The Journal of Thoracic and Cardiovascular Surgery
Volume 133, Issue 1 , Pages 13-20.e1 , January 2007

Increased cerebral and renal endothelial nitric oxide synthase gene expression after cardiopulmonary bypass in the rat

Presented in part at the Society of Cardiovascular Anesthesiologists Meeting, Miami, Fla, April 29, 2003.

  • C. David Mazer, MD

      Affiliations

    • Department of Anesthesia, University of Toronto, St. Michael’s Hospital, Seneca College, Toronto, Ontario, Canada
    • Department of Physiology, University of Toronto, St. Michael’s Hospital, Seneca College, Toronto, Ontario, Canada
    • Corresponding Author InformationAddress for reprints: C David Mazer, MD, Professor, Department of Anesthesia, University of Toronto, St Michael’s Hospital, 30 Bond St, Toronto, Ontario, M5B 1W8 Canada
  • ,
  • Francoise Briet, PhD

      Affiliations

    • Department of Anesthesia, University of Toronto, St. Michael’s Hospital, Seneca College, Toronto, Ontario, Canada
  • ,
  • Katherine R. Blight, MD

      Affiliations

    • Department of Anesthesia, University of Toronto, St. Michael’s Hospital, Seneca College, Toronto, Ontario, Canada
  • ,
  • Duncan J. Stewart, MD

      Affiliations

    • Division of Cardiology, University of Toronto, St. Michael’s Hospital, Seneca College, Toronto, Ontario, Canada
  • ,
  • Malcolm Robb, PhD

      Affiliations

    • Division of Cardiology, University of Toronto, St. Michael’s Hospital, Seneca College, Toronto, Ontario, Canada
  • ,
  • Zhilan Wang, MSc

      Affiliations

    • Department of Anesthesia, University of Toronto, St. Michael’s Hospital, Seneca College, Toronto, Ontario, Canada
  • ,
  • Alana M. Harrington, HBSc

      Affiliations

    • Department of Anesthesia, University of Toronto, St. Michael’s Hospital, Seneca College, Toronto, Ontario, Canada
  • ,
  • William Mak, PhD

      Affiliations

    • Department of Anesthesia, University of Toronto, St. Michael’s Hospital, Seneca College, Toronto, Ontario, Canada
    • Biotechnology Centre for Applied Research and Training, Seneca College, Toronto, Ontario, Canada.
  • ,
  • Xiaomao Li, PhD

      Affiliations

    • Department of Anesthesia, University of Toronto, St. Michael’s Hospital, Seneca College, Toronto, Ontario, Canada
    • Biotechnology Centre for Applied Research and Training, Seneca College, Toronto, Ontario, Canada.
  • ,
  • Gregory M.T. Hare, MD, PhD

      Affiliations

    • Department of Anesthesia, University of Toronto, St. Michael’s Hospital, Seneca College, Toronto, Ontario, Canada
    • Department of Physiology, University of Toronto, St. Michael’s Hospital, Seneca College, Toronto, Ontario, Canada

Received 19 October 2005 ,Revised 17 May 2006 ,Accepted 13 June 2006.

