; http://dx.doi.org/10.1152/ajpheart.01237.2006; PMID: 17483235
   PubMedGoogle Scholar
• Shapiro NI, Arnold R, Sherwin R, O’Connor J, Najarro G, Singh S, Lundy D, Nelson T, Trzeciak SW, Jones AE, Emergency Medicine Shock Research Network (EMShockNet). The association of near-infrared spectroscopy-derived tissue oxygenation measurements with sepsis syndromes, organ dysfunction and mortality in emergency department patients with sepsis. Crit Care 2011; 15:R223; http://dx.doi.org/10.1186/cc10463; PMID: 21939529
   PubMed Web of Science ®Google Scholar
• Trzeciak S, McCoy JV, Phillip Dellinger R, Arnold RC, Rizzuto M, Abate NL, Shapiro NI, Parrillo JE, Hollenberg SM, Microcirculatory Alterations in Resuscitation and Shock (MARS) investigators. Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis. Intensive Care Med 2008; 34:2210 - 7; http://dx.doi.org/10.1007/s00134-008-1193-6; PMID: 18594793
   PubMed Web of Science ®Google Scholar
• De Backer D, Creteur J, Dubois MJ, Sakr Y, Vincent JL. Microvascular alterations in patients with acute severe heart failure and cardiogenic shock. Am Heart J 2004; 147:91 - 9; http://dx.doi.org/10.1016/j.ahj.2003.07.006; PMID: 14691425
   PubMed Web of Science ®Google Scholar
• den Uil CA, Lagrand WK, van der Ent M, Jewbali LS, Cheng JM, Spronk PE, Simoons ML. Impaired microcirculation predicts poor outcome of patients with acute myocardial infarction complicated by cardiogenic shock. Eur Heart J 2010; 31:3032 - 9; http://dx.doi.org/10.1093/eurheartj/ehq324; PMID: 20829210
   PubMed Web of Science ®Google Scholar
• Creteur J, Carollo T, Soldati G, Buchele G, De Backer D, Vincent JL. The prognostic value of muscle StO2 in septic patients. Intensive Care Med 2007; 33:1549 - 56; http://dx.doi.org/10.1007/s00134-007-0739-3; PMID: 17572876
   PubMed Web of Science ®Google Scholar
• Top AP, Ince C, de Meij N, van Dijk M, Tibboel D. Persistent low microcirculatory vessel density in nonsurvivors of sepsis in pediatric intensive care. Crit Care Med 2011; 39:8 - 13; http://dx.doi.org/10.1097/CCM.0b013e3181fb7994; PMID: 21076287
   PubMed Web of Science ®Google Scholar
• Marik PE. Sublingual capnography: a clinical validation study. Chest 2001; 120:923 - 7; http://dx.doi.org/10.1378/chest.120.3.923; PMID: 11555530
   PubMed Web of Science ®Google Scholar
• Creteur J, De Backer D, Sakr Y, Koch M, Vincent JL. Sublingual capnometry tracks microcirculatory changes in septic patients. Intensive Care Med 2006; 32:516 - 23; http://dx.doi.org/10.1007/s00134-006-0070-4; PMID: 16485092
   PubMed Web of Science ®Google Scholar
• Vallée F, Mateo J, Dubreuil G, Poussant T, Tachon G, Ouanounou I, Payen D. Cutaneous ear lobe Pco₂ at 37°C to evaluate microperfusion in patients with septic shock. Chest 2010; 138:1062 - 70; http://dx.doi.org/10.1378/chest.09-2690; PMID: 20472858
   PubMed Web of Science ®Google Scholar
• Levy B, Gawalkiewicz P, Vallet B, Briancon S, Nace L, Bollaert PE. Gastric capnometry with air-automated tonometry predicts outcome in critically ill patients. Crit Care Med 2003; 31:474 - 80; http://dx.doi.org/10.1097/01.CCM.0000050445.48656.28; PMID: 12576954
   PubMed Web of Science ®Google Scholar
