Применение оксида азота для защиты миокарда при ишемической болезни сердца

Авторы:
  • Ю. К. Подоксенов
    ФГБНУ «Томский национальный исследовательский медицинский центр Российской академии наук», Научно-исследовательский институт кардиологии, Томск, Россия; ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава России, Томск, Россия
  • Н. О. Каменщиков
    ФГБНУ «Томский национальный исследовательский медицинский центр Российской академии наук», Научно-исследовательский институт кардиологии, Томск, Россия
  • И. А. Мандель
    ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России, Москва, Россия; ФГБУ «Федеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий Федерального медико-биологического агентства», Москва, Россия
Журнал: Анестезиология и реаниматология. 2019;(2): 34-47
Просмотрено: 606 Скачано: 3
РЕЗЮМЕ Оксид азота (NO) является небольшим свободным радикалом и имеет огромное значение в физиологии и патофизиологии. Продукция достаточного уровня NO необходима для регуляции сосудистого тонуса и поддержания адекватного кровотока во всех органах. Известно, что классический синтез NO с помощью NO-синтаз дополняется путями восстановления нитритов в условиях гипоксии. Метаболизм NO играет существенную роль в механизмах кардиопротекции при ишемически-реперфузионном повреждении в условиях острого инфаркта миокарда или хирургического лечения ишемической болезни сердца с применением искусственного кровообращения. Нарушение регуляции механизмов, участвующих в образовании NO, является важной причиной сердечно-сосудистых заболеваний, и это должно стать целью лечебного воздействия. В представленном обзоре обсуждаются кардиопротективные свойства NO, пути их реализации, а также возможности и перспективы применения NO при сердечно-сосудистых заболеваниях.
Ключевые слова:
  • оксид азота
  • ишемическая болезнь сердца
  • защита миокарда

КАК ЦИТИРОВАТЬ:

Подоксенов Ю.К., Каменщиков Н.О., Мандель И.А. Применение оксида азота для защиты миокарда при ишемической болезни сердца. Анестезиология и реаниматология. 2019;(2):34-47. https://doi.org/10.17116/anaesthesiology201902134

Список литературы:

  1. Tejero J, Shiva S, Gladwin MT. Gladwin Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation. Physiological Reviews. 2019;99(1):311-379. https://doi.org/10.1152/physrev.00036.2017
  2. Spath NB, Mills NL, Cruden NL. Novel cardioprotective and regenerative therapies in acute myocardial infarction: a review of recent and ongoing clinical trials. Future Cardiology. 2016;12(6):655-672. https://doi.org/10.2217/fca-2016-0044
  3. Murillo D, Kamga C, Mo L, Shiva S. Nitrite as a mediator of ischemic preconditioning and cytoprotection. Nitric Oxide: Biology and Chemistry. 2011;25(2):70-80. https://doi.org/10.1016/j.niox.2011.01.003
  4. Ломиворотов В.В., Караськов А.М. Прекондиционирование в кардиохирургии. Отв. ред. Ломиворотов В.Н. Новосибирск: Гео, 2010.
  5. Мандель И.А., Подоксенов Ю.К., Михеев С.Л. и др. Влияние гипоксическо-гипероксического прекондиционирования на развитие периоперационных осложнений и транспорт кислорода в коронарной хирургии с применением искусственного кровообращения. Анестезиология и реаниматология. 2018;63(1):38-45.
  6. Yau JM, Alexander JH, Hafley G, et al. PREVENT IV Investigators. Impact of perioperative myocardial infarction on angiographic and clinical outcomes following coronary artery bypass grafting (from Project of Ex-vivo Vein graft Engineering via Transfection [PREVENT] IV). The American Journal of Cardiology. 2008;102(5):546-551.
  7. Mebazaa A, Pitsis AA, Rudiger A, et al. Clinical review: practical recommendations on the management of perioperative heart failure in cardiac surgery. Critical Care. 2010;14(2):201. https://doi.org/10.1186/cc8153
  8. Tritapepe L, De Santis V, Vitale D, et al. Levosimendan pre-treatment improves outcomes in patients undergoing coronary artery bypass graft surgery. British Journal of Anaesthesia. 2009;102(2):198-204. https://doi.org/10.1093/bja/aen367
  9. Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochemical Journal. 2001;357(3):593-615.
  10. Bryan NS, Bian K, Murad F. Discovery of the nitric oxide signaling pathway and targets for drug development. Frontiers in Bioscience (Landmark Edition). 2009;14(1):1-18.
  11. Forte M, Conti V, Damato A, et al. Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases. Oxidative Medicine and Cellular Longevity. 2016;2016:7364138. https://doi.org/10.1155/2016/7364138
  12. Toledo Jr JC, Augusto O. Connecting the chemical and biological properties of nitric oxide. Chemical Research in Toxicology. 2012;25(5):975-989.
  13. Paul M. Vanhoutte Nitric Oxide: From Good to Bad. Annals of Vascular Diseases. 2018;11(1):41-51. https://doi.org/10.3400/avd.ra.17-00134
  14. Ratnam S, Mookerjea S. The regulation of superoxide generation and nitric oxide synthesis by C-reactive protein. Immunology. 1998;94(4):560.
  15. Nathan C. Nitric oxide as a secretory product of mammalian cells. Federation of American Societies for Experimental Biology Journal. 1992;6(12):3051-3064.
