Table of Contents
ISRN Anesthesiology
Volume 2014 (2014), Article ID 905238, 28 pages
http://dx.doi.org/10.1155/2014/905238
Review Article

Inflammatory Response in Patients under Coronary Artery Bypass Grafting Surgery and Clinical Implications: A Review of the Relevance of Dexmedetomidine Use

1Departamento de Bioquimica e Biologia Molecular, Programa de Pos-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil
2Department of Biochemistry, School of Sciences, Federal University of Technology of Akure, Ondo State, Nigeria

Received 10 September 2013; Accepted 9 October 2013; Published 27 April 2014

Academic Editors: S. D. Bergese, F. Cavaliere, S. Cho, and D. Ma

Copyright © 2014 Neusa Maria Heinzmann Bulow et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Sander, C. von Heymann, V. von Dossow et al., “Increased interleukin-6 after cardiac surgery predicts infection,” Anesthesia and Analgesia, vol. 102, no. 6, pp. 1623–1629, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. J. M. Murkin, “Panvascular inflammation and mechanisms of injury in perioperative CNS outcomes,” Seminars in Cardiothoracic and Vascular Anesthesia, vol. 14, no. 3, pp. 190–195, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. M. E. Plomondon, J. C. Cleveland Jr., S. T. Ludwig et al., “Off-pump coronary artery bypass is associated with improved risk-adjusted outcomes,” Annals of Thoracic Surgery, vol. 72, no. 1, pp. 114–119, 2001. View at Publisher · View at Google Scholar · View at Scopus
  4. S. Wan, J.-L. Leclerc, and J.-L. Vincent, “Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies,” Chest, vol. 112, no. 3, pp. 676–692, 1997. View at Google Scholar · View at Scopus
  5. M. M. Elahi, J. S. Khan, and B. M. Matata, “Deleterious effects of cardiopulmonary bypass in coronary artery surgery and scientific interpretation of off-pump's logic,” Acute Cardiac Care, vol. 8, no. 4, pp. 196–209, 2006. View at Publisher · View at Google Scholar · View at Scopus
  6. B. M. Matata, A. W. Sosnowski, and M. Galiñanes, “Off-pump bypass graft operation significantly reduces oxidative stress and inflammation,” Annals of Thoracic Surgery, vol. 69, no. 3, pp. 785–791, 2000. View at Publisher · View at Google Scholar · View at Scopus
  7. B. M. Matata and M. Galiñanes, “Cardiopulmonary bypass exacerbates oxidative stress but does not increase proinflammatory cytokine release in patients with diabetes compared with patients without diabetes: regulatory effects of exogenous nitric oxide,” Journal of Thoracic and Cardiovascular Surgery, vol. 120, no. 1, pp. 1–11, 2000. View at Google Scholar · View at Scopus
  8. E. P. Stover, L. C. Siegel, R. Parks et al., “Variability in transfusion practice for coronary artery bypass surgery persists despite national consensus guidelines: a 24-institution study,” Anesthesiology, vol. 88, no. 2, pp. 327–333, 1998. View at Publisher · View at Google Scholar · View at Scopus
  9. S. C. Stamou, P. C. Hill, G. Dangas et al., “Stroke after coronary artery bypass: incidince, predictors, and clinical outcome,” Stroke, vol. 32, no. 7, pp. 1508–1512, 2001. View at Google Scholar · View at Scopus
  10. J. P. Mathew, R. Parks, J. S. Savino et al., “Atrial fibrillation following coronary artery bypass graft surgery: predictors, outcomes, and resource utilization. MultiCenter Study of Perioperative Ischemia Research Group,” Journal of the American Medical Association, vol. 276, no. 4, pp. 300–306, 1996. View at Publisher · View at Google Scholar · View at Scopus
  11. E. A. Rose, “Off-pump coronary-artery bypass surgery,” The New England Journal of Medicine, vol. 348, no. 5, pp. 379–380, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. R. Ascione, M. Caputo, and G. D. Angelini, “Off-pump coronary artery bypass grafting: not a flash in the pan,” Annals of Thoracic Surgery, vol. 75, no. 1, pp. 306–313, 2003. View at Publisher · View at Google Scholar · View at Scopus
  13. J. E. Hall, T. D. Uhrich, J. A. Barney, S. R. Arain, and T. J. Ebert, “Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions,” Anesthesia and Analgesia, vol. 90, no. 3, pp. 699–705, 2000. View at Google Scholar · View at Scopus
  14. J. H. Gibbon Jr., “Application of a mechanical heart and lung apparatus to cardiac surgery,” Minnesota medicine, vol. 37, no. 3, pp. 171–185, 1954. View at Google Scholar · View at Scopus
  15. Y.-F. Chen, W.-C. Tsai, C.-C. Lin et al., “Effect of leukocyte depletion on endothelial cell activation and transendothelial migration of leukocytes during cardiopulmonary bypass,” Annals of Thoracic Surgery, vol. 78, no. 2, pp. 634–642, 2004. View at Publisher · View at Google Scholar · View at Scopus
  16. T. Okamura, N. Ishibashi, D. Zurakowski, and R. A. Jonas, “Cardiopulmonary Bypass Increases Permeability of the Blood-Cerebrospinal Fluid Barrier,” Annals of Thoracic Surgery, vol. 89, no. 1, pp. 187–194, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. O. J. Warren, A. J. Smith, C. Alexiou et al., “The inflammatory response to cardiopulmonary bypass: part 1—mechanisms of pathogenesis,” Journal of Cardiothoracic and Vascular Anesthesia, vol. 23, no. 2, pp. 223–231, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. K. C. Wood, L. L. Hsu, and M. T. Gladwin, “Sickle cell disease vasculopathy: a state of nitric oxide resistance,” Free Radical Biology and Medicine, vol. 44, no. 8, pp. 1506–1528, 2008. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Kumar and U. Bandyopadhyay, “Free heme toxicity and its detoxification systems in human,” Toxicology Letters, vol. 157, no. 3, pp. 175–188, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. D. J. Schaer, P. W. Buehler, A. I. Alayash, J. D. Belcher, and G. M. Vercellotti, “Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins,” Blood, vol. 121, pp. 1276–1284, 2013. View at Google Scholar
  21. I. C. Vermeulen Windsant, S. J. Hanssen, W. A. Buurman, and M. J. Jacobs, “Cardiovascular surgery and organ damage: time to reconsider the role of hemolysis,” Journal of Thoracic and Cardiovascular Surgery, vol. 142, no. 1, pp. 1–11, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Haase, R. Bellomo, and A. Haase-Fielitz, “Novel biomarkers, oxidative stress, and the role of labile iron toxicity in cardiopulmonary bypass-associated acute kidney injury,” Journal of the American College of Cardiology, vol. 55, no. 19, pp. 2024–2033, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. F. Farina, D. S. Davila, J. B. T. Rocha et al., “Metals, oxidative stress and neurodegeneration: a focus on iron, manganese and mercury,” Neurochemistry International, vol. 62, no. 5, pp. 575–594, 2012. View at Publisher · View at Google Scholar
  24. M. Haase, A. Haase-Fielitz, and R. Bellomo, “Cardiopulmonary bypass, hemolysis, free iron, acute kidney injury and the impact of bicarbonate,” Contributions to Nephrology, vol. 165, pp. 28–32, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. C. Ritter, M. E. Andrades, A. Reinke, S. Menna-Barreto, J. C. F. Moreira, and F. Dal-Pizzol, “Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis,” Critical Care Medicine, vol. 32, no. 2, pp. 342–349, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Vulcano, R. P. Meiss, and M. A. Isturiz, “Deferoxamine reduces tissue injury and lethality in LPS-treated mice,” International Journal of Immunopharmacology, vol. 22, no. 8, pp. 635–644, 2000. View at Publisher · View at Google Scholar · View at Scopus
  27. D. Vlahakos, N. Arkadopoulos, G. Kostopanagiotou et al., “Deferoxamine attenuates lipid peroxidation, blocks interleukin-6 production, ameliorates sepsis inflammatory response syndrome, and confers renoprotection after acute hepatic ischemia in pigs,” Artificial Organs, vol. 36, no. 4, pp. 400–408, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. L. H. Edmunds, “Extracorporeal perfusion,” in Cardiac Surgery in the Adult, L. H. Edmunds, Ed., pp. 255–294, McGraw-Hill, New York, NY, USA, 1997. View at Google Scholar
  29. M. Rossi, G. Sganga, M. Mazzone et al., “Cardiopulmonary bypass in man: role of the intestine in a self-limiting inflammatory response with demonstrable bacterial translocation,” Annals of Thoracic Surgery, vol. 77, no. 2, pp. 612–618, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. B. Krishnadasam, J. Griscavage-Ennis, and G. S. Aldea, “Reperfusion injury during cardiopulmonary bypass,” in Leukocyte Depletion in Cardiac Surgery and Cardiology, G. Matheis, A. Moritz, and M. Scholz, Eds., p. 54, Karger, Basel, Switzerland, 2002. View at Google Scholar