• Dubin A, Edul VS, Pozo MO, Murias G, Canullán CM, Martins EF, Ferrara G, Canales HS, Laporte M, Estenssoro E, et al. Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia. Crit Care Med 2008; 36:535 - 42; http://dx.doi.org/10.1097/01.CCM.0000300083.74726.43; PMID: 18216603
   PubMed Web of Science ®Google Scholar
• Rosengarten B, Hecht M, Auch D, Ghofrani HA, Schermuly RT, Grimminger F, Kaps M. Microcirculatory dysfunction in the brain precedes changes in evoked potentials in endotoxin-induced sepsis syndrome in rats. Cerebrovasc Dis 2007; 23:140 - 7; http://dx.doi.org/10.1159/000097051; PMID: 17124395
   PubMed Web of Science ®Google Scholar
• Eltzschig HK, Carmeliet P. Hypoxia and inflammation. N Engl J Med 2011; 364:656 - 65; http://dx.doi.org/10.1056/NEJMra0910283; PMID: 21323543
   PubMed Web of Science ®Google Scholar
• Corrêa TD, Vuda M, Blaser AR, Takala J, Djafarzadeh S, Dünser MW, Silva E, Lensch M, Wilkens L, Jakob SM. Effect of treatment delay on disease severity and need for resuscitation in porcine fecal peritonitis. Crit Care Med 2012; 40:2841 - 9; http://dx.doi.org/10.1097/CCM.0b013e31825b916b; PMID: 22890256
   PubMed Web of Science ®Google Scholar
• Rivers EP, Kruse JA, Jacobsen G, Shah K, Loomba M, Otero R, Childs EW. The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock. Crit Care Med 2007; 35:2016 - 24; http://dx.doi.org/10.1097/01.CCM.0000281637.08984.6E; PMID: 17855815
   PubMed Web of Science ®Google Scholar
• Pareznik R, Knezevic R, Voga G, Podbregar M. Changes in muscle tissue oxygenation during stagnant ischemia in septic patients. Intensive Care Med 2006; 32:87 - 92; http://dx.doi.org/10.1007/s00134-005-2841-8; PMID: 16261341
   PubMed Web of Science ®Google Scholar
• De Blasi RA, Palmisani S, Alampi D, Mercieri M, Romano R, Collini S, Pinto G. Microvascular dysfunction and skeletal muscle oxygenation assessed by phase-modulation near-infrared spectroscopy in patients with septic shock. Intensive Care Med 2005; 31:1661 - 8; http://dx.doi.org/10.1007/s00134-005-2822-y; PMID: 16205889
   PubMed Web of Science ®Google Scholar
• Girardis M, Rinaldi L, Busani S, Flore I, Mauro S, Pasetto A. Muscle perfusion and oxygen consumption by near-infrared spectroscopy in septic-shock and non-septic-shock patients. Intensive Care Med 2003; 29:1173 - 6; http://dx.doi.org/10.1007/s00134-003-1805-0; PMID: 12774160
   PubMed Web of Science ®Google Scholar
• Skarda DE, Mulier KE, Myers DE, Taylor JH, Beilman GJ. Dynamic near-infrared spectroscopy measurements in patients with severe sepsis. Shock 2007; 27:348 - 53; http://dx.doi.org/10.1097/01.shk.0000239779.25775.e4; PMID: 17414414
   PubMed Web of Science ®Google Scholar
• 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 - 5; http://dx.doi.org/10.1164/ajrccm.153.1.8542115; PMID: 8542115
   PubMed Web of Science ®Google Scholar
• Beach JM, McGahren ED, Duling BR. Capillaries and arterioles are electrically coupled in hamster cheek pouch. Am J Physiol 1998; 275:H1489 - 96; PMID: 9746501
   PubMedGoogle Scholar
• 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 - 406; PMID: 11514312
   PubMed Web of Science ®Google Scholar
• Marechal X, Favory R, Joulin O, Montaigne D, Hassoun S, Decoster B, Zerimech F, Neviere R. Endothelial glycocalyx damage during endotoxemia coincides with microcirculatory dysfunction and vascular oxidative stress. Shock 2008; 29:572 - 6; PMID: 18414231
