Neuroprotective Strategies during Cardiac Surgery with Cardiopulmonary Bypass

Aortocoronary bypass or valve surgery usually require cardiac arrest using cardioplegic solutions. Although, in principle, in a number of cases beating heart surgery (so-called off-pump technique) is possible, aortic or valve surgery or correction of congenital heart diseases mostly require cardiopulmonary arrest. During this condition, the heart-lung machine also named cardiopulmonary bypass (CPB) has to take over the circulation. It is noteworthy that the invention of a machine bypassing the heart and lungs enabled complex cardiac operations, but possible negative effects of the CPB on other organs, especially the brain, cannot be neglected. Thus, neuroprotection during CPB is still a matter of great interest. In this review, we will describe the impact of CPB on the brain and focus on pharmacological and non-pharmacological strategies to protect the brain.

[1]  Sherif Hafez,et al.  Response to Letter Regarding Article, "Matrix Metalloprotease 3 Exacerbates Hemorrhagic Transformation and Worsens Functional Outcomes in Hyperglycemic Stroke". , 2016, Stroke.

[2]  F. Mohr,et al.  Epigallocatechin gallate attenuates cardiopulmonary bypass-associated lung injury. , 2016, The Journal of surgical research.

[3]  S. Hyon,et al.  Green Tea Polyphenol Prevents Diabetic Rats From Acute Kidney Injury After Cardiopulmonary Bypass. , 2016, The Annals of thoracic surgery.

[4]  Hao Wang,et al.  Poly(ADP-ribose) polymerase 1 inhibition protects cardiomyocytes from inflammation and apoptosis in diabetic cardiomyopathy , 2016, Oncotarget.

[5]  F. Sharp,et al.  Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke , 2016, Front. Cell. Neurosci..

[6]  Sherif Hafez,et al.  Matrix Metalloprotease 3 Exacerbates Hemorrhagic Transformation and Worsens Functional Outcomes in Hyperglycemic Stroke , 2016, Stroke.

[7]  G. Faggian,et al.  Hemoglobin Concentration Affects Electroencephalogram During Cardiopulmonary Bypass: An Indication for Neuro-Protective Values. , 2016, Artificial organs.

[8]  Z. Qin,et al.  Lack of Efficacy of Ulinastatin Therapy During Cardiopulmonary Bypass Surgery , 2015, Chinese medical journal.

[9]  J. Klopfenstein,et al.  Matrix Metalloproteinase-12 Induces Blood–Brain Barrier Damage After Focal Cerebral Ischemia , 2015, Stroke.

[10]  S. Dhein,et al.  Hippocampal Neuroprotection by Minocycline and Epigallo‐Catechin‐3‐Gallate Against Cardiopulmonary Bypass‐Associated Injury , 2015, Brain pathology.

[11]  T. Ottens,et al.  Low incidence of early postoperative cerebral edema after coronary artery bypass grafting. , 2015, Journal of cardiothoracic and vascular anesthesia.

[12]  J. Torres,et al.  Neuroprotection After Major Cardiovascular Surgery , 2015, Current Treatment Options in Neurology.

[13]  S. Gill,et al.  The role of TIMPs in regulation of extracellular matrix proteolysis. , 2015, Matrix biology : journal of the International Society for Matrix Biology.

[14]  A. Jovanovic,et al.  Mild hypoxia in vivo regulates cardioprotective SUR2A: A role for Akt and LDH , 2015, Biochimica et biophysica acta.

[15]  A. Brassai,et al.  Role of synaptic and nonsynaptic glutamate receptors in ischaemia induced neurotoxicity , 2015, Brain Research Bulletin.

[16]  F. Liu,et al.  The neuroprotective effects of β-hydroxybutyrate on Aβ-injected rat hippocampus in vivo and in Aβ-treated PC-12 cells in vitro , 2015, Free radical research.

[17]  A. Blann,et al.  Effects of propofol and isoflurane on haemodynamics and the inflammatory response in cardiopulmonary bypass surgery , 2015, British journal of biomedical science.

[18]  A. Jovanovic,et al.  Upregulation of cardioprotective SUR2A by sub-hypoxic drop in oxygen , 2014, Biochimica et biophysica acta.

