Inhaled carbon monoxide protects time-dependently from loss of hypoxic pulmonary vasoconstriction in endotoxemic mice

Respiratory Research

Jörg Weimann⁴  Udo X. Kaisers⁶  Stephan A. Loer²  Daniel D. Oswald¹  Charlotte E. Teunissen³  Marleen J. A. Koel-Simmelink³  Thilo Busch⁶  Maria T. Voelker⁶  Cornelius J. Busch⁵  Regis R. Lamberts²  Nora Jahn⁶ 

[1] Department of Anaesthesiology, Universitätsklinikum, Münster, Germany;Department of Anaesthesiology, Institute for Cardiovascular Research (ICaR-VU), VU University Medical Centre, Amsterdam, The Netherlands;Department of Clinical Chemistry, Neurological Laboratory and Biobank, VU University Medical Centre, Amsterdam, The Netherlands;Department of Anaesthesia and Intensive Care Medicine, Sankt Gertrauden-Krankenhaus, Berlin, Germany;Department of Anaesthesiology, Ruprecht-Karls-University, Heidelberg, Germany;Department of Anaesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany

关键词: Endotoxemia;    Sepsis;    Pulmonary circulation;    HPV;    CO;   

Others  :  1233516
DOI  :  10.1186/s12931-015-0274-7

 received in 2015-04-17, accepted in 2015-09-07,  发布年份 2015

【 摘 要 】

Background

Inhaled carbon monoxide (CO) appears to have beneficial effects on endotoxemia-induced impairment of hypoxic pulmonary vasoconstriction (HPV). This study aims to specify correct timing of CO application, it’s biochemical mechanisms and effects on inflammatory reactions.

Methods

Mice (C57BL/6; n = 86) received lipopolysaccharide (LPS, 30 mg/kg) intraperitoneally and subsequently breathed 50 ppm CO continuously during defined intervals of 3, 6, 12 or 18 h. Two control groups received saline intraperitoneally and additionally either air or CO, and one control group received LPS but breathed air only. In an isolated lung perfusion model vasoconstrictor response to hypoxia (FiO ₂  = 0.01) was quantified by measurements of pulmonary artery pressure. Pulmonary capillary pressure was estimated by double occlusion technique. Further, inflammatory plasma cytokines and lung tissue mRNA of nitric-oxide-synthase-2 (NOS-2) and heme oxygenase-1 (HO-1) were measured.

Results

HPV was impaired after LPS-challenge (p < 0.01). CO exposure restored HPV-responsiveness if administered continuously for full 18 h, for the first 6 h and if given in the interval between the 3 ^rdand 6 ^thhour after LPS-challenge (p < 0.05). Preserved HPV was attributable to recovered arterial resistance and associated with significant reduction in NOS-2 mRNA when compared to controls (p < 0.05). We found no effects on inflammatory plasma cytokines.

Conclusion

Low-dose CO prevented LPS-induced impairment of HPV in a time-dependent manner, associated with a decreased NOS-2 expression.

【 授权许可】

   
2015 Jahn et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

Fig. 6.

Fig. 7.