  31. N. B. Aydin, H. Gercekoglu, B. Aksu et al., “Endotoxemia in coronary artery bypass surgery: a comparison of the off-pump technique and conventional cardiopulmonary bypass,” Journal of Thoracic and Cardiovascular Surgery, vol. 125, no. 4, pp. 843–848, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. H. M. Oudemans-van Straaten, P. G. M. Jansen, F. J. Hoek et al., “Intestinal permeability, circulating endotoxin, and postoperative systemic responses in cardiac surgery patients,” Journal of Cardiothoracic and Vascular Anesthesia, vol. 10, no. 2, pp. 187–194, 1996. View at Publisher · View at Google Scholar · View at Scopus
  33. U. Koca, Ç. G. Olguner, B. U. Ergür et al., “The effects of dexmedetomidine on secondary acute lung and kidney injuries in the rat model of intra-abdominal sepsis,” The Scientific World Journal, vol. 2013, Article ID 292687, 11 pages, 2013. View at Publisher · View at Google Scholar
  34. H. A. Vohra, R. Whistance, A. Modi, and S. K. Ohri, “The inflammatory response to miniaturised extracorporeal circulation: a review of the literature,” Mediators of Inflammation, vol. 2009, Article ID 707042, 7 pages, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. P. Menasché, “The inflammatory response to cardiopulmonary bypass and its impact on post-operative myocardial function,” Current Opinion in Cardiology, vol. 10, pp. 597–604, 1995. View at Google Scholar
  36. D. Journois, “Hemofiltration during cardiopulmonary bypass,” Kidney International, vol. 53, no. 66, pp. S-174–S-177, 1998. View at Google Scholar · View at Scopus
  37. G. Clermont, C. Vergely, S. Jazayeri et al., “Systemic free radical activation is a major event involved in myocardial oxidative stress related to cardiopulmonary bypass,” Anesthesiology, vol. 96, no. 1, pp. 80–87, 2002. View at Google Scholar · View at Scopus
  38. S. W. Davies, J. P. Duffy, D. G. Wickens et al., “Time-course of free radical activity during coronary artery operations with cardiopulmonary bypass,” Journal of Thoracic and Cardiovascular Surgery, vol. 105, no. 6, pp. 979–987, 1993. View at Google Scholar · View at Scopus
  39. P. E. Ballmer, W. H. Reinhart, P. Jordan, E. Buhler, U. K. Moser, and K. F. Gey, “Depletion of plasma vitamin C but not of vitamin E in response to cardiac operations,” Journal of Thoracic and Cardiovascular Surgery, vol. 108, no. 2, pp. 311–320, 1994. View at Google Scholar · View at Scopus
  40. H. J. Toivonen and M. Ahotupa, “Free radical reaction products and antioxidant capacity in arterial plasma during coronary artery bypass grafting,” Journal of Thoracic and Cardiovascular Surgery, vol. 108, no. 1, pp. 140–147, 1994. View at Google Scholar · View at Scopus
  41. A. Akila, B. D'souza, P. Vishwanath, and V. D'souza, “Oxidative injury and antioxidants in coronary artery bypass graft surgery: off-pump CABG significantly reduces oxidative stress,” Clinica Chimica Acta, vol. 375, no. 1-2, pp. 147–152, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. J. Milei, P. Forcada, C. G. Fraga et al., “Relationship between oxidative stress, lipid peroxidation, and ultrastructural damage in patients with coronary artery disease undergoing cardioplegic arrest/reperfusion,” Cardiovascular Research, vol. 73, no. 4, pp. 710–719, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. C. W. Hogue Jr., C. A. Palin, and J. E. Arrowsmith, “Cardiopulmonary bypass management and neurologic outcomes: an evidence-based appraisal of current practices,” Anesthesia and Analgesia, vol. 103, no. 1, pp. 21–37, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. P. L. C. Smith, “The systemic inflammatory response to cardiopulmonary bypass and the brain,” Perfusion, vol. 11, no. 3, pp. 196–199, 1996. View at Google Scholar · View at Scopus
  45. J. M. Murkin, “Etiology and incidence of brain dysfunction after cardiac surgery,” Journal of Cardiothoracic and Vascular Anesthesia, vol. 13, no. 4, pp. 12–17, 1999. View at Google Scholar · View at Scopus
  46. F. de Lange, J. M. Dieleman, B. Jungwirth, and C. J. Kalkman, “Effects of cardiopulmonary bypass on neurocognitive performance and cytokine release in old and diabetic rats,” British Journal of Anaesthesia, vol. 99, no. 2, pp. 177–183, 2007. View at Publisher · View at Google Scholar · View at Scopus
  47. S. Westaby, K. Saatvedt, S. White, T. Katsumata, W. van Oeveren, and P. W. Halligan, “Is there a relationship between cognitive dysfunction and systemic inflammatory response after cardiopulmonary bypass?” Annals of Thoracic Surgery, vol. 71, no. 2, pp. 667–672, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. A. Parolari, M. Camera, F. Alamanni et al., “Systemic inflammation after on-pump and off-pump coronary bypass surgery: a one-month follow-up,” Annals of Thoracic Surgery, vol. 84, no. 3, pp. 823–828, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. C. Coimba, M. Drake, F. Boris-Moller et al., “Long-lasting neuroprotective effect of postischemic hypothermia and treatment with an antiimflammatory/antipyretic drug,” Stroke, vol. 27, pp. 1578–1585, 1996. View at Google Scholar
  50. D. S. Warner, H. Sheng, and I. Batinić-Haberle, “Oxidants, antioxidants and the ischemic brain,” Journal of Experimental Biology, vol. 207, no. 18, pp. 3221–3231, 2004. View at Publisher · View at Google Scholar · View at Scopus
  51. A. E. van Harten, T. W. L. Scheeren, and A. R. Absalom, “A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia,” Anaesthesia, vol. 67, no. 3, pp. 280–293, 2012. View at Publisher · View at Google Scholar · View at Scopus
  52. P. Währborg, J. E. Booth, T. Clayton et al., “Neuropsychological outcome after percutaneous coronary intervention or coronary artery bypass grafting: results from the Stent or Surgery (SoS) trial,” Circulation, vol. 110, no. 22, pp. 3411–3417, 2004. View at Publisher · View at Google Scholar · View at Scopus
  53. B. Ø. Jensen, L. S. Rasmussen, and D. A. Steinbrüchel, “Cognitive outcomes in elderly high-risk patients 1 year after off-pump versus on-pump coronary artery bypass grafting. A randomized trial,” European Journal of Cardio-thoracic Surgery, vol. 34, no. 5, pp. 1016–1021, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. D. van Dijk, M. Spoor, R. Hijman et al., “Cognitive and cardiac outcomes 5 years after off-pump vs on-pump coronary artery bypass graft surgery,” Journal of the American Medical Association, vol. 297, no. 7, pp. 701–708, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. M. F. Newman, J. P. Mathew, H. P. Grocott et al., “Central nervous system injury associated with cardiac surgery,” The Lancet, vol. 368, no. 9536, pp. 694–703, 2006. View at Publisher · View at Google Scholar · View at Scopus
  56. C. S. Ernest, B. M. Murphy, M. U. C. Worcester et al., “Cognitive function in candidates for coronary artery bypass graft surgery,” Annals of Thoracic Surgery, vol. 82, no. 3, pp. 812–818, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. O. A. Selnes, M. A. Grega, M. M. Bailey et al., “Cognition 6 years after surgical or medical therapy for coronary artery disease,” Annals of Neurology, vol. 63, no. 5, pp. 581–590, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. D. van Dijk, K. G. M. Moons, H. M. Nathoe et al., “Cognitive outcomes five years after not undergoing coronary artery bypass graft surgery,” Annals of Thoracic Surgery, vol. 85, no. 1, pp. 60–64, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. O. A. Selnes, L. Pham, S. Zeger, and G. M. McKhann, “Defining cognitive change after CABG: decline versus normal variability,” Annals of Thoracic Surgery, vol. 82, no. 2, pp. 388–390, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. D. van Dijk and C. J. Kalkman, “Why are cerebral microemboli not associated with cognitive decline?” Anesthesia and Analgesia, vol. 109, no. 4, pp. 1006–1008, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. B. Jungwirth, B. Eckel, M. Blobner, K. Kellermann, E. F. Kochs, and G. B. Mackensen, “The impact of cardiopulmonary bypass on systemic interleukin-6 release, cerebral nuclear factor-kappa B expression, and neurocognitive outcome in rats,” Anesthesia and Analgesia, vol. 110, no. 2, pp. 312–320, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. B. S. Silbert, D. A. Scott, L. A. Evered, M. S. Lewis, and P. T. Maruff, “Preexisting cognitive impairment in patients scheduled for elective coronary artery bypass graft surgery,” Anesthesia and Analgesia, vol. 104, no. 5, pp. 1023–1028, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. F. Winningham-Major, J. L. Staecker, S. W. Barger, S. Coats, and L. J. van Eldik, “Neurite extension and neuronal survival activities of recombinant S100β proteins that differ in the content and position of cysteine residues,” Journal of Cell Biology, vol. 109, no. 6, pp. 3063–3071, 1989. View at Publisher · View at Google Scholar · View at Scopus