  16. Ignarro LJ. Endothelium-derived nitric oxide: actions and properties. Federation of American Societies for Experimental Biology Journal. 1989;3(1):31-36.
  17. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288(5789):373-376.
  18. Ignarro LJ, Harbison RG, Wood KS, Kadowitz PJ. Activation of purified soluble guanylate cyclase by endothelium-derived relaxing factor from intrapulmonary artery and vein: stimulation by acetylcholine, bradykinin and arachidonic acid. Journal of Pharmacology and Experimental Therapeutics. 1986;237(3):893-900.
  19. Holzmann S. Endothelium-induced relaxation by acetylcholine associated with larger rises in cyclic GMP in coronary arterial strips. Journal of Cyclic Nucleotide Research. 1982;8(6):409-419.
  20. Carrier M, Khalil A, Tourigny A, et al. Effect of L-arginine on metabolic recovery of the ischemic myocardium. The Annals of Thoracic Surgery. 1996;61(6):1651-1657.
  21. Azuma H, Ishikawa M, Sekizaki S. Endothelium‐dependent inhibition of platelet aggregation. British Journal of Pharmacology. 1986;88(2):411-415.
  22. Palmer RMJ, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327(6122):524-526.
  23. Arnold WP, Mittal CK, Katsuki S, Murad F. Nitric oxide activates guanylate cyclase and increases guanosine 3′: 5′-cyclic monophosphate levels in various tissue preparations. Proceedings of the National Academy of Sciences of the United States of America. 1977;74(8):3203-3207.
  24. Murad F. Guanylate cyclase: activation by azide, nitro compounds, nitric oxide, and hydroxyl radical and inhibition by hemoglobin and myoglobin. Advances in Cyclic Nucleotide Research. 1978;9:145-158.
  25. Gruetter CA, Barry BK, McNamara DB, et al. Relaxation of bovine coronary artery and activation of coronary arterial guanylate cyclase by nitric oxide, nitroprusside and a carcinogenic nitrosoamine. Journal of Cyclic Nucleotide Research. 1979;5(3):211-224.
  26. Koshland DE. Molecule of the year. Science. 1991;254(5039):1705.
  27. Lyamina NP, Dolotovskaya PV, Lyamina NV, et al. Nitric oxide production and intensity of free radical processes in young men with high normal and hypertensive blood pressure. Medical Science Monitor. 2003;9(7):CR304-CR310.
  28. Ding HL, Ryder JW, Stull JT, Kamm KE. Signaling processes for initiating smooth muscle contraction upon neural stimulation. Journal of Biological Chemistry. 2009;284(23):15541-15548.
  29. Ziolo MT, Bers DM. The real estate of NOS signaling: location, location, location. Circulation Research. 2003;92(12):1279-1281.
  30. Jones SP, Girod WG, Palazzo AJ, et al. Myocardial ischemia-reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase. American Journal of Physiology. Heart and Circulatory Physiology. 1999;276(5):H1567-H1573.
  31. Xi L, Jarrett NC, Hess ML, Kukreja RC. Essential role of inducible nitric oxide synthase in monophosphoryl lipid A-induced late cardioprotection: evidence from pharmacological inhibition and gene knockout mice. Circulation. 1999;99(16):2157-2163.
  32. Barouch LA, Harrison RW, Skaf MW, et al. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature. 2002;416(6878):337-339.
  33. Omar SA, Webb AJ. Nitrite reduction and cardiovascular protection. Journal of Molecular and Cellular Cardiology. 2014;73:57-69. https://doi.org/10.1016/j.yjmcc.2014.01.012
  34. Mangano DT. Perioperative cardiac morbidity. Canadian Journal of Anesthesia. 1994;41:R13-R19.
  35. Zahler S, Massoudy P, Hartl H, et al. Acute cardiac inflammatory responses to postischemic reperfusion during cardiopulmonary bypass. Cardiovascular Research. 1999;41(3):722-730.
  36. Kusuoka H, Marban E. Cellular mechanisms of myocardial stunning. Annual Review of Physiology.1992;54(1):243-256.
  37. Bical O, Gerhardt MF, Paumier D, et al. Comparison of different types of cardioplegia and reperfusion on myocardial metabolism and free radical activity. Circulation. 1991;84(5 Suppl):III375-III379.
  38. Brunton TL. On the use of nitrite of amyl in angina pectoris. Lancet. 1867;90(2291):97-98.
  39. Xia Z, Li H, Irwin MG. Myocardial ischaemia reperfusion injury: the challenge of translating ischaemic and anaesthetic protection from animal models to humans. British Journal of Anaesthesia. 2016;117(Suppl 2):44-62. https://doi.org/10.1093/bja/aew267
  40. Bice JS, Jones BR, Chamberlain GR, Baxter GF. Nitric oxide treatments as adjuncts to reperfusion in acute myocardial infarction: a systematic review of experimental and clinical studies. Basic Research in Cardiology. 2016;111(2):23. https://doi.org/10.1007/s00395-016-0540-y
  41. Mathru M, Huda R, Solanki DR, Hays S, Lang JD. Inhaled nitric oxide attenuates reperfusion inflammatory responses in humans. Anesthesiology. 2007;106:275-282.