【 参考文献 】

• [1]Naeije R, Brimioulle S. Physiology in medicine: importance of hypoxic pulmonary vasoconstriction in maintaining arterial oxygenation during acute respiratory failure. Crit Care. 2001; 5:67-71. BioMed Central Full Text
• [2]Sommer N, Dietrich A, Schermuly RT, Ghofrani HA, Gudermann T, Schulz R et al.. Regulation of hypoxic pulmonary vasoconstriction: basic mechanisms. Eur Respir J. 2008; 32:1639-51.
• [3]Brimioulle S, Julien V, Gust R, Kozlowski JK, Naeije R, Schuster DP. Importance of hypoxic vasoconstriction in maintaining oxygenation during acute lung injury. Crit Care Med. 2002; 30:874-80.
• [4]Petersen B, Bloch KD, Ichinose F, Shin HS, Shigematsu M, Bagchi A et al.. Activation of Toll-like receptor 2 impairs hypoxic pulmonary vasoconstriction in mice. Am J Physiol Lung Cell Mol Physiol. 2008; 294:L300-8.
• [5]Ullrich R, Bloch KD, Ichinose F, Steudel W, Zapol WM. Hypoxic pulmonary blood flow redistribution and arterial oxygenation in endotoxin-challenged NOS2-deficient mice. J Clin Invest. 1999; 104:1421-9.
• [6]Erickson SE, Martin GS, Davis JL, Matthay MA, Eisner MD. Recent trends in acute lung injury mortality: 1996–2005. Crit Care Med. 2009; 37:1574-9.
• [7]Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M et al.. Incidence and outcomes of acute lung injury. N Engl J Med. 2005; 353:1685-93.
• [8]Stapleton RD, Wang BM, Hudson LD, Rubenfeld GD, Caldwell ES, Steinberg KP. Causes and timing of death in patients with ARDS. Chest. 2005; 128:525-32.
• [9]The ARDS. Definition Task Force*. Acute respiratory distress syndrome: The Berlin definition. JAMA. 2012; 307:2526-33.
• [10]Fuchs B, Sommer N, Dietrich A, Schermuly RT, Ghofrani HA, Grimminger F et al.. Redox signaling and reactive oxygen species in hypoxic pulmonary vasoconstriction. Respir Physiol Neurobiol. 2010; 174:282-91.
• [11]Baboolal HA, Ichinose F, Ullrich R, Kawai N, Bloch KD, Zapol WM. Reactive oxygen species scavengers attenuate endotoxin-induced impairment of hypoxic pulmonary vasoconstriction in mice. Anesthesiology. 2002; 97:1227-33.
• [12]Ghosh S, Wilson MR, Choudhury S, Yamamoto H, Goddard ME, Falusi B et al.. Effects of inhaled carbon monoxide on acute lung injury in mice. Am J Physiol Lung Cell Mol Physiol. 2005; 288:L1003-9.
• [13]Kristof AS, Goldberg P, Laubach V, Hussain SN. Role of inducible nitric oxide synthase in endotoxin-induced acute lung injury. Am J Respir Crit Care Med. 1998; 158:1883-9.
• [14]Mazzola S, Forni M, Albertini M, Bacci ML, Zannoni A, Gentilini F et al.. Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs. FASEB J. 2005; 19:2045-7.
• [15]Spohr F, Cornelissen AJ, Busch C, Gebhard MM, Motsch J, Martin EO et al.. Role of endogenous nitric oxide in endotoxin-induced alteration of hypoxic pulmonary vasoconstriction in mice. Am J Physiol Heart Circ Physiol. 2005; 289:H823-31.
• [16]Spohr F, Busch CJ, Teschendorf P, Weimann J. Selective inhibition of guanylate cyclase prevents impairment of hypoxic pulmonary vasoconstriction in endotoxemic mice. J Physiol Pharmacol. 2009; 60:107-12.
• [17]Dolinay T, Szilasi M, Liu M, Choi AM. Inhaled carbon monoxide confers antiinflammatory effects against ventilator-induced lung injury. Am J Respir Crit Care Med. 2004; 170:613-20.
• [18]Goebel U, Siepe M, Mecklenburg A, Stein P, Roesslein M, Schwer CI et al.. Carbon monoxide inhalation reduces pulmonary inflammatory response during cardiopulmonary bypass in pigs. Anesthesiology. 2008; 108:1025-36.