  64. F. Tramontina, M. C. Leite, D. Gonçalves et al., “High glutamate decreases S100B secretion by a mechanism dependent on the glutamate transporter,” Neurochemical Research, vol. 31, no. 6, pp. 815–820, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. R. Donato, G. Sorci, F. Riuzzi et al., “S100B's double life: intracellular regulator and extracellular signal,” Biochimica et Biophysica Acta, vol. 1793, no. 6, pp. 1008–1022, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. D. F. de Souza, K. Wartchow, F. Hansen et al., “Interleukin-6-induced S100B secretion is inhibited by haloperidol and risperidone,” Progress in Neuro-Psychopharmacology & Biological Psychiatry, vol. 43, pp. 14–22, 2013. View at Google Scholar
  67. D. F. de Souza, M. C. Leite, A. Quincozes-Santos et al., “S100B secretion is stimulated by IL-1β in glial cultures and hippocampal slices of rats: likely involvement of MAPK pathway,” Journal of Neuroimmunology, vol. 206, no. 1-2, pp. 52–57, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. C. Beer, D. Blacker, M. Bynevelt, G. J. Hankey, and I. B. Puddey, “Systemic markers of inflammation are independently associated with S100B concentration: results of an observational study in subjects with acute ischaemic stroke,” Journal of Neuroinflammation, vol. 7, article 71, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. A. Reichenberg, R. Yirmiya, A. Schuld et al., “Cytokine-associated emotional and cognitive disturbances in humans,” Archives of General Psychiatry, vol. 58, no. 5, pp. 445–452, 2001. View at Google Scholar · View at Scopus
  70. H. J. Huttunen, J. Kuja-Panula, G. Sorci, A. L. Agneletti, R. Donato, and H. Rauvala, “Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation,” Journal of Biological Chemistry, vol. 275, no. 51, pp. 40096–40105, 2000. View at Publisher · View at Google Scholar · View at Scopus
  71. A. Bierhaus, P. M. Humpert, M. Morcos et al., “Understanding RAGE, the receptor for advanced glycation end products,” Journal of Molecular Medicine, vol. 83, no. 11, pp. 876–886, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. C. Adami, G. Sorci, E. Blasi, A. L. Agneletti, F. Bistoni, and R. Donato, “S100B expression in and effects on microglia,” Glia, vol. 33, pp. 131–142, 2001. View at Google Scholar
  73. J. Hu, F. Castets, J. L. Guevara, and L. J. van Eldiki, “S100β stimulates inducible nitric oxide synthase activity and mRNA levels in rat cortical astrocytes,” Journal of Biological Chemistry, vol. 271, no. 5, pp. 2543–2547, 1996. View at Publisher · View at Google Scholar · View at Scopus
  74. T. V. Petrova, J. Hu, and L. J. van Eldik, “Modulation of glial activation by astrocyte-derived protein S100B: differential responses of astrocyte and microglial cultures,” Brain Research, vol. 853, no. 1, pp. 74–80, 2000. View at Publisher · View at Google Scholar · View at Scopus
  75. J. Hu, A. Ferreira, and L. J. van Eldik, “S100β induces neuronal cell death through nitric oxide release from astrocytes,” Journal of Neurochemistry, vol. 69, no. 6, pp. 2294–2301, 1997. View at Google Scholar · View at Scopus
  76. S. H. Kim, C. J. Smith, and L. J. van Eldik, “Importance of MAPK pathways for microglial pro-inflammatory cytokine IL-1β production,” Neurobiology of Aging, vol. 25, no. 4, pp. 431–439, 2004. View at Publisher · View at Google Scholar · View at Scopus
  77. S. Westaby, P. Johnsson, A. J. Parry et al., “Serum S100 protein: a potential marker for cerebral events during cardiopulmonary bypass,” Annals of Thoracic Surgery, vol. 61, no. 1, pp. 88–92, 1996. View at Publisher · View at Google Scholar · View at Scopus
  78. S. Blomquist, P. Johnsson, C. Lührs et al., “The appearance of S-100 protein in serum during and immediately after cardiopulmonary bypass surgery: a possible marker for cerebral injury,” Journal of Cardiothoracic and Vascular Anesthesia, vol. 11, no. 6, pp. 699–703, 1997. View at Publisher · View at Google Scholar · View at Scopus
  79. D. Barbut, F. S. Yao, D. N. Hager, P. Kavanaugh, R. R. Trifiletti, and J. P. Gold, “Comparison of transcranial Doppler ultrasonography and transesophageal echocardiography to monitor emboli during coronary artery bypass surgery,” Stroke, vol. 27, no. 1, pp. 87–90, 1996. View at Google Scholar · View at Scopus
  80. H. Jönsson, P. Johnsson, C. Alling, S. Westaby, and S. Blomquist, “Significance of serum S100 release after coronary artery bypass grafting,” Annals of Thoracic Surgery, vol. 65, no. 6, pp. 1639–1644, 1998. View at Publisher · View at Google Scholar · View at Scopus
  81. H. P. Grocott, N. D. Croughwell, D. W. Amory et al., “Cerebral emboli and serum S100β during cardiac operations,” Annals of Thoracic Surgery, vol. 65, no. 6, pp. 1645–1650, 1998. View at Publisher · View at Google Scholar · View at Scopus
  82. A. Jonsson, “As compared to neuron-specific enolase, S100B protein correlate more specific to the stroke volume and clinical outcome in ischemic stroke,” Kaka-Orinska, 2010.
  83. B. C. van Munster, J. C. Korevaar, A. H. Zwinderman, M. Levi, W. J. Wiersinga, and S. E. De Rooij, “Time-course of cytokines during delirium in elderly patients with hip fractures,” Journal of the American Geriatrics Society, vol. 56, no. 9, pp. 1704–1709, 2008. View at Publisher · View at Google Scholar · View at Scopus
  84. H. Worthmann, A. B. Tryc, A. Goldbecker et al., “The temporal profile of inflammatory markers and mediators in blood after acute ischemic stroke differs depending on stroke outcome,” Cerebrovascular Diseases, vol. 30, no. 1, pp. 85–92, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. J. W. W. Thomason, A. Shintani, J. F. Peterson, B. T. Pun, J. C. Jackson, and E. W. Ely, “Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients,” Critical Care, vol. 9, no. 4, pp. R375–381, 2005. View at Google Scholar · View at Scopus
  86. P. Pandharipande, B. A. Cotton, A. Shintani et al., “Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients,” The Journal of trauma, vol. 65, no. 1, pp. 34–41, 2008. View at Google Scholar · View at Scopus
  87. M. Lundström, A. Edlund, G. Bucht, S. Karlsson, and Y. Gustafson, “Dementia after delirium in patients with femoral neck fractures,” Journal of the American Geriatrics Society, vol. 51, no. 7, pp. 1002–1006, 2003. View at Publisher · View at Google Scholar · View at Scopus
  88. V. H. Perry, “The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease,” Brain, Behavior, and Immunity, vol. 18, no. 5, pp. 407–413, 2004. View at Publisher · View at Google Scholar · View at Scopus
  89. M. Herrmann, A. D. Ebert, I. Galazky, M. T. Wunderlich, W. S. Kunz, and C. Huth, “Neurobehavioral outcome prediction after cardiac surgery: role of neurobiochemical markers of damage to neuronal and glial brain tissue,” Stroke, vol. 31, no. 3, pp. 645–650, 2000. View at Google Scholar · View at Scopus
  90. Z. P. Khan, C. N. Ferguson, and R. M. Jones, “Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role,” Anaesthesia, vol. 54, no. 2, pp. 146–165, 1999. View at Publisher · View at Google Scholar · View at Scopus
  91. D. S. Carollo, B. D. Nossaman, and U. Ramadhyani, “Dexmedetomidine: a review of clinical applications,” Current Opinion in Anaesthesiology, vol. 21, no. 4, pp. 457–461, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. J. C. Eisenach, M. de Kock, and W. Klimscha, “α2-Adrenergic agonists for regional anesthesia: a clinical review of clonidine (1984–1995),” Anesthesiology, vol. 85, no. 3, pp. 655–674, 1996. View at Google Scholar · View at Scopus
  93. M. Maze and W. Tranquilli, “Alpha-2 adrenoceptor agonists: defining the role in clinical anesthesia,” Anesthesiology, vol. 74, no. 3, pp. 581–605, 1991. View at Google Scholar · View at Scopus
  94. S. Fürst, “Transmitters involved in antinociception in the spinal cord,” Brain Research Bulletin, vol. 48, no. 2, pp. 129–141, 1999. View at Publisher · View at Google Scholar · View at Scopus
  95. H. M. Loick, C. Schmidt, H. van Aken et al., “High thoracic epidural anesthesia, but not clonidine, attenuates the perioperative stress response via sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass grafting,” Anesthesia and Analgesia, vol. 88, no. 4, pp. 701–709, 1999. View at Google Scholar · View at Scopus