  42. Lang JD Jr, Teng X, Chumley P, et al. Inhaled NO accelerates restoration of liver function in adults followin orthotopic liver transplantation. Journal of Clinical Investigation. 2007;117:2583-2591.
  43. Heiss C, Lauer T, Dejam A, et al. Plasma nitroso compounds are decreased in patients with endothelial dysfunction. Journal of the American College of Cardiology. 2006;47(3):573-579.
  44. Bolli R. The late phase of preconditioning. Circulation Research. 2000;87(11):972-983.
  45. Björne H, Govoni M, Törnberg DC, et al. Intragastric nitric oxide is abolished in intubated patients and restored by nitrite. Critical Care Medicine. 2005;33(8):1722-1727.
  46. Rifkind JM, Mohanty JG, Nagababu E, et al. Potential Modulation of Vascular Function by Nitric Oxide and Reactive Oxygen Species Released From Erythrocytes. Frontiers in Physiology. 2018;9:690. https://doi.org/10.3389/fphys.2018.00690
  47. Nagasaka Y, Fernandez BO, Steinbicker AU, et al. Pharmacological preconditioning with inhaled nitric oxide (NO): Organspecific differences in the lifetime of blood and tissue NO metabolites. Nitric Oxide. 2018;80:52-60. https://doi.org/10.1016/j.niox.2018.08.006
  48. Vaughn MW, Huang KT, Kuo L, Liao J.C. Erythrocytes possess an intrinsic barrier to nitric oxide consumption. Journal of Biological Chemistry. 2000;275(4):2342-2348.
  49. Jansson EA, Huang L, Malkey R, et al. A mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis. Nature Chemical Biology. 2008;4(7):411-417. https://doi.org/10.1038/nchembio.92
  50. Liao JC, Hein TW, Vaughn MW, et al. Intravascular flow decreases erythrocyte consumption of nitric oxide. Proceedings of the National Academy of Sciences of the United States of America. 1999;96(15):8757-8761.
  51. Helms CC, Gladwin MT, Kim-Shapiro DB. Erythrocytes and Vascular Function: Oxygen and Nitric Oxide. Frontiers in Physiology. 2018;9:125. https://doi.org/10.3389/fphys.2018.00125
  52. Totzeck M, Hendgen-Cotta UB, Luedike P, et al. Nitrite Regulates Hypoxic Vasodilation via Myoglobin-Dependent Nitric Oxide Generation. Circulation. 2012;126(3):325-334. https://doi.org/10.1161/CIRCULATIONAHA.111.087155
  53. Rassaf T, Ferdinandy P, Schulz R. Nitrite in organ protection. Review. British Journal of Pharmacology. 2014;17:1-11. https://doi.org/10.1111/bph.12291
  54. Minneci PC, Deans KJ, Zhi H, et al.. Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin. The Journal of Clinical Investigation. 2005;115(12):3409-3417.
  55. Totzeck M, Hendgen-Cotta UB, Rassaf T. Nitrite-Nitric Oxide Signaling and Cardioprotection. Advances in Experimental Medicine & Biology. 2017;982:335-346. https://doi.org/10.1007/978-3-319-55330-6_18
  56. Chouchani ET, James AM, Methner C, et al. Identification and quantification of protein S-nitrosation by nitrite in the mouse heart during ischemia. Journal of Biological Chemistry. 2017;292(35):14486-14495. https://doi.org/10.1074/jbc.M117.798744
  57. Shiva S, Sack MN, Greer JJ, et al. Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer. The Journal of Experimental Medicine. 2007;204(9):2089-2102.https://doi.org/10.1084/jem.20070198
  58. Miller MJ. Preconditioning for cardioprotection against ischemia reperfusion injury: the roles of nitric oxide, reactive oxygen species, heat shock proteins, reactive hyperemia and antioxidants — a mini review. Canadian Journal of Cardiology. 2001;17(10):1075-1082.
  59. Nakano A, Liu GS, Heusch G, et al. Exogenous nitric oxide can trigger a preconditioned state through a free radical mechanism, but endogenous nitric oxide is not a trigger of classical ischemic preconditioning. Journal of Molecular and Cellular Cardiology. 2000;32(7):1159-1167.
  60. Lu HR, Remeysen P, De FC. Does the antiarrhythmic effect of ischemic preconditioning in rats involve the L-arginine nitric oxide pathway? Journal of Cardiovascular Pharmacology. 1995;25(4):524-530.
  61. Ferdinandy P, Szilvassy Z, Horvath LI, et al. Loss of pacing-induced preconditioning in rat hearts: role of nitric oxide and cholesterol-enriched diet. Journal of Molecular and Cellular Cardiology. 1997;29(12):3321-3333.
  62. Lochner A, Marais E, Genade S, Moolman JA. Nitric oxide: a trigger for classic preconditioning? American Journal of Physiology. Heart and Circulatory Physiology. 2000;279(6):H2752-H2765.
  63. Yao Z, Gross GJ. Role of nitric oxide, muscarinic receptors, and the ATP-sensitive K+ channel in mediating the effects of acetylcholine to mimic preconditioning in dogs. Circulation Research. 1993;73(6):1193-1201.
  64. Bugge E, Ytrehus K. Bradykinin protects against infarction but does not mediate ischemic preconditioning in the isolated rat heart. Journal of Molecular and Cellular Cardiology. 1996;28(12):2333-2341.
