Endothelial and Microcirculatory Function and Dysfunction in Sepsis

Clinics in Chest Medicine

Volumn 37, Issue 2, 2016, Pages 263-275

  Colbert, James F ^a   Schmidt, Eric P ^a  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

Author keywords

Glycocalyx; Glycosaminoglycans; Heparan sulfate; Intravital microscopy; Microcirculation; Sepsis

Indexed keywords

ACTIVATED PROTEIN C; ALBUMIN; ALCIAN BLUE; CYTOKINE; DOBUTAMINE; DOXYCYCLINE; DROTRECOGIN; GLYCOSAMINOGLYCAN; HETASTARCH; HYDROCORTISONE; LACTIC ACID; METHYLENE BLUE; NORADRENALIN; OXYGEN; PATHOGEN ASSOCIATED MOLECULAR PATTERN; PROTEOGLYCAN; ROSUVASTATIN; SPHINGOSINE 1 PHOSPHATE; TOLL LIKE RECEPTOR;

BLOOD CLOTTING; CYTOKINE STORM; DRUG MEGADOSE; DRUG TARGETING; EDEMA; ENDOTHELIAL DYSFUNCTION; ENZYME LINKED IMMUNOSORBENT ASSAY; FLUID THERAPY; GLYCOCALYX; HEMOFILTRATION; HUMAN; INTRAVITAL MICROSCOPY; LATEX AGGLUTINATION TEST; LEUKOCYTE ADHERENCE; MASS SPECTROMETRY; META ANALYSIS (TOPIC); MICROANGIOPATHY; MICROCIRCULATION; NEUTROPHIL CHEMOTAXIS; NONHUMAN; OXYGEN TENSION; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN INDUCTION; REVIEW; SEPSIS; SPECTROMETRY; THROMBOELASTOGRAPHY; TISSUE OXYGENATION; ANIMAL; ENDOTHELIUM; PROCEDURES;

ANIMALS; ENDOTHELIUM; GLYCOSAMINOGLYCANS; HUMANS; INTRAVITAL MICROSCOPY; MICROCIRCULATION; SEPSIS;

EID: 84959465333     PISSN: 02725231     EISSN: 15578216     Source Type: Journal    
DOI: 10.1016/j.ccm.2016.01.009     Document Type: Review

References (121)