  96. A. W. Wallace, D. Galindez, A. Salahieh et al., “Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery,” Anesthesiology, vol. 101, no. 2, pp. 284–293, 2004. View at Publisher · View at Google Scholar · View at Scopus
  97. R. D. Stevens, H. Burri, and M. R. Tramèr, “Efficacy of clonidine for prevention of perioperative myocardial ischemia: a critical appraisal and meta-analysis of the literature,” Anesthesia & Analgesia, vol. 97, pp. 623–633, 2003. View at Google Scholar
  98. K. Nishina, K. Mikawa, T. Uesugi et al., “Efficacy of clonidine for prevention of perioperative myocardial ischemia: a critical appraisal and meta-analysis of the literature,” Anesthesiology, vol. 96, no. 2, pp. 323–329, 2002. View at Google Scholar · View at Scopus
  99. V. von Dossow, N. Baehr, M. Moshirzadeh et al., “Clonidine attenuated early proinflammatory response in T-cell subsets after cardiac surgery,” Anesthesia and Analgesia, vol. 103, no. 4, pp. 809–814, 2006. View at Publisher · View at Google Scholar · View at Scopus
  100. J. E. Ellis, S. Pedlow, and J. Bains, “Premedication with clonidine does not attenuate suppression of certain lymphocyte subsets after surgery,” Anesthesia and Analgesia, vol. 87, no. 6, pp. 1426–1430, 1998. View at Google Scholar · View at Scopus
  101. T. Dorman, K. Clarkson, B. A. Rosenfeld, C. Shanholtz, P. A. Lipsett, and M. J. Breslow, “Effects of clonidine on prolonged postoperative sympathetic response,” Critical Care Medicine, vol. 25, no. 7, pp. 1147–1152, 1997. View at Publisher · View at Google Scholar · View at Scopus
  102. P. J. Kulka, M. Tryba, and M. Zenz, “Dose-response effects of intravenous clonidine on stress response during induction of anesthesia in coronary artery bypass graft patients,” Anesthesia and Analgesia, vol. 80, no. 2, pp. 263–268, 1995. View at Publisher · View at Google Scholar · View at Scopus
  103. N. D. Nader, T. A. Ignatowski, C. J. Kurek, P. R. Knight, and R. N. Spengler, “Clonidine suppresses plasma and cerebrospinal fluid concentrations of TNF-α during the perioperative period,” Anesthesia and Analgesia, vol. 93, no. 2, pp. 363–369, 2001. View at Google Scholar · View at Scopus
  104. J. Persec, Z. Persec, and I. Husedzinovic, “Postoperative pain and systemic inflammatory stress response after preoperative analgesia with clonidine or levobupivacaine: a randomized controlled trial,” Wiener Klinische Wochenschrift, vol. 121, no. 17-18, pp. 558–563, 2009. View at Publisher · View at Google Scholar · View at Scopus
  105. A. T. Guerlach and J. F. Dasta, “Dexmedetomidine: an updated review,” Annals of Pharmacotherapy, vol. 41, pp. 245–252, 2007. View at Google Scholar
  106. D. Ma, N. Rajakumaraswamy, and M. Maze, “α2-adrenoceptor agonists: shedding light on neuroprotection?” British Medical Bulletin, vol. 71, pp. 77–92, 2005. View at Publisher · View at Google Scholar · View at Scopus
  107. V. Fagerholm, M. Scheinin, and M. Haaparanta, “α2A-Adrenoceptor antagonism increases insulin secretion and synergistically augments the insulinotropic effect of glibenclamide in mice,” British Journal of Pharmacology, vol. 154, no. 6, pp. 1287–1296, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. K. Takada, D. J. Clark, M. F. Davies et al., “Meperidine exerts agonist activity at the α2B-adrenoceptor subtype,” Anesthesiology, vol. 96, no. 6, pp. 1420–1426, 2002. View at Publisher · View at Google Scholar · View at Scopus
  109. V. Fagerholm, J. Rokka, L. Nyman et al., “Autoradiographic characterization of α2C-adrenoceptors in the human striatum,” Synapse, vol. 62, no. 7, pp. 508–515, 2008. View at Publisher · View at Google Scholar · View at Scopus
  110. E. Moura, J. Afonso, L. Hein, and M. A. Vieira-Coelho, “α2-adrenoceptor subtypes involved in the regulation of catecholamine release from the adrenal medulla of mice,” British Journal of Pharmacology, vol. 149, no. 8, pp. 1049–1058, 2006. View at Publisher · View at Google Scholar · View at Scopus
  111. I. Takamatsu, A. Iwase, M. Ozaki, T. Kazama, K. Wada, and M. Sekiguchi, “Dexmedetomidine reduces long-term potentiation in mouse hippocampus,” Anesthesiology, vol. 108, no. 1, pp. 94–102, 2008. View at Publisher · View at Google Scholar · View at Scopus
  112. R. M. Venn, M. D. Karol, and R. M. Grounds, “Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive care,” British Journal of Anaesthesia, vol. 88, no. 5, pp. 669–675, 2002. View at Publisher · View at Google Scholar · View at Scopus
  113. A. M. de Wolf, R. J. Fragen, M. J. Avram, P. C. Fitzgerald, and F. Rahimi-Danesh, “The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment,” Anesthesia and Analgesia, vol. 93, no. 5, pp. 1205–1209, 2001. View at Google Scholar · View at Scopus
  114. P. Talke, C. A. Richardson, M. Scheinin, and D. M. Fisher, “Postoperative pharmacokinetics and sympatholytic effects of dexmedetomidine,” Anesthesia and Analgesia, vol. 85, no. 5, pp. 1136–1142, 1997. View at Publisher · View at Google Scholar · View at Scopus
  115. A. Kallio, M. Scheinin, M. Koulu et al., “Effects of dexmedetomidine, a selective α2-adrenoceptor agonist, on hemodynamic control mechanisms,” Clinical Pharmacology and Therapeutics, vol. 46, no. 1, pp. 33–42, 1989. View at Google Scholar · View at Scopus
  116. T. J. Ebert, J. E. Hall, J. A. Barney, T. D. Uhrich, and M. D. Colinco, “The effects of increasing plasma concentrations of dexmedetomidine in humans,” Anesthesiology, vol. 93, no. 2, pp. 382–394, 2000. View at Google Scholar · View at Scopus
  117. V. S. B. Jorden, R. M. Pousman, M. M. Sanford, P. A. J. Thorborg, and M. P. Hutchens, “Dexmedetomidine overdose in the perioperative setting,” Annals of Pharmacotherapy, vol. 38, no. 5, pp. 803–807, 2004. View at Publisher · View at Google Scholar · View at Scopus
  118. M. A. E. Ramsay and D. L. Luterman, “Dexmedetomidine as a total intravenous anesthetic agent,” Anesthesiology, vol. 101, no. 3, pp. 787–790, 2004. View at Publisher · View at Google Scholar · View at Scopus
  119. J. Sleigh, “All hands on dex,” Anaesthesia, vol. 67, pp. 1193–1197, 2012. View at Google Scholar
  120. M. Aho, O. Erkola, A. Kallio, H. Scheinin, and K. Korttila, “Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing abdominal hysterectomy,” Anesthesia and Analgesia, vol. 75, no. 6, pp. 940–946, 1992. View at Google Scholar · View at Scopus
  121. H. Ishii, T. Kohno, T. Yamakura, M. Ikoma, and H. Baba, “Action of dexmedetomidine on the substantia gelatinosa neurons of the rat spinal cord,” European Journal of Neuroscience, vol. 27, no. 12, pp. 3182–3190, 2008. View at Publisher · View at Google Scholar · View at Scopus
  122. L. E. Nelson, T. You, M. Maze, and N. P. Franks, “Evidence that the mechanism of hypnotic action in dexmedetomidine and muscimol-induced anesthesia converges on the endogenous sleep pathway,” Anesthesiology, vol. 95, p. A1368, 2001. View at Google Scholar
  123. R. R. Al-Metwalli, H. A. Mowafi, S. A. Ismail et al., “Effect of intra-articular dexmedetomidine on postoperative analgesia after arthroscopic knee surgery,” British Journal of Anaesthesia, vol. 101, no. 3, pp. 395–399, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. T. Yoshitomi, A. Kohjitani, S. Maeda, H. Higuchi, M. Shimada, and T. Miyawaki, “Dexmedetomidine enhances the local anesthetic action of lidocaine via an α-2a adrenoceptor,” Anesthesia and Analgesia, vol. 107, no. 1, pp. 96–101, 2008. View at Publisher · View at Google Scholar · View at Scopus
  125. A. Turkmen, A. Altan, N. Turgut, S. Vatansever, and S. Gokkaya, “The correlation between the richmond agitation-sedation scale and bispectral index during dexmedetomidine sedation,” European Journal of Anaesthesiology, vol. 23, no. 4, pp. 300–304, 2006. View at Publisher · View at Google Scholar · View at Scopus
  126. R. Aantaa, “Assessment of the sedative effects of dexmedetomidine, an α2-adrenoceptor agonist, with analysis of saccadic eye movements,” Pharmacology and Toxicology, vol. 68, no. 5, pp. 394–398, 1991. View at Google Scholar · View at Scopus
  127. W. J. Elias, M. E. Durieux, D. Huss, and R. C. Frysinger, “Dexmedetomidine and arousal affect subthalamic neurons,” Movement Disorders, vol. 23, no. 9, pp. 1317–1320, 2008. View at Publisher · View at Google Scholar · View at Scopus