   PubMed Web of Science ®Google Scholar
• Henry CB, Duling BR. TNF-alpha increases entry of macromolecules into luminal endothelial cell glycocalyx. Am J Physiol Heart Circ Physiol 2000; 279:H2815 - 23; PMID: 11087236
   PubMed Web of Science ®Google Scholar
• Nieuwdorp M, Meuwese MC, Mooij HL, van Lieshout MH, Hayden A, Levi M, Meijers JC, Ince C, Kastelein JJ, Vink H, et al. Tumor necrosis factor-alpha inhibition protects against endotoxin-induced endothelial glycocalyx perturbation. Atherosclerosis 2009; 202:296 - 303; http://dx.doi.org/10.1016/j.atherosclerosis.2008.03.024; PMID: 18550063
   PubMed Web of Science ®Google Scholar
• Hofmann-Kiefer KF, Kemming GI, Chappell D, Flondor M, Kisch-Wedel H, Hauser A, Pallivathukal S, Conzen P, Rehm M. Serum heparan sulfate levels are elevated in endotoxemia. Eur J Med Res 2009; 14:526 - 31; PMID: 20149986
   PubMed Web of Science ®Google Scholar
• Constantinescu AA, Vink H, Spaan JA. Endothelial cell glycocalyx modulates immobilization of leukocytes at the endothelial surface. Arterioscler Thromb Vasc Biol 2003; 23:1541 - 7; http://dx.doi.org/10.1161/01.ATV.0000085630.24353.3D; PMID: 12855481
   PubMed Web of Science ®Google Scholar
• Cabrales P, Vázquez BY, Tsai AG, Intaglietta M. Microvascular and capillary perfusion following glycocalyx degradation. J Appl Physiol 2007; 102:2251 - 9; http://dx.doi.org/10.1152/japplphysiol.01155.2006; PMID: 17347383
   PubMed Web of Science ®Google Scholar
• De Backer D, Donadello K, Favory R. Link between coagulation abnormalities and microcirculatory dysfunction in critically ill patients. Curr Opin Anaesthesiol 2009; 22:150 - 4; http://dx.doi.org/10.1097/ACO.0b013e328328d1a1; PMID: 19390244
   PubMed Web of Science ®Google Scholar
• Piagnerelli M, Boudjeltia KZ, Vanhaeverbeek M, Vincent JL. Red blood cell rheology in sepsis. Intensive Care Med 2003; 29:1052 - 61; http://dx.doi.org/10.1007/s00134-003-1783-2; PMID: 12802488
   PubMed Web of Science ®Google Scholar
• Eichelbrönner O, Sielenkämper 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 - 70; http://dx.doi.org/10.1097/00003246-200006000-00030; PMID: 10890634
   PubMed Web of Science ®Google Scholar
• Karvunidis T, Chvojka J, Lysak D, Sykora R, Krouzecky A, Radej J, Novak I, Matejovic M. Septic shock and chemotherapy-induced cytopenia: effects on microcirculation. Intensive Care Med 2012; 38:1336 - 44; http://dx.doi.org/10.1007/s00134-012-2582-4; PMID: 22584795
   PubMed Web of Science ®Google Scholar
• Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol 2007; 176:231 - 41; http://dx.doi.org/10.1083/jcb.200606027; PMID: 17210947
   PubMed Web of Science ®Google Scholar
• Pottecher J, Deruddre S, Teboul JL, Georger JF, Laplace C, Benhamou D, Vicaut E, Duranteau J. Both passive leg raising and intravascular volume expansion improve sublingual microcirculatory perfusion in severe sepsis and septic shock patients. Intensive Care Med 2010; 36:1867 - 74; http://dx.doi.org/10.1007/s00134-010-1966-6; PMID: 20725823
   PubMed Web of Science ®Google Scholar
• Hoffmann JN, Vollmar B, Laschke MW, Inthorn D, Schildberg FW, Menger MD. Hydroxyethyl starch (130 kD), but not crystalloid volume support, improves microcirculation during normotensive endotoxemia. Anesthesiology 2002; 97:460 - 70; http://dx.doi.org/10.1097/00000542-200208000-00025; PMID: 12151938