[19]  T. Dawson,et al.  Poly(ADP-ribose) polymerase-dependent energy depletion occurs through inhibition of glycolysis , 2014, Proceedings of the National Academy of Sciences.

[20]  B. Rybojad,et al.  Disturbance in venous outflow from the cerebral circulation intensifies the release of blood-brain barrier injury biomarkers in patients undergoing cardiac surgery. , 2014, Journal of cardiothoracic and vascular anesthesia.

[21]  P. Kochanek,et al.  Minocycline attenuates brain tissue levels of TNF-α produced by neurons after prolonged hypothermic cardiac arrest in rats. , 2014, Resuscitation.

[22]  V. Borutaite,et al.  In the eye of the storm: mitochondrial damage during heart and brain ischaemia , 2013, The FEBS journal.

[23]  M. Aldemir,et al.  Comparison of the Effects of Desflurane and Propofol Anesthesia on the Inflammatory Response and S100β Protein During Coronary Artery Bypass Grafting , 2013, Inflammation.

[24]  E. Şener,et al.  Comparing S-100 beta protein levels and neurocognitive functions between patients undergoing on-pump and off-pump coronary artery bypass grafting. , 2013, The Journal of surgical research.

[25]  Yun Lin Ang,et al.  Cognitive outcome after on- and off-pump coronary artery bypass grafting surgery: a systematic review and meta-analysis. , 2013, Journal of cardiothoracic and vascular anesthesia.

[26]  J. Coselli,et al.  A meta-analysis of deep hypothermic circulatory arrest versus moderate hypothermic circulatory arrest with selective antegrade cerebral perfusion. , 2013, Annals of cardiothoracic surgery.

[27]  Tie-zheng Zhang,et al.  Penehyclidine hydrochloride attenuates the cerebral injury in a rat model of cardiopulmonary bypass. , 2013, Canadian journal of physiology and pharmacology.

[28]  Shengshou Hu,et al.  Ulinastatin as a neuroprotective and anti‐inflammatory agent in infant piglets model undergoing surgery on hypothermic low‐flow cardiopulmonary bypass , 2013, Paediatric anaesthesia.

[29]  S. Yao,et al.  The efficacy of parecoxib on systemic inflammatory response associated with cardiopulmonary bypass during cardiac surgery. , 2013, British journal of clinical pharmacology.

[30]  Randall B. Griepp,et al.  Hypothermia for aortic surgery. , 2013, The Journal of thoracic and cardiovascular surgery.

[31]  F. Mohr,et al.  Cerebral Protection during Controlled Hypoperfusion in a Piglet Model: Comparison of Moderate (25°C) versus Deep (18°C) Hypothermia at Various Flow Rates Using Intraoperative Measurements and Ex vivo Investigation , 2012, Thoracic and Cardiovascular Surgeon.

[32]  J. Tijssen,et al.  Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial. , 2012, JAMA.

[33]  M. Pugliese,et al.  ATP-dependent potassium channel blockade strengthens microglial neuroprotection after hypoxia–ischemia in rats , 2012, Experimental Neurology.

[34]  C. Glasier,et al.  Ketamine as a neuroprotective and anti-inflammatory agent in children undergoing surgery on cardiopulmonary bypass: A pilot randomized, double-blind, placebo-controlled trial , 2012, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[35]  Y. Zorlutuna,et al.  Clinical evaluation of leukocyte filtration as an alternative anti-inflammatory strategy to aprotinin in high-risk patients undergoing coronary revascularization , 2012, Surgery Today.

[36]  Z. Dai,et al.  Up-regulation of hypoxia inducible factor-1α by cobalt chloride correlates with proliferation and apoptosis in PC-2 cells , 2012, Journal of Experimental & Clinical Cancer Research.

[37]  Neetu Singh,et al.  Hypoxia Inducible Factor-1: Its Potential Role In Cerebral Ischemia , 2012, Cellular and Molecular Neurobiology.

[38]  S. Gandhi,et al.  Nitric oxide delivery during cardiopulmonary bypass reduces postoperative morbidity in children--a randomized trial. , 2013, The Journal of thoracic and cardiovascular surgery.

[39]  B. Lima,et al.  Results of Proximal Arch Replacement Using Deep Hypothermia for Circulatory Arrest: Is Moderate Hypothermia Really Justifiable? , 2011, The American surgeon.