  128. Y.-W. Hsu, L. I. Cortinez, K. M. Robertson et al., “Dexmedetomidine pharmacodynamics: part I—crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers,” Anesthesiology, vol. 101, no. 5, pp. 1066–1076, 2004. View at Publisher · View at Google Scholar · View at Scopus
  129. J. T. Coull, M. E. P. Jones, T. D. Egan, C. D. Frith, and M. Maze, “Attentional effects of noradrenaline vary with arousal level: selective activation of thalamic pulvinar in humans,” NeuroImage, vol. 22, no. 1, pp. 315–322, 2004. View at Publisher · View at Google Scholar · View at Scopus
  130. E. Deutsch and J. D. Tobias, “Hemodynamic and respiratory changes following dexmedetomidine administration during general anesthesia: sevoflurane vs desflurane,” Paediatric Anaesthesia, vol. 17, no. 5, pp. 438–444, 2007. View at Publisher · View at Google Scholar · View at Scopus
  131. A. Koroglu, H. Teksan, O. Sagir, A. Yucel, H. I. Toprak, and O. M. Ersoy, “A comparison of the sedative, hemodynamic, and respiratory effects of dexmedetomidine and propofol in children undergoing magnetic resonance imaging,” Anesthesia and Analgesia, vol. 103, no. 1, pp. 63–67, 2006. View at Publisher · View at Google Scholar · View at Scopus
  132. P. A. Arpino, K. Kalafatas, and B. T. Thompson, “Feasibility of dexmedetomidine in facilitating extubation in the intensive care unit,” Journal of Clinical Pharmacy and Therapeutics, vol. 33, no. 1, pp. 25–30, 2008. View at Publisher · View at Google Scholar · View at Scopus
  133. T. B. Corcoran, A. Engel, H. Sakamoto, A. O'Shea, S. O'Callaghan-Enright, and G. D. Shorten, “The effects of propofol on neutrophil function, lipid peroxidation and inflammatory response during elective coronary artery bypass grafting in patients with impaired ventricular function,” British Journal of Anaesthesia, vol. 97, no. 6, pp. 825–831, 2006. View at Publisher · View at Google Scholar · View at Scopus
  134. M. Arslan, F. M. Çomu, A. Kuçuk, L. Ozturk, and F. Yaylak, “Dexmedetomidine protects against lipid peroxidation and erythrocyte deformability alterations in experimental hepatic ischemia reperfusion injury,” Libyan Journal of Medicine, vol. 7, article 18185, 2012. View at Google Scholar
  135. J. B. T. Rocha, N. M. Heinzmann Bulow, E. F. M. Correa, C. Scholze, C. W. Nogueira, and N. B. Barbosa, “Dexmedetomidine protects blood γ-aminolevulinate dehydratase from inactivation caused by hyperoxygenation in total intravenous anesthesia,” Human and Experimental Toxicology, vol. 30, no. 4, pp. 289–295, 2011. View at Publisher · View at Google Scholar · View at Scopus
  136. R. H. Straub, M. Herrmann, G. Berkmiller et al., “Neuronal regulation of interleukin 6 secretion in murine spleen: adrenergic and opioidergic control,” Journal of Neurochemistry, vol. 68, no. 4, pp. 1633–1639, 1997. View at Google Scholar · View at Scopus
  137. J. Szelényi, J. P. Kiss, and E. S. Vizi, “Differential involvement of sympathetic nervous system and immune system in the modulation of TNF-α production by α2- and β-adrenoceptors in mice,” Journal of Neuroimmunology, vol. 103, no. 1, pp. 34–40, 2000. View at Publisher · View at Google Scholar · View at Scopus
  138. T. Taniguchi, Y. Kidani, H. Kanakura, Y. Takemoto, and K. Yamamoto, “Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats,” Critical Care Medicine, vol. 32, no. 6, pp. 1322–1326, 2004. View at Publisher · View at Google Scholar · View at Scopus
  139. S. Hofer, J. Steppan, T. Wagner et al., “Central sympatholytics prolong survival in experimental sepsis,” Critical Care, vol. 13, no. 1, article R11, 2009. View at Publisher · View at Google Scholar · View at Scopus
  140. M. Can, S. Gul, S. Bektas, V. Hanci, and S. Acikgoz, “Effects of dexmedetomidine or methylprednisolone on inflammatory responses in spinal cord injury,” Acta Anaesthesiologica Scandinavica, vol. 53, no. 8, pp. 1068–1072, 2009. View at Publisher · View at Google Scholar · View at Scopus
  141. M. Maze, R. Virtanen, D. Daunt, S. J. M. Banks, E. P. Stover, and D. Feldman, “Effects of dexmedetomidine, a novel imidazole sedative-anesthetic agent, on adrenal steroidogenesis: in vivo and in vitro studies,” Anesthesia and Analgesia, vol. 73, no. 2, pp. 204–208, 1991. View at Google Scholar · View at Scopus
  142. R. M. Venn, A. Bryant, G. M. Hall, and R. M. Grounds, “Effects of dexmedetomidine on adrenocortical function, and the cardiovascular, endocrine and inflammatory responses in post-operative patients needing sedation in the intensive care unit,” British Journal of Anaesthesia, vol. 86, no. 5, pp. 650–656, 2001. View at Publisher · View at Google Scholar · View at Scopus
  143. N. M. H. Bulow, N. B. V. Barbosa, and J. B. T. Rocha, “Opioid consumption in total intravenous anesthesia is reduced with dexmedetomidine: a comparative study with remifentanil in gynecologic videolaparoscopic surgery,” Journal of Clinical Anesthesia, vol. 19, no. 4, pp. 280–285, 2007. View at Publisher · View at Google Scholar · View at Scopus
  144. P. P. Pandharipande, B. T. Pun, D. L. Herr et al., “Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial,” Journal of the American Medical Association, vol. 298, no. 22, pp. 2644–2653, 2007. View at Publisher · View at Google Scholar · View at Scopus
  145. A. T. Gerlach, C. V. Murphy, and J. F. Dasta, “An updated focused review of dexmedetomidine in adults,” Annals of Pharmacotherapy, vol. 43, no. 12, pp. 2064–2074, 2009. View at Publisher · View at Google Scholar · View at Scopus
  146. S. Sulaiman, R. B. Karthekeyan, M. Vakamudi, A. S. Sundar, H. Ravullapalli, and R. Gandham, “The effects of dexmedetomidine on attenuation of stress response to endotracheal intubation in patients undergoing elective off-pump coronary artery bypass grafting,” Annals of Cardiac Anaesthesia, vol. 15, no. 1, pp. 39–43, 2012. View at Publisher · View at Google Scholar · View at Scopus
  147. B. Scheinin, L. Lindgren, T. Randell, H. Scheinin, and M. Scheinin, “Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone and peroperative fentanyl,” British Journal of Anaesthesia, vol. 68, no. 2, pp. 126–131, 1992. View at Google Scholar · View at Scopus
  148. S. Sukegawa, M. Inoue, H. Higuchi, Y. Tomoyasu, S. Maeda, and T. Miyawaki, “Locally injected dexmedetomidine inhibits carrageenin-induced inflammatory reactions in injected region,” in Proceedings of the American Society of Anesthesiologists Annual Meeting, 2011, A1590.
  149. Y.-C. Lai, P.-S. Tsai, and C.-J. Huang, “Effects of dexmedetomidine on regulating endotoxin-induced up-regulation of inflammatory molecules in murine macrophages,” Journal of Surgical Research, vol. 154, no. 2, pp. 212–219, 2009. View at Publisher · View at Google Scholar · View at Scopus
  150. H. Yagmurdur, N. Ozcan, F. Dokumaci, K. Kilinc, F. Yilmaz, and H. Basar, “Dexmedetomidine reduces the ischemia-reperfusion injury markers during upper extremity surgery with tourniquet,” Journal of Hand Surgery, vol. 33, no. 6, pp. 941–947, 2008. View at Publisher · View at Google Scholar · View at Scopus
  151. A. Bekker, M. Haile, R. Kline et al., “The effect of intraoperative infusion of dexmedetomidine on the quality of recovery after major spinal surgery,” Journal of Neurosurgical Anesthesiology, vol. 25, no. 1, pp. 16–24, 2012. View at Publisher · View at Google Scholar
  152. J. Gu, J. Chen, P. Xia, G. Tao, H. Zhao, and D. Ma, “Dexmedetomidine attenuates remote lung injury induced by renal ischemia-reperfusion in mice,” Acta Anaesthesiologica Scandinavica, vol. 55, no. 10, pp. 1272–1278, 2011. View at Publisher · View at Google Scholar · View at Scopus
  153. X. Wu, X. Song, N. Li, L. Zhan, Q. Meng, and Z. Xia, “Protective effects of dexmedetomidine on blunt chest trauma-induced pulmonary contusion in rats,” Journal of Trauma and Acute Care Surgery, vol. 74, pp. 524–530, 2013. View at Google Scholar
  154. S.-H. Kang, Y.-S. Kim, T.-H. Hong et al., “Effects of dexmedetomidine on inflammatory responses in patients undergoing laparoscopic cholecystectomy,” Acta Anaesthesiologica Scandinavica, vol. 57, pp. 480–487, 2013. View at Google Scholar
  155. M. Tasdogan, D. Memis, N. Sut, and M. Yuksel, “Results of a pilot study on the effects of propofol and dexmedetomidine on inflammatory responses and intraabdominal pressure in severe sepsis,” Journal of Clinical Anesthesia, vol. 21, no. 6, pp. 394–400, 2009. View at Publisher · View at Google Scholar · View at Scopus
  156. R. D. Sanders, D. Ma, and M. Maze, “Anaesthesia induced neuroprotection,” Best Practice and Research, vol. 19, no. 3, pp. 461–474, 2005. View at Publisher · View at Google Scholar · View at Scopus
