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Biomarkers in cardiovascular surgery biomarkers as early predictors for organ damage after cardiac surgery

Year 2015, Volume: 5 Issue: 1, 65 - 74, 03.05.2015

Abstract

A biomarker is a measureable substance produced by the body and used to diagnose or determine the biologic state. Most biomarkers used in the clinical medicine are the genes, proteins or other chemical substances that are expressed in the pathology or organ damage, allowing for early and fast diagnosis and treatment. Ideally, biomarkers must be generally highly sensitive in order to make an early diagnosis; provide certain cut-off values to enable risk assessment, therapeutic guidance and have prognostic value. Cardiopulmonary bypass (CPB) is a model of extracorporeal circulation consisting primarily of a pump, a reservoir and an oxygenerator. At the initiation of CPB, blood is drained from the patient into the extracorporeal circuit which has non-endothelial surface. The inflammatory process occurs after cardiac surgery in varied degrees depending on the genotypes and peroperative parameters or complexity of the cardiac pathology. This process is mediated by cellular, noncellular or humoral components of the blood. Today, safe clinical biomarkers are detected by gene technology and proteomics techniques. Using these innovative technologies, the discovery, validation and clinical use of several biomarkers have revolutionized the diagnosis and management in the field of cardiovascular surgery as well as other major medical disciplines.