[40]  D. Low,et al.  Neurological Complications of Thoracic Endovascular Aortic Repair , 2011, Seminars in cardiothoracic and vascular anesthesia.

[41]  Cheuk-Kwan Sun,et al.  Combination of cyclosporine and erythropoietin improves brain infarct size and neurological function in rats after ischemic stroke , 2011, Journal of Translational Medicine.

[42]  Attila Tárnok,et al.  Modulation of the cellular and humoral immune response to pediatric open heart surgery by methylprednisolone , 2011, Cytometry. Part B, Clinical cytometry.

[43]  E. Pérez-Payá,et al.  Tyrosine phosphorylation turns alkaline transition into a biologically relevant process and makes human cytochrome c behave as an anti-apoptotic switch , 2011, JBIC Journal of Biological Inorganic Chemistry.

[44]  M. Munir,et al.  Clinical effectiveness of centrifugal pump to produce pulsatile flow during cardiopulmonary bypass in patients undergoing cardiac surgery. , 2011, Artificial organs.

[45]  G. Rakhorst,et al.  Reply to the Editor: Clinical Effectiveness of Centrifugal Pump to Produce Pulsatile Flow During Cardiopulmonary Bypass in Patients Undergoing Cardiac Surgery , 2011 .

[46]  H. Vélez,et al.  Lowest safe hematocrit level on cardiopulmonary bypass in patients undergoing coronary artery bypass grafting. , 2011, Boletin de la Asociacion Medica de Puerto Rico.

[47]  C. Long,et al.  Effects of pulsatile and nonpulsatile perfusion on cerebral regional oxygen saturation and endothelin-1 in tetralogy of fallot infants. , 2011, Artificial organs.

[48]  H. Sievers,et al.  Leukocyte depletion during cardiopulmonary bypass in routine adult cardiac surgery. , 2011, Interactive cardiovascular and thoracic surgery.

[49]  G. Vingerhoets,et al.  The effect of CABG on neurocognitive functioning , 2010, Acta cardiologica.

[50]  M. Bunc,et al.  Importance of erythropoietin in brain protection after cardiac surgery: a pilot study. , 2010, The heart surgery forum.

[51]  J. Gagné,et al.  Investigation of PARP-1, PARP-2, and PARG interactomes by affinity-purification mass spectrometry , 2010, Proteome Science.

[52]  H. Reichmann,et al.  Recombinant Human Erythropoietin in the Treatment of Acute Ischemic Stroke , 2009, Stroke.

[53]  M. Elahi,et al.  Inspired nitric oxide and modulation of oxidative stress during cardiac surgery. , 2009, Current drug safety.

[54]  A. Jekabsone,et al.  Nitric oxide protects the heart from ischemia-induced apoptosis and mitochondrial damage via protein kinase G mediated blockage of permeability transition and cytochrome c release , 2009, Journal of Biomedical Science.

[55]  E. Tireli,et al.  Influence of Methylprednisolone on Levels of Neuron‐Specific Enolase in Cardiac Surgery: A Corticosteroid Derivative to Decrease Possible Neuronal Damage , 2009, Journal of cardiac surgery.

[56]  L. Rasmussen,et al.  Cognitive outcomes in elderly high-risk patients 1 year after off-pump versus on-pump coronary artery bypass grafting. A randomized trial. , 2008, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[57]  K. Akinosoglou,et al.  The methodologies of hypothermic circulatory arrest and of antegrade and retrograde cerebral perfusion for aortic arch surgery. , 2008, Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia.

[58]  Somsuvra B. Ghatak,et al.  Pexelizumab and its role in the treatment of myocardial infarction and in coronary artery bypass graft surgery: a review. , 2008, Recent patents on cardiovascular drug discovery.

[59]  Joel D. Graham,et al.  Reducing the Effects of the Systemic Inflammatory Response to Cardiopulmonary Bypass: Can Single Dose Steroids Blunt Systemic Inflammatory Response Syndrome? , 2008, ASAIO journal.

[60]  D. Sulemanji,et al.  Dexmedetomidine during coronary artery bypass grafting surgery: is it neuroprotective? – A preliminary study , 2007, Acta anaesthesiologica Scandinavica.