  157. E. L. Janke and S. Samra, “Dexmedetomidine and neuroprotection,” Seminars in Anesthesia, Perioperative Medicine and Pain, vol. 25, no. 2, pp. 71–76, 2006. View at Publisher · View at Google Scholar · View at Scopus
  158. M. F. Newman, “Open heart surgery and cognitive decline,” Cleveland Clinic journal of medicine, vol. 74, pp. S52–S55, 2007. View at Google Scholar · View at Scopus
  159. N. Stroobant, G. van Nooten, D. de Bacquer, Y. van Belleghem, and G. Vingerhoets, “Neuropsychological functioning 3-5 years after coronary artery bypass grafting: does the pump make a difference?” European Journal of Cardio-thoracic Surgery, vol. 34, no. 2, pp. 396–401, 2008. View at Publisher · View at Google Scholar · View at Scopus
  160. H. P. Grocott, “Genetic influences on cerebral outcome after cardiac surgery,” Seminars in Cardiothoracic and Vascular Anesthesia, vol. 10, no. 4, pp. 291–296, 2006. View at Publisher · View at Google Scholar · View at Scopus
  161. K. M. Taylor, “Central nervous system effects of cardiopulmonary bypass,” Annals of Thoracic Surgery, vol. 66, no. 5, pp. S20–S24, 1998. View at Publisher · View at Google Scholar · View at Scopus
  162. C. W. Hogue Jr., T. Hershey, D. Dixon et al., “Preexisting cognitive impairment in women before cardiac surgery and its relationship with C-reactive protein concentrations,” Anesthesia and Analgesia, vol. 102, no. 6, pp. 1602–1608, 2006. View at Publisher · View at Google Scholar · View at Scopus
  163. P. M. Ho, D. B. Arciniegas, J. Grigsby et al., “Predictors of cognitive decline following coronary artery bypass graft surgery,” Annals of Thoracic Surgery, vol. 77, no. 2, pp. 597–603, 2004. View at Publisher · View at Google Scholar · View at Scopus
  164. C. G. Koch, L. Li, M. Shishehbor et al., “Socioeconomic status and comorbidity as predictors of preoperative quality of life in cardiac surgery,” Journal of Thoracic and Cardiovascular Surgery, vol. 136, no. 3, pp. 665–672, 2008. View at Publisher · View at Google Scholar · View at Scopus
  165. N. Stroobant and G. Vingerhoets, “Depression, anxiety, and neuropsychological performance in coronary artery bypass graft patients: a follow-up study,” Psychosomatics, vol. 49, no. 4, pp. 326–331, 2008. View at Publisher · View at Google Scholar · View at Scopus
  166. R. Ille, T. Lahousen, S. Schweiger, P. Hofmann, and H.-P. Kapfhammer, “Influence of patient-related and surgery-related risk factors on cognitive performance, emotional state, and convalescence after cardiac surgery,” Cardiovascular Revascularization Medicine, vol. 8, no. 3, pp. 166–169, 2007. View at Publisher · View at Google Scholar · View at Scopus
  167. N. A. Nussmeier and B. E. Searles, “Inflammatory brain injury after cardiopulmonary bypass: is it real?” Anesthesia and Analgesia, vol. 110, no. 2, pp. 288–290, 2010. View at Publisher · View at Google Scholar · View at Scopus
  168. S. Singh, P. Kapoor, U. Chowdhury, and U. Kiran, “Comparison of S100 levels, and their correlation with hemodynamic indices in patients undergoing coronary artery bypass grafting with three different anesthetic techniques,” Annals of Cardiac Anaesthesia, vol. 14, no. 3, pp. 197–202, 2011. View at Publisher · View at Google Scholar · View at Scopus
  169. A. Kleindienst, F. Hesse, M. R. Bullock, and M. Buchfelder, “The neurotrophic protein S100B: value as a marker of brain damage and possible therapeutic implications,” Progress in Brain Research, vol. 161, pp. 317–325, 2007. View at Publisher · View at Google Scholar · View at Scopus
  170. R. R. Riker, Y. Shehabi, P. M. Bokesch et al., “Dexmedetomidine vs midazolam for sedation of critically Ill patients A randomized trial,” Journal of the American Medical Association, vol. 301, no. 5, pp. 489–499, 2009. View at Publisher · View at Google Scholar · View at Scopus
  171. J. R. Maldonado, A. Wysong, P. J. A. van der Starre, T. Block, C. Miller, and B. A. Reitz, “Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery,” Psychosomatics, vol. 50, no. 3, pp. 206–217, 2009. View at Publisher · View at Google Scholar · View at Scopus
  172. E. Ruokonen, I. Parviainen, S. M. Jakob et al., “Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation,” Intensive Care Medicine, vol. 35, no. 2, pp. 282–290, 2009. View at Publisher · View at Google Scholar · View at Scopus
  173. W. Mayo, V. Lemaire, J. Malaterre et al., “Pregnenolone sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus,” Neurobiology of Aging, vol. 26, no. 1, pp. 103–114, 2005. View at Publisher · View at Google Scholar · View at Scopus
  174. E. A. Keller, A. Zamparini, L. N. Borodinsky, M. C. Gravielle, and M. L. Fiszman, “Role of allopregnanolone on cerebellar granule cells neurogenesis,” Developmental Brain Research, vol. 153, no. 1, pp. 13–17, 2004. View at Publisher · View at Google Scholar · View at Scopus
  175. C. Correa-Sales, B. C. Rabin, and M. Maze, “A hypnotic response to dexmedetomidine, an α2 agonist, is mediated in the locus coeruleus in rats,” Anesthesiology, vol. 76, no. 6, pp. 948–952, 1992. View at Google Scholar · View at Scopus
  176. V. A. Kulkarni, S. Jha, and V. A. Vaidya, “Depletion of norepinephrine decreases the proliferation, but does not influence the survival and differentiation, of granule cell progenitors in the adult rat hippocampus,” European Journal of Neuroscience, vol. 16, no. 10, pp. 2008–2012, 2002. View at Publisher · View at Google Scholar · View at Scopus
  177. P. Mohapel, G. Leanza, M. Kokaia, and O. Lindvall, “Forebrain acetylcholine regulates adult hippocampal neurogenesis and learning,” Neurobiology of Aging, vol. 26, no. 6, pp. 939–946, 2005. View at Publisher · View at Google Scholar · View at Scopus
  178. A. Tung, S. Herrera, C. A. Fornal, and B. L. Jacobs, “The effect of prolonged anesthesia with isoflurane, propofol, dexmedetomidine, or ketamine on neural cell proliferation in the adult rat,” Anesthesia and Analgesia, vol. 106, no. 6, pp. 1772–1777, 2008. View at Publisher · View at Google Scholar · View at Scopus
  179. W. E. Hoffman, E. Kochs, C. Werner, C. Thomas, and R. F. Albrecht, “Dexmedetomidine improves neurologic outcome from incomplete ischemia in the rat. Reversal by the α2-adrenergic antagonist atipamezole,” Anesthesiology, vol. 75, no. 2, pp. 328–332, 1991. View at Google Scholar · View at Scopus
  180. W. E. Hoffman, V. L. Baughman, and R. F. Albrecht, “Interaction of catecholamines and nitrous oxide ventilation during incomplete brain ischemia in rats,” Anesthesia and Analgesia, vol. 77, no. 5, pp. 908–912, 1993. View at Google Scholar · View at Scopus
  181. C. Maier, G. K. Steinberg, G. H. Sun, G. T. Zhi, and M. Maze, “Neuroprotection by the α2-adrenoreceptor agonist dexmedetomidine in a focal model of cerebral ischemia,” Anesthesiology, vol. 79, no. 2, pp. 306–312, 1993. View at Google Scholar · View at Scopus
  182. J. Kuhmonen, J. Pokorný, R. Miettinen et al., “Neuroprotective effects of dexmedetomidine in the gerbil hippocampus after transient global ischemia,” Anesthesiology, vol. 87, no. 2, pp. 371–377, 1997. View at Publisher · View at Google Scholar · View at Scopus
  183. V. Laudenbach, J. Mantz, H. Lagercrantz, J.-M. Desmonts, P. Evrard, and P. Gressens, “Effects of α2-adrenoceptor agonists on perinatal excitotoxic brain injury: comparison of clonidine and dexmedetomidine,” Anesthesiology, vol. 96, no. 1, pp. 134–141, 2002. View at Google Scholar · View at Scopus
  184. L. Peng, A. C. H. Yu, K. Y. Fung, V. Prévot, and L. Hertz, “α-adrenergic stimulation of ERK phosphorylation in astrocytes is α2-specific and may be mediated by transactivation,” Brain Research, vol. 978, no. 1-2, pp. 65–71, 2003. View at Publisher · View at Google Scholar · View at Scopus
  185. B. Li, T. Du, H. Li et al., “Signalling pathways for transactivation by dexmedetomidine of epidermal growth factor receptors in astrocytes and its paracrine effect on neurons,” British Journal of Pharmacology, vol. 154, no. 1, pp. 191–203, 2008. View at Publisher · View at Google Scholar · View at Scopus
  186. L. Hertz, D. Lovatt, S. A. Goldman, and M. Nedergaard, “Adrenoceptors in brain: cellular gene expression and effects on astrocytic metabolism and [Ca2+]i,” Neurochemistry International, vol. 57, no. 4, pp. 411–420, 2010. View at Publisher · View at Google Scholar · View at Scopus
  187. L. Peng, T. Du, J. Xu et al., “Adrenergic and V1-ergic agonists/antagonists affecting recovery from Brain Trauma in the Lund project Act on astrocytes,” Current Signal Transduction Therapy, vol. 7, pp. 43–55, 2012. View at Google Scholar