1. Ince C. The microcirculation is the motor of sepsis. Crit Care 2005, 9(Suppl 4):S13-S19.
2. Kuebler W.M. Inflammatory pathways and microvascular responses in the lung. Pharmacol Rep 2005, 57(Suppl):196-205.
3. Marki A., Esko J.D., Pries A.R., et al. Role of the endothelial surface layer in neutrophil recruitment. J Leukoc Biol 2015, 98(4):503-515.
4. Donaldson I.M. Celsus: de medicina, florence 1478. Part 1. J R Coll Physicians Edinb 2014, 44(3):252-254.
5. Schmidt E.P., Lee W.L., Zemans R.L., et al. On, around, and through: neutrophil-endothelial interactions in innate immunity. Physiology (Bethesda) 2011, 26(5):334-347.
6. Rossaint J., Zarbock A. Tissue-specific neutrophil recruitment into the lung, liver, and kidney. J Innate Immun 2013, 5(4):348-357.
7. Mehta D., Malik A.B. Signaling mechanisms regulating endothelial permeability. Physiol Rev 2006, 86(1):279-367.
8. Negrini D., Passi A., Moriondo A. The role of proteoglycans in pulmonary edema development. Intensive Care Med 2008, 34(4):610-618.
9. Levi M., van der Poll T., Schultz M. Systemic versus localized coagulation activation contributing to organ failure in critically ill patients. Semin Immunopathol 2012, 34(1):167-179.
10. Dixon B. The role of microvascular thrombosis in sepsis. Anaesth Intensive Care 2004, 32(5):619-629.
11. Echtenacher B., Weigl K., Lehn N., et al. Tumor necrosis factor-dependent adhesions as a major protective mechanism early in septic peritonitis in mice. Infect Immun 2001, 69(6):3550-3555.
12. Ranieri V.M., Thompson B.T., Barie P.S., et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012, 366(22):2055-2064.
13. Abraham E., Reinhart K., Opal S., et al. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 2003, 290(2):238-247.
14. Warren B.L., Eid A., Singer P., et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 2001, 286(15):1869-1878.
15. Melican K., Boekel J., Mansson L.E., et al. Bacterial infection-mediated mucosal signalling induces local renal ischaemia as a defence against sepsis. Cell Microbiol 2008, 10(10):1987-1998.
16. Mizgerd J.P. Acute lower respiratory tract infection. N Engl J Med 2008, 358(7):716-727.
17. Nielubowicz G.R., Mobley H.L. Host-pathogen interactions in urinary tract infection. Nat Rev Urol 2010, 7(8):430-441.
18. Bull T.M., Clark B., McFann K., et al. Pulmonary vascular dysfunction is associated with poor outcomes in patients with acute lung injury. Am J Respir Crit Care Med 2010, 182(9):1123-1128.
19. Ostergaard L., Granfeldt A., Secher N., et al. Microcirculatory dysfunction and tissue oxygenation in critical illness. Acta Anaesthesiol Scand 2015, 59(10):1246-1259.
20. Hayes M.A., Timmins A.C., Yau E.H., et al. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994, 330(24):1717-1722.
21. Hebert P.C., Wells G., Blajchman M.A., et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999, 340(6):409-417.
22. Peake S.L., Delaney A., Bailey M., et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014, 371(16):1496-1506.
23. Mouncey P.R., Osborn T.M., Power G.S., et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015, 372(14):1301-1311.
24. Yealy D.M., Kellum J.A., Huang D.T., et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014, 370(18):1683-1693.
25. Lam C., Tyml K., Martin C., et al. Microvascular perfusion is impaired in a rat model of normotensive sepsis. J Clin Invest 1994, 94(5):2077-2083.
26. Lee W.L., Slutsky A.S. Sepsis and endothelial permeability. N Engl J Med 2010, 363(7):689-691.
27. Opal S.M., van der Poll T. Endothelial barrier dysfunction in septic shock. J Intern Med 2015, 277(3):277-293.
28. Schmidt E.P., Yang Y., Janssen W.J., et al. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med 2012, 18(8):1217-1223.
29. de Stoppelaar S.F., van 't Veer C., van der Poll T. The role of platelets in sepsis. Thromb Haemost 2014, 112(4):666-677.
30. Tyml K. Role of connexins in microvascular dysfunction during inflammation. Can J Physiol Pharmacol 2011, 89(1):1-12.
31. Matthay M.A., Ware L.B., Zimmerman G.A. The acute respiratory distress syndrome. J Clin Invest 2012, 122(8):2731-2740.
32. Prowle J.R., Bellomo R. Sepsis-associated acute kidney injury: macrohemodynamic and microhemodynamic alterations in the renal circulation. Semin Nephrol 2015, 35(1):64-74.
33. Taccone F.S., Su F., De Deyne C., et al. Sepsis is associated with altered cerebral microcirculation and tissue hypoxia in experimental peritonitis. Crit Care Med 2014, 42(2):e114-e122.
34. Page A.V., Liles W.C. Biomarkers of endothelial activation/dysfunction in infectious diseases. Virulence 2013, 4(6):507-516.
35. Klijn E., Den Uil C.A., Bakker J., et al. The heterogeneity of the microcirculation in critical illness. Clin Chest Med 2008, 29(4):643-654. viii.