  65. Richard V, Blanc T, Kaeffer N, et al. Myocardial and coronary endothelial protective effects of acetylcholine after myocardial ischaemia and reperfusion in rats: role of nitric oxide. British Journal of Pharmacology. 1995;115(8):1532-1538.
  66. Takano H, Tang X-L, Qiu Y, et al. Nitric oxide donors induce late preconditioning against myocardial stunning and infarction in conscious rabbits via an antioxidant-sensitive mechanism. Circulation Research. 1998;83(1):73-84.
  67. Banerjee S, Tang X-L, Qiu Y, et al. Nitroglycerin induces late preconditioning against myocardial stunning via a PKC-dependent pathway. American Journal of Physiology. Heart and Circulatory Physiology.1999;277(6):H2488-H2494.
  68. Hill M, Takano H, Tang X-L, et al. Nitroglycerin induces late preconditioning against myocardial infarction in conscious rabbits despite development of nitrate tolerance. Circulation. 2001;104(6):694-699.
  69. Nagasaka Y, Fernandez BO, Garcia-Saura MF, et al. Brief Periods of Nitric Oxide Inhalation Protect Against Myocardial Ischemia-Reperfusion Injury. Anesthesiology. 2008;109(4):675-682. https://doi.org/10.1097/aln.0b013e318186316e
  70. Каменщиков Н.О., Мандель И.А., Подоксенов Ю.К., и др. Защита миокарда от ишемически-реперфузионного повреждения посредством подачи оксида азота в контур экстракорпоральной циркуляции при проведении искусственного кровообращения. Патология кровообращения и кардиохирургия. 2017;21(4):79-86. https://doi.org/10.21688/1681-3472-2017-4-79-86
  71. Bolli R. The early and late phases of preconditioning against myocardial stunning and the essential role of oxyradicals in the late phase: an overview. Basic Research in Cardiology. 1996;91(1):57-63.
  72. Kuzuya T, Hoshida S, Yamashita N, et al. Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia. Circulation Research. 1993;72(6):1293-1299.
  73. Marber MS, Latchman DS, Walker JM, Yellon DM. Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction. Circulation. 1993;88(3):1264-1272.
  74. Sun JZ, Tang XL, Knowlton AA, et al. Late preconditioning against myocardial stunning. An endogenous protective mechanism that confers resistance to postischemic dysfunction 24 h after brief ischemia in conscious pigs. The Journal of Clinical Investigation. 1995;95(1):388-403.
  75. Kositprapa C, Ockaili RA, Kukreja RC. Bradykinin B2receptor is involved in the late phase of preconditioning in rabbit heart. Journal of Molecular and Cellular Cardiology. 2001;33(7):1355-1362.
  76. Kis A, Végh A, Papp JG, Parratt JR. Repeated cardiac pacing extends the time during which canine hearts are protected against ischaemia-induced arrhythmias: role of nitric oxide. Journal of Molecular and Cellular Cardiology. 1999;31(6):1229-1241.
  77. Bolli R, Dawn B, Tang XL, et al. The nitric oxide hypothesis of late preconditioning. Basic Research in Cardiology. 1998;93(5):325-338.
  78. Bolli R, Bhatti ZA, Tang XL, et al. Evidence that late preconditioning against myocardial stunning in conscious rabbits is triggered by the generation of nitric oxide. Circulation Research. 1997;81(1):42-52.
  79. Qiu Y, Rizvi A, Tang XL, et al. Nitric oxide triggers late preconditioning against myocardial infarction in conscious rabbits. American Journal of Physiology. Heart and Circulatory Physiology. 1997;273(6):H2931-H2936.
  80. Guo Y, Wu WJ, Zhu XP, et al. Exercise-induced late preconditioning is triggered by generation of nitric oxide. Journal of Molecular and Cellular Cardiology. 2001;33(6):A41.
  81. Bolli R, Manchikalapudi S, Tang XL, et al. The protective effect of late preconditioning against myocardial stunning in conscious rabbits is mediated by nitric oxide synthase: evidence that nitric oxide acts both as a trigger and as a mediator of the late phase of ischemic preconditioning. Circulation Research. 1997;81(6):1094-1107.
  82. Xuan YT, Tang XL, Qiu Y, et al. Biphasic response of cardiac NO synthase isoforms to ischemic preconditioning in conscious rabbits. American Journal of Physiology. Heart and Circulatory Physiology. 2000;279(5):H2360-H2371.
  83. Takano H, Manchikalapudi S, Tang XL, et al. Nitric oxide synthase is the mediator of late preconditioning against myocardial infarction in conscious rabbits. Circulation. 1998;98(5):441-449.
  84. Guo Y, Bao W, Tang XL, et al. Nitric oxide donors induce late preconditioning against myocardial infarction in mice. Journal of Molecular and Cellular Cardiology. 1999;31:A11.
  85. Ping P, Takano H, Zhang J, et al. Isoform-selective activation of protein kinase C by nitric oxide in the heart of conscious rabbits: a signaling mechanism for both nitric oxide–induced and ischemia-induced preconditioning. Circulation Research. 1999;84(5):587-604.
  86. Vondriska TM, Zhang J, Song C, et al. Protein Kinase C ε–Src Modules Direct Signal Transduction in Nitric Oxide–Induced Cardioprotection: Complex Formation as a Means for Cardioprotective Signaling. Circulation Research. 2001;88(12):1306-1313.