• [19]Otterbein LE, Mantell LL, Choi AM. Carbon monoxide provides protection against hyperoxic lung injury. Am J Physiol. 1999; 276:L688-94.
• [20]Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev. 2006; 86:583-650.
• [21]Morse D, Pischke SE, Zhou Z, Davis RJ, Flavell RA, Loop T et al.. Suppression of inflammatory cytokine production by carbon monoxide involves the JNK pathway and AP-1. J Biol Chem. 2003; 278:36993-8.
• [22]Hoetzel A, Dolinay T, Schmidt R, Choi AM, Ryter SW. Carbon monoxide in sepsis. Antioxid Redox Signal. 2007; 9:2013-26.
• [23]Takaki S, Takeyama N, Kajita Y, Yabuki T, Noguchi H, Miki Y et al.. Beneficial effects of the heme oxygenase-1/carbon monoxide system in patients with severe sepsis/septic shock. Intensive Care Med. 2010; 36:42-8.
• [24]Zegdi R, Perrin D, Burdin M, Boiteau R, Tenaillon A. Increased endogenous carbon monoxide production in severe sepsis. Intensive Care Med. 2002; 28:793-6.
• [25]Christou H, Morita T, Hsieh CM, Koike H, Arkonac B, Perrella MA et al.. Prevention of hypoxia-induced pulmonary hypertension by enhancement of endogenous heme oxygenase-1 in the rat. Circ Res. 2000; 86:1224-9.
• [26]Mishra S, Fujita T, Lama VN, Nam D, Liao H, Okada M et al.. Carbon monoxide rescues ischemic lungs by interrupting MAPK-driven expression of early growth response 1 gene and its downstream target genes. Proc Natl Acad Sci U S A. 2006; 103:5191-6.
• [27]Otterbein LE, Bach FH, Alam J, Soares M, Tao LH, Wysk M et al.. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med. 2000; 6:422-8.
• [28]Ryter SW, Otterbein LE. Carbon monoxide in biology and medicine. Bioessays. 2004; 26:270-80.
• [29]Ryter SW, Otterbein LE, Morse D, Choi AM. Heme oxygenase/carbon monoxide signaling pathways: regulation and functional significance. Mol Cell Biochem. 2002; 234–235:249-63.
• [30]Oswald D, Busch CJ, Reich C, Kuebler WM, Weimann J. Inhaled carbon monoxide (iCO) prevents LPS-induced impairment of hypoxic pulmonary vasoconstriction (HPV) in mice. Eur J Anaesthesiol. 2007; 24:58-9.
• [31]Spohr F, Busch CJ, Reich C, Motsch J, Gebhard MM, Kuebler WM et al.. 4-Aminopyridine restores impaired hypoxic pulmonary vasoconstriction in endotoxemic mice. Anesthesiology. 2007; 107:597-604.
• [32]Weimann J, Bloch KD, Takata M, Steudel W, Zapol WM. Congenital NOS2 deficiency protects mice from LPS-induced hyporesponsiveness to inhaled nitric oxide. Anesthesiology. 1999; 91:1744-53.
• [33]Hakim TS, Kelly S. Occlusion pressures vs. micropipette pressures in the pulmonary circulation. J Appl Physiol. 1989; 67:1277-85.
• [34]Hakim TS, Sugimori K, Ferrario L. Analysis of the double occlusion which provides four pressure gradients. Eur Respir J. 1996; 9:2578-83.
• [35]Archer SL, Reeve HL, Michelakis E, Puttagunta L, Waite R, Nelson DP et al.. O2 sensing is preserved in mice lacking the gp91 phox subunit of NADPH oxidase. Proc Natl Acad Sci U S A. 1999; 96:7944-9.
• [36]Ferrario L, Amin HM, Sugimori K, Camporesi EM, Hakim TS. Site of action of endogenous nitric oxide on pulmonary vasculature in rats. Pflugers Arch. 1996; 432:523-7.
• [37]Ichinose F, Zapol WM, Sapirstein A, Ullrich R, Tager AM, Coggins K et al.. Attenuation of hypoxic pulmonary vasoconstriction by endotoxemia requires 5-lipoxygenase in mice. Circ Res. 2001; 88:832-8.
• [38]Archer SL, Wu XC, Thebaud B, Nsair A, Bonnet S, Tyrrell B et al.. Preferential expression and function of voltage-gated, O2-sensitive K+ channels in resistance pulmonary arteries explains regional heterogeneity in hypoxic pulmonary vasoconstriction: ionic diversity in smooth muscle cells. Circ Res. 2004; 95:308-18.