References 

  1. Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, et al. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med. 2001;344:395–402
  2. Karkouti K, Beattie WS, Wijeysundera DN, Rao V, Chan C, Dattilo KM, et al. Hemodilution during cardiopulmonary bypass is an independent risk factor for acute renal failure in adult cardiac surgery. J Thorac Cardiovasc Surg. 2005;129:391–400
  3. Stafford-Smith M, Podgoreanu M, Swaminathan M, Phillips-Bute B, Mathew JP, Hauser EH, et al. Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery. Am J Kidney Dis. 2005;45:519–530
  4. Swaminathan M, Phillips-Bute BG, Conlon PJ, Smith PK, Newman MF, Stafford-Smith M. The association of lowest hematocrit during cardiopulmonary bypass with acute renal injury after coronary artery bypass surgery. Ann Thorac Surg. 2003;76:784–791
  5. Habib RH, Zacharias A, Schwann TA, Riordan CJ, Durham SJ, Shah A. Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed?. J Thorac Cardiovasc Surg. 2003;125:1438–1450
  6. Jonas RA, Wypij D, Roth SJ, Bellinger DC, Visconti KJ, du Plessis AJ, et al. The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: results of a randomized trial in infants. J Thorac Cardiovasc Surg. 2003;126:1765–1774
  7. Stafford-Smith M, Grocott HP. Renal medullary hypoxia during experimental cardiopulmonary bypass: a pilot study. Perfusion. 2005;20:53–58
  8. Whitaker DC, Newman SP, Stygall J, Hope-Wynne C, Harrison MJ, Walesby RK. The effect of leucocyte-depleting arterial line filters on cerebral microemboli and neuropsychological outcome following coronary artery bypass surgery. Eur J Cardiothorac Surg. 2004;25:267–274
  9. Ma D, Yang H, Lynch J, Franks NP, Maze M, Grocott HP. Xenon attenuates cardiopulmonary bypass–induced neurologic and neurocognitive dysfunction in the rat. Anesthesiology. 2003;98:690–698
  10. Sato Y, Laskowitz DT, Bennett ER, Newman MF, Warner DS, Grocott HP. Differential cerebral gene expression during cardiopulmonary bypass in the rat: evidence for apoptosis?. Anesth Analg. 2002;94:1389–1394table
  11. Mutch WA, Ryner LN, Kozlowski P, Scarth G, Warrian RK, Lefevre GR, et al. Cerebral hypoxia during cardiopulmonary bypass: a magnetic resonance imaging study. Ann Thorac Surg. 1997;64:695–701
  12. Kadoi Y, Saito S, Goto F, Fujita N. Decrease in jugular venous oxygen saturation during normothermic cardiopulmonary bypass predicts short-term postoperative neurologic dysfunction in elderly patients. J Am Coll Cardiol. 2001;38:1450–1455
  13. Homi HM, Yang H, Pearlstein RD, Grocott HP. Hemodilution during cardiopulmonary bypass increases cerebral infarct volume after middle cerebral artery occlusion in rats. Anesth Analg. 2004;99:974–981
  14. Ortiz PA, Garvin JL. Cardiovascular and renal control in NOS-deficient mouse models. Am J Physiol Regul Integr Comp Physiol. 2003;284:R628–R638
  15. Hudetz AG, Wood JD, Kampine JP. 7-Nitroindazole impedes erythrocyte flow response to isovolemic hemodilution in the cerebral capillary circulation. J Cereb Blood Flow Metab. 2000;20:220–224
  16. Tsui SS, Kirshbom PM, Davies MJ, Jacobs MT, Greeley WJ, Kern FH, et al. Nitric oxide production affects cerebral perfusion and metabolism after deep hypothermic circulatory arrest. Ann Thorac Surg. 1996;61:1699–1707
  17. Plochl W, Liam BL, Cook DJ, Orszulak TA. Cerebral response to haemodilution during cardiopulmonary bypass in dogs: the role of nitric oxide synthase. Br J Anaesth. 1999;82:237–243
  18. Podgoreanu MV, Michelotti GA, Sato Y, Smith MP, Lin S, Morris RW, et al. Differential cardiac gene expression during cardiopulmonary bypass: ischemia-independent upregulation of proinflammatory genes. J Thorac Cardiovasc Surg. 2005;130:330–339
