Dexmedetomidine Increases MMP-12 and MBP Concentrations after Coronary Artery Bypass Graft Surgery with Extracorporeal Circulation Anaesthesia without Impacting Cognitive Function: A Randomised Control Trial

Postoperative neurological deficits remain a concern for patients undergoing cardiac surgeries. Even minor injuries can lead to neurocognitive decline (i.e., postoperative cognitive dysfunction). Dexmedetomidine may be beneficial given its reported neuroprotective effect. We aimed to investigate the effects of dexmedetomidine on brain injury during cardiac surgery anaesthesia. This prospective observational study analysed data for 46 patients who underwent coronary artery bypass graft surgery with extracorporeal circulation between August 2018 and March 2019. The patients were divided into two groups: control (CON) with typical anaesthesia and dexmedetomidine (DEX) with dexmedetomidine infusion. Concentrations of the biomarkers matrix metalloproteinase-12 (MMP-12) and myelin basic protein (MBP) were measured preoperatively and at 24 and 72 h postoperatively. Cognitive evaluations were performed preoperatively, at discharge, and 3 months after discharge using Addenbrooke’s Cognitive Examination version III (ACE-III). The primary endpoint was the ACE-III score at discharge. Increased MMP-12 and MBP concentrations were observed in the DEX group 24 and 72 h postoperatively. No significant differences in ACE-III scores were observed between the groups at discharge; however, the values were increased when compared with initial values after 3 months (p = 0.000). The current results indicate that the administration of dexmedetomidine as an adjuvant to anaesthesia can increase MMP-12 and MBP levels without effects on neurocognitive outcomes at discharge and 3 months postoperatively.

[1]  C. Fornal,et al.  Therapeutic efficacy of matrix metalloproteinase-12 suppression on neurological recovery after ischemic stroke: Optimal treatment timing and duration , 2022, Frontiers in Neuroscience.

[2]  S. Tobis,et al.  Applying ACE-III, M-ACE and MMSE to Diagnostic Screening Assessment of Cognitive Functions within the Polish Population , 2022, International journal of environmental research and public health.

[3]  M. Munari,et al.  Effect of dexmedetomidine on hemodynamic responses to tracheal intubation: A meta-analysis with meta-regression and trial sequential analysis. , 2021, Journal of clinical anesthesia.

[4]  C. S. Govêia,et al.  Dexmedetomidine reduces postoperative cognitive and behavioral dysfunction in adults submitted to general anesthesia for non-cardiac surgery: meta-analysis of randomized clinical trials , 2021, Brazilian journal of anesthesiology.

[5]  E. Krutenkova,et al.  Neurodegeneration, Myelin Loss and Glial Response in the Three-Vessel Global Ischemia Model in Rat , 2020, International journal of molecular sciences.

[6]  W. Mi,et al.  Dexmedetomidine improves early postoperative neurocognitive disorder in elderly male patients undergoing thoracoscopic lobectomy , 2020, Experimental and therapeutic medicine.

[7]  V. Seifert,et al.  Dexmedetomidine as adjunct in awake craniotomy – improvement or not? , 2020, Anaesthesiology intensive therapy.

[8]  J. Dudka,et al.  MMP-9 and MMP-2 regulation in patients undergoing non-oncological and non-vascular elective surgery independent of the use of propofol or sevoflurane , 2019, Pharmacological reports : PR.

[9]  Li Ma,et al.  Effects of dexmedetomidine on postoperative cognitive function in patients undergoing coronary artery bypass grafting , 2018, Experimental and Therapeutic Medicine.

[10]  J. Hodges,et al.  Addenbrooke’s Cognitive Examination III: Psychometric Characteristics and Relations to Functional Ability in Dementia , 2018, Journal of the International Neuropsychological Society.

[11]  K. Boini,et al.  Post-stroke mRNA expression profile of MMPs: effect of genetic deletion of MMP-12 , 2018, Stroke and Vascular Neurology.