References

  • da Cruz EM, Ivy D. Jaggers J. Pediatric and Congenital Cardiology, Cardiac Surgery and Intensive Care. London 2014, Volume I.p. 857- 879
  • Yuh DD, Vricella LA, Yang S, Doty JR. Johns Hopkins Textbook of Cardiothoracic Surgery, 2nd Edition, 2014.p.973-983.
  • Edward MB, Timothy HP, Marion CJ. The systemic inflammatory response. Ann. Thorac. Surg. 1997; 64: 31-37.
  • Jacobs ML, O’Brien SM, Jacobs JP, Mavroudis C, Lacour-Gayet F, Pasquali SK, et al. An empirically based tool for analyzing morbidity associated with operations for congenital heart disease. J Thorac Cardiovasc Surg. 2013; 145(4): 1046-1057 e1.
  • Auerbach SR, Richmond ME, Lamour JM, Blume ED, Addonizio LJ, Shaddy RE, Mahony L, Pahl E, Hsu DT. Bnp levels predict outcome in pediatric heart failure patients: post hoc analysis of the pediatric carvedilol trial. Circ Heart Fail. 2010; 3: 606-611.
  • Bettencourt P, Azevedo A, Pimenta J, Frioes F, Ferreira S, Ferreira A. N-terminal-pro-brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients. Circulation. 2004; 110: 2168-2174.
  • Cohen S, Springer C, Avital A, Perles Z, Rein AJ, Argaman Z, Nir A. Amino-terminal pro-brain type natriuretic peptide: heart or lung disease in pediatric respiratory distress. Pediatrics. 2005; 115: 1347- 1350.
  • Trevisanuto D, Lachin M, Zaninotto M, Pellegrino PA, Plebani M, Cantarutti F, Zanardo V. Cardiac troponin t in newborn infants with transient myocardial ischemia. Biol Neonate. 1998; 73: 161-165.
  • Lauer B, Niederau C, Kuhl U, Schannwell M, Pauschinger M, Strauer BE, Schultheiss HP. Cardiac troponin t in patients with clinically suspected myocarditis. J Am Coll Cardiol. 1997; 30: 1354-1359.
  • Dengler TJ, Zimmermann R, Braun K, Muller-Bardoff M, Zehelein J, Sack FU, Schnabel PA, Kubler W, Katus HA. Elevated serum concentrations of cardiac troponin t in acute allograft rejection after human heart transplantation. J Am Coll Cardiol. 1998; 32: 405-412.
  • Kardys I, Knetsch AM, Bleumink GS, Deckers JW, Hofman A, Stricker BH, Witteman JC. C-reactive protein and risk of heart failure. The Rotterdam study. Am Heart J. 2006; 152: 514-520.
  • Neuhold S, Huelsmann M, Strunk G, Stoiser B, Struck J, Morgenthaler NG, Bergmann A, Moertl D, Berger R, Pacher R. Comparison of copeptin, b-type natriuretic peptide, and amimo-terminal pro-b-type natriuretic peptide in patients with chronic heart failure: prediction of death at different stages of the disease. J Am Coll Cardiol. 2008; 52: 266-272.
  • de Boer RA, Voors AA, Muntendam P, van Gilst WH, van Veldhuisen DJ. Galectin-3: a novel mediator of heart failure development and progression. Eur J Heart Fail. 2009; 11: 811-817.
  • Khan SQ, Ng K, Dhillon O, Kelly D, Quinn P, Squire IB, Davies je, NG LL. Growth-differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction. Eur Heart J. 2009; 30: 1057-1065.
  • King MK, Coker ML, Goldberg A, McElmurray JH 3rd, Gunasinghe HR, Mukherjee R, Zile MR, O’Neill TP, Spinale FG. Selective matrix metalloproteinase inhibition with developing heart failure: effects on left ventricular function and structure. Circ Res. 92: 177-185.
  • Majnemer A, Limperopoulos C, Shevell M, Rosenblatt B, Rohlicek C, Tchervenkov C. Long-term neuromotor outcome at school entry of infants with congenital heart defects requiring open heart surgery. J Pediatr. 2006; 148: 72-77.
  • Hoffman GM. Detection and prevention of neurologic injury in the intensive care unit. Cardiol Young. 2005; 15(Suppl 1): 149-153.
  • Mahle WT, Tavani F, Zimmerman RA, Nicolson SC, Galli KK, Gaynor JW, Clancy RR, Montenegro LM, Spray TL, Chiavacci RM, Wernovsky G, Kurth CD. An MRI study of neurological injury before and after congenital heart surgery. Circulation. 2002; 106: I109-I114.
  • Murkin JM, Adams SJ, Novick RJ, Quantz M, Bainbridge D, Iglesias I, et al. Monitoring brain oxygen saturation during coronary bypass surgery: a randomized, prospective study. Anesth Analg. 2007; 104(1): 51-58.
  • Rao V, İvanov J, Weisel RD, Cohen G, Borger MA, Mickle DA. Lactate release during reperfusion predicts low cardiac output syndrome after coronary bypass surgery. Ann Thorac Surg. 2001; 71(6): 1925-30.
  • Chakravarti SB, Mittnacht AJ, Katz JC, Nguyen K, Joashi U, Srivastava S. Multisite near-infrared spectroscopy predicts elevated blood lactate level in children after cardiac surgery. J Cardiothorac Vasc Anesth. 2009; 23(5): 663-7.
  • Ali MS, Harmer M, Vaughan R. Serum s100 protein as a marker of cerebral damage during cardiac surgery. Br J Anaesth. 2000; 85: 287- 298.
  • Davidson A, McKenzie I, Cochrane A. Delayed rises in serum s100b levels and adverse neurological outcome in infants and children undergoing cardiopulmonary bypass. Paediatr Anaesth. 2004;14:495- 500.
  • Gazzolo D, Masetti P, Meli M, Grutzfeld D, Michetti F. Elevated s100b protein as an early indicator of intracranial haemorrhage in infants subjected to extracorporeal membrane oxygenation. Acta Paediatr. 2002; 91: 218-221.
  • Bembea MM, Savage W, Strouse JJ, Schwartz JM, Graham E, Thompson CB, Everett A. Glial fibrillary acidic protein as abrain injury biomarker in children undergoing extracorporeal membrane oxygenation. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care SOC. 2011; 12: 572-579.
  • Brophy GM, Mondello S, Papa L, Robicsek SA, Gabrielli A, Tepas J 3rd, Buki A, Robertson C, Tortella FC, Hayes RL, Wang KK. Biokinetic analysis of ubiquitin c-terminal hydrolase-l1 (uch-l1) in severe traumatic brain injury patient biofluids. J Neurotrauma .2011; 28: 861-870.
  • Mondello S, Linnet A, Buki A, Robicsek S, Gabrielli A, Tepas J, Papa L, Brophy GM, Tortella F, Hayes RL, Wang KK. Clinical utility of serum levels of ubiquitin c-terminal hydrolase as a biomarker for severe traumatic brain injury. Neurosurgery. 2012; 70: 666-675.
  • Barrett CS, Bratton SL, Salvin JW, Laussen PC, Rycus PT, Thiagarajan RR. Neurological injury after extracorporeal membrane oxygenation use to aid pediatric cardiopulmonary ressuscitation. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2009; 10: 445-451.
  • Ricci Z, Di Nardo M, Iacoella C, Netto R, Picca S, Cogo P. Pediatric RIFLE for acute kidney injury diagnosis and prognosis for children undergoing cardiac surgery: a single-center prospective observational study. Pediatr Cardiol. 2013; 34(6): 1404-1408.
  • Seitz S, Rauh M, Gloeckler M, Cesnjevar R, Dittrich S, Koch AM. Cystatin C and neutrophil gelatinase-associated lipocalin: biomarkers for acute kidney injury after congenital heart surgery. Swiss Med Wkly. 2013;143:w13744.
  • Washburn KK, Zapitelli M, Arıkan AA, Loftis L, Yalavarthy R, Parikh CR, Edelstein CL, Goldstein SL. Urinary interleukin-18 is an acute kidney injury biomarker in critically ill children. Nephrol Dial Transplant. 2008; 23: 566-572.
  • Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, Syed H, Ali S, Barasch J, Devarajan P. Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol. 2008; 3: 665-673.
  • Parikh CR, Abraham E, Ancukiewicz M, Edelstein CL. Urine il-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. J Am Soc Nephrol. 2005; 16; 3046-3052.
  • Parikh CR, Jani A, Mishra J, Ma Q, Kelly C, Barasch J, Edelstein CL, Devarajan P. Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. Am J Transplant. 2006; 6: 1639-1645.
  • Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, Sanicola M. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem. 1998; 273: 4135- 4142.
  • Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney injury molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002; 62: 237-244.
  • Liangos O, Perianayagam MC, Vaidya VS, Han WK, Wald R, Tighiouart H, MacKinnon RW, Li L, Balakrishnan VS, Pereira BJ, Bonventre JV, Jaber BL. Urinary n-acetyl-beta-(d)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol. 2007; 18: 904-912.
  • Portilla D, Dent C, Sugaya T. Nagothu KK, Kundi I, Moore P, Noiri E, Devarajan P. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int. 2008; 73: 465-472.
  • Andropoulos DB, Brady KM, Easley RB, Fraser CD Jr. Neuroprotection in pediatric cardiac surgery: what is on the horizon? Prog Pediatr Cardiol. 2010; 29: 113-122.
  • Krawczeski CD, Goldstein SL, Woo JG, Wang Y, Piyaphanee N, Ma Q, Bennett M, Devarajan P. Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol. 2011; 58: 2301-2309.