36. De Backer D., Hollenberg S., Boerma C., et al. How to evaluate the microcirculation: report of a round table conference. Crit Care 2007, 11(5):R101.
37. Arnold R.C., Parrillo J.E., Phillip Dellinger R., et al. Point-of-care assessment of microvascular blood flow in critically ill patients. Intensive Care Med 2009, 35(10):1761-1766.
38. Boerma E.C., Mathura K.R., van der Voort P.H., et al. Quantifying bedside-derived imaging of microcirculatory abnormalities in septic patients: a prospective validation study. Crit Care 2005, 9(6):R601-R606.
39. Sallisalmi M., Oksala N., Pettila V., et al. Evaluation of sublingual microcirculatory blood flow in the critically ill. Acta Anaesthesiol Scand 2012, 56(3):298-306.
40. Vellinga N.A., Boerma E.C., Koopmans M., et al. International study on microcirculatory shock occurrence in acutely ill patients. Crit Care Med 2015, 43(1):48-56.
41. Boerma E.C., van der Voort P.H., Spronk P.E., et al. Relationship between sublingual and intestinal microcirculatory perfusion in patients with abdominal sepsis. Crit Care Med 2007, 35(4):1055-1060.
42. De Backer D., Creteur J., Preiser J.C., et al. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 2002, 166(1):98-104.
43. Sakr Y., Dubois M.J., De Backer D., et al. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med 2004, 32(9):1825-1831.
44. Trzeciak S., Dellinger R.P., Parrillo J.E., et al. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med 2007, 49(1):88-98. 98.e81-2.
45. Edul V.S., Enrico C., Laviolle B., et al. Quantitative assessment of the microcirculation in healthy volunteers and in patients with septic shock. Crit Care Med 2012, 40(5):1443-1448.
46. Paize F., Sarginson R., Makwana N., et al. Changes in the sublingual microcirculation and endothelial adhesion molecules during the course of severe meningococcal disease treated in the paediatric intensive care unit. Intensive Care Med 2012, 38(5):863-871.
47. Creteur J., De Backer D., Sakr Y., et al. Sublingual capnometry tracks microcirculatory changes in septic patients. Intensive Care Med 2006, 32(4):516-523.
48. Cohen J. The immunopathogenesis of sepsis. Nature 2002, 420(6917):885-891.
49. Natanson C., Esposito C.J., Banks S.M. The sirens' songs of confirmatory sepsis trials: selection bias and sampling error. Crit Care Med 1998, 26(12):1927-1931.
50. Opal S.M., Laterre P.F., Francois B., et al. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA 2013, 309(11):1154-1162.
51. Rice T.W., Wheeler A.P., Bernard G.R., et al. A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis. Crit Care Med 2010, 38(8):1685-1694.
52. Hotchkiss R.S., Monneret G., Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol 2013, 13(12):862-874.
53. De Backer D., Creteur J., Dubois M.J., et al. The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit Care Med 2006, 34(2):403-408.
54. Schmidt E.P., Damarla M., Rentsendorj O., et al. Soluble guanylyl cyclase contributes to ventilator-induced lung injury in mice. Am J Physiol Lung Cell Mol Physiol 2008, 295(6):L1056-L1065.
55. Forstermann U. Janus-faced role of endothelial NO synthase in vascular disease: uncoupling of oxygen reduction from NO synthesis and its pharmacological reversal. Biol Chem 2006, 387(12):1521-1533.
56. Kuebler W.M. The Janus-faced regulation of endothelial permeability by cyclic GMP. Am J Physiol Lung Cell Mol Physiol 2011, 301(2):L157-L160.
57. Boerma E.C., Koopmans M., Konijn A., 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(1):93-100.
58. Trzeciak S., Glaspey L.J., Dellinger R.P., et al. Randomized controlled trial of inhaled nitric oxide for the treatment of microcirculatory dysfunction in patients with sepsis. Crit Care Med 2014, 42(12):2482-2492.
59. Vincent J.L., Zhang H., Szabo C., et al. Effects of nitric oxide in septic shock. Am J Respir Crit Care Med 2000, 161(6):1781-1785.
60. Trzeciak S., Cinel I., Phillip Dellinger R., et al. Resuscitating the microcirculation in sepsis: the central role of nitric oxide, emerging concepts for novel therapies, and challenges for clinical trials. Acad Emerg Med 2008, 15(5):399-413.
61. Yang Y., Schmidt E.P. The endothelial glycocalyx: an important regulator of the pulmonary vascular barrier. Tissue Barriers 2013, 1(1):e23494.
62. Luft J.H. Fine structures of capillary and endocapillary layer as revealed by ruthenium red. Fed Proc 1966, 25(6):1773-1783.
63. Potter D.R., Damiano E.R. The hydrodynamically relevant endothelial cell glycocalyx observed in vivo is absent in vitro. Circ Res 2008, 102(7):770-776.