• [39]Fike CD, Gordon JB, Kaplowitz MR. Micropipette and vascular occlusion pressures in isolated lungs of newborn lambs. J Appl Physiol. 1993; 75:1854-60.
• [40]Nemzek JA, Fry C, Abatan O. Low-dose carbon monoxide treatment attenuates early pulmonary neutrophil recruitment after acid aspiration. Am J Physiol Lung Cell Mol Physiol. 2008; 294:L644-53.
• [41]Acute lung injury and the acute respiratory distress syndrome in Ireland: a prospective audit of epidemiology and management. Crit Care. 2008; 12:R30. BioMed Central Full Text
• [42]Pelosi P, D’Onofrio D, Chiumello D, Paolo S, Chiara G, Capelozzi VL et al.. Pulmonary and extrapulmonary acute respiratory distress syndrome are different. Eur Respir J Suppl. 2003; 42:48s-56.
• [43]Stone JR, Marletta MA. Soluble guanylate cyclase from bovine lung: activation with nitric oxide and carbon monoxide and spectral characterization of the ferrous and ferric states. Biochemistry. 1994; 33:5636-40.
• [44]Vassalli F, Pierre S, Julien V, Bouckaert Y, Brimioulle S, Naeije R. Inhibition of hypoxic pulmonary vasoconstriction by carbon monoxide in dogs. Crit Care Med. 2001; 29:359-66.
• [45]Sylvester JT, McGowan C. The effects of agents that bind to cytochrome P-450 on hypoxic pulmonary vasoconstriction. Circ Res. 1978; 43:429-37.
• [46]Tamayo L, Lopez-Lopez JR, Castaneda J, Gonzalez C. Carbon monoxide inhibits hypoxic pulmonary vasoconstriction in rats by a cGMP-independent mechanism. Pflugers Arch. 1997; 434:698-704.
• [47]Song R, Kubo M, Morse D, Zhou Z, Zhang X, Dauber JH et al.. Carbon monoxide induces cytoprotection in rat orthotopic lung transplantation via anti-inflammatory and anti-apoptotic effects. Am J Pathol. 2003; 163:231-42.
• [48]Ryter SW, Choi AM. Heme oxygenase-1/carbon monoxide: from metabolism to molecular therapy. Am J Respir Cell Mol Biol. 2009; 41:251-60.
• [49]Clayton CE, Carraway MS, Suliman HB, Thalmann ED, Thalmann KN, Schmechel DE et al.. Inhaled carbon monoxide and hyperoxic lung injury in rats. Am J Physiol Lung Cell Mol Physiol. 2001; 281:L949-57.
• [50]Kim HS, Loughran PA, Billiar TR. Carbon monoxide decreases the level of iNOS protein and active dimer in IL-1beta-stimulated hepatocytes. Nitric Oxide. 2008; 18:256-65.
• [51]Sarady JK, Zuckerbraun BS, Bilban M, Wagner O, Usheva A, Liu F et al.. Carbon monoxide. Protection against endotoxic shock involves reciprocal effects on iNOS in the lung and liver. FASEB J. 2004; 18:854-6.
• [52]Sarady JK, Otterbein SL, Liu F, Otterbein LE, Choi AM. Carbon monoxide modulates endotoxin-induced production of granulocyte macrophage colony-stimulating factor in macrophages. Am J Respir Cell Mol Biol. 2002; 27:739-45.
• [53]Nagasaki A, Gotoh T, Isobe H, Mori M. Regulation of the genes for arginase isoforms and related enzymes in mouse macrophages by lipopolysaccharide. Am J Physiol. 1999; 277:E110-7.
• [54]Plonka PM, Chlopicki S, Wisniewska M, Plonka BK. Kinetics of increased generation of (.)NO in endotoxaemic rats as measured by EPR. Acta Biochim Pol. 2003; 50:807-13.
• [55]Santhanam L, Lim HK, Lim HK, Miriel V, Brown T, Patel M et al.. Inducible NO synthase dependent S-nitrosylation and activation of arginase1 contribute to age-related endothelial dysfunction. Circ Res. 2007; 101:692-702.
• [56]Petersen B, Busch CJ, Bloch KD, Zapol WM. Arginase inhibition restores hypoxic pulmonary vasoconstriction in endotoxemic mice. Am J Respir Crit Care Med. 2012; 185:A4830.