  87. Dawn B, Xuan YT, Qiu Y, et al. Bifunctional role of protein tyrosine kinases in late preconditioning against myocardial stunning in conscious rabbits. Circulation Research. 1999;85(12):1154-1163.
  88. Tang XL, Kodani E, Takano H, et al. Protein tyrosine kinase signaling is necessary for NO donor-induced late preconditioning against myocardial stunning in conscious rabbits. American Journal of Physiology. Heart and Circulatory Physiology. 2003;284(4): H1441-1448.
  89. Xuan YT, Tang XL, Banerjee S, et al. Nuclear factor-κB plays an essential role in the late phase of ischemic preconditioning in conscious rabbits. Circulation Research. 1999;84(9):1095-1109.
  90. Jones WK, Flaherty MP, Tang XL, et al. Ischemic preconditioning increases iNOS transcript levels in conscious rabbits via a nitric oxide-dependent mechanism. Journal of Molecular and Cellular Cardiology. 1999;31(8):1469-1481.
  91. Баутин А.Е., Галагудза М.М., Ташханов Д.М., и др. Экспрессия протеинкиназы С при дистантном ишемическом прекондиционировании во время кардиохирургических вмешательств. Анестезиология и реаниматология. 2015;60(6):4-8.
  92. Tang X, Rizvi AN, Qui Y, et al. Evidence that the hydroxyl radical triggers late preconditioning against myocardial stunning in conscious rabbits. Circulation. 1997;96(8S):I-255.
  93. Imagawa J, Yellon DM, Baxter GF. Pharmacological evidence that inducible nitric oxide synthase is a mediator of delayed preconditioning. British Journal of Pharmacology.1999;126(3):701-708.
  94. Guo Y, Jones WK, Xuan YT, et al. The late phase of ischemic preconditioning is abrogated by targeted disruption of the inducible NO synthase gene. Proceedings of the National Academy of Sciences of the United States of America. 1999;96(20):11507-11512.
  95. Wang Y, Guo Y, Zhang SX, et al. Ischemic preconditioning upregulates inducible nitric oxide synthase in cardiac myocyte. Journal of Molecular and Cellular Cardiology. 2002;34(1):5-15.
  96. Guo YR, Bao WK, Tang XL, et al. Pharmacological preconditioning (PC) with adenosine A (1) and opioid delta (1) receptor agonists is iNOS-dependent. Circulation. 2000;102(18):121-121.
  97. Zhao T, Xi L, Chelliah J, et al. Inducible nitric oxide synthase mediates delayed myocardial protection induced by activation of adenosine A1 receptors: evidence from gene-knockout mice. Circulation. 2000;102(8):902-907.
  98. Takano H, Bolli R, Black Jr RG, Kodani E, Tang XL, Yang Z, Bhattacharya S, Auchampach JA. A1 or A3 adenosine receptors induce late preconditioning against infarction in conscious rabbits by different mechanisms. Circulation Research. 2001;88(5):520-528.
  99. Guo YR, Jones WK, Bao WK, Tang XL, Wu WJ, Bolli R. Targeted disruption of the iNOS gene abrogates NO donor-induced late preconditioning. Circulation. 1999;100(18):562-562.
  100. Xi L, Salloum F, Tekin D, Jarrett NC, Kukreja RC. Glycolipid RC-552 induces delayed preconditioning-like effect via iNOS-dependent pathway in mice. American Journal of Physiology. Heart and Circulatory Physiology. 1999;277(6):H2418-H2424.
  101. Zhao L, Weber PA, Smith JR, Comerford ML, Elliott GT. Role of inducible nitric oxide synthase in pharmacological «preconditioning» with monophosphoryl lipid A. Journal of Molecular and Cellular Cardiology. 1997;29(6):1567-1576.
  102. Elliott GT, Sowell CG, Walker EB, Weber PA, Moore J, Gross GJ. The novel glycolipid RC-552 attenuates myocardial stunning and reduces infarct size in dogs. Journal of Molecular and Cellular Cardiology. 2000;32(7):1327-1339.
  103. Kodani E. Role of cyclic guanosine monophosphate in nitric oxide-dependent late preconditioning in conscious rabbits. Circulation. 2000;102:II-270.
  104. Jung F, Palmer LA, Zhou N, Johns RA. Hypoxic regulation of inducible nitric oxide synthase via hypoxia inducible factor-1 in cardiac myocytes. Circulation Research. 2000;86(3):319-325.
  105. Kitakaze M, Node K, Komamura K, Minamino T, Inoue M, Hori M, Kamada T. Evidence for nitric oxide generation in the cardiomyocytes: its augmentation by hypoxia. Journal of Molecular and Cellular Cardiology. 1995;27(10):2149-2154.
  106. Ferreiro CR, Chagas ACP, Carvalho MHC, Dantas AP, Jatene MB, de Souza LCB, da Luz PL. Influence of hypoxia on nitric oxide synthase activity and gene expression in children with congenital heart disease: a novel pathophysiological adaptive mechanism. Circulation. 2001;103(18):2272-2276.
  107. Watanabe AM, Besch Jr HR. Interaction between cyclic adenosine monophosphate and cyclic gunaosine monophosphate in guinea pig ventricular myocardium. Circulation Research. 1975;37(3):309-317.