   PubMed Web of Science ®Google Scholar
• Sakr Y, Chierego M, Piagnerelli M, Verdant C, Dubois MJ, Koch M, Creteur J, Gullo A, Vincent JL, De Backer D. Microvascular response to red blood cell transfusion in patients with severe sepsis. Crit Care Med 2007; 35:1639 - 44; http://dx.doi.org/10.1097/01.CCM.0000269936.73788.32; PMID: 17522571
   PubMed Web of Science ®Google Scholar
• Secchi A, Wellmann R, Martin E, Schmidt H. Dobutamine maintains intestinal villus blood flow during normotensive endotoxemia: an intravital microscopic study in the rat. J Crit Care 1997; 12:137 - 41; http://dx.doi.org/10.1016/S0883-9441(97)90043-5; PMID: 9328853
   PubMed Web of Science ®Google Scholar
• Schwarte LA, Picker O, Bornstein SR, Fournell A, Scheeren TW. Levosimendan is superior to milrinone and dobutamine in selectively increasing microvascular gastric mucosal oxygenation in dogs. Crit Care Med 2005; 33:135 - 42, discussion 246-7; http://dx.doi.org/10.1097/01.CCM.0000150653.89451.6F; PMID: 15644660
   PubMed Web of Science ®Google Scholar
• Nakajima Y, Baudry N, Duranteau J, Vicaut E. Effects of vasopressin, norepinephrine, and L-arginine on intestinal microcirculation in endotoxemia. Crit Care Med 2006; 34:1752 - 7; http://dx.doi.org/10.1097/01.CCM.0000218812.73741.6C; PMID: 16625119
   PubMed Web of Science ®Google Scholar
• Georger JF, Hamzaoui O, Chaari A, Maizel J, Richard C, Teboul JL. Restoring arterial pressure with norepinephrine improves muscle tissue oxygenation assessed by near-infrared spectroscopy in severely hypotensive septic patients. Intensive Care Med 2010; 36:1882 - 9; http://dx.doi.org/10.1007/s00134-010-2013-3; PMID: 20689910
   PubMed Web of Science ®Google Scholar
• Deruddre S, Cheisson G, Mazoit JX, Vicaut E, Benhamou D, Duranteau J. Renal arterial resistance in septic shock: effects of increasing mean arterial pressure with norepinephrine on the renal resistive index assessed with Doppler ultrasonography. Intensive Care Med 2007; 33:1557 - 62; http://dx.doi.org/10.1007/s00134-007-0665-4; PMID: 17486316
   PubMed Web of Science ®Google Scholar
• Dubin A, Pozo MO, Casabella CA, Pálizas F Jr., Murias G, Moseinco MC, Kanoore Edul VS, Pálizas F, Estenssoro E, Ince C. Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care 2009; 13:R92; http://dx.doi.org/10.1186/cc7922; PMID: 19534818
   PubMed Web of Science ®Google Scholar
• Thooft A, Favory R, Salgado DR, Taccone FS, Donadello K, De Backer D, Creteur J, Vincent JL. Effects of changes in arterial pressure on organ perfusion during septic shock. Crit Care 2011; 15:R222; http://dx.doi.org/10.1186/cc10462; PMID: 21936903
   PubMed Web of Science ®Google Scholar
• 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 - 6; http://dx.doi.org/10.1016/S0140-6736(02)11393-6; PMID: 12423989
   PubMed Web of Science ®Google Scholar
• Edul VS, Ferrara G, Pozo MO, Murias G, Martins E, Canullén C, Canales HS, Estenssoro E, Ince C, Dubin A. Failure of nitroglycerin (glyceryl trinitrate) to improve villi hypoperfusion in endotoxaemic shock in sheep. Crit Care Resusc 2011; 13:252 - 61; PMID: 22129287
   PubMed Web of Science ®Google Scholar