[61]  D. Heal,et al.  KTX 0101: a potential metabolic approach to cytoprotection in major surgery and neurological disorders. , 2006, CNS drug reviews.

[62]  M. Bernaudin,et al.  Expression of the gene encoding the pro-apoptotic BNIP3 protein and stimulation of hypoxia-inducible factor-1α (HIF-1α) protein following focal cerebral ischemia in rats , 2006, Neurochemistry International.

[63]  J. Simard,et al.  Newly expressed SUR1-regulated NCCa-ATP channel mediates cerebral edema after ischemic stroke , 2006, Nature Medicine.

[64]  M. Borger,et al.  Reducing Cerebral Emboli During Cardiopulmonary Bypass , 2005, Seminars in cardiothoracic and vascular anesthesia.

[65]  B. Zhong,et al.  Synthesis of the optical isomers of a new anticholinergic drug, penehyclidine hydrochloride (8018). , 2005, Bioorganic & medicinal chemistry letters.

[66]  G. Semenza,et al.  Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1. , 2005, Blood.

[67]  D. Bainbridge,et al.  Does Off-pump Coronary Artery Bypass Reduce Mortality, Morbidity, and Resource Utilization When Compared with Conventional Coronary Artery Bypass? A Meta-analysis of Randomized Trials , 2005, Anesthesiology.

[68]  G. Murphy,et al.  Side Effects of Cardiopulmonary Bypass: , 2004, Journal of cardiac surgery.

[69]  J. Copeland,et al.  The effect of methylprednisolone treatment on the cardiopulmonary bypass-induced systemic inflammatory response. , 2004, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[70]  J. Maessen,et al.  Neurological complications after coronary artery bypass grafting related to the performance of cardiopulmonary bypass. , 2004, Chest.

[71]  N. Gormus,et al.  The cerebroprotective effects of pentoxifylline and aprotinin during cardiopulmonary bypass in dogs , 2004, Perfusion.

[72]  Volkmar Falk,et al.  Stroke after cardiac surgery: a risk factor analysis of 16,184 consecutive adult patients. , 2003, The Annals of thoracic surgery.

[73]  S Karthikeyan,et al.  Assessment of neurocognitive impairment after off-pump and on-pump techniques for coronary artery bypass graft surgery: prospective randomised controlled trial , 2002, BMJ : British Medical Journal.

[74]  G. Vingerhoets,et al.  Short-term and long-term neurocognitive outcome in on-pump versus off-pump CABG. , 2002, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[75]  A. Ündar,et al.  Do S100β protein level increases due to inflammation during cardiopulmonary bypass occur without any neurological deficit? , 2002, Perfusion.

[76]  Karel G M Moons,et al.  Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial. , 2002, JAMA.

[77]  Takashi Sato,et al.  β-hydroxybutyrate, a cerebral function improving agent, protects rat brain against ischemic damage caused by permanent and transient focal cerebral ischemia , 2002 .

[78]  P. Rosseel,et al.  Dexamethasone decreases the pro- to anti-inflammatory cytokine ratio during cardiac surgery. , 2002, British journal of anaesthesia.

[79]  M. Beach,et al.  Glucocorticoid effects on the inflammatory and clinical responses to cardiac surgery. , 2002, Journal of cardiothoracic and vascular anesthesia.

[80]  W. Baumgartner,et al.  Pharmacologically induced preconditioning with diazoxide: a novel approach to brain protection. , 2001, The Annals of thoracic surgery.

[81]  G. Semenza,et al.  Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. , 2001, Trends in molecular medicine.

[82]  S. Vogt,et al.  Serum S-100beta protein release in coronary artery bypass grafting: laminar versus pulsatile flow. , 2001, The Thoracic and cardiovascular surgeon.

[83]  V. Jäntti,et al.  The N-methyl-D-aspartate antagonist memantine has no neuroprotective effect during hypothermic circulatory arrest: a study in the chronic porcine model. , 2001, The Journal of thoracic and cardiovascular surgery.

[84]  C. Elger,et al.  Potassium channel openers depolarize hippocampal mitochondria , 2001, Brain Research.

[85]  Mark F. Newman,et al.  Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. , 2001, The New England journal of medicine.

[86]  M. Kelm,et al.  Endogenous nitric oxide and myocardial adaptation to ischemia. , 2000, Circulation research.