Kalp cerrahisi sonrasında organ hasarının erken belirteçleri olarak biyo-belirteçler

Year 2015, Volume: 5 Issue: 1, 65 - 74, 03.05.2015

Abstract

“Biyo-belirteç” vücut tarafından üretilen, ölçülebilir ve biyolojik durumun teşhis ve ayrımını yansıtan kimyasal maddelerdir. Klinik tıpta kullanılan birçok “biyo-belirteç” gen, protein ve diğer kimyasal maddeler olup patoloji ve organ hasarını erken, hızlı tanı ve tedavi için yönlendirmektedir. Hiçbir biyo-belirteç ideal olmamakla birlikte genel özellikleri bakımından yüksek duyarlı olmalı, erken teşhis yaptırabilmeli, belli bir kesim noktasına göre ilgili olguda risk değerlendirmesi yapılabilmesini sağlamalı, ayrıca tedaviye yanıtı yönlendirebilmeli ve ilgili hasar veya hastalık durumu için prognostik olmalıdır. İlgili yanıt ya da karakteristiği istatistiksel olarak güçlü olmalıdır. Ek olarak biyobelirteçler patoloji için özgün olmalı, diğer nedenlerden ayırt ettirebilmeli, hastalığın şiddeti ve klinik sonuçlar ile paralel olmalıdır. Kardiyopulmoner bypas (KPB), bir ekstrakorporeal dolaşım modeli olup esas olarak bir pompa, rezervuar ve oksijeneratörden oluşur. KPB’ın başlangıcında kan hastadan bu endotelyal yüzey içermeyen ekstrakorporeal dolaşıma katılarak hastanın genotipi, peroperatif parametreler ve patolojinin kompleksitesine göre kalp cerrahisi sonrasında değişik derecelerde gelişen ve kanın hücresel, hücre dışı veya humoral bileşenleri tarafından yönetilen inflamatuvar süreci başlatır. Günümüzde güvenli klinik biyo-belirteçler gen teknolojileri ve proteomiks teknikleri ile tespit edilmektedir. Bu yenilikçi tekniklerin kullanımı ile birçok değişik biyobelirteçler keşfedilip klinik uygulamaya girmiş ve diğer majör tıp dallarında olduğu gibi kalp cerrahisi alanında da çığır açmıştır.