• Boerma EC, Koopmans M, Konijn A, Kaiferova K, Bakker AJ, van Roon EN, Buter H, Bruins N, Egbers PH, Gerritsen RT, et al. Effects of nitroglycerin on sublingual microcirculatory blood flow in patients with severe sepsis/septic shock after a strict resuscitation protocol: a double-blind randomized placebo controlled trial. Crit Care Med 2010; 38:93 - 100; http://dx.doi.org/10.1097/CCM.0b013e3181b02fc1; PMID: 19730258
   PubMed Web of Science ®Google Scholar
• den Uil CA, Caliskan K, Lagrand WK, van der Ent M, Jewbali LS, van Kuijk JP, Spronk PE, Simoons ML. Dose-dependent benefit of nitroglycerin on microcirculation of patients with severe heart failure. Intensive Care Med 2009; 35:1893 - 9; http://dx.doi.org/10.1007/s00134-009-1591-4; PMID: 19639300
   PubMed Web of Science ®Google Scholar
• Salgado DR, He X, Su F, de Sousa DB, Penaccini L, Maciel LK, Taccone F, Rocco JR, Silva E, De Backer D, et al. Sublingual microcirculatory effects of enalaprilat in an ovine model of septic shock. Shock 2011; 35:542 - 9; http://dx.doi.org/10.1097/SHK.0b013e3182115e6a; PMID: 21283060
   PubMed Web of Science ®Google Scholar
• Pranskunas A, Vellinga NA, Pilvinis V, Koopmans M, Boerma EC. Microcirculatory changes during open label magnesium sulphate infusion in patients with severe sepsis and septic shock. BMC Anesthesiol 2011; 11:12; http://dx.doi.org/10.1186/1471-2253-11-12; PMID: 21672227
   PubMedGoogle Scholar
• Schmidt TS, Alp NJ. Mechanisms for the role of tetrahydrobiopterin in endothelial function and vascular disease. Clin Sci (Lond) 2007; 113:47 - 63; PMID: 17555404
   PubMed Web of Science ®Google Scholar
• Crabtree MJ, Smith CL, Lam G, Goligorsky MS, Gross SS. Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS. Am J Physiol Heart Circ Physiol 2008; 294:H1530 - 40; http://dx.doi.org/10.1152/ajpheart.00823.2007; PMID: 18192221
   PubMedGoogle Scholar
• Ihlemann N, Rask-Madsen C, Perner A, Dominguez H, Hermann T, Køber L, Torp-Pedersen C. Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects. Am J Physiol Heart Circ Physiol 2003; 285:H875 - 82; PMID: 12730050
   PubMed Web of Science ®Google Scholar
• Maglione M, Hermann M, Hengster P, Schneeberger S, Mark W, Obrist P, Werner-Felmayer G, Werner ER, Margreiter R, Brandacher G. Tetrahydrobiopterin attenuates microvascular reperfusion injury following murine pancreas transplantation. Am J Transplant 2006; 6:1551 - 9; http://dx.doi.org/10.1111/j.1600-6143.2006.01345.x; PMID: 16827855
   PubMed Web of Science ®Google Scholar
• Tyml K, Li F, Wilson JX. Septic impairment of capillary blood flow requires nicotinamide adenine dinucleotide phosphate oxidase but not nitric oxide synthase and is rapidly reversed by ascorbate through an endothelial nitric oxide synthase-dependent mechanism. Crit Care Med 2008; 36:2355 - 62; http://dx.doi.org/10.1097/CCM.0b013e31818024f6; PMID: 18596627
   PubMed Web of Science ®Google Scholar
• He X, Su F, Velissaris D, Salgado DR, de Souza Barros D, Lorent S, Taccone FS, Vincent JL, De Backer D. Administration of tetrahydrobiopterin improves the microcirculation and outcome in an ovine model of septic shock. Crit Care Med 2012; 40:2833 - 40; http://dx.doi.org/10.1097/CCM.0b013e31825b88ba; PMID: 22846780