  19. Graham MR, Warrian RK, Girling LG, Doiron L, Lefevre GR, Cheang M, et al. Fractal or biologically variable delivery of cardioplegic solution prevents diastolic dysfunction after cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2002;123:63–71
  20. Boo YC, Hwang J, Sykes M, Michell BJ, Kemp BE, Lum H, et al. Shear stress stimulates phosphorylation of eNOS at Ser(635) by a protein kinase A–dependent mechanism. Am J Physiol Heart Circ Physiol. 2002;283:H1819–H1828
  21. Joshi S, Young WL, Duong DH, Ostapkovich ND, Aagaard BD, Hashimoto T, et al. Intracarotid infusion of the nitric oxide synthase inhibitor, l-NMMA, modestly decreases cerebral blood flow in human subjects. Anesthesiology. 2000;93:699–707
  22. Jones SC, Easley KA, Radinsky CR, Chyatte D, Furlan AJ, Perez-Trepichio AD. Nitric oxide synthase inhibition depresses the height of the cerebral blood flow-pressure autoregulation curve during moderate hypotension. J Cereb Blood Flow Metab. 2003;23:1085–1095
  23. Hayashi Y, Sawa Y, Fukuyama N, Nakazawa H, Matsuda H. Inducible nitric oxide production is an adaptation to cardiopulmonary bypass–induced inflammatory response. Ann Thorac Surg. 2001;72:149–155
  24. Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991;88:4651–4655
  25. Radomski MW, Palmer RM, Moncada S. An l-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci U S A. 1990;87:5193–5197
  26. Mayers I, Hurst T, Puttagunta L, Radomski A, Mycyk T, Sawicki G, et al. Cardiac surgery increases the activity of matrix metalloproteinases and nitric oxide synthase in human hearts. J Thorac Cardiovasc Surg. 2001;122:746–752
  27. Bloch W, Mehlhorn U, Krahwinkel A, Reiner M, Dittrich M, Schmidt A, et al. Ischemia increases detectable endothelial nitric oxide synthase in rat and human myocardium. Nitric Oxide. 2001;5:317–333
  28. Philip I, Plantefeve G, Vuillaumier-Barrot S, Vicaut E, LeMarie C, Henrion D, et al. G894T polymorphism in the endothelial nitric oxide synthase gene is associated with an enhanced vascular responsiveness to phenylephrine. Circulation. 1999;99:3096–3098
  29. Guo Y, Ward ME, Beasjours S, Mori M, Hussain SN. Regulation of cerebellar nitric oxide production in response to prolonged in vivo hypoxia. J Neurosci Res. 1997;49:89–97
  30. Kuo NT, Benhayon D, Przybylski RJ, Martin RJ, LaManna JC. Prolonged hypoxia increases vascular endothelial growth factor mRNA and protein in adult mouse brain. J Appl Physiol. 1999;86:260–264
  31. Hindman BJ, Moore SA, Cutkomp J, Smith T, Ross-Barta SE, Dexter F, et al. Brain expression of inducible cyclooxygenase 2 messenger RNA in rats undergoing cardiopulmonary bypass. Anesthesiology. 2001;95:1380–1388
  32. Teichert AM, Miller TL, Tai SC, Wang Y, Bei X, Robb GB, et al. In vivo expression profile of an endothelial nitric oxide synthase promoter-reporter transgene. Am J Physiol Heart Circ Physiol. 2000;278:H1352–H1361
  33. Abassi Z, Gurbanov K, Rubinstein I, Better OS, Hoffman A, Winaver J. Regulation of intrarenal blood flow in experimental heart failure: role of endothelin and nitric oxide. Am J Physiol. 1998;274:F766–F774

 This work is attributed to the Department of Anesthesia, St Michael’s Hospital, University of Toronto.Supported by St Michael’s Hospital, Anemia Institute for Research and Education, Physicians’ Services Incorporated Foundation, Canadian Anesthesiologists’ Society. Dr Hare is a recipient of the Bristol-Myers Squibb-Canadian Anesthesiologists’ Society Career Scientist Award.

PII: S0022-5223(06)01568-6

doi: 10.1016/j.jtcvs.2006.06.047

The Journal of Thoracic and Cardiovascular Surgery
Volume 133, Issue 1 , Pages 13-20.e1 , January 2007