  188. L. Liu, F. Ji, J. Liang, H. He, Y. Fu, and M. Cao, “Inhibition by dexmedetomidine of the activation of spinal dorsal horn glias and the intracellular ERK signaling pathway induced by nerve injury,” Brain Research, vol. 1427, pp. 1–9, 2012. View at Publisher · View at Google Scholar · View at Scopus
  189. B. Xu, W. S. Zhang, J. L. Yang et al., “Evidence for suppression of spinal glial activation by dexmedetomidine in a rat model of monoarthritis.,” Clinical and Experimental Pharmacology and Physiology, vol. 37, pp. 158–166, 2010. View at Google Scholar
  190. C. Chrysostomou and C. G. Schmitt, “Dexmedetomidine: sedation, analgesia and beyond,” Expert Opinion on Drug Metabolism and Toxicology, vol. 4, no. 5, pp. 619–627, 2008. View at Publisher · View at Google Scholar · View at Scopus
  191. M. Schoeler, P. D. Loetscher, R. Rossaint et al., “Dexmedetomidine is neuroprotective in an in vitro model for traumatic brain injury,” BMC Neurology, vol. 12, p. 20, 2012. View at Publisher · View at Google Scholar · View at Scopus
  192. M. Zhang, X. Shan, L. Gu, L. Hertz, and L. Peng, “Dexmedetomidine causes neuroprotection via astrocytic α2-adrenergic receptor stimulation and HB-EGF release,” Journal of Anesthesiology & Clinical Science, 2013. View at Publisher · View at Google Scholar
  193. E. D. Hall, R. A. Vaishnav, and A. G. Mustafa, “Antioxidant Therapies for Traumatic Brain Injury,” Neurotherapeutics, vol. 7, no. 1, pp. 51–61, 2010. View at Publisher · View at Google Scholar · View at Scopus
  194. P. S. Eriksson, E. Perfilieva, T. Björk-Eriksson et al., “Neurogenesis in the adult human hippocampus,” Nature Medicine, vol. 4, no. 11, pp. 1313–1317, 1998. View at Publisher · View at Google Scholar · View at Scopus
  195. T. J. Shors, G. Miesegaes, A. Beylin, M. Zhao, T. Rydel, and E. Gould, “Neurogenesis in the adult is involved in the formation of trace memories,” Nature, vol. 410, pp. 372–376, 2001. View at Google Scholar
  196. B. Leuner, E. Gould, and T. J. Shors, “Is there a link between adult neurogenesis and learning?” Hippocampus, vol. 16, no. 3, pp. 216–224, 2006. View at Publisher · View at Google Scholar · View at Scopus
  197. L. Henriksen, E. Hjelms, and T. Lindeburgh, “Brain hyperperfusion during cardiac operations. Cerebral blood flow measured in man by intra-arterial injection of xenon 133: evidence suggestive of intraoperative microembolism,” Journal of Thoracic and Cardiovascular Surgery, vol. 86, no. 2, pp. 202–208, 1983. View at Google Scholar · View at Scopus
  198. A. V. Govier, J. G. Reves, and R. D. McKay, “Factors and their influence on regional cerebral blood flow during nonpulsatile cardiopulmonary bypass,” Annals of Thoracic Surgery, vol. 38, no. 6, pp. 592–600, 1984. View at Google Scholar · View at Scopus
  199. J. M. Murkin, J. K. Farrar, W. A. Tweed, F. N. McKenzie, and G. Guiraudon, “Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO2,” Anesthesia and Analgesia, vol. 66, no. 9, pp. 825–832, 1987. View at Google Scholar · View at Scopus
  200. Y. M. Ganushchak, E. J. Fransen, C. Visser, D. S. de Jong, and J. G. Maessen, “Neurological complications after coronary artery bypass grafting related to the performance of cardiopulmonary bypass,” Chest, vol. 125, no. 6, pp. 2196–2205, 2004. View at Publisher · View at Google Scholar · View at Scopus
  201. W. E. Hoffman, E. Kochs, C. Werner, C. Thomas, and R. F. Albrecht, “Dexmedetomidine improves neurologic outcome from incomplete ischemia in the rat. Reversal by the α2-adrenergic antagonist atipamezole,” Anesthesiology, vol. 75, no. 2, pp. 328–332, 1991. View at Google Scholar · View at Scopus
  202. S. Dahmani, D. Rouelle, P. Gressens, and J. Mantz, “Characterization of the postconditioning effect of dexmedetomidine in mouse organotypic hippocampal slice cultures exposed to oxygen and glucose deprivation,” Anesthesiology, vol. 112, no. 2, pp. 373–383, 2010. View at Publisher · View at Google Scholar · View at Scopus
  203. K. Engelhard, C. Werner, E. Eberspächer et al., “The effect of the α2-agonist dexmedetomidine and the N-methyl-D-aspartate antagonist S(+)-ketamine on the expression of apoptosis-regulating proteins after incomplete cerebral ischemia and reperfusion in rats,” Anesthesia and Analgesia, vol. 96, no. 2, pp. 524–531, 2003. View at Publisher · View at Google Scholar · View at Scopus
  204. K. Sato, T. Kimura, T. Nishikawa, Y. Tobe, and Y. Masaki, “Neuroprotective effects of a combination of dexmedetomidine and hypothermia after incomplete cerebral ischemia in rats,” Acta Anaesthesiologica Scandinavica, vol. 54, no. 3, pp. 377–382, 2010. View at Publisher · View at Google Scholar · View at Scopus
  205. O. Eser, H. Fidan, O. Sahin et al., “The influence of dexmedetomidine on ischemic rat hippocampus,” Brain Research, vol. 1218, pp. 250–256, 2008. View at Publisher · View at Google Scholar · View at Scopus
  206. J. Afonso and F. Reis, “Dexmedetomidine: current role in anesthesia and intensive care,” Revista Brasileira de Anestesiologia, vol. 62, no. 1, pp. 118–133, 2012. View at Publisher · View at Google Scholar · View at Scopus
  207. S. Dahmani, A. Paris, V. Jannier et al., “Dexmedetomidine increases hippocampal phosphorylated extracellular signal-regulated protein kinase 1 and 2 content by an α2-adrenoceptor- independent mechanism: evidence for the involvement of imidazoline I1 receptors,” Anesthesiology, vol. 108, no. 3, pp. 457–466, 2008. View at Publisher · View at Google Scholar · View at Scopus
  208. J. Shen, Y. Wu, J.-Y. Xu et al., “ERK- and Akt-dependent neuroprotection by erythropoietin (EPO) against glyoxal-AGEs via modulation of Bcl-xL, Bax, and BAD,” Investigative Ophthalmology and Visual Science, vol. 51, no. 1, pp. 35–46, 2010. View at Publisher · View at Google Scholar · View at Scopus
  209. H. Kocoglu, K. Karaaslan, E. Gonca, O. Bozdogan, and N. Gulcu, “Preconditionin effects of dexmedetomidine on myocardial ischemia/reperfusion injury in rats,” Current Therapeutic Research, vol. 69, no. 2, pp. 150–158, 2008. View at Publisher · View at Google Scholar · View at Scopus
  210. H. Kocoglu, H. Ozturk, H. Ozturk, F. Yilmaz, and N. Gulcu, “Effect of dexmedetomidine on ischemia-reperfusion injury in rat kidney: a histopathologic study,” Renal Failure, vol. 31, no. 1, pp. 70–74, 2009. View at Publisher · View at Google Scholar · View at Scopus
  211. S. Dahmani, D. Rouelle, P. Gressens, and J. Mantz, “Effects of dexmedetomidine on hippocampal focal adhesion kinase tyrosine phosphorylation in physiologic and ischemic conditions,” Anesthesiology, vol. 103, no. 5, pp. 969–977, 2005. View at Publisher · View at Google Scholar · View at Scopus
  212. R. C. Prielipp, M. H. Wall, J. R. Tobin et al., “Dexmedetomidine-induced sedation in volunteers decreases regional and global cerebral blood flow,” Anesthesia and Analgesia, vol. 95, no. 4, pp. 1052–1059, 2002. View at Google Scholar · View at Scopus
  213. M. H. Zornow, M. Maze, J. B. Dyck, and S. L. Shafer, “Dexmedetomidine decreases cerebral blood flow velocity in humans,” Journal of Cerebral Blood Flow and Metabolism, vol. 13, no. 2, pp. 350–353, 1993. View at Google Scholar · View at Scopus
  214. J. C. Drummond, A. V. Dao, D. M. Roth et al., “Effect of dexmedetomidine on cerebral blood flow velocity, cerebral metabolic rate, and carbon dioxide response in normal humans,” Anesthesiology, vol. 108, no. 2, pp. 225–232, 2008. View at Publisher · View at Google Scholar · View at Scopus
  215. M. Schoeler, P. D. Loetscher, R. Rossaint et al., “Dexmedetomidine is neuroprotective in an in vitro model for traumatic brain injury,” BMC Neurology, vol. 12, p. 20, 2012. View at Publisher · View at Google Scholar · View at Scopus
  216. D. S. Sulemanji, A. Dönmez, D. Aldemir, A. Sezgin, and S. Türkoglu, “Dexmedetomidine during coronary artery bypass grafting surgery: is it neuroprotective?—a preliminary study,” Acta Anaesthesiologica Scandinavica, vol. 51, no. 8, pp. 1093–1098, 2007. View at Publisher · View at Google Scholar · View at Scopus
  217. M. T. Bell, F. Ferenc Puskas, P. D. Smith et al., “Attenuation of spinal cord ischemia-reperfusion injury by specific α-2a receptor activation with dexmedetomidine,” Journal of Vascular Surgery, vol. 56, pp. 1398–1402, 2012. View at Google Scholar
  218. J. Gu, P. Sun, H. Zhao et al., “Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice,” Critical Care, vol. 15, no. 3, article R153, 2011. View at Publisher · View at Google Scholar · View at Scopus