   PubMed Web of Science ®Google Scholar
• Wilson JX. Mechanism of action of vitamin C in sepsis: ascorbate modulates redox signaling in endothelium. Biofactors 2009; 35:5 - 13; http://dx.doi.org/10.1002/biof.7; PMID: 19319840
   PubMed Web of Science ®Google Scholar
• Armour J, Tyml K, Lidington D, Wilson JX. Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat. J Appl Physiol 2001; 90:795 - 803; PMID: 11181585
   PubMed Web of Science ®Google Scholar
• Tyml K, Li F, Wilson JX. Delayed ascorbate bolus protects against maldistribution of microvascular blood flow in septic rat skeletal muscle. Crit Care Med 2005; 33:1823 - 8; http://dx.doi.org/10.1097/01.CCM.0000172548.34622.DE; PMID: 16096461
   PubMed Web of Science ®Google Scholar
• Gierer P, Hoffmann JN, Mahr F, Menger MD, Mittlmeier T, Gradl G, Vollmar B. Activated protein C reduces tissue hypoxia, inflammation, and apoptosis in traumatized skeletal muscle during endotoxemia. Crit Care Med 2007; 35:1966 - 71; http://dx.doi.org/10.1097/01.CCM.0000275270.14835.2A; PMID: 17568327
   PubMed Web of Science ®Google Scholar
• Gupta A, Berg DT, Gerlitz B, Sharma GR, Syed S, Richardson MA, Sandusky G, Heuer JG, Galbreath EJ, Grinnell BW. Role of protein C in renal dysfunction after polymicrobial sepsis. J Am Soc Nephrol 2007; 18:860 - 7; http://dx.doi.org/10.1681/ASN.2006101167; PMID: 17301189
   PubMed Web of Science ®Google Scholar
• De Backer D, Verdant C, Chierego M, Koch M, Gullo A, Vincent JL. Effects of drotrecogin alfa activated on microcirculatory alterations in patients with severe sepsis. Crit Care Med 2006; 34:1918 - 24; http://dx.doi.org/10.1097/01.CCM.0000220498.48773.3C; PMID: 16715034
   PubMed Web of Science ®Google Scholar
• Hoffmann JN, Vollmar B, Römisch J, Inthorn D, Schildberg FW, Menger MD. Antithrombin effects on endotoxin-induced microcirculatory disorders are mediated mainly by its interaction with microvascular endothelium. Crit Care Med 2002; 30:218 - 25; http://dx.doi.org/10.1097/00003246-200201000-00031; PMID: 11902265
   PubMed Web of Science ®Google Scholar
• Iba T, Takayama T. Enoxaparin attenuates endothelial damage with less bleeding compared with unfractionated heparin in endotoxemic rats. Shock 2009; 32:530 - 4; http://dx.doi.org/10.1097/SHK.0b013e3181a2e279; PMID: 19295478
   PubMed Web of Science ®Google Scholar
• Iba T, Okamoto K, Ohike T, Tajirika T, Aihara K, Watanabe S, Kayhanian H. Enoxaparin and fondaparinux attenuates endothelial damage in endotoxemic rats. J Trauma Acute Care Surg 2012; 72:177 - 82; PMID: 22310127
   PubMedGoogle Scholar
• Hoffmann JN, Vollmar B, Inthorn D, Schildberg FW, Menger MD. The thrombin antagonist hirudin fails to inhibit endotoxin-induced leukocyte/endothelial cell interaction and microvascular perfusion failure. Shock 2000; 14:528 - 34; http://dx.doi.org/10.1097/00024382-200014050-00006; PMID: 11092685
   PubMed Web of Science ®Google Scholar
• Donati A, Romanelli M, Botticelli L, Valentini A, Gabbanelli V, Nataloni S, Principi T, Pelaia P, Bezemer R, Ince C. Recombinant activated protein C treatment improves tissue perfusion and oxygenation in septic patients measured by near-infrared spectroscopy. Crit Care 2009; 13:Suppl 5 S12; http://dx.doi.org/10.1186/cc8010; PMID: 19951384
   PubMedGoogle Scholar