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Impact of remote ischemic preconditioning preceding coronary artery bypass grafting on inducing neuroprotection
Authors:Hrvoje Gasparovic  Tomislav Kopjar  Milan Rados  Alan Anticevic  Marko Rados  Branko Malojcic  Visnja Ivancan  Tea Fabijanic  Maja Cikes  Davor Milicic  Vladimir Gasparovic  Bojan Biocina
Affiliation:1. Department of Cardiac Surgery, University Hospital Center Zagreb, University of Zagreb, Zagreb, Croatia;4. Department of Radiology, University Hospital Center Zagreb, University of Zagreb, Zagreb, Croatia;5. Department of Neurology, University Hospital Center Zagreb, University of Zagreb, Zagreb, Croatia;6. Departments of Cardiology and Internal Medicine, University Hospital Center Zagreb, University of Zagreb, Zagreb, Croatia;2. Center of Excellence for Basic, Clinical and Translational Neuroscience, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia;3. Departments of Psychiatry and Psychology, Yale University School of Medicine, New Haven, Conn
Abstract:

Background

Neurological complications after coronary artery bypass grafting (CABG) reduce quality of life, increase mortality, and inflate resource utilization. The risk of postoperative neurological complications parallels the increasing risk burden of the contemporary patient population. We evaluated the efficacy of remote ischemic preconditioning (RIPC) on inducing neuroprotection.

Methods

Seventy patients undergoing first-time CABG were randomly assigned to RIPC or a sham procedure. Structural brain magnetic resonance imaging (MRI) was complemented with functional connectivity MRI to gain a whole-brain global connectivity analysis. Paired neurocognitive and MRI data were acquired pre- and postoperatively. The primary end point was a composite of new ischemic brain lesions and neurocognitive impairment. Secondary end points included brain connectivity profiles, pooled ischemic volumes, and individual components of the primary outcome. The Shapiro–Wilk test was used to determine whether a data set followed a normal distribution. The Fisher exact test was used to calculate the measures of association for categorical variables, whereas continuous data were tested with either the Mann–Whitney U test or the Student t test.

Results

There was no between-group difference in the incidence of the primary end point (9 [27%] in the RIPC group vs 8 [24%] in the control group, odds ratio, 1.17 [95% confidence interval, 0.34-4.06]; P = 1.0). Although RIPC did not reduce the incidence of brain ischemia (8/33 [24%] vs 7/33 [21%]; P = 1.0), the pooled ischemic volume was lower in the RIPC group (157 [interquartile range, 125-231] vs 777 [interquartile range, 564-965] mm3; P = .004). Postoperative neurocognition was marginally superior in the RIPC group as evidenced by a lower absolute number of abnormal neurocognitive tests in the RIPC group (7/99 [7%] vs 16/99 [16%]; odds ratio, 0.40 [95% confidence interval, 0.14-1.09]; P = .074). Robust reductions of functional connectivity profiles for the associative thalamus were documented in both groups, irrespective of RIPC (RIPC group, t = 3.31; P < .01; and the control group, t = 3.52; P < .01).

Conclusions

Silent brain ischemia occurs frequently after CABG. RIPC did not reduce the incidence of the primary outcome. However, RIPC significantly reduced the pooled volume of ischemic brain lesions. Surgery adversely affected global brain connectivity, with RIPC conferring no demonstrable protection. The association of RIPC with superior neurocognitive test scores failed to cross the threshold for significance.
Keywords:remote ischemic preconditioning  CABG  MRI  functional connectivity  neurocognitive outcome  BOLD  blood oxygen level-dependent  CABG  coronary artery bypass grafting  CI  confidence interval  CIFTI  Connectivity Informatics Technology Initiative  FSL  FMRIB Software Library  HCP  Human Connectome Project  MOCA  Montreal Cognitive Assessment  MRI  magnetic resonance imaging  OR  odds ratio  RIPC  remote ischemic preconditioning  RIPCAGE  Impact of Remote Ischemic Preconditioning Preceding Coronary Artery Bypass Grafting on Inducing nEuroprotection  rs-fcMRI  resting-state functional connectivity magnetic resonance imaging  TE  echo time  TMT  Trail Making Test  TR  repetition time
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