  108. Balligand JL, Kelly RA, Marsden PA, Smith TW, Michel T. Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proceedings of the National Academy of Sciences of the United States of America. 1993;90(1):347-351.
  109. Schulz R, Nava E, Moncada S. Induction and potential biological relevance of a Ca2+‐independent nitric oxide synthase in the myocardium British Journal of Pharmacology. 1992;105(3):575-580.
  110. Finkel MS, Oddis CV, Jacob TD, Watkins SC, Hattler BG, Simmons RL. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science. 1992;257(5068):387-389.
  111. Brady AJ, Warren JB, Poole-Wilson PA, Williams TJ, Harding S. E. Nitric oxide attenuates cardiac myocyte contraction. American Journal of Physiology. Heart and Circulatory Physiology. 1993;265(1):H176-H182.
  112. Ungureanu-Longrois D, Balligand JL, Kelly RA, Smith TW. Myocardial contractile dysfunction in the systematic inflammatory response syndrome: role of a cytokine-inducible nitric oxide synthase in cardiac myocytes. Journal of Molecular and Cellular Cardiology. 1995;27(1):155-167.
  113. Balligand JL, Kobzik L, Han X, Kaye DM, Belhassen L, O’Hara DS, Kelly RA, Smith TW, Michel T. Nitric oxide-dependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes. Journal of Biological Chemistry. 1995;270(24):14582-14586.
  114. Shah AM, Lewis MJ. Modulation of myocardial contraction by endocardial and coronary vascular endothelium. Trends in Cardiovascular Medicine. 1993;3(3):98-103.
  115. Lohmann SM, Fischmeister R, Walter U. Signal transduction by cGMP in heart. Basic Research in Cardiology. 1991;86(6):503-514.
  116. Weiss HR, Rodriguez E, Tse J, Scholz PM. Effect of increased myocardial cyclic GMP induced by cyclic GMP‐phosphodiesterase inhibition on oxygen consumption and supply of rabbit hearts. Clinical and Experimental Pharmacology and Physiology. 1994;21(8):607-614.
  117. Shen W, Xu X, Ochoa M, Zhao G, Wolin MS, Hintze TH. Role of nitric oxide in the regulation of oxygen consumption in conscious dogs. Circulation Research. 1994;75(6):1086-1095.
  118. King CE, Melinyshyn MJ, Mewburn JD, Curtis SE, Winn MJ, Cain SM, Chapler CK. Canine hindlimb blood flow and O2 uptake after inhibition of EDRF/NO synthesis. Journal of Applied Physiology. 1994;76(3):1166-1171.
  119. Shen W, Hintze TH, Wolin MS. Nitric oxide: an important signaling mechanism between vascular endothelium and parenchymal cells in the regulation of oxygen consumption. Circulation. 1995;92(12):3505-3512.
  120. Xie YW, Shen W, Zhao G, Xu X, Wolin MS, Hintze TH. Role of endothelium-derived nitric oxide in the modulation of canine myocardial mitochondrial respiration in vitro: implications for the development of heart failure. Circulation Research. 1996;79(3):381-387.
  121. Hanafy KA, Krumenacker JS, Murad F. NO, nitrotyrosine, and cyclic GMP in signal transduction. Medical Science Monitor. 2001;7(4):801-819.
  122. Sasaki N, Sato T, Ohler A, O’rourke B, Marbán E. Activation of mitochondrial ATP-dependent potassium channels by nitric oxide. Circulation. 2000;101(4):439-445.
  123. Takano H, Tang XL, Bolli R. Differential role of KATP channels in late preconditioning against myocardial stunning and infarction in rabbits. American Journal of Physiology. Heart and Circulatory Physiology. 2000;279(5):H2350-H2359.
  124. Hausenloy DJ, Maddock HL, Baxter GF, Yellon DM. Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning? Cardiovascular Research. 2002;55(3):534-543.
  125. Xia C, Bao Z, Yue C, Sanborn BM, Liu M. Phosphorylation and regulation of G-protein-activated phospholipase C-β3 by cGMP-dependent protein kinases. Journal of Biological Chemistry. 2001;276(23):19770-19777.
  126. Koller A, Schlossmann J, Ashman K, Uttenweiler-Joseph S, Ruth P., Hofmann F. Association of phospholamban with a cGMP kinase signaling complex. Biochemical and Biophysical Research Communications. 2003;300(1):155-160.
  127. Lemasters JJ, Theruvath TP, Zhong Z, Nieminen AL. Mitochondrial calcium and the permeability transition in cell death. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 2009;1787(11):1395-1401.
  128. Heusch G, Post H, Michel MC, Kelm M, Schulz R. Endogenous nitric oxide and myocardial adaptation to ischemia. Circulation Research. 2000;87(2):146-152.
  129. Maulik N, Engelman DT, Watanabe M, Engelman RM, Rousou JA, Flack JE 3rd, Deaton DW, Gorbunov NV, Elsayed NM, Kagan VE, Das DK. Nitric oxide/carbon monoxide. A molecular switch for myocardial preservation during ischemia. Circulation. 1996;94(9 Suppl):II398-II406.
  130. Rubbo H, Radi R, Trujillo M, Telleri R, Kalyanaraman B, Barnes S, Kirk M, Freeman BA. Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. Journal of Biological Chemistry. 1994;269(42):26066-26075.