References

  • da Cruz EM, Ivy D. Jaggers J. Pediatric and Congenital Cardiology, Cardiac Surgery and Intensive Care. London 2014, Volume I.p. 857- 879
  • Yuh DD, Vricella LA, Yang S, Doty JR. Johns Hopkins Textbook of Cardiothoracic Surgery, 2nd Edition, 2014.p.973-983.
  • Edward MB, Timothy HP, Marion CJ. The systemic inflammatory response. Ann. Thorac. Surg. 1997; 64: 31-37.
  • Jacobs ML, O’Brien SM, Jacobs JP, Mavroudis C, Lacour-Gayet F, Pasquali SK, et al. An empirically based tool for analyzing morbidity associated with operations for congenital heart disease. J Thorac Cardiovasc Surg. 2013; 145(4): 1046-1057 e1.
  • Auerbach SR, Richmond ME, Lamour JM, Blume ED, Addonizio LJ, Shaddy RE, Mahony L, Pahl E, Hsu DT. Bnp levels predict outcome in pediatric heart failure patients: post hoc analysis of the pediatric carvedilol trial. Circ Heart Fail. 2010; 3: 606-611.
  • Bettencourt P, Azevedo A, Pimenta J, Frioes F, Ferreira S, Ferreira A. N-terminal-pro-brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients. Circulation. 2004; 110: 2168-2174.
  • Cohen S, Springer C, Avital A, Perles Z, Rein AJ, Argaman Z, Nir A. Amino-terminal pro-brain type natriuretic peptide: heart or lung disease in pediatric respiratory distress. Pediatrics. 2005; 115: 1347- 1350.
  • Trevisanuto D, Lachin M, Zaninotto M, Pellegrino PA, Plebani M, Cantarutti F, Zanardo V. Cardiac troponin t in newborn infants with transient myocardial ischemia. Biol Neonate. 1998; 73: 161-165.
  • Lauer B, Niederau C, Kuhl U, Schannwell M, Pauschinger M, Strauer BE, Schultheiss HP. Cardiac troponin t in patients with clinically suspected myocarditis. J Am Coll Cardiol. 1997; 30: 1354-1359.
  • Dengler TJ, Zimmermann R, Braun K, Muller-Bardoff M, Zehelein J, Sack FU, Schnabel PA, Kubler W, Katus HA. Elevated serum concentrations of cardiac troponin t in acute allograft rejection after human heart transplantation. J Am Coll Cardiol. 1998; 32: 405-412.
  • Kardys I, Knetsch AM, Bleumink GS, Deckers JW, Hofman A, Stricker BH, Witteman JC. C-reactive protein and risk of heart failure. The Rotterdam study. Am Heart J. 2006; 152: 514-520.
  • Neuhold S, Huelsmann M, Strunk G, Stoiser B, Struck J, Morgenthaler NG, Bergmann A, Moertl D, Berger R, Pacher R. Comparison of copeptin, b-type natriuretic peptide, and amimo-terminal pro-b-type natriuretic peptide in patients with chronic heart failure: prediction of death at different stages of the disease. J Am Coll Cardiol. 2008; 52: 266-272.
  • de Boer RA, Voors AA, Muntendam P, van Gilst WH, van Veldhuisen DJ. Galectin-3: a novel mediator of heart failure development and progression. Eur J Heart Fail. 2009; 11: 811-817.
  • Khan SQ, Ng K, Dhillon O, Kelly D, Quinn P, Squire IB, Davies je, NG LL. Growth-differentiation factor-15 as a prognostic marker in patients with acute myocardial infarction. Eur Heart J. 2009; 30: 1057-1065.
  • King MK, Coker ML, Goldberg A, McElmurray JH 3rd, Gunasinghe HR, Mukherjee R, Zile MR, O’Neill TP, Spinale FG. Selective matrix metalloproteinase inhibition with developing heart failure: effects on left ventricular function and structure. Circ Res. 92: 177-185.
  • Majnemer A, Limperopoulos C, Shevell M, Rosenblatt B, Rohlicek C, Tchervenkov C. Long-term neuromotor outcome at school entry of infants with congenital heart defects requiring open heart surgery. J Pediatr. 2006; 148: 72-77.
  • Hoffman GM. Detection and prevention of neurologic injury in the intensive care unit. Cardiol Young. 2005; 15(Suppl 1): 149-153.
  • Mahle WT, Tavani F, Zimmerman RA, Nicolson SC, Galli KK, Gaynor JW, Clancy RR, Montenegro LM, Spray TL, Chiavacci RM, Wernovsky G, Kurth CD. An MRI study of neurological injury before and after congenital heart surgery. Circulation. 2002; 106: I109-I114.
  • Murkin JM, Adams SJ, Novick RJ, Quantz M, Bainbridge D, Iglesias I, et al. Monitoring brain oxygen saturation during coronary bypass surgery: a randomized, prospective study. Anesth Analg. 2007; 104(1): 51-58.
  • Rao V, İvanov J, Weisel RD, Cohen G, Borger MA, Mickle DA. Lactate release during reperfusion predicts low cardiac output syndrome after coronary bypass surgery. Ann Thorac Surg. 2001; 71(6): 1925-30.