[12]  J. Klopfenstein,et al.  MMP-12, a Promising Therapeutic Target for Neurological Diseases , 2017, Molecular Neurobiology.

[13]  S. Mohajerani,et al.  Impact of Dexmedetomidine on Hemodynamic Changes during and after Coronary Artery Bypass Grafting , 2017, Annals of cardiac anaesthesia.

[14]  Zhongmin Li,et al.  The Effect of Dexmedetomidine on Outcomes of Cardiac Surgery in Elderly Patients. , 2016, Journal of cardiothoracic and vascular anesthesia.

[15]  J. Montaner,et al.  Plasma Matrix Metalloproteinases in Patients With Stroke During Intensive Rehabilitation Therapy. , 2016, Archives of physical medicine and rehabilitation.

[16]  M. Fernández-Matarrubia,et al.  Addenbrooke's cognitive examination III: diagnostic utility for mild cognitive impairment and dementia and correlation with standardized neuropsychological tests , 2016, International Psychogeriatrics.

[17]  Xu Liu,et al.  Dexmedetomidine sedation reduces atrial fibrillation after cardiac surgery compared to propofol: a randomized controlled trial , 2016, Critical Care.

[18]  S. Lobo,et al.  Dexmedetomidine as an Anesthetic Adjuvant in Cardiac Surgery: a Cohort Study , 2016, Brazilian journal of cardiovascular surgery.

[19]  Hong Liu,et al.  The Influence of Perioperative Dexmedetomidine on Patients Undergoing Cardiac Surgery: A Meta-Analysis , 2016, PloS one.

[20]  Quan Zhou,et al.  Effect of dexmedetomidine on myocardial ischemia-reperfusion injury in patients undergoing cardiac surgery with cardiopulmonary bypass: a meta-analysis , 2016 .

[21]  A. Rodríguez-Rodríguez,et al.  Brain injury biomarkers in the setting of cardiac surgery: Still a world to explore , 2016, Brain injury.

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

[23]  Yuhong Li,et al.  Effect of dexmedetomidine on early postoperative cognitive dysfunction and peri-operative inflammation in elderly patients undergoing laparoscopic cholecystectomy , 2015, Experimental and therapeutic medicine.

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

[25]  J. Klopfenstein,et al.  Post-transcriptional inactivation of matrix metalloproteinase-12 after focal cerebral ischemia attenuates brain damage , 2015, Scientific Reports.

[26]  G. Cheung,et al.  Performance of three cognitive screening tools in a sample of older New Zealanders , 2015, International Psychogeriatrics.

[27]  D. Sessler,et al.  Dexmedetomidine sedation after cardiac surgery decreases atrial arrhythmias. , 2014, Journal of clinical anesthesia.

[28]  Zhongmin Li,et al.  Perioperative dexmedetomidine improves mortality in patients undergoing coronary artery bypass surgery. , 2014, Journal of cardiothoracic and vascular anesthesia.

[29]  Frans R. J. Verhey,et al.  The impact of early dementia diagnosis and intervention on informal caregivers , 2013, Progress in Neurobiology.

[30]  Lining Huang,et al.  Protective effect of dexmedetomidine in coronary artery bypass grafting surgery , 2013, Experimental and therapeutic medicine.

[31]  J. Hammon Brain protection during cardiac surgery: circa 2012. , 2013, The journal of extra-corporeal technology.

[32]  Zhongmin Li,et al.  Perioperative Dexmedetomidine Improves Outcomes of Cardiac Surgery , 2013, Circulation.

[33]  A. Fijałkowska,et al.  Emotional sequelae among survivors of critical illness: a long-term retrospective study , 2013, European journal of anaesthesiology.

[34]  Carmine Zoccali,et al.  Sample size calculations: basic principles and common pitfalls. , 2010, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[35]  H. Hagberg,et al.  Expression of MMP-12 after Neonatal Hypoxic-Ischemic Brain Injury in Mice , 2009, Developmental Neuroscience.