  219. B. Tufanogullari, P. F. White, M. P. Peixoto et al., “Dexmedetomidine infusion during laparoscopic bariatric surgery: the effect on recovery outcome variables,” Anesthesia and Analgesia, vol. 106, no. 6, pp. 1741–1748, 2008. View at Publisher · View at Google Scholar · View at Scopus
  220. P. Jalowiecki, R. Rudner, M. Gonciarz, P. Kawecki, M. Petelenz, and P. Dziurdzik, “Sole use of dexmedetomidine has limited utility for conscious sedation during outpatient colonoscopy,” Anesthesiology, vol. 103, no. 2, pp. 269–273, 2005. View at Publisher · View at Google Scholar · View at Scopus
  221. M. Muntazar and F. C. Kumar, “Cardiac arrest, a preventable yet a possible risk of dexmedetomidine: fact or fiction?” Anesthesiology, vol. 101, no. 6, pp. 1478–1480, 2004. View at Google Scholar · View at Scopus
  222. A. N. Shah, J. Koneru, A. Nicoara, L. B. Goldfeder, K. Thomas, and F. A. Ehlert, “Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale,” Pacing and Clinical Electrophysiology, vol. 30, no. 9, pp. 1158–1160, 2007. View at Publisher · View at Google Scholar · View at Scopus
  223. D. L. Herr, S. T. J. Sum-Ping, and M. England, “ICU sedation after coronary artery bypass graft surgery: dexmedetomidine-based versus propofol-based sedation regimens,” Journal of Cardiothoracic and Vascular Anesthesia, vol. 17, no. 5, pp. 576–584, 2003. View at Publisher · View at Google Scholar · View at Scopus
  224. J. Jalonen, M. Hynynen, A. Kuitunen et al., “Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting,” Anesthesiology, vol. 86, no. 2, pp. 331–345, 1997. View at Publisher · View at Google Scholar · View at Scopus
  225. H. Karakaya Kabukçu, N. Sahin, Y. Temel, and T. Aydogdu Titiz, “Hemodynamics in coronary artery bypass surgery: effects of intraoperative dexmedetomidine administration,” Anaesthesist, vol. 60, no. 5, pp. 427–431, 2011. View at Publisher · View at Google Scholar · View at Scopus
  226. H. Guo, S. Takahashi, S. Cho, T. Hara, S. Tomiyasu, and K. Sumikawa, “The effects of dexmedetomidine on left ventricular function during hypoxia and reoxygenation in isolated rat hearts,” Anesthesia and Analgesia, vol. 100, no. 3, pp. 629–635, 2005. View at Publisher · View at Google Scholar · View at Scopus
  227. H. Chen, H. Higashino, K. Maeda et al., “Reduction of cardiac norepinephrine improves postischemic heart function in stroke-prone spontaneously hypertensive rats,” Journal of Cardiovascular Pharmacology, vol. 38, no. 6, pp. 821–832, 2001. View at Publisher · View at Google Scholar · View at Scopus
  228. P. M. Mertes, J. P. Carteaux, Y. Jaboin et al., “Estimation of myocardial interstitial norepinephrine release after brain death using cardiac microdialysis,” Transplantation, vol. 57, no. 3, pp. 371–377, 1994. View at Google Scholar · View at Scopus
  229. K. A. Bybee and A. Prasad, “Stress-related cardiomyopathy syndromes,” Circulation, vol. 118, no. 4, pp. 397–409, 2008. View at Publisher · View at Google Scholar · View at Scopus
  230. V. C. Hachinski, K. E. Smith, and M. D. Silver, “Acute myocardial and plasma catecholamine changes in experimental stroke,” Stroke, vol. 17, no. 3, pp. 387–390, 1986. View at Google Scholar · View at Scopus
  231. V. H. Lee, J. K. Oh, S. L. Mulvagh, and E. F. M. Wijdicks, “Mechanisms in neurogenic stress cardiomyopathy after aneurysmal subarachnoid hemorrhage,” Neurocritical Care, vol. 5, no. 3, pp. 243–249, 2006. View at Publisher · View at Google Scholar · View at Scopus
  232. H. M. Willigers, F. W. Prinzen, P. M. Roekaerts, S. de Lange, and M. E. Durieux, “Dexmedetomidine decreases perioperative myocardial lactate release in dogs,” Anesthesia and Analgesia, vol. 96, no. 3, pp. 657–664, 2003. View at Google Scholar · View at Scopus
  233. M. Karamazyn, R. E. Beamish, and N. S. Dhalla, “Involvement of calcium in coronary vasoconstriction due to prolonged hypoxia,” American Heart Journal, vol. 107, no. 2, pp. 293–297, 1984. View at Google Scholar · View at Scopus
  234. D. Pinsky, M. Oz, H. Liao et al., “Restoration of the cAMP second messenger pathway enhances cardiac preservation for transplantation in a heterotopic rat model,” Journal of Clinical Investigation, vol. 92, no. 6, pp. 2994–3002, 1993. View at Google Scholar · View at Scopus
  235. M. Kitakaze, M. Hori, K. Gotoh et al., “Beneficial effects of α2-adrenoceptor activity on ischemic myocardium during coronary hypoperfusion in dogs,” Circulation Research, vol. 65, no. 6, pp. 1623–1645, 1989. View at Google Scholar · View at Scopus
  236. M. F. Oliver, L. Goldman, D. G. Julian, and I. Holme, “Effect of mivazerol on perioperative cardiac complications during non-cardiac surgery in patients with coronary heart disease: the European Mivazerol Trial (EMIT),” Anesthesiology, vol. 91, no. 4, pp. 951–961, 1999. View at Publisher · View at Google Scholar · View at Scopus
  237. D. N. Wijeysundera, J. S. Naik, and W. S. Beattie, “Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications: a meta-analysis,” American Journal of Medicine, vol. 114, no. 9, pp. 742–752, 2003. View at Publisher · View at Google Scholar · View at Scopus
  238. A. J. Rough, L. H. Kudo, and C. Hébert, “Dexmedetomidine inhibits osmotic water permeability in the rat cortical collecting duct,” Journal of Pharmacology and Experimental Therapeutics, vol. 281, no. 1, pp. 62–69, 1997. View at Google Scholar · View at Scopus
  239. F. T. Billings IV, S. W. C. Chen, M. Kim et al., “α2-Adrenergic agonists protect against radiocontrast-induced nephropathy in mice,” American Journal of Physiology—Renal Physiology, vol. 295, no. 3, pp. F741–F748, 2008. View at Publisher · View at Google Scholar · View at Scopus
  240. M. Taoda, Y. U. Adachi, Y. Uchihashi, K. Watanabe, T. Satoh, and E. S. Vizi, “Effect of dexmedetomidine on the release of [3H]-noradrenaline from rat kidney cortex slices: characterization of α2-adrenoceptor,” Neurochemistry International, vol. 38, no. 4, pp. 317–322, 2001. View at Publisher · View at Google Scholar · View at Scopus
  241. R. M. Venn, P. J. Newman, and R. M. Grounds, “A phase II study to evaluate the efficacy of dexmedetomidine for sedation in the medical intensive care unit,” Intensive Care Medicine, vol. 29, no. 2, pp. 201–207, 2003. View at Google Scholar · View at Scopus
  242. K. Reid, Y. Hayashi, T.-Z. Guo, C. Correa-Sales, C. Nacif-Coelho, and M. Maze, “Chronic administration of an α2 adrenergic agonist desensitizes rats to the anesthetic effects of dexmedetomidine,” Pharmacology Biochemistry and Behavior, vol. 47, no. 1, pp. 171–175, 1994. View at Publisher · View at Google Scholar · View at Scopus
  243. A. G. Doufas, C.-M. Lin, M.-I. Suleman et al., “Dexmedetomidine and meperidine additively reduce the shivering threshold in humans,” Stroke, vol. 34, no. 5, pp. 1218–1223, 2003. View at Publisher · View at Google Scholar · View at Scopus
  244. E. G. Elvan, B. Öç, Ş. Uzun, E. Karabulut, F. Coşkun, and Ü. Aypar, “Dexmedetomidine and postoperative shivering in patients undergoing elective abdominal hysterectomy,” European Journal of Anaesthesiology, vol. 25, no. 5, pp. 357–364, 2008. View at Publisher · View at Google Scholar · View at Scopus
  245. G. A. Maccioli, “Dexmedetomidine to facilitate drug withdrawal,” Anesthesiology, vol. 98, no. 2, pp. 575–577, 2003. View at Publisher · View at Google Scholar · View at Scopus
  246. A. S. Multz, “Prolonged dexmedetomidine infusion as an adjunct in treating sedation-induced withdrawal,” Anesthesia and Analgesia, vol. 96, no. 4, pp. 1054–1055, 2003. View at Google Scholar · View at Scopus
  247. K. Baddigam, P. Russo, J. Russo, and J. D. Tobias, “Dexmedetomidine in the treatment of withdrawal syndromes in cardiothoracic surgery patients,” Journal of Intensive Care Medicine, vol. 20, no. 2, pp. 118–123, 2005. View at Publisher · View at Google Scholar · View at Scopus
  248. A. Rovasalo, H. Tohmo, R. Aantaa, E. Kettunen, and R. Palojoki, “Dexmedetomidine as an adjuvant in the treatment of alcohol withdrawal delirium: a case report,” General Hospital Psychiatry, vol. 28, no. 4, pp. 362–363, 2006. View at Publisher · View at Google Scholar · View at Scopus
  249. J. Darrouj, N. Puri, E. Prince, A. Lomonaco, A. Spevetz, and D. R. Gerber, “Dexmedetomidine infusion as adjunctive therapy to benzodiazepines for acute alcohol withdrawal,” Annals of Pharmacotherapy, vol. 42, no. 11, pp. 1703–1705, 2008. View at Publisher · View at Google Scholar · View at Scopus