  • Chakravarti SB, Mittnacht AJ, Katz JC, Nguyen K, Joashi U, Srivastava S. Multisite near-infrared spectroscopy predicts elevated blood lactate level in children after cardiac surgery. J Cardiothorac Vasc Anesth. 2009; 23(5): 663-7.
  • Ali MS, Harmer M, Vaughan R. Serum s100 protein as a marker of cerebral damage during cardiac surgery. Br J Anaesth. 2000; 85: 287- 298.
  • Davidson A, McKenzie I, Cochrane A. Delayed rises in serum s100b levels and adverse neurological outcome in infants and children undergoing cardiopulmonary bypass. Paediatr Anaesth. 2004;14:495- 500.
  • Gazzolo D, Masetti P, Meli M, Grutzfeld D, Michetti F. Elevated s100b protein as an early indicator of intracranial haemorrhage in infants subjected to extracorporeal membrane oxygenation. Acta Paediatr. 2002; 91: 218-221.
  • Bembea MM, Savage W, Strouse JJ, Schwartz JM, Graham E, Thompson CB, Everett A. Glial fibrillary acidic protein as abrain injury biomarker in children undergoing extracorporeal membrane oxygenation. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care SOC. 2011; 12: 572-579.
  • Brophy GM, Mondello S, Papa L, Robicsek SA, Gabrielli A, Tepas J 3rd, Buki A, Robertson C, Tortella FC, Hayes RL, Wang KK. Biokinetic analysis of ubiquitin c-terminal hydrolase-l1 (uch-l1) in severe traumatic brain injury patient biofluids. J Neurotrauma .2011; 28: 861-870.
  • Mondello S, Linnet A, Buki A, Robicsek S, Gabrielli A, Tepas J, Papa L, Brophy GM, Tortella F, Hayes RL, Wang KK. Clinical utility of serum levels of ubiquitin c-terminal hydrolase as a biomarker for severe traumatic brain injury. Neurosurgery. 2012; 70: 666-675.
  • Barrett CS, Bratton SL, Salvin JW, Laussen PC, Rycus PT, Thiagarajan RR. Neurological injury after extracorporeal membrane oxygenation use to aid pediatric cardiopulmonary ressuscitation. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2009; 10: 445-451.
  • Ricci Z, Di Nardo M, Iacoella C, Netto R, Picca S, Cogo P. Pediatric RIFLE for acute kidney injury diagnosis and prognosis for children undergoing cardiac surgery: a single-center prospective observational study. Pediatr Cardiol. 2013; 34(6): 1404-1408.
  • Seitz S, Rauh M, Gloeckler M, Cesnjevar R, Dittrich S, Koch AM. Cystatin C and neutrophil gelatinase-associated lipocalin: biomarkers for acute kidney injury after congenital heart surgery. Swiss Med Wkly. 2013;143:w13744.
  • Washburn KK, Zapitelli M, Arıkan AA, Loftis L, Yalavarthy R, Parikh CR, Edelstein CL, Goldstein SL. Urinary interleukin-18 is an acute kidney injury biomarker in critically ill children. Nephrol Dial Transplant. 2008; 23: 566-572.
  • Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, Syed H, Ali S, Barasch J, Devarajan P. Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol. 2008; 3: 665-673.
  • Parikh CR, Abraham E, Ancukiewicz M, Edelstein CL. Urine il-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. J Am Soc Nephrol. 2005; 16; 3046-3052.
  • Parikh CR, Jani A, Mishra J, Ma Q, Kelly C, Barasch J, Edelstein CL, Devarajan P. Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. Am J Transplant. 2006; 6: 1639-1645.
  • Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, Sanicola M. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem. 1998; 273: 4135- 4142.
  • Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney injury molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002; 62: 237-244.
  • Liangos O, Perianayagam MC, Vaidya VS, Han WK, Wald R, Tighiouart H, MacKinnon RW, Li L, Balakrishnan VS, Pereira BJ, Bonventre JV, Jaber BL. Urinary n-acetyl-beta-(d)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol. 2007; 18: 904-912.
  • Portilla D, Dent C, Sugaya T. Nagothu KK, Kundi I, Moore P, Noiri E, Devarajan P. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int. 2008; 73: 465-472.
  • Andropoulos DB, Brady KM, Easley RB, Fraser CD Jr. Neuroprotection in pediatric cardiac surgery: what is on the horizon? Prog Pediatr Cardiol. 2010; 29: 113-122.
  • Krawczeski CD, Goldstein SL, Woo JG, Wang Y, Piyaphanee N, Ma Q, Bennett M, Devarajan P. Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol. 2011; 58: 2301-2309.
There are 40 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Tijen Alkan Bozkaya This is me