64. Chappell D., Jacob M., Paul O., et al. The glycocalyx of the human umbilical vein endothelial cell: an impressive structure ex vivo but not in culture. Circ Res 2009, 104(11):1313-1317.
65. Ebong E.E., Macaluso F.P., Spray D.C., et al. Imaging the endothelial glycocalyx in vitro by rapid freezing/freeze substitution transmission electron microscopy. Arterioscler Thromb Vasc Biol 2011, 31(8):1908-1915.
66. Wiesinger A., Peters W., Chappell D., et al. Nanomechanics of the endothelial glycocalyx in experimental sepsis. PLoS One 2013, 8(11):e80905.
67. Curry F.E., Adamson R.H. Endothelial glycocalyx: permeability barrier and mechanosensor. Ann Biomed Eng 2012, 40(4):828-839.
68. Florian J.A., Kosky J.R., Ainslie K., et al. Heparan sulfate proteoglycan is a mechanosensor on endothelial cells. Circ Res 2003, 93(10):e136-e142.
69. Mulivor A.W., Lipowsky H.H. Inhibition of glycan shedding and leukocyte-endothelial adhesion in postcapillary venules by suppression of matrixmetalloprotease activity with doxycycline. Microcirculation 2009, 16(8):657-666.
70. Cabrales P., Vazquez B.Y., Tsai A.G., et al. Microvascular and capillary perfusion following glycocalyx degradation. J Appl Physiol (1985) 2007, 102(6):2251-2259.
71. Zuurbier C.J., Demirci C., Koeman A., et al. Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells. J Appl Physiol (1985) 2005, 99(4):1471-1476.
72. Lygizos M.I., Yang Y., Altmann C.J., et al. Heparanase mediates renal dysfunction during early sepsis in mice. Physiol Rep 2013, 1(6):e00153.
73. Marechal X., Favory R., Joulin O., et al. Endothelial glycocalyx damage during endotoxemia coincides with microcirculatory dysfunction and vascular oxidative stress. Shock 2008, 29(5):572-576.
74. Nieuwdorp M., Meuwese M.C., Mooij H.L., et al. Tumor necrosis factor-alpha inhibition protects against endotoxin-induced endothelial glycocalyx perturbation. Atherosclerosis 2009, 202(1):296-303.
75. Nelson A., Berkestedt I., Schmidtchen A., et al. Increased levels of glycosaminoglycans during septic shock: relation to mortality and the antibacterial actions of plasma. Shock 2008, 30(6):623-627.
76. Sallisalmi M., Tenhunen J., Yang R., et al. Vascular adhesion protein-1 and syndecan-1 in septic shock. Acta Anaesthesiol Scand 2012, 56(3):316-322.
77. Ostrowski S.R., Berg R.M.G., Windeløv N.A., et al. Coagulopathy, catecholamines, and biomarkers of endothelial damage in experimental human endotoxemia and in patients with severe sepsis: a prospective study. J Crit Care 2013, 28(5):586-596.
78. Schmidt E.P., Li G., Li L., et al. The circulating glycosaminoglycan signature of respiratory failure in critically ill adults. J Biol Chem 2014, 289(12):8194-8202.
79. Nelson A., Berkestedt I., Bodelsson M. Circulating glycosaminoglycan species in septic shock. Acta Anaesthesiol Scand 2014, 58(1):36-43.
80. Berg S., Brodin B., Hesselvik F., et al. Elevated levels of plasma hyaluronan in septicaemia. Scand J Clin Lab Invest 1988, 48(8):727-732.
81. Steppan J., Hofer S., Funke B., et al. Sepsis and major abdominal surgery lead to flaking of the endothelial glycocalix. J Surg Res 2011, 165(1):136-141.
82. Yagmur E., Koch A., Haumann M., et al. Hyaluronan serum concentrations are elevated in critically ill patients and associated with disease severity. Clin Biochem 2012, 45(1-2):82-87.
83. Oragui E.E., Nadel S., Kyd P., et al. Increased excretion of urinary glycosaminoglycans in meningococcal septicemia and their relationship to proteinuria. Crit Care Med 2000, 28(8):3002-3008.
84. Sun X., Li L., Overdier K.H., et al. Analysis of total human urinary glycosaminoglycan disaccharides by liquid chromatography-tandem mass spectrometry. Anal Chem 2015, 87(12):6220-6227.
85. Ostrowski S.R., Johansson P.I. Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy. J Trauma Acute Care Surg 2012, 73(1):60-66.
86. Nieuwdorp M., Meuwese M.C., Mooij H.L., et al. Measuring endothelial glycocalyx dimensions in humans: a potential novel tool to monitor vascular vulnerability. J Appl Physiol (1985) 2008, 104(3):845-852.
87. Michel C.C., Curry F.R. Glycocalyx volume: a critical review of tracer dilution methods for its measurement. Microcirculation 2009, 16(3):213-219.
88. Donati A., Damiani E., Domizi R., et al. Alteration of the sublingual microvascular glycocalyx in critically ill patients. Microvasc Res 2013, 90:86-89.
89. Shapiro N.I., Angus D.C. A review of therapeutic attempts to recruit the microcirculation in patients with sepsis. Minerva Anestesiol 2014, 80(2):225-235.
90. De Backer D., Verdant C., Chierego M., et al. Effects of drotrecogin alfa activated on microcirculatory alterations in patients with severe sepsis. Crit Care Med 2006, 34(7):1918-1924.
91. Bernard G.R., Vincent J.L., Laterre P.F., et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001, 344(10):699-709.