  131. Moncada S, Erusalimsky JD. Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nature Reviews Molecular Cell Biology. 2002;3(3):214.
  132. Shiva S, Brookes PS, Patel RP, Anderson PG, Darley-Usmar VM. Nitric oxide partitioning into mitochondrial membranes and the control of respiration at cytochrome C oxidase. Proceedings of the National Academy of Sciences of the United States of America. 2001;98(13):7212-7217.
  133. Giufzfrè A, Sarti P, D’Itri E, Buse G, Soulimane T, Brunori M. On the mechanism of inhibition of cytochrome c oxidase by nitric oxide. Journal of Biological Chemistry. 1996;271(52):33404-33408.
  134. Taylor CT, Moncada S. Nitric oxide, cytochrome C oxidase, and the cellular response to hypoxia. Arteriosclerosis, Thrombosis, and Vascular Biology. 2010;30(4):643-647.
  135. Rakhit RD, Mojet MH, Marber MS, Duchen MR. Mitochondria as targets for nitric oxide-induced protection during simulated ischemia and reoxygenation in isolated neonatal cardiomyocytes. Circulation. 2001;103(21):2617-2623.
  136. West MB, Rokosh G, Obal D, Velayutham M, Xuan YT, Hill BG, Keith RJ, Schrader J, Guo Y, Conklin DJ, Prabhu SD, Zweier JL, Bolli R, Bhatnagar A. Cardiac myocyte-specific expression of inducible nitric oxide synthase protects against ischemia/reperfusion injury by preventing mitochondrial permeability transition. Circulation. 2008;118(19)1970-1978. https://doi.org/10.1161/CIRCULATIONAHA.108.791533
  137. Shinmura K, Xuan YT, Tang XL, Kodani E, Han H, Zhu Y, Bolli R. Inducible nitric oxide synthase modulates cyclooxygenase-2 activity in the heart of conscious rabbits during the late phase of ischemic preconditioning. Circulation Research. 2002;90(5):602-608.
  138. Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97(12):1129-1135.
  139. Jones SP, Trocha SD, Lefer DJ. Pretreatment with simvastatin attenuates myocardial dysfunction after ischemia and chronic reperfusion. Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21(12):2059-2064.
  140. Jones SP, Gibson MF, Rimmer DM 3rd, Gibson TM, Sharp BR, Lefer DJ. Direct vascular and cardioprotective effects of rosuvastatin, a new HMG-CoA reductase inhibitor. Journal of the American College of Cardiology. 2002;40(6):1172-1178.
  141. Bell RM, Yellon DM. Atorvastatin, administered at the onset of reperfusion, and independent oflipid lowering, protects the myocardiumby up-regulating a pro-survival pathway. Journal of the American College of Cardiology. 2003;41(3):508-515.
  142. Reffelmann T, Kloner RA. Effects of sildenafil on myocardial infarct size, microvascular function, and acute ischemic left ventricular dilation. Cardiovascular Research. 2003;59(2):441-449.
  143. Salloum F, Yin C, Xi L, Kukreja RC. Sildenafil induces delayed preconditioning through inducible nitric oxide synthase–dependent pathway in mouse heart. Circulation Research. 2003;92(6):595-597.
  144. Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER, Bedja D, Gabrielson KL, Wang Y, Kass DA. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nature Medicine. 2005;11(2):214-222.
  145. Fisher PW, Salloum F, Das A, Hyder H, Kukreja RC. Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity. Circulation. 2005;111(13):1601-1610.
  146. Yang XP, Liu YH, Shesely EG, Bulagannawar M, Liu F, Carretero OA. Endothelial nitric oxide gene knockout mice: cardiac phenotypes and the effect of angiotensin-converting enzyme inhibitor on myocardial ischemia/reperfusion injury. Hypertension. 1999;34(1):24-30.
  147. Yang B, Li D, Phillips MI, Mehta P, Mehta JL. Myocardial angiotensin II receptor expression and ischemia-reperfusion injury. Vascular Medicine. 1998;3(2):121-130.
  148. Toda N, Toda H, Hatano Y. Nitric OxideInvolvement in the Effects of Anesthetic Agents. Anesthesiology: The Journal of the American Society of Anesthesiologists. 2007;107(5):822-842.
  149. Janssens SP, Bogaert J, Zalewski J, Toth A, Adriaenssens T, Belmans A, Bennett J, Claus P, Desmet W, Dubois C, Goetschalckx K, Sinnaeve P, Vandenberghe K, Vermeersch P, Lux A, Szelid Z, Durak M, Lech P, Zmudka K, Pokreisz P, Vranckx P, Merkely B, Bloch KD, Van de Werf F; NOMI investigators. Nitric oxide for inhalation in ST-elevation myocardial infarction (NOMI): a multicentre, double-blind, randomized controlled trial. European Heart Journal. 2018;39:2717-2725. https://doi.org/10.1093/eurheartj/ehy232
  150. Lobo M, Ibanez B. Take a deep (nitric oxide) breath and follow the reverse translational research pathway. European Heart Journal. 2018;39(Issue 29):2726-2729. https://doi.org/10.1093/eurheartj/ehy355
  151. Nazir SA, Khan J, Mahmoud IZ. Adenosine and sodium nitroprusside versus control for the attenuation of infarct size and microvascular obstruction: the REFLO-STEMI trial. Journal of the American College of Cardiology. 2015;65(10):A216.