Publication Date May 3, 2015
Submission Date May 3, 2015
Published in Issue Year 2015 Volume: 5 Issue: 1

Cite

APA Alkan Bozkaya, T. (2015). Kalp cerrahisi sonrasında organ hasarının erken belirteçleri olarak biyo-belirteçler. Clinical and Experimental Health Sciences, 5(1), 65-74. https://doi.org/10.5455/musbed.20141223012352
AMA Alkan Bozkaya T. Kalp cerrahisi sonrasında organ hasarının erken belirteçleri olarak biyo-belirteçler. Clinical and Experimental Health Sciences. October 2015;5(1):65-74. doi:10.5455/musbed.20141223012352
Chicago Alkan Bozkaya, Tijen. “Kalp Cerrahisi sonrasında Organ hasarının Erken belirteçleri Olarak Biyo-belirteçler”. Clinical and Experimental Health Sciences 5, no. 1 (October 2015): 65-74. https://doi.org/10.5455/musbed.20141223012352.
EndNote Alkan Bozkaya T (October 1, 2015) Kalp cerrahisi sonrasında organ hasarının erken belirteçleri olarak biyo-belirteçler. Clinical and Experimental Health Sciences 5 1 65–74.
IEEE T. Alkan Bozkaya, “Kalp cerrahisi sonrasında organ hasarının erken belirteçleri olarak biyo-belirteçler”, Clinical and Experimental Health Sciences, vol. 5, no. 1, pp. 65–74, 2015, doi: 10.5455/musbed.20141223012352.
ISNAD Alkan Bozkaya, Tijen. “Kalp Cerrahisi sonrasında Organ hasarının Erken belirteçleri Olarak Biyo-belirteçler”. Clinical and Experimental Health Sciences 5/1 (October 2015), 65-74. https://doi.org/10.5455/musbed.20141223012352.
JAMA Alkan Bozkaya T. Kalp cerrahisi sonrasında organ hasarının erken belirteçleri olarak biyo-belirteçler. Clinical and Experimental Health Sciences. 2015;5:65–74.
MLA Alkan Bozkaya, Tijen. “Kalp Cerrahisi sonrasında Organ hasarının Erken belirteçleri Olarak Biyo-belirteçler”. Clinical and Experimental Health Sciences, vol. 5, no. 1, 2015, pp. 65-74, doi:10.5455/musbed.20141223012352.
Vancouver Alkan Bozkaya T. Kalp cerrahisi sonrasında organ hasarının erken belirteçleri olarak biyo-belirteçler. Clinical and Experimental Health Sciences. 2015;5(1):65-74.

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