[36]  L. Rasmussen,et al.  Cognitive dysfunction after cardiovascular surgery. , 2009, Minerva anestesiologica.

[37]  E. Marcantonio,et al.  Serologic Markers of Brain Injury and Cognitive Function After Cardiopulmonary Bypass , 2006, Annals of surgery.

[38]  L. Rasmussen,et al.  Postoperative cognitive dysfunction: incidence and prevention. , 2006, Best practice & research. Clinical anaesthesiology.

[39]  D. Mark,et al.  Association of Neurocognitive Function and Quality of Life 1 Year After Coronary Artery Bypass Graft (CABG) Surgery , 2006, Psychosomatic medicine.

[40]  Jiankun Cui,et al.  A Highly Specific Inhibitor of Matrix Metalloproteinase-9 Rescues Laminin from Proteolysis and Neurons from Apoptosis in Transient Focal Cerebral Ischemia , 2005, The Journal of Neuroscience.

[41]  E. Lo,et al.  Induction of Caspase-Mediated Cell Death by Matrix Metalloproteinases in Cerebral Endothelial Cells after Hypoxia—Reoxygenation , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[42]  S. DeKosky,et al.  Looking Backward to Move Forward: Early Detection of Neurodegenerative Disorders , 2003, Science.

[43]  K. Arai,et al.  Lipoprotein receptor–mediated induction of matrix metalloproteinase by tissue plasminogen activator , 2003, Nature Medicine.

[44]  Eng H. Lo,et al.  Neurological diseases: Mechanisms, challenges and opportunities in stroke , 2003, Nature Reviews Neuroscience.

[45]  W. White,et al.  Report of the Substudy Assessing the Impact of Neurocognitive Function on Quality of Life 5 Years After Cardiac Surgery , 2001, Stroke.

[46]  M. Fini,et al.  Effects of Matrix Metalloproteinase-9 Gene Knock-Out on the Proteolysis of Blood–Brain Barrier and White Matter Components after Cerebral Ischemia , 2001, The Journal of Neuroscience.

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

[48]  P. S. Mathuranath,et al.  A brief cognitive test battery to differentiate Alzheimer's disease and frontotemporal dementia , 2000, Neurology.

[49]  S. Shapiro,et al.  Matrix metalloproteinases cleave tissue factor pathway inhibitor. Effects on coagulation. , 2000, The Journal of biological chemistry.

[50]  M. Fujimura,et al.  Early Appearance of Activated Matrix Metalloproteinase-9 after Focal Cerebral Ischemia in Mice: A Possible Role in Blood—Brain Barrier Dysfunction , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[51]  J. Koziol,et al.  Matrix Metalloproteinases Increase Very Early during Experimental Focal Cerebral Ischemia , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[52]  R. Pierce,et al.  Matrix metalloproteinases generate angiostatin: effects on neovascularization. , 1998, Journal of immunology.

[53]  G. Rosenberg,et al.  Matrix Metalloproteinases in Cerebrovascular Disease , 1998, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[54]  T Kobayashi,et al.  Expression and localization of matrix metalloproteinase-12 in the aorta of cholesterol-fed rabbits: relationship to lesion development. , 1998, The American journal of pathology.

[55]  P. Rabbitt,et al.  Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study , 1998, The Lancet.

[56]  I. Fidler,et al.  Macrophage-Derived Metalloelastase Is Responsible for the Generation of Angiostatin in Lewis Lung Carcinoma , 1997, Cell.

[57]  S. Chandler,et al.  Macrophage metalloelastase degrades matrix and myelin proteins and processes a tumour necrosis factor-alpha fusion protein. , 1996, Biochemical and biophysical research communications.

[58]  P. Johnsson Markers of cerebral ischemia after cardiac surgery. , 1996, Journal of cardiothoracic and vascular anesthesia.