92. Abraham E., Laterre P.F., Garg R., et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med 2005, 353(13):1332-1341.
93. Thooft A., Favory R., Salgado D.R., et al. Effects of changes in arterial pressure on organ perfusion during septic shock. Crit Care 2011, 15(5):R222.
94. Dubin A., Pozo M.O., Casabella C.A., et al. Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care 2009, 13(3):R92.
95. Asfar P., Meziani F., Hamel J.F., et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med 2014, 370(17):1583-1593.
96. Russell J.A. Adding fuel to the fire-the supranormal oxygen delivery trials controversy. Crit Care Med 1998, 26(6):981-983.
97. Buchele G.L., Silva E., Ospina-Tascon G.A., et al. Effects of hydrocortisone on microcirculatory alterations in patients with septic shock. Crit Care Med 2009, 37(4):1341-1347.
98. Sprung C.L., Caralis P.V., Marcial E.H., et al. The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study. N Engl J Med 1984, 311(18):1137-1143.
99. Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med 1987, 317(11):659-665. Veterans Administration Systemic Sepsis Cooperative Study Group.
100. Cronin L., Cook D.J., Carlet J., et al. Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med 1995, 23(8):1430-1439.
101. Sprung C.L., Annane D., Keh D., et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008, 358(2):111-124.
102. Berlot G., Bianco N., Tomasini A., et al. Changes in microvascular blood flow during coupled plasma filtration and adsorption. Anaesth Intensive Care 2011, 39(4):687-689.
103. Ruiz C., Hernandez G., Godoy C., et al. Sublingual microcirculatory changes during high-volume hemofiltration in hyperdynamic septic shock patients. Crit Care 2010, 14(5):R170.
104. Cruz D.N., Antonelli M., Fumagalli R., et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA 2009, 301(23):2445-2452.
105. Ospina-Tascon G., Neves A.P., Occhipinti G., et al. Effects of fluids on microvascular perfusion in patients with severe sepsis. Intensive Care Med 2010, 36(6):949-955.
106. Dubin A., Pozo M.O., Casabella C.A., et al. Comparison of 6% hydroxyethyl starch 130/0.4 and saline solution for resuscitation of the microcirculation during the early goal-directed therapy of septic patients. J Crit Care 2010, 25(4):659.e651-659.e658.
107. Finfer S., McEvoy S., Bellomo R., et al. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med 2011, 37(1):86-96.
108. Brunkhorst F.M., Engel C., Bloos F., et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008, 358(2):125-139.
109. Myburgh J.A., Finfer S., Bellomo R., et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012, 367(20):1901-1911.
110. Perner A., Haase N., Guttormsen A.B., et al. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med 2012, 367(2):124-134.
111. Zarychanski R., Abou-Setta A.M., Kanji S., et al. The efficacy and safety of heparin in patients with sepsis: a systematic review and metaanalysis. Crit Care Med 2015, 43(3):511-518.
112. Levi M., Levy M., Williams M.D., et al. Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated). Am J Respir Crit Care Med 2007, 176(5):483-490.
113. Wang L., Fuster M., Sriramarao P., et al. Endothelial heparan sulfate deficiency impairs L-selectin- and chemokine-mediated neutrophil trafficking during inflammatory responses. Nat Immunol 2005, 6(9):902-910.
114. Goetz R., Mohammadi M. Exploring mechanisms of FGF signalling through the lens of structural biology. Nat Rev Mol Cell Biol 2013, 14(3):166-180.
115. Al-Banna N.A., Pavlovic D., Bac V.H., et al. Acute administration of antibiotics modulates intestinal capillary perfusion and leukocyte adherence during experimental sepsis. Int J Antimicrob Agents 2013, 41(6):536-543.
116. Becker B.F., Jacob M., Leipert S., et al. Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases. Br J Clin Pharmacol 2015, 80(3):389-402.
117. Zeng Y., Adamson R.H., Curry F.R., et al. Sphingosine-1-phosphate protects endothelial glycocalyx by inhibiting syndecan-1 shedding. Am J Physiol Heart Circ Physiol 2014, 306(3):H363-H372.
118. Meuwese M.C., Mooij H.L., Nieuwdorp M., et al. Partial recovery of the endothelial glycocalyx upon rosuvastatin therapy in patients with heterozygous familial hypercholesterolemia. J Lipid Res 2009, 50(1):148-153.
119. Kruger P., Bailey M., Bellomo R., et al. A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis. Am J Respir Crit Care Med 2013, 187(7):743-750.
120. Blum C.A., Nigro N., Briel M., et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015, 385(9977):1511-1518.
121. Torres A., Sibila O., Ferrer M., et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA 2015, 313(7):677-686.