[87]  A. Rajek,et al.  Pulsatility does not change cerebral oxygenation during cardiopulmonary bypass , 2000, Acta anaesthesiologica Scandinavica.

[88]  Guido Kroemer,et al.  Mitochondrio‐nuclear translocation of AIF in apoptosis and necrosis , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[89]  P. Illés,et al.  Neuroprotection by ATP-dependent potassium channels in rat neocortical brain slices during hypoxia , 1999, Neuroscience Letters.

[90]  M. Jäättelä,et al.  Hsp70 exerts its anti‐apoptotic function downstream of caspase‐3‐like proteases , 1998, The EMBO journal.

[91]  P. Carmeliet,et al.  Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis , 1998, Nature.

[92]  S. Snyder,et al.  Journal Club: Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia , 1998 .

[93]  S. Snyder,et al.  Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia , 1997, Nature Medicine.

[94]  R. Weichselbaum,et al.  Role for Bcl-xL as an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[95]  T. Orszulak,et al.  Effect of pump flow rate on cerebral blood flow during hypothermic cardiopulmonary bypass in adults. , 1997, Journal of cardiothoracic and vascular anesthesia.

[96]  B. Ebert,et al.  Hypoxia and Mitochondrial Inhibitors Regulate Expression of Glucose Transporter-1 via Distinct Cis-acting Sequences (*) , 1995, The Journal of Biological Chemistry.

[97]  S. Kourembanas,et al.  Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5' enhancer. , 1995, Circulation research.

[98]  C. Cooper,et al.  Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase , 1994, FEBS letters.

[99]  C. Bodian,et al.  Hypothermic circulatory arrest in operations on the thoracic aorta. Determinants of operative mortality and neurologic outcome. , 1994, The Journal of thoracic and cardiovascular surgery.

[100]  G. Bydder,et al.  Brain swelling in first hour after coronary artery bypass surgery , 1993, The Lancet.

[101]  K. Suzuki,et al.  Substrate specificities and activation mechanisms of matrix metalloproteinases. , 1991, Biochemical Society transactions.

[102]  L. Ignarro,et al.  Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[103]  R. Furchgott,et al.  The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine , 1980, Nature.

[104]  G F Cahill,et al.  Brain metabolism during fasting. , 1967, The Journal of clinical investigation.

[105]  J. H. Gibbon,et al.  Application of a mechanical heart and lung apparatus to cardiac surgery. , 1954, Minnesota medicine.

[106]  Bigelow Wg Application of hypothermia to cardiac surgery. , 1954 .

[107]  M. DeBakey,et al.  SURGICAL CONSIDERATIONS OF INTRATHORACIC ANEURYSMS OF THE AORTA AND GREAT VESSELS , 1952, Annals of surgery.

[108]  W. Bayliss On the local reactions of the arterial wall to changes of internal pressure , 1902, The Journal of physiology.

[109]  C. Elsberg AN EXPERIMENTAL INVESTIGATION OF THE TREATMENT OF WOUNDS OF THE HEART BY MEANS OF SUTURE OF THE HEART MUSCLE , 1899, The Journal of experimental medicine.

[110]  Seong‐Ryong Lee,et al.  Protective effect of resveratrol against neuronal damage following transient global cerebral ischemia in mice. , 2016, The Journal of nutritional biochemistry.

[111]  F. Mohr,et al.  Protective effects of pulsatile flow during cardiopulmonary bypass. , 2015, The Annals of thoracic surgery.

[112]  F. Mohr,et al.  Reno-protective effects of epigallocatechingallate in a small piglet model of extracorporeal circulation. , 2013, Pharmacological research.

[113]  K M Taylor,et al.  The systemic inflammatory response syndrome and cardiopulmonary bypass. , 2005, International journal of surgery.

[114]  R. Baker,et al.  The Octopus II stabilizing system: biochemical and neuropsychological outcomes in coronary artery bypass surgery. , 2001, The heart surgery forum.

[115]  W. van Oeveren,et al.  The role of different types of corticosteroids on the inflammatory mediators in cardiopulmonary bypass. , 1991, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[116]  Henny H. Billett,et al.  hemoglobin and hematocrit , 2022 .

[117]  W. G. Bigelow Application of hypothermia to cardiac surgery. , 1954, Minnesota medicine.