  152. Jones DA, Andiapen M, Van-Eijl TJ, Webb AJ, Antoniou S, Schilling RJ, Ahluwalia A, Mathur A. The safety and efficacy of intracoronary nitrite infusion during acute myocardial 70 infarction (NITRITE-AMI): study protocol of a randomised controlled trial. BMJ Open. 2013;3(4):e002813-e002813.
  153. Leesar MA, Stoddard MF, Dawn B, Jasti VG, Masden R, Bolli R. Delayed preconditioning-mimetic action of nitroglycerin in patients undergoing coronary angioplasty. Circulation. 2001;103(24):2935-2941.
  154. Amit G, Cafri C, Yaroslavtsev S, Fuchs S, Paltiel O, Abu-Ful A, Weinstein JM, Wolak A, Ilia R, Zahger D. Intracoronary nitroprusside for the prevention of the no-reflow phenomenon after primary percutaneous coronary intervention in acute myocardial infarction. A randomized, double-blind, placebo-controlled clinical trial. American Heart Journal. 2006;152(5):887.e9-e887.
  155. Tai YH, Chang KY, Liao SW, Chung KC, Shih CC, Ho ST, Lu CC, Tsou MY. Intravenous loading of nitroglycerin during rewarming of cardiopulmonary bypass improves metabolic homeostasis in cardiac surgery: a retrospective analysis. Journal of Anesthesia. 2016;30(5):779-788. https://doi.org/10.1007/s00540-016-2207-0
  156. Bin JP, Doctor A, Lindner J, Hendersen EM, Le DE, Leong-Poi H, Fisher NG, Christiansen J, Kaul S. Effects of nitroglycerin on erythrocyte rheology and oxygen unloading: novel role of S-nitrosohemoglobin in relieving myocardial ischemia. Circulation. 2006;113:2502-2508.
  157. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. Lancet. 1995;345(8951):669-685.
  158. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell’infarto Miocardico. Lancet. 1994;343:1115-1122.
  159. Li Q, Bolli R, Guo Y, Bao W,Wu WJ, French B, Tang X-L, Jones WK. Adenovirus-mediated elevation of endothelial nitric oxide synthase (eNOS) as a strategy to protect against ischemic injury. Journal of Molecular and Cellular Cardiology. 2000;32:A23.
  160. Li QH, Guo YR, Lowenstein C, Stevenson S, Wu W J, Liao LF, Bolli R. Inducible nitric oxide synthase gene therapy with a new generation adenovirus protects against myocardial infarction in vivo. Circulation. 2001;104(17):228-228.
  161. Vermeulen Windsant IC, de Wit NC, Sertorio JT, van Bijnen AA, Ganushchak YM, Heijmans JH, Tanus-Santos JE, Jacobs MJ, Maessen JG, Buurman WA. Hemolysis during cardiac surgery is associated with increased intravascular nitric oxide consumption and perioperative kidney and intestinal tissue damage. Frontiers in Physiology. 2014;5:340.
  162. Reiter CD, Wang X, Tanus-Santos JE, Hogg N, Cannon RO 3rd, Schechter AN, Gladwin MT. Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nature Medicine. 2002;8(12):1383-1389.
  163. Cheung AT, Cruz-Shiavone GE, Meng QC, Pochettino A, Augoustides JA, Bavaria JE, Ochroch EA. Cardiopulmonary bypass, hemolysis, and nitroprusside-induced cyanide production. Anesthesia and Analgesia. 2007;105(1):29-33.
  164. Keh D, Gerlach M, Kürer I, Falke KJ, Gerlach H. Reduction of platelet trapping in membrane oxygenators by transmembraneous application of gaseous nitric oxide. The International Journal of Artificial organs. 1996;19(5):291-293.
  165. Mellgren K, Friberg LG, Mellgren G, Hedner T, Wennmalm A, Wadenvik H. Nitric oxide in the oxygenator sweep gas reduces platelet activation during experimental perfusion. The Annals of Thoracic Surgery. 1996;61(4):1194-1198.
  166. Chello M, Mastroroberto P, Marchese AR, Maltese G, Santangelo E, Amantea B. Nitric oxide inhibits neutrophil adhesion during experimental extracorporeal circulation. Anesthesiology. 1998;89(2):443-448.
  167. Checchia PA, Bronicki RA, Muenzer JT, Dixon D, Raithel S, Gandhi SK, Huddleston CB. Nitric oxide delivery during cardiopulmonary bypass reduces postoperative morbidity in children — a randomized trial. The Journal of Thoracic and Cardiovascular Surgery. 2013;146(3):530-536.
  168. James C, Millar J, Horton S, Brizard C, Molesworth C, Butt W. Nitric oxide administration during paediatric cardiopulmonary bypass: a randomised controlled trial. Intensive Care Medicine. 2016;42(11):1744-1752.
  169. Gianetti J, Del Sarto P, Bevilacqua S, Vassalle C, De Filippis R, Kacila M, Farneti PA, Clerico A, Glauber M, Biagini A. Supplemental nitric oxide and its effect on myocardial injury and function in patients undergoing cardiac surgery with extracorporeal circulation. The Journal of Thoracic and Cardiovascular Surgery. 2004;